Differential diagnoses of depression

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Depression (differential diagnoses)
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Neuroimaging can be a valuable tool in the diagnostic work-up of various psychiatric disorders including depression.[1]

Depression, one of the most commonly diagnosed psychiatric disorders,[2][3] is being diagnosed in increasing numbers in various segments of the population worldwide.[4][5] 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 suicides, the individuals had seen a physician within the prior year before their death, 45–66% within the prior month. About a third of those who died by suicide had contact with mental health services in the prior year, a fifth within the preceding month.[6][7][8][9][10]

There are many psychiatric and medical conditions that may mimic some or all of the symptoms of depression or may occur

comorbid to it.[11][12][13] 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.[14]

Many psychiatric disorders such as depression are diagnosed by

allied health professionals with little or no medical training,[15] 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.[16][17][18][19][20][21] According to one study, "non-medical mental health care providers may be at increased risk of not recognizing masked medical illnesses in their patients."[22]

Misdiagnosis or missed diagnoses may lead to lack of treatment or ineffective and potentially harmful treatment which may worsen the underlying causative disorder.[23][24] A conservative estimate is that 10% of all psychological symptoms may be due to medical reasons,[25] with the results of one study suggesting that about half of individuals with a serious mental illness "have general medical conditions that are largely undiagnosed and untreated and may cause or exacerbate psychiatric symptoms".[26][27]

In a case of misdiagnosed depression recounted in

MRI finally was performed, it showed the presence of a tumor. However, she was told by a neurologist that it was benign. After a worsening of symptoms, and upon the second opinion of another neurologist, the tumor was removed. After the surgery, she no longer had depressive symptoms.[28]

Autoimmune disorders

  • food grains
    , most notably wheat, and also 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."[29]

Bacterial-viral-parasitic infection

MRI
brain scan: Neurocysticercosis
  • bacterium transmitted by the Deer tick (Ixodes scapularis). 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.[32][33] Lyme disease is an underdiagnosed illness, partially as a result of the complexity and unreliability of serologic testing.[34]
"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.[35]
  • Syphilis; the prevalence of which is on the rise, is another of the "great imitators", which if left untreated can progress to neurosyphilis 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."[36]
  • eggs of the pork tapeworm via contact with contaminated fecal matter or eating infected vegetables or undercooked pork.[37] "While cysticercosis is endemic in Latin America, it is an emerging disease with increased prevalence in the United States."[38] "The rate of depression in those with neurocysticercosis is higher than in the general population."[39]
  • 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,[41][42] in addition, studies have linked seropositivity with an increased rate of suicide[43]
  • vectors for disease transmission to humans are various species of mosquito.[44][45] WNV which is endemic to Southern Europe, Africa the Middle East and Asia[46] 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."[47]

Blood disorders

  • Anemia: is a decrease in normal number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.[48] Depressive symptoms are associated with anemia in a general population of older persons living in the community.[49]

Chronic fatigue syndrome

Between 1 and 4 million Americans are believed to have

cerebral blood flow.[52]

CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression.[53]

Dietary disorders

"Fructose malabsorption may play a role in the development of depressed mood. Fructose malabsorption should be considered in patients with symptoms of major depression...."[55]
"Fructose and sorbitol reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression."[56]

Endocrine system disorders

Dysregulation of the

thyroid (HPT) axis have been shown in patients with primary depression.[57]

HPT and HPA axes abnormalities observed in patients with depression
(Musselman DL, Nemeroff CB. 1996)

HPT axes irregularities:

HPA axes irregularities:

  • adrenocorticoid
    hypersecretion
  • enlarged pituitary and adrenal gland size (organomegaly)
  • elevated
    corticotropin-releasing factor
    (CRF) concentrations

Adrenal gland

Thyroid and parathyroid glands

Location of the thyroid and parathyroid glands in front of the layrnx.

Pituitary tumors

Tumors of the

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.[65][66]

"... patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression".[67]

Pancreas

  • Hypoglycemia: an overproduction of insulin causes reduced blood levels of glucose. 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.[68]

Neurological

CNS Tumors

In addition to pituitary tumors, tumors in various locations in the central nervous system may cause depressive symptoms and be misdiagnosed as depression.[28][69]

Post concussion syndrome

post concussion syndrome symptoms in patients with depression utilizing the British Columbia Postconcussion Symptom Inventory: "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.[76]

Pseudobulbar affect

Diagnostic differences between PBA and depression

amyotrophic lateral sclerosis, 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.[78]

Multiple sclerosis

myelin sheaths of cells in the brain and spinal cord are irreparably damaged. Symptoms of depression are very common in patients at all stages of the disease and may be exacerbated by medical treatments, notably interferon beta-1a.[79]

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.[80] There have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts.[81][82]

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.[83][84] 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.[85]

Link Between Smoking Depression and Suicide

"Current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt."[86]

"It would seem unwise, nevertheless, to rule out the possibility that smoking might be among the antecedent factors associated with the development of depression."[87]

"Abstinence from cigarettes for prolonged periods may be associated with a decrease in depressive symptomatology."[88]

"The stress induction model of smoking suggests, however, that smoking causes stress and concomitant negative affect."[89]

Medication

Various medications have been suspected of 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, have been recognized for decades as having a definitive relationship with the development of depression.[90]

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.[91]

  • Topical
    blood brain barrier where it may have neurotoxic effects.[92]
  • 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 and hepatitis C treatment. All three classes of interferons may cause depression and suicidal ideation.[93]

Chronic exposure to organophosphates

The neuropsychiatric effects of chronic organophosphate exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue.[94]

Neuropsychiatric

Bipolar disorder

  • contraindicated as it may exacerbate hypomania, mania, or cycling between moods.[95][96] There is ongoing debate about whether this should be classified as a separate disorder because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a continuum between the two.[97]

Nutritional deficiencies

Nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. Insufficient or inadequate nutrition can have a profound effect on mental health. The emerging field of nutritional neuroscience explores the various connections between diet, neurological functioning and mental health.

Sleep disorders

  • Insomnia: 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.[104][105] It can be transient, acute or chronic. It can be a primary disorder or a co-morbid one.
  • 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 limbs.[106] 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."[107]
  • Sleep apnea is a sleep disorder characterized by pauses in breathing during sleep. Each episode, called an apnea, 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.[108]
  • Circadian rhythm sleep disorders, of which few clinicians are aware, often go untreated or are treated inappropriately, as when misdiagnosed as either primary insomnia or as a psychiatric condition.[109]

See also

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Bibliography

External links
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