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Depression (differential diagnoses)

Depression (differential diagnoses)

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Depression, one of the most commonly diagnosed psychiatric disorders, is being diagnosed in increasing numbers in various segments of the population worldwide. Depression in the United States alone affects 17.6 million Americans each year or 1 in 6 people. Depressed patients are at increased risk of type 2 diabetes, cardiovascular disease and suicide. Within the next twenty years depression is expected to become the second leading cause of disability worldwide and the leading cause in high-income nations, including the United States. In approximately 75% of completed suicides the individuals had seen a physician within the prior year before their death, 45%-66% within the prior month. Approximately 33% - 41% of those who completed suicide had contact with mental health services in the prior year, 20% within the prior month.

There are many psychiatric and medical conditions that may mimic some or all of the symptoms of depression, or may occur comorbid to it. A disorder either psychiatric or medical that shares symptoms and characteristics of another disorder, and may be the true cause of the presenting symptoms is known as a differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

.

Many psychiatric disorders such as depression are diagnosed by allied health professionals with little or no medical training, and are made on the basis of presenting symptoms without proper consideration of the underlying cause, adequate screening of differential diagnoses is often not conducted.
According to one study "non-medical mental health care providers may be at increased risk of not recognizing masked medical illnesses in their patients."

Misdiagnosis or missed diagnoses may lead to lack of treatment or ineffective and potentially harmful treatment which may worsen the underlying causative disorder. A conservative estimate is that 10% of all psychological symptoms may be due to medical reasons, with the results of one study suggesting that about 50% of individuals with a serious mental illness "have general medical conditions that are largely undiagnosed and untreated and may cause or exacerbate psychiatric symptoms."

In a case of misdiagnosed depression recounted in Newsweek
Newsweek
Newsweek is an American weekly news magazine published in New York City. It is distributed throughout the United States and internationally. It is the second-largest news weekly magazine in the U.S., having trailed Time in circulation and advertising revenue for most of its existence...

, a writer received treatment for depression for years; during the last 10 years of her depression the symptoms worsened, resulting in multiple suicide attempts and psychiatric hospitalizations. When an MRI finally was performed it showed the presence of a tumor. She was however told by a neurologist that it was benign. After a worsening of symptoms, upon the second opinion of another neurologist, the tumor was removed. After the surgery she no longer suffered from "depression".

Autoimmune disorders

  • Celiac disease; is an autoimmune disorder in which the body is unable to digest gluten
    Gluten
    Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...

    , found in various grains such as rye and barley. Current research has shown its neuropsychiatric symptoms may manifest without the gastrointestinal symptoms.

"However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology."

  • Lupus
    Lupus
    Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...

    : Systemic lupus erythematosus (SLE), is a chronic autoimmune
    Autoimmunity
    Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

     connective tissue disease
    Connective tissue disease
    A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...

     that can affect any part of the body. Lupus can cause or worsen depression.

Bacterial-viral-parasitic infection


  • Lyme disease
    Lyme disease
    Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

    ; is a bacterial infection caused by Borrelia burgdorferi
    Borrelia burgdorferi
    Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....

    , a spirochete bacterium transmitted by the Deer tick
    Deer Tick
    Deer Tick is an American indie folk band from Providence, Rhode Island led by guitarist and singer-songwriter John McCauley. Deer Tick's music has been described as a combination of folk, blues, and country.-History:...

     (ixodes scapulari). Lyme disease is one of a group of diseases which have earned the name the "great imitator" for their propensity to mimic the symptoms of a wide variety of medical and neuropsychiatric disorders. Lyme disease is an underdiagnosed illness, partially as a result of the complexity and unreliability of serologic testing
    Serology
    Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

    .
"Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

  • Syphilis
    Syphilis
    Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

    ; the prevalence of which is on the rise, is another of the "great imitators", which if left untreated can progress to neurosyphilis
    Neurosyphilis
    Neurosyphilis is an infection of the brain or spinal cord caused by the bacterium Treponema pallidum. It usually occurs in people who have had untreated syphilis for many years, usually about 10 - 20 years after first infection.-Symptoms and signs:...

     and affect the brain, can present with solely neuropsychiatric symptoms. "This case emphasises that neurosyphilis still has to be considered in the differential diagnosis within the context of psychiatric conditions and diseases. Owing to current epidemiological data and difficulties in diagnosing syphilis, routine screening tests in the psychiatric field are necessary."
  • Neurocysticercosis (NCC): is an infection of the brain or spinal cord caused by the larva
    Larva
    A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...

    l stage of the pork tapeworm, Taenia solium. NCC is the most common helminthic (parasitic worm) infestation of the central nervous system worldwide. Humans develop cysticercosis when they ingest eggs
    Egg (biology)
    An egg is an organic vessel in which an embryo first begins to develop. In most birds, reptiles, insects, molluscs, fish, and monotremes, an egg is the zygote, resulting from fertilization of the ovum, which is expelled from the body and permitted to develop outside the body until the developing...

     of the pork tapeworm via contact with contaminated fecal matter or eating infected vegetables or undercooked pork. "While cysticercosis is endemic in Latin America
    Latin America
    Latin America is a region of the Americas where Romance languages  – particularly Spanish and Portuguese, and variably French – are primarily spoken. Latin America has an area of approximately 21,069,500 km² , almost 3.9% of the Earth's surface or 14.1% of its land surface area...

    , it is an emerging disease with increased prevalence in the United States." "The rate of depression in those with neurocysticercosis is higher than in the general population."
  • Toxoplasmosis
    Toxoplasmosis
    Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...

    ; is an infection caused by Toxoplasma gondii
    Toxoplasma gondii
    Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals . Toxoplasmosis, the disease of which T...

    an intracellular
    Intracellular
    Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

     protozoan parasite. Humans can be infected in 3 different ways: ingestion of tissue cysts, ingestion of oocysts, or in utero
    In utero
    In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...

     infection with tachyzoites. One of the prime methods for transmission to humans is contact with the feces of the host species, the domesticated cat. Toxoplasma gondii infects approximately 30% of the world's human population, but causes overt clinical symptoms in only a small segment of those infected. Exposure to Toxoplasma gondii (seropositivity) without developing Toxoplasmosis has been proven to alter various characteristics of human behavior as well as being a causative factor in some cases of depression, in addition, studies have linked seropositivity with an increased rate of suicide
  • West Nile virus
    West Nile virus
    West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

     (WNV); which can cause encephalitis
    Encephalitis
    Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

     has been reported to be a causal factor in developing depression in 31% of those infected in a study conducted in Houston, Texas and reported to the Center for Disease Control (CDC). The primary vectors for disease transmission to humans are various species of mosquito. WNV which is endemic to Southern Europe, Africa the Middle East and Asia was first identified in the United States in 1999. Between 1999 and 2006, 20,000 cases of confirmed symptomatic WNV were reported in the United States, with estimates of up to 1 million being infected. "WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future."

Blood disorders

  • Anemia
    Anemia
    Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

    : is a decrease in normal number of red blood cell
    Red blood cell
    Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

    s (RBCs) or less than the normal quantity of hemoglobin
    Hemoglobin
    Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

     in the blood. Depressive symptoms are associated with anemia in a general population of older persons living in the community.

Chronic fatigue syndrome


Between 1 and 4 million Americans are believed to have Chronic Fatigue Syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

 (CFS), yet only 50% have consulted a physician for symptoms of CFS. In addition individuals with CFS symptoms often have an undiagnosed medical or psychiatric disorder such as diabetes, thyroid disease or substance abuse. CFS, at one time considered to be psychosomatic in nature, is now considered to be a valid medical condition in which early diagnosis and treatment can aid in alleviating or completely resolving symptoms. While frequently misdiagnosed as depression, differences have been noted in rate of cerebral blood flow
Cerebral blood flow
Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...

.

CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression.

Dietary disorders

  • Fructose malabsorption
    Fructose malabsorption
    Fructose malabsorption, formerly named "dietary fructose intolerance," is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose in the entire intestine.Fructose...

     and lactose intolerance
    Lactose intolerance
    Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...

    ; deficient fructose
    Fructose
    Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

     transport by the duodenum
    Duodenum
    The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

    , or by the deficiency of the enzyme, lactase
    Lactase
    Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...

     in the mucosal lining, respectively. As a result of this malabsorption the saccharides reach the colon
    Colon (anatomy)
    The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

     and are digested by bacteria which convert them to short chain fatty acids, CO2, and H2
    H2
    -Roads and transportation:* Interstate H-2, a highway in Hawaii, located on the island of Oahu* London Buses route H2* HII, the IATA airport code for Lake Havasu City Airport-Science:...

    . Approximately 50% of those afflicted exhibit the physical signs of irritable bowel syndrome
    Irritable bowel syndrome
    Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...


"Fructose malabsorption may play a role in the development of depressed mood. Fructose malabsorption should be considered in patients with symptoms of major depression...."

"Fructose and sorbitol
Sorbitol
Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

 reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression."

Endocrine system disorders


Dysregulation of the endocrine system may present with various neuropsychiatric symptoms; irregularities in the hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

-pituitary
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

- adrenal
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 (HPA) axis and the hypothalamic-pituitary-thyroid (HPT) axis have been shown in patients with primary depression.

HPT axes irregularities:
  • alterations in thyroid-stimulating hormone
    Thyroid-stimulating hormone
    Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

     (TSH) response to thyrotropin-releasing hormone
    Thyrotropin-releasing hormone
    Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

     (TRH)
  • an abnormally high rate of antithyroid antibodies
  • elevated cerebrospinal fluid
    Cerebrospinal fluid
    Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

     (CSF) TRH concentrations.


HPA axes irregularities:
  • adrenocorticoid hypersecretion
  • enlarged pituitary and adrenal gland size (organomegaly
    Organomegaly
    Organomegaly is the abnormal enlargement of organs. For example, clitoromegaly is the enlargement of the clitoris, hepatomegaly is enlargement of the liver, cardiomegaly is enlargement of the heart, and splenomegaly is enlargement of the spleen....

    )
  • elevated corticotropin-releasing factor (CSF) concentrations


Adrenal gland

  • Addison's disease
    Addison's disease
    Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

    : also known as chronic adrenal insufficiency
    Adrenal insufficiency
    Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

    , hypocortisolism, and hypocorticism
    Cortisol
    Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

    ) is a rare endocrine disorder wherein the adrenal gland
    Adrenal gland
    In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

    s, located above the kidneys, produce insufficient steroid hormone
    Steroid hormone
    A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

    s (glucocorticoid
    Glucocorticoid
    Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

    s and often mineralocorticoid
    Mineralocorticoid
    Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...

    s). "Addison's disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed."

Thyroid and parathyroid glands


  • Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

    : an autoimmune disease where the thyroid is overactive, resulting in hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

     and thyrotoxicosis.
  • Hashimoto's thyroiditis
    Hashimoto's thyroiditis
    Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

    : also known chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes. Hashimoto's thyroiditis is associated with thyroid peroxidase
    Thyroid peroxidase
    Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...

     and thyroglobulin
    Thyroglobulin
    Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

     autoantibodies
  • Hypothyroidism
    Hypothyroidism
    Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

  • Hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

  • Hypoparathyroidism
    Hypoparathyroidism
    Hypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...

    ; can affect calcium
    Calcium
    Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

     homeostasis
    Homeostasis
    Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

    , supplementation of which has completely resolved cases of depression in which hypoparathyroidism is the sole causative factor.

Pituitary tumors


Tumors of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 are fairly common in the general population with estimates ranging as high as 25%. Most tumors are considered to be benign and are often an incidental finding discovered during autopsy or as of neuroimaging in which case they are dubbed "incidentaloma
Incidentaloma
In medicine, an incidentaloma is a tumor found by coincidence without clinical symptoms or suspicion. It is a common problem: up to 7% of all patients over 60 may harbor a benign growth, often of the adrenal gland, which is detected when diagnostic imaging is used for the analysis of unrelated...

s". Even in benign cases, pituitary tumors can affect cognitive, behavioral and emotional changes. Pituitary microadenomas are smaller than 10 mm in diameter and are generally considered benign, yet the presence of a microadenoma has been positively identified as a risk factor for suicide.

"... patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression".

Pancreas

  • Hypoglycemia
    Hypoglycemia
    Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

    : an overproduction of insulin
    Insulin
    Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

     causes reduced blood levels of glucose
    Glucose
    Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

    . In one study of patients recovering from acute lung injury in intensive care, those patients who developed hypoglycemia while hospitalized showed an increased rate of depression.

Neurological


In addition to pituitary tumors, tumors in various locations in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 may cause depressive symptoms and be misdiagnosed as depression.

Post concussion syndrome


Post-concussion syndrome
Post-concussion syndrome
Post-concussion syndrome, also known as postconcussive syndrome or PCS, and historically called shell shock, is a set of symptoms that a person may experience for weeks, months, or occasionally up to a year or more after a concussion – a mild form of traumatic brain injury . PCS may also...

(PCS), is a set of symptoms that a person may experience for weeks, months, or occasionally years after a concussion with a prevalence rate of 38–80% in mild traumatic brain injuries, it may also occur in moderate and severe cases of traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

. A diagnosis may be made when symptoms resulting from concussion, depending on criteria, last for more than three to six months after the injury, in which case it is termed persistent postconcussive syndrome (PPCS). In a study of the prevalence of post concussion syndrome symptoms in patients with depression utilizing the British Columbia Postconcussion Symptom Inventory
British Columbia Postconcussion Symptom Inventory
The British Columbia Postconcussion Symptom Inventory , is a 16 item self-report inventory designed to measure both the frequency, and intensity of the ICD-10 criteria for Post concussion syndrome, which is a common occurrence in cases of mild traumatic brain injury...

: "Approximately 9 out of 10 patients with depression met liberal self-report criteria for a postconcussion syndrome and more than 5 out of 10 met conservative criteria for the diagnosis." These self reported rates were significantly higher than those obtained in a scheduled clinical interview. Normal controls have exhibited symptoms of PCS as well as those seeking psychological services. There is considerable debate over the diagnosis of PCS in part because of the medico-legal and thus monetary ramifications of receiving the diagnosis.

Pseudobulbar affect



Pseudobulbar affect
Pseudobulbar affect
Pseudobulbar affect , emotional lability, labile affect or emotional incontinence refers to a neurologic disorder characterized by involuntary crying or uncontrollable episodes of crying and/or laughing, or other emotional displays. PBA occurs secondary to neurologic disease or brain injury...

 (PBA) is an affective disinhibition syndrome that is largely unrecognized in clinical settings and thus often untreated due to ignorance of the clinical manifestations of the disorder; it may be misdiagnosed as depression. It often occurs secondary to various neurodegenerative diseases such as amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

, and also can result from head trauma. PBA is characterized by involuntary and inappropriate outbursts of laughter and/or crying. PBA has a high prevalence rate with estimates of 1.5 - 2 million cases in the United States alone.

Neurotoxicity


Various compounds have been shown to have neurotoxic effects many of which have been implicated as having a causal relationship in the development of depression.

Cigarette smoking


There has been research which suggests a correlation between cigarette smoking and depression. The results of one recent study suggest that smoking cigarettes may have a direct causal effect on the development of depression. There have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts.

In a study conducted among nurses, those smoking between 1-24 cigarettes per day had twice the suicide risk; 25 cigarettes or more, 4 times the suicide risk, than those who had never smoked. In a study of 300,000 male U.S. Army soldiers, a definitive link between suicide and smoking was observed with those smoking over a pack a day having twice the suicide rate of non-smokers.


"Current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt."

"It would seem unwise, nevertheless, to rule out the possibility that smoking might be among the antecedent factors associated with the development of depression."

"Abstinence from cigarettes for prolonged periods may be associated with a decrease in depressive symptomatology."

"The stress induction model of smoking suggests, however, that smoking causes stress and concomitant negative affect."


Medication


Various medications have been suspected of a having a causal relation in the development of depression; this has been classified as "organic mood syndrome". Some classes of medication such as those used to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, have been recognized for decades as having a definitive relationship with the development of depression.

Monitoring of those taking medications which have shown a relationship with depression is often indicated, as well as the necessity of factoring in the use of such medications in the diagnostic process.
  • Topical Tretinoin
    Tretinoin
    Tretinoin is the acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel...

     (Retin-A); derived from Vitamin A
    Vitamin A
    Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...

     and used for various medical conditions such as in topical solutions used to treat acne vulgaris
    Acne vulgaris
    Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...

    . Although applied externally to the skin, it may enter the bloodstream and cross the blood brain barrier where it may have neurotoxic effects.

  • Interferons; proteins produced by the human body, three types have been identified alpha, beta and gamma. Synthetic versions are utilized in various medications used to treat different medical conditions such as the use of interferon-alpha in cancer treatment
    Chemotherapy
    Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

     and hepatitis C
    Hepatitis C
    Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

     treatment. All three classes of interferons may cause depression and suicidal ideation.

Chronic Exposure to Organophosphates


The neurophsychiatric effects of chronic organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue.

Bipolar disorder

  • Bipolar disorder
    Bipolar disorder
    Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

     is frequently misdiagnosed as major depression, and is thus treated with antidepressants alone which is not only not efficacious it is often contraindicated as it may exacerbate hypomania, mania, or cycling between moods. J Clin Psychiatry. 2005 Nov;66(11):1432-40.
"Misdiagnosed bipolar patients received inappropriate and costly treatment regimens involving overuse of antidepressants and underuse of potentially effective medications. ... It is recommended that steps be taken to minimize misdiagnosis in clinical settings."

Nutritional deficiencies


Nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. Insufficient or inadeqaute nutrition can have a profound effect on mental health. The emerging field of Nutritional Neuroscience
Nutritional Neuroscience
Nutritional neuroscience: is the scientific discipline that studies the role of various components of the average diet such as protein, carbohydrates, and fats, dietary supplements and synthetic hormones, and food additives have on neurochemistry, neurobiology, and behavior.Recent research on...

 explores the various connections between diet, neurological functioning and mental health.
  • Vitamin B6
    Vitamin B6
    Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

    :pyridoxal phosphate (PLP) the active form of B6 is a cofactor in the dopamine serotonin pathway, a deficiency in Vitamin B6 may cause depressive symptoms.
  • Folate (vitamin B9) - Vitamin B

    Depression, one of the most commonly diagnosed psychiatric disorders, is being diagnosed in increasing numbers in various segments of the population worldwide. Depression in the United States alone affects 17.6 million Americans each year or 1 in 6 people. Depressed patients are at increased risk of type 2 diabetes, cardiovascular disease and suicide. Within the next twenty years depression is expected to become the second leading cause of disability worldwide and the leading cause in high-income nations, including the United States. In approximately 75% of completed suicides the individuals had seen a physician within the prior year before their death, 45%-66% within the prior month. Approximately 33% - 41% of those who completed suicide had contact with mental health services in the prior year, 20% within the prior month.

    There are many psychiatric and medical conditions that may mimic some or all of the symptoms of depression, or may occur comorbid to it. A disorder either psychiatric or medical that shares symptoms and characteristics of another disorder, and may be the true cause of the presenting symptoms is known as a
    differential diagnosis
    Differential diagnosis
    A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

    .

    Many psychiatric disorders such as depression are diagnosed by allied health professionals with little or no medical training, and are made on the basis of presenting symptoms without proper consideration of the underlying cause, adequate screening of differential diagnoses is often not conducted.
    According to one study "non-medical mental health care providers may be at increased risk of not recognizing masked medical illnesses in their patients."

    Misdiagnosis or missed diagnoses may lead to lack of treatment or ineffective and potentially harmful treatment which may worsen the underlying causative disorder. A conservative estimate is that 10% of all psychological symptoms may be due to medical reasons, with the results of one study suggesting that about 50% of individuals with a serious mental illness "have general medical conditions that are largely undiagnosed and untreated and may cause or exacerbate psychiatric symptoms."

    In a case of misdiagnosed depression recounted in Newsweek
    Newsweek
    Newsweek is an American weekly news magazine published in New York City. It is distributed throughout the United States and internationally. It is the second-largest news weekly magazine in the U.S., having trailed Time in circulation and advertising revenue for most of its existence...

    , a writer received treatment for depression for years; during the last 10 years of her depression the symptoms worsened, resulting in multiple suicide attempts and psychiatric hospitalizations. When an MRI finally was performed it showed the presence of a tumor. She was however told by a neurologist that it was benign. After a worsening of symptoms, upon the second opinion of another neurologist, the tumor was removed. After the surgery she no longer suffered from "depression".

    Autoimmune disorders

    • Celiac disease; is an autoimmune disorder in which the body is unable to digest gluten
      Gluten
      Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...

      , found in various grains such as rye and barley. Current research has shown its neuropsychiatric symptoms may manifest without the gastrointestinal symptoms.

    "However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology."

    • Lupus
      Lupus
      Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...

      : Systemic lupus erythematosus (SLE), is a chronic autoimmune
      Autoimmunity
      Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

       connective tissue disease
      Connective tissue disease
      A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...

       that can affect any part of the body. Lupus can cause or worsen depression.

    Bacterial-viral-parasitic infection


    • Lyme disease
      Lyme disease
      Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

      ; is a bacterial infection caused by Borrelia burgdorferi
      Borrelia burgdorferi
      Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....

      , a spirochete bacterium transmitted by the Deer tick
      Deer Tick
      Deer Tick is an American indie folk band from Providence, Rhode Island led by guitarist and singer-songwriter John McCauley. Deer Tick's music has been described as a combination of folk, blues, and country.-History:...

       (ixodes scapulari). Lyme disease is one of a group of diseases which have earned the name the "great imitator" for their propensity to mimic the symptoms of a wide variety of medical and neuropsychiatric disorders. Lyme disease is an underdiagnosed illness, partially as a result of the complexity and unreliability of serologic testing
      Serology
      Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

      .
    "Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

    • Syphilis
      Syphilis
      Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

      ; the prevalence of which is on the rise, is another of the "great imitators", which if left untreated can progress to neurosyphilis
      Neurosyphilis
      Neurosyphilis is an infection of the brain or spinal cord caused by the bacterium Treponema pallidum. It usually occurs in people who have had untreated syphilis for many years, usually about 10 - 20 years after first infection.-Symptoms and signs:...

       and affect the brain, can present with solely neuropsychiatric symptoms. "This case emphasises that neurosyphilis still has to be considered in the differential diagnosis within the context of psychiatric conditions and diseases. Owing to current epidemiological data and difficulties in diagnosing syphilis, routine screening tests in the psychiatric field are necessary."
    • Neurocysticercosis (NCC): is an infection of the brain or spinal cord caused by the larva
      Larva
      A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...

      l stage of the pork tapeworm, Taenia solium. NCC is the most common helminthic (parasitic worm) infestation of the central nervous system worldwide. Humans develop cysticercosis when they ingest eggs
      Egg (biology)
      An egg is an organic vessel in which an embryo first begins to develop. In most birds, reptiles, insects, molluscs, fish, and monotremes, an egg is the zygote, resulting from fertilization of the ovum, which is expelled from the body and permitted to develop outside the body until the developing...

       of the pork tapeworm via contact with contaminated fecal matter or eating infected vegetables or undercooked pork. "While cysticercosis is endemic in Latin America
      Latin America
      Latin America is a region of the Americas where Romance languages  – particularly Spanish and Portuguese, and variably French – are primarily spoken. Latin America has an area of approximately 21,069,500 km² , almost 3.9% of the Earth's surface or 14.1% of its land surface area...

      , it is an emerging disease with increased prevalence in the United States." "The rate of depression in those with neurocysticercosis is higher than in the general population."
    • Toxoplasmosis
      Toxoplasmosis
      Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...

      ; is an infection caused by Toxoplasma gondii
      Toxoplasma gondii
      Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals . Toxoplasmosis, the disease of which T...

      an intracellular
      Intracellular
      Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

       protozoan parasite. Humans can be infected in 3 different ways: ingestion of tissue cysts, ingestion of oocysts, or in utero
      In utero
      In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...

       infection with tachyzoites. One of the prime methods for transmission to humans is contact with the feces of the host species, the domesticated cat. Toxoplasma gondii infects approximately 30% of the world's human population, but causes overt clinical symptoms in only a small segment of those infected. Exposure to Toxoplasma gondii (seropositivity) without developing Toxoplasmosis has been proven to alter various characteristics of human behavior as well as being a causative factor in some cases of depression, in addition, studies have linked seropositivity with an increased rate of suicide
    • West Nile virus
      West Nile virus
      West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

       (WNV); which can cause encephalitis
      Encephalitis
      Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

       has been reported to be a causal factor in developing depression in 31% of those infected in a study conducted in Houston, Texas and reported to the Center for Disease Control (CDC). The primary vectors for disease transmission to humans are various species of mosquito. WNV which is endemic to Southern Europe, Africa the Middle East and Asia was first identified in the United States in 1999. Between 1999 and 2006, 20,000 cases of confirmed symptomatic WNV were reported in the United States, with estimates of up to 1 million being infected. "WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future."

    Blood disorders

    • Anemia
      Anemia
      Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

      : is a decrease in normal number of red blood cell
      Red blood cell
      Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

      s (RBCs) or less than the normal quantity of hemoglobin
      Hemoglobin
      Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

       in the blood. Depressive symptoms are associated with anemia in a general population of older persons living in the community.

    Chronic fatigue syndrome


    Between 1 and 4 million Americans are believed to have Chronic Fatigue Syndrome
    Chronic fatigue syndrome
    Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

     (CFS), yet only 50% have consulted a physician for symptoms of CFS. In addition individuals with CFS symptoms often have an undiagnosed medical or psychiatric disorder such as diabetes, thyroid disease or substance abuse. CFS, at one time considered to be psychosomatic in nature, is now considered to be a valid medical condition in which early diagnosis and treatment can aid in alleviating or completely resolving symptoms. While frequently misdiagnosed as depression, differences have been noted in rate of cerebral blood flow
    Cerebral blood flow
    Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...

    .

    CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression.

    Dietary disorders

    • Fructose malabsorption
      Fructose malabsorption
      Fructose malabsorption, formerly named "dietary fructose intolerance," is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose in the entire intestine.Fructose...

       and lactose intolerance
      Lactose intolerance
      Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...

      ; deficient fructose
      Fructose
      Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

       transport by the duodenum
      Duodenum
      The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

      , or by the deficiency of the enzyme, lactase
      Lactase
      Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...

       in the mucosal lining, respectively. As a result of this malabsorption the saccharides reach the colon
      Colon (anatomy)
      The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

       and are digested by bacteria which convert them to short chain fatty acids, CO2, and H2
      H2
      -Roads and transportation:* Interstate H-2, a highway in Hawaii, located on the island of Oahu* London Buses route H2* HII, the IATA airport code for Lake Havasu City Airport-Science:...

      . Approximately 50% of those afflicted exhibit the physical signs of irritable bowel syndrome
      Irritable bowel syndrome
      Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...


    "Fructose malabsorption may play a role in the development of depressed mood. Fructose malabsorption should be considered in patients with symptoms of major depression...."

    "Fructose and sorbitol
    Sorbitol
    Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

     reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression."

    Endocrine system disorders


    Dysregulation of the endocrine system may present with various neuropsychiatric symptoms; irregularities in the hypothalamic
    Hypothalamus
    The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

    -pituitary
    Pituitary gland
    In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

    - adrenal
    Adrenal gland
    In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

     (HPA) axis and the hypothalamic-pituitary-thyroid (HPT) axis have been shown in patients with primary depression.

    HPT axes irregularities:
    • alterations in thyroid-stimulating hormone
      Thyroid-stimulating hormone
      Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

       (TSH) response to thyrotropin-releasing hormone
      Thyrotropin-releasing hormone
      Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

       (TRH)
    • an abnormally high rate of antithyroid antibodies
    • elevated cerebrospinal fluid
      Cerebrospinal fluid
      Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

       (CSF) TRH concentrations.


    HPA axes irregularities:
    • adrenocorticoid hypersecretion
    • enlarged pituitary and adrenal gland size (organomegaly
      Organomegaly
      Organomegaly is the abnormal enlargement of organs. For example, clitoromegaly is the enlargement of the clitoris, hepatomegaly is enlargement of the liver, cardiomegaly is enlargement of the heart, and splenomegaly is enlargement of the spleen....

      )
    • elevated corticotropin-releasing factor (CSF) concentrations

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Adrenal gland

  • Addison's disease
    Addison's disease
    Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

    : also known as chronic adrenal insufficiency
    Adrenal insufficiency
    Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

    , hypocortisolism, and hypocorticism
    Cortisol
    Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

    ) is a rare endocrine disorder wherein the adrenal gland
    Adrenal gland
    In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

    s, located above the kidneys, produce insufficient steroid hormone
    Steroid hormone
    A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

    s (glucocorticoid
    Glucocorticoid
    Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

    s and often mineralocorticoid
    Mineralocorticoid
    Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...

    s). "Addison's disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed."

Thyroid and parathyroid glands


  • Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

    : an autoimmune disease where the thyroid is overactive, resulting in hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

     and thyrotoxicosis.
  • Hashimoto's thyroiditis
    Hashimoto's thyroiditis
    Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

    : also known chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes. Hashimoto's thyroiditis is associated with thyroid peroxidase
    Thyroid peroxidase
    Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...

     and thyroglobulin
    Thyroglobulin
    Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

     autoantibodies
  • Hypothyroidism
    Hypothyroidism
    Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

  • Hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

  • Hypoparathyroidism
    Hypoparathyroidism
    Hypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...

    ; can affect calcium
    Calcium
    Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

     homeostasis
    Homeostasis
    Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

    , supplementation of which has completely resolved cases of depression in which hypoparathyroidism is the sole causative factor.

Pituitary tumors


Tumors of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 are fairly common in the general population with estimates ranging as high as 25%. Most tumors are considered to be benign and are often an incidental finding discovered during autopsy or as of neuroimaging in which case they are dubbed "incidentaloma
Incidentaloma
In medicine, an incidentaloma is a tumor found by coincidence without clinical symptoms or suspicion. It is a common problem: up to 7% of all patients over 60 may harbor a benign growth, often of the adrenal gland, which is detected when diagnostic imaging is used for the analysis of unrelated...

s". Even in benign cases, pituitary tumors can affect cognitive, behavioral and emotional changes. Pituitary microadenomas are smaller than 10 mm in diameter and are generally considered benign, yet the presence of a microadenoma has been positively identified as a risk factor for suicide.

"... patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression".

Pancreas

  • Hypoglycemia
    Hypoglycemia
    Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

    : an overproduction of insulin
    Insulin
    Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

     causes reduced blood levels of glucose
    Glucose
    Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

    . In one study of patients recovering from acute lung injury in intensive care, those patients who developed hypoglycemia while hospitalized showed an increased rate of depression.

Neurological


In addition to pituitary tumors, tumors in various locations in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 may cause depressive symptoms and be misdiagnosed as depression.

Post concussion syndrome


Post-concussion syndrome
Post-concussion syndrome
Post-concussion syndrome, also known as postconcussive syndrome or PCS, and historically called shell shock, is a set of symptoms that a person may experience for weeks, months, or occasionally up to a year or more after a concussion – a mild form of traumatic brain injury . PCS may also...

(PCS), is a set of symptoms that a person may experience for weeks, months, or occasionally years after a concussion with a prevalence rate of 38–80% in mild traumatic brain injuries, it may also occur in moderate and severe cases of traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

. A diagnosis may be made when symptoms resulting from concussion, depending on criteria, last for more than three to six months after the injury, in which case it is termed persistent postconcussive syndrome (PPCS). In a study of the prevalence of post concussion syndrome symptoms in patients with depression utilizing the British Columbia Postconcussion Symptom Inventory
British Columbia Postconcussion Symptom Inventory
The British Columbia Postconcussion Symptom Inventory , is a 16 item self-report inventory designed to measure both the frequency, and intensity of the ICD-10 criteria for Post concussion syndrome, which is a common occurrence in cases of mild traumatic brain injury...

: "Approximately 9 out of 10 patients with depression met liberal self-report criteria for a postconcussion syndrome and more than 5 out of 10 met conservative criteria for the diagnosis." These self reported rates were significantly higher than those obtained in a scheduled clinical interview. Normal controls have exhibited symptoms of PCS as well as those seeking psychological services. There is considerable debate over the diagnosis of PCS in part because of the medico-legal and thus monetary ramifications of receiving the diagnosis.

Pseudobulbar affect



Pseudobulbar affect
Pseudobulbar affect
Pseudobulbar affect , emotional lability, labile affect or emotional incontinence refers to a neurologic disorder characterized by involuntary crying or uncontrollable episodes of crying and/or laughing, or other emotional displays. PBA occurs secondary to neurologic disease or brain injury...

 (PBA) is an affective disinhibition syndrome that is largely unrecognized in clinical settings and thus often untreated due to ignorance of the clinical manifestations of the disorder; it may be misdiagnosed as depression. It often occurs secondary to various neurodegenerative diseases such as amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

, and also can result from head trauma. PBA is characterized by involuntary and inappropriate outbursts of laughter and/or crying. PBA has a high prevalence rate with estimates of 1.5 - 2 million cases in the United States alone.
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Neurotoxicity


Various compounds have been shown to have neurotoxic effects many of which have been implicated as having a causal relationship in the development of depression.

Cigarette smoking


There has been research which suggests a correlation between cigarette smoking and depression. The results of one recent study suggest that smoking cigarettes may have a direct causal effect on the development of depression. There have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts.

In a study conducted among nurses, those smoking between 1-24 cigarettes per day had twice the suicide risk; 25 cigarettes or more, 4 times the suicide risk, than those who had never smoked. In a study of 300,000 male U.S. Army soldiers, a definitive link between suicide and smoking was observed with those smoking over a pack a day having twice the suicide rate of non-smokers.


"Current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt."

"It would seem unwise, nevertheless, to rule out the possibility that smoking might be among the antecedent factors associated with the development of depression."

"Abstinence from cigarettes for prolonged periods may be associated with a decrease in depressive symptomatology."

"The stress induction model of smoking suggests, however, that smoking causes stress and concomitant negative affect."

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Medication


Various medications have been suspected of a having a causal relation in the development of depression; this has been classified as "organic mood syndrome". Some classes of medication such as those used to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, have been recognized for decades as having a definitive relationship with the development of depression.

Monitoring of those taking medications which have shown a relationship with depression is often indicated, as well as the necessity of factoring in the use of such medications in the diagnostic process.
  • Topical Tretinoin
    Tretinoin
    Tretinoin is the acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel...

     (Retin-A); derived from Vitamin A
    Vitamin A
    Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...

     and used for various medical conditions such as in topical solutions used to treat acne vulgaris
    Acne vulgaris
    Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...

    . Although applied externally to the skin, it may enter the bloodstream and cross the blood brain barrier where it may have neurotoxic effects.

  • Interferons; proteins produced by the human body, three types have been identified alpha, beta and gamma. Synthetic versions are utilized in various medications used to treat different medical conditions such as the use of interferon-alpha in cancer treatment
    Chemotherapy
    Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

     and hepatitis C
    Hepatitis C
    Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

     treatment. All three classes of interferons may cause depression and suicidal ideation.

Chronic Exposure to Organophosphates


The neurophsychiatric effects of chronic organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue.

Bipolar disorder

  • Bipolar disorder
    Bipolar disorder
    Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

     is frequently misdiagnosed as major depression, and is thus treated with antidepressants alone which is not only not efficacious it is often contraindicated as it may exacerbate hypomania, mania, or cycling between moods. J Clin Psychiatry. 2005 Nov;66(11):1432-40.
"Misdiagnosed bipolar patients received inappropriate and costly treatment regimens involving overuse of antidepressants and underuse of potentially effective medications. ... It is recommended that steps be taken to minimize misdiagnosis in clinical settings."

Nutritional deficiencies


Nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. Insufficient or inadeqaute nutrition can have a profound effect on mental health. The emerging field of Nutritional Neuroscience
Nutritional Neuroscience
Nutritional neuroscience: is the scientific discipline that studies the role of various components of the average diet such as protein, carbohydrates, and fats, dietary supplements and synthetic hormones, and food additives have on neurochemistry, neurobiology, and behavior.Recent research on...

 explores the various connections between diet, neurological functioning and mental health.
  • Vitamin B6
    Vitamin B6
    Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

    :pyridoxal phosphate (PLP) the active form of B6 is a cofactor in the dopamine serotonin pathway, a deficiency in Vitamin B6 may cause depressive symptoms.
  • Folate (vitamin B9) - Vitamin B

    Depression, one of the most commonly diagnosed psychiatric disorders, is being diagnosed in increasing numbers in various segments of the population worldwide. Depression in the United States alone affects 17.6 million Americans each year or 1 in 6 people. Depressed patients are at increased risk of type 2 diabetes, cardiovascular disease and suicide. Within the next twenty years depression is expected to become the second leading cause of disability worldwide and the leading cause in high-income nations, including the United States. In approximately 75% of completed suicides the individuals had seen a physician within the prior year before their death, 45%-66% within the prior month. Approximately 33% - 41% of those who completed suicide had contact with mental health services in the prior year, 20% within the prior month.

    There are many psychiatric and medical conditions that may mimic some or all of the symptoms of depression, or may occur comorbid to it. A disorder either psychiatric or medical that shares symptoms and characteristics of another disorder, and may be the true cause of the presenting symptoms is known as a
    differential diagnosis
    Differential diagnosis
    A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

    .

    Many psychiatric disorders such as depression are diagnosed by allied health professionals with little or no medical training, and are made on the basis of presenting symptoms without proper consideration of the underlying cause, adequate screening of differential diagnoses is often not conducted.
    According to one study "non-medical mental health care providers may be at increased risk of not recognizing masked medical illnesses in their patients."

    Misdiagnosis or missed diagnoses may lead to lack of treatment or ineffective and potentially harmful treatment which may worsen the underlying causative disorder. A conservative estimate is that 10% of all psychological symptoms may be due to medical reasons, with the results of one study suggesting that about 50% of individuals with a serious mental illness "have general medical conditions that are largely undiagnosed and untreated and may cause or exacerbate psychiatric symptoms."

    In a case of misdiagnosed depression recounted in Newsweek
    Newsweek
    Newsweek is an American weekly news magazine published in New York City. It is distributed throughout the United States and internationally. It is the second-largest news weekly magazine in the U.S., having trailed Time in circulation and advertising revenue for most of its existence...

    , a writer received treatment for depression for years; during the last 10 years of her depression the symptoms worsened, resulting in multiple suicide attempts and psychiatric hospitalizations. When an MRI finally was performed it showed the presence of a tumor. She was however told by a neurologist that it was benign. After a worsening of symptoms, upon the second opinion of another neurologist, the tumor was removed. After the surgery she no longer suffered from "depression".

    Autoimmune disorders

    • Celiac disease; is an autoimmune disorder in which the body is unable to digest gluten
      Gluten
      Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...

      , found in various grains such as rye and barley. Current research has shown its neuropsychiatric symptoms may manifest without the gastrointestinal symptoms.

    "However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology."

    • Lupus
      Lupus
      Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...

      : Systemic lupus erythematosus (SLE), is a chronic autoimmune
      Autoimmunity
      Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...

       connective tissue disease
      Connective tissue disease
      A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...

       that can affect any part of the body. Lupus can cause or worsen depression.

    Bacterial-viral-parasitic infection


    • Lyme disease
      Lyme disease
      Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

      ; is a bacterial infection caused by Borrelia burgdorferi
      Borrelia burgdorferi
      Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....

      , a spirochete bacterium transmitted by the Deer tick
      Deer Tick
      Deer Tick is an American indie folk band from Providence, Rhode Island led by guitarist and singer-songwriter John McCauley. Deer Tick's music has been described as a combination of folk, blues, and country.-History:...

       (ixodes scapulari). Lyme disease is one of a group of diseases which have earned the name the "great imitator" for their propensity to mimic the symptoms of a wide variety of medical and neuropsychiatric disorders. Lyme disease is an underdiagnosed illness, partially as a result of the complexity and unreliability of serologic testing
      Serology
      Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

      .
    "Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

    • Syphilis
      Syphilis
      Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

      ; the prevalence of which is on the rise, is another of the "great imitators", which if left untreated can progress to neurosyphilis
      Neurosyphilis
      Neurosyphilis is an infection of the brain or spinal cord caused by the bacterium Treponema pallidum. It usually occurs in people who have had untreated syphilis for many years, usually about 10 - 20 years after first infection.-Symptoms and signs:...

       and affect the brain, can present with solely neuropsychiatric symptoms. "This case emphasises that neurosyphilis still has to be considered in the differential diagnosis within the context of psychiatric conditions and diseases. Owing to current epidemiological data and difficulties in diagnosing syphilis, routine screening tests in the psychiatric field are necessary."
    • Neurocysticercosis (NCC): is an infection of the brain or spinal cord caused by the larva
      Larva
      A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...

      l stage of the pork tapeworm, Taenia solium. NCC is the most common helminthic (parasitic worm) infestation of the central nervous system worldwide. Humans develop cysticercosis when they ingest eggs
      Egg (biology)
      An egg is an organic vessel in which an embryo first begins to develop. In most birds, reptiles, insects, molluscs, fish, and monotremes, an egg is the zygote, resulting from fertilization of the ovum, which is expelled from the body and permitted to develop outside the body until the developing...

       of the pork tapeworm via contact with contaminated fecal matter or eating infected vegetables or undercooked pork. "While cysticercosis is endemic in Latin America
      Latin America
      Latin America is a region of the Americas where Romance languages  – particularly Spanish and Portuguese, and variably French – are primarily spoken. Latin America has an area of approximately 21,069,500 km² , almost 3.9% of the Earth's surface or 14.1% of its land surface area...

      , it is an emerging disease with increased prevalence in the United States." "The rate of depression in those with neurocysticercosis is higher than in the general population."
    • Toxoplasmosis
      Toxoplasmosis
      Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...

      ; is an infection caused by Toxoplasma gondii
      Toxoplasma gondii
      Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma. The definitive host of T. gondii is the cat, but the parasite can be carried by many warm-blooded animals . Toxoplasmosis, the disease of which T...

      an intracellular
      Intracellular
      Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

       protozoan parasite. Humans can be infected in 3 different ways: ingestion of tissue cysts, ingestion of oocysts, or in utero
      In utero
      In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...

       infection with tachyzoites. One of the prime methods for transmission to humans is contact with the feces of the host species, the domesticated cat. Toxoplasma gondii infects approximately 30% of the world's human population, but causes overt clinical symptoms in only a small segment of those infected. Exposure to Toxoplasma gondii (seropositivity) without developing Toxoplasmosis has been proven to alter various characteristics of human behavior as well as being a causative factor in some cases of depression, in addition, studies have linked seropositivity with an increased rate of suicide
    • West Nile virus
      West Nile virus
      West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

       (WNV); which can cause encephalitis
      Encephalitis
      Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

       has been reported to be a causal factor in developing depression in 31% of those infected in a study conducted in Houston, Texas and reported to the Center for Disease Control (CDC). The primary vectors for disease transmission to humans are various species of mosquito. WNV which is endemic to Southern Europe, Africa the Middle East and Asia was first identified in the United States in 1999. Between 1999 and 2006, 20,000 cases of confirmed symptomatic WNV were reported in the United States, with estimates of up to 1 million being infected. "WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future."

    Blood disorders

    • Anemia
      Anemia
      Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

      : is a decrease in normal number of red blood cell
      Red blood cell
      Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

      s (RBCs) or less than the normal quantity of hemoglobin
      Hemoglobin
      Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

       in the blood. Depressive symptoms are associated with anemia in a general population of older persons living in the community.

    Chronic fatigue syndrome


    Between 1 and 4 million Americans are believed to have Chronic Fatigue Syndrome
    Chronic fatigue syndrome
    Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...

     (CFS), yet only 50% have consulted a physician for symptoms of CFS. In addition individuals with CFS symptoms often have an undiagnosed medical or psychiatric disorder such as diabetes, thyroid disease or substance abuse. CFS, at one time considered to be psychosomatic in nature, is now considered to be a valid medical condition in which early diagnosis and treatment can aid in alleviating or completely resolving symptoms. While frequently misdiagnosed as depression, differences have been noted in rate of cerebral blood flow
    Cerebral blood flow
    Cerebral blood flow, or CBF, is the blood supply to the brain in a given time. In an adult, CBF is typically 750 millitres per minute or 15% of the cardiac output. This equates to 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. CBF is tightly regulated to meet the brain's...

    .

    CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression.

    Dietary disorders

    • Fructose malabsorption
      Fructose malabsorption
      Fructose malabsorption, formerly named "dietary fructose intolerance," is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose in the entire intestine.Fructose...

       and lactose intolerance
      Lactose intolerance
      Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...

      ; deficient fructose
      Fructose
      Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

       transport by the duodenum
      Duodenum
      The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

      , or by the deficiency of the enzyme, lactase
      Lactase
      Lactase , a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers...

       in the mucosal lining, respectively. As a result of this malabsorption the saccharides reach the colon
      Colon (anatomy)
      The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...

       and are digested by bacteria which convert them to short chain fatty acids, CO2, and H2
      H2
      -Roads and transportation:* Interstate H-2, a highway in Hawaii, located on the island of Oahu* London Buses route H2* HII, the IATA airport code for Lake Havasu City Airport-Science:...

      . Approximately 50% of those afflicted exhibit the physical signs of irritable bowel syndrome
      Irritable bowel syndrome
      Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...


    "Fructose malabsorption may play a role in the development of depressed mood. Fructose malabsorption should be considered in patients with symptoms of major depression...."

    "Fructose and sorbitol
    Sorbitol
    Sorbitol, also known as glucitol, Sorbogem® and Sorbo®, is a sugar alcohol that the human body metabolizes slowly. It can be obtained by reduction of glucose, changing the aldehyde group to a hydroxyl group. Sorbitol is found in apples, pears, peaches, and prunes...

     reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression."

    Endocrine system disorders


    Dysregulation of the endocrine system may present with various neuropsychiatric symptoms; irregularities in the hypothalamic
    Hypothalamus
    The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

    -pituitary
    Pituitary gland
    In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

    - adrenal
    Adrenal gland
    In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

     (HPA) axis and the hypothalamic-pituitary-thyroid (HPT) axis have been shown in patients with primary depression.

    HPT axes irregularities:
    • alterations in thyroid-stimulating hormone
      Thyroid-stimulating hormone
      Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

       (TSH) response to thyrotropin-releasing hormone
      Thyrotropin-releasing hormone
      Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

       (TRH)
    • an abnormally high rate of antithyroid antibodies
    • elevated cerebrospinal fluid
      Cerebrospinal fluid
      Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

       (CSF) TRH concentrations.


    HPA axes irregularities:
    • adrenocorticoid hypersecretion
    • enlarged pituitary and adrenal gland size (organomegaly
      Organomegaly
      Organomegaly is the abnormal enlargement of organs. For example, clitoromegaly is the enlargement of the clitoris, hepatomegaly is enlargement of the liver, cardiomegaly is enlargement of the heart, and splenomegaly is enlargement of the spleen....

      )
    • elevated corticotropin-releasing factor (CSF) concentrations

{{Clear}}

Adrenal gland

  • Addison's disease
    Addison's disease
    Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

    : also known as chronic adrenal insufficiency
    Adrenal insufficiency
    Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

    , hypocortisolism, and hypocorticism
    Cortisol
    Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

    ) is a rare endocrine disorder wherein the adrenal gland
    Adrenal gland
    In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

    s, located above the kidneys, produce insufficient steroid hormone
    Steroid hormone
    A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

    s (glucocorticoid
    Glucocorticoid
    Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

    s and often mineralocorticoid
    Mineralocorticoid
    Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...

    s). "Addison's disease presenting with psychiatric features in the early stage has the tendency to be overlooked and misdiagnosed."

Thyroid and parathyroid glands


  • Graves' disease
    Graves' disease
    Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...

    : an autoimmune disease where the thyroid is overactive, resulting in hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

     and thyrotoxicosis.
  • Hashimoto's thyroiditis
    Hashimoto's thyroiditis
    Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...

    : also known chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes. Hashimoto's thyroiditis is associated with thyroid peroxidase
    Thyroid peroxidase
    Thyroid peroxidase or thyroperoxidase is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobulin for the production of thyroxine or triiodothyronine , thyroid hormones. In humans, thyroperoxidase is encoded by the TPO...

     and thyroglobulin
    Thyroglobulin
    Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....

     autoantibodies
  • Hypothyroidism
    Hypothyroidism
    Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

  • Hyperthyroidism
    Hyperthyroidism
    Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...

  • Hypoparathyroidism
    Hypoparathyroidism
    Hypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...

    ; can affect calcium
    Calcium
    Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

     homeostasis
    Homeostasis
    Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

    , supplementation of which has completely resolved cases of depression in which hypoparathyroidism is the sole causative factor.

Pituitary tumors


Tumors of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 are fairly common in the general population with estimates ranging as high as 25%. Most tumors are considered to be benign and are often an incidental finding discovered during autopsy or as of neuroimaging in which case they are dubbed "incidentaloma
Incidentaloma
In medicine, an incidentaloma is a tumor found by coincidence without clinical symptoms or suspicion. It is a common problem: up to 7% of all patients over 60 may harbor a benign growth, often of the adrenal gland, which is detected when diagnostic imaging is used for the analysis of unrelated...

s". Even in benign cases, pituitary tumors can affect cognitive, behavioral and emotional changes. Pituitary microadenomas are smaller than 10 mm in diameter and are generally considered benign, yet the presence of a microadenoma has been positively identified as a risk factor for suicide.

"... patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression".

Pancreas

  • Hypoglycemia
    Hypoglycemia
    Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

    : an overproduction of insulin
    Insulin
    Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

     causes reduced blood levels of glucose
    Glucose
    Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

    . In one study of patients recovering from acute lung injury in intensive care, those patients who developed hypoglycemia while hospitalized showed an increased rate of depression.

Neurological


In addition to pituitary tumors, tumors in various locations in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 may cause depressive symptoms and be misdiagnosed as depression.

Post concussion syndrome


Post-concussion syndrome
Post-concussion syndrome
Post-concussion syndrome, also known as postconcussive syndrome or PCS, and historically called shell shock, is a set of symptoms that a person may experience for weeks, months, or occasionally up to a year or more after a concussion – a mild form of traumatic brain injury . PCS may also...

(PCS), is a set of symptoms that a person may experience for weeks, months, or occasionally years after a concussion with a prevalence rate of 38–80% in mild traumatic brain injuries, it may also occur in moderate and severe cases of traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

. A diagnosis may be made when symptoms resulting from concussion, depending on criteria, last for more than three to six months after the injury, in which case it is termed persistent postconcussive syndrome (PPCS). In a study of the prevalence of post concussion syndrome symptoms in patients with depression utilizing the British Columbia Postconcussion Symptom Inventory
British Columbia Postconcussion Symptom Inventory
The British Columbia Postconcussion Symptom Inventory , is a 16 item self-report inventory designed to measure both the frequency, and intensity of the ICD-10 criteria for Post concussion syndrome, which is a common occurrence in cases of mild traumatic brain injury...

: "Approximately 9 out of 10 patients with depression met liberal self-report criteria for a postconcussion syndrome and more than 5 out of 10 met conservative criteria for the diagnosis." These self reported rates were significantly higher than those obtained in a scheduled clinical interview. Normal controls have exhibited symptoms of PCS as well as those seeking psychological services. There is considerable debate over the diagnosis of PCS in part because of the medico-legal and thus monetary ramifications of receiving the diagnosis.

Pseudobulbar affect



Pseudobulbar affect
Pseudobulbar affect
Pseudobulbar affect , emotional lability, labile affect or emotional incontinence refers to a neurologic disorder characterized by involuntary crying or uncontrollable episodes of crying and/or laughing, or other emotional displays. PBA occurs secondary to neurologic disease or brain injury...

 (PBA) is an affective disinhibition syndrome that is largely unrecognized in clinical settings and thus often untreated due to ignorance of the clinical manifestations of the disorder; it may be misdiagnosed as depression. It often occurs secondary to various neurodegenerative diseases such as amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...

, and also can result from head trauma. PBA is characterized by involuntary and inappropriate outbursts of laughter and/or crying. PBA has a high prevalence rate with estimates of 1.5 - 2 million cases in the United States alone.
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Neurotoxicity


Various compounds have been shown to have neurotoxic effects many of which have been implicated as having a causal relationship in the development of depression.

Cigarette smoking


There has been research which suggests a correlation between cigarette smoking and depression. The results of one recent study suggest that smoking cigarettes may have a direct causal effect on the development of depression. There have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts.

In a study conducted among nurses, those smoking between 1-24 cigarettes per day had twice the suicide risk; 25 cigarettes or more, 4 times the suicide risk, than those who had never smoked. In a study of 300,000 male U.S. Army soldiers, a definitive link between suicide and smoking was observed with those smoking over a pack a day having twice the suicide rate of non-smokers.


"Current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt."

"It would seem unwise, nevertheless, to rule out the possibility that smoking might be among the antecedent factors associated with the development of depression."

"Abstinence from cigarettes for prolonged periods may be associated with a decrease in depressive symptomatology."

"The stress induction model of smoking suggests, however, that smoking causes stress and concomitant negative affect."

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Medication


Various medications have been suspected of a having a causal relation in the development of depression; this has been classified as "organic mood syndrome". Some classes of medication such as those used to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, have been recognized for decades as having a definitive relationship with the development of depression.

Monitoring of those taking medications which have shown a relationship with depression is often indicated, as well as the necessity of factoring in the use of such medications in the diagnostic process.
  • Topical Tretinoin
    Tretinoin
    Tretinoin is the acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel...

     (Retin-A); derived from Vitamin A
    Vitamin A
    Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...

     and used for various medical conditions such as in topical solutions used to treat acne vulgaris
    Acne vulgaris
    Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...

    . Although applied externally to the skin, it may enter the bloodstream and cross the blood brain barrier where it may have neurotoxic effects.

  • Interferons; proteins produced by the human body, three types have been identified alpha, beta and gamma. Synthetic versions are utilized in various medications used to treat different medical conditions such as the use of interferon-alpha in cancer treatment
    Chemotherapy
    Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

     and hepatitis C
    Hepatitis C
    Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...

     treatment. All three classes of interferons may cause depression and suicidal ideation.

Chronic Exposure to Organophosphates


The neurophsychiatric effects of chronic organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

 exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue.

Bipolar disorder

  • Bipolar disorder
    Bipolar disorder
    Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

     is frequently misdiagnosed as major depression, and is thus treated with antidepressants alone which is not only not efficacious it is often contraindicated as it may exacerbate hypomania, mania, or cycling between moods. J Clin Psychiatry. 2005 Nov;66(11):1432-40.
"Misdiagnosed bipolar patients received inappropriate and costly treatment regimens involving overuse of antidepressants and underuse of potentially effective medications. ... It is recommended that steps be taken to minimize misdiagnosis in clinical settings."

Nutritional deficiencies


Nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. Insufficient or inadeqaute nutrition can have a profound effect on mental health. The emerging field of Nutritional Neuroscience
Nutritional Neuroscience
Nutritional neuroscience: is the scientific discipline that studies the role of various components of the average diet such as protein, carbohydrates, and fats, dietary supplements and synthetic hormones, and food additives have on neurochemistry, neurobiology, and behavior.Recent research on...

 explores the various connections between diet, neurological functioning and mental health.
  • Vitamin B6
    Vitamin B6
    Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...

    :pyridoxal phosphate (PLP) the active form of B6 is a cofactor in the dopamine serotonin pathway, a deficiency in Vitamin B6 may cause depressive symptoms.
  • Folate (vitamin B9) - Vitamin B{{ssub
    Vitamin B12
    Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

     cobalamin : Low blood plasma
    Blood plasma
    Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

     and particularly red cell folate and diminished levels of Vitamin B{{ssub|12}} have been found in patients with depressive disorders. "[W]e suggest that oral doses of both folic acid (800 µg/(mcg)
    Microgram
    In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...

     daily) and vitamin B12 (1 mg
    Mg
    MG, M.G., M-G and variants may refer to:Business* MG Cars , a British automobile manufacturer, now part of SAIC* Champion Air , an American charter airline with IATA code MGEducation...

     daily) should be tried to improve treatment outcome in depression."

  • Long chain fatty acids: higher levels of omega-6 and lower levels of omega-3 fatty acids has been associated with depression
    Depression (mood)
    Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

     and behavioral change.

Sleep disorders

  • Insomnia
    Insomnia
    Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

    : While the inability to fall asleep is often a symptom of depression, it can also in some instances serve as the trigger for developing a depressive disorder. It can be transient, acute or chronic. It can be a primary disorder or a co-morbid one.
  • Restless legs syndrome
    Restless legs syndrome
    Restless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...

    :(RLS), also known as Wittmaack-Ekbom's syndrome, is characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can also affect the arms or torso, and even phantom limb
    Phantom limb
    A phantom limb is the sensation that an amputated or missing limb is still attached to the body and is moving appropriately with other body parts. 2 out of 3 combat veterans report this feeling. Approximately 60 to 80% of individuals with an amputation experience phantom sensations in their...

    s. Restless Leg syndrome has been associated with Major depressive disorder. "Adjusted odds ratio for diagnosis of major depressive disorder... suggested a strong association between restless legs syndrome and major depressive disorder and/or panic disorder."
  • Sleep apnea
    Sleep apnea
    Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...

     is a sleep disorder
    Sleep disorder
    A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning...

     characterized by pauses in breathing during sleep
    Sleep
    Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

    . Each episode, called an apnea
    Apnea
    Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...

    , lasts long enough for one or more breaths to be missed; such episodes occur repeatedly throughout the sleep cycle. Undiagnosed sleep apnea may cause or contribute to the severity of depression.
  • Circadian rhythm sleep disorders, of which too few clinicians are aware, often go untreated or are treated inappropriately, as when misdiagnosed as either primary insomnia or as a psychiatric condition.

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