Differential diagnoses of depression

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Neuroimaging can be a valuable tool in the diagnostic work-up of various psychiatric disorders including depression. Mrt big.jpg
Neuroimaging can be a valuable tool in the diagnostic work-up of various psychiatric disorders including depression.

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]

Contents

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 for 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 Newsweek , 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. 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

"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 Neurocysticercosis.gif
MRI brain scan: Neurocysticercosis
"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]

Blood disorders

Chronic fatigue syndrome

Between 1 and 4 million Americans are believed to have chronic fatigue syndrome (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. [50] While frequently misdiagnosed as depression, [51] differences have been noted in rate of 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 endocrine system may present with various neuropsychiatric symptoms; irregularities in the hypothalamic-pituitary- adrenal (HPA) axis and the hypothalamic-pituitary-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:

Adrenal gland

Thyroid and parathyroid glands

Illu thyroid parathyroid.jpg

Pituitary tumors

Tumors of the pituitary gland are fairly common in the general population with estimates ranging as high as 25%. [62] 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 "incidentalomas". Even in benign cases, pituitary tumors can affect cognitive, behavioral and emotional changes. [63] [64] 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. [65] [66]

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

Pancreas

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 (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. [70] 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). [71] [72] [73] [74] [75] In a study of the prevalence of 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 PBA is not depression.png
Diagnostic differences between PBA and depression

Pseudobulbar affect (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. [77] It often occurs secondary to various neurodegenerative diseases such as 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

Multiple sclerosis is a chronic demyelinating disease in which the 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]

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

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

See also

Related Research Articles

<span class="mw-page-title-main">Bipolar disorder</span> Mental disorder that causes periods of depression and abnormally elevated mood

Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually also a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others. The risk of suicide is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30–40% engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder.

<span class="mw-page-title-main">Catatonia</span> Psychiatric behavioural syndrome

Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. It has historically been related to schizophrenia, but catatonia is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions. Catatonia is now a stand-alone diagnosis, and the term is used to describe a feature of the underlying disorder.

<span class="mw-page-title-main">Major depressive disorder</span> Mental disorder involving persistent low mood, low self-esteem, and loss of interest

Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since.

<span class="mw-page-title-main">Mood disorder</span> Mental disorder affecting the mood of an individual, over a long period of time

A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD).

<span class="mw-page-title-main">Akathisia</span> Movement disorder involving a feeling of inner restlessness

Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and forth, or pace, while some may just have an uneasy feeling in their body. The most severe cases may result in poor adherence to medications, exacerbation of psychiatric symptoms, and, because of this, aggression, violence, and/or suicidal thoughts. Akathisia is also associated with threatening behaviour and physical aggression in mentally disordered patients. However, the attempts to find potential links between akathisia and emerging suicidal or homicidal behaviour were not systematic and were mostly based on a limited number of case reports and small case series. Apart from these few low-quality studies, there is another more recent and better quality study that concludes akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication.

Schizoaffective disorder is a mental disorder characterized by abnormal thought processes and an unstable mood. This diagnosis requires symptoms of both schizophrenia (psychosis) and a mood disorder: either bipolar disorder or depression. The main criterion is the presence of psychotic symptoms for at least two weeks without any mood symptoms. Schizoaffective disorder can often be misdiagnosed when the correct diagnosis may be psychotic depression, bipolar I disorder, schizophreniform disorder, or schizophrenia. This is a problem as treatment and prognosis differ greatly for most of these diagnoses. many people with schizoaffective disorder have other mental disorder including anxiety disorders

<span class="mw-page-title-main">Mood swing</span> Extreme or rapid change in mood

A mood swing is an extreme or sudden change of mood. Such changes can play a positive part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be categorized as part of a mental illness, such as bipolar disorder, where erratic and disruptive mood swings are a defining feature.

Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms. PMDD causes significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptoms occur in the luteal phase, improve within a few days after the onset of menses, and are minimal or absent in the week after menses. PMDD has a profound impact on a woman’s quality of life and dramatically increases the risk of suicidal ideation and even suicide attempts. Many women of reproductive age experience discomfort or mild mood changes prior to menstruation. However, 5–8% experience severe premenstrual syndrome causing significant distress or functional impairment. Within this population of reproductive age, some will meet the criteria for PMDD.

<span class="mw-page-title-main">Depression (mood)</span> State of low mood and aversion to activity

Depression is a mental state of low mood and aversion to activity. It affects more than 280 million people of all ages. Depression affects a person's thoughts, behavior, feelings, and sense of well-being. Depressed people often experience loss of motivation or interest in, or reduced pleasure or joy from, experiences that would normally bring them pleasure or joy.

Adjustment disorder is a maladaptive response to a psychosocial stressor. It is classified as a mental disorder. The maladaptive response usually involves otherwise normal emotional and behavioral reactions that manifest more intensely than usual, causing marked distress, preoccupation with the stressor and its consequences, and functional impairment.

Dysthymia, also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with longer-lasting symptoms. The concept was used by Robert Spitzer as a replacement for the term "depressive personality" in the late 1970s.

Atypical depression is defined in the DSM-IV as depression that shares many of the typical symptoms of major depressive disorder or dysthymia but is characterized by improved mood in response to positive events. In contrast to those with atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also often features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment.

<span class="mw-page-title-main">Psychotic depression</span> Medical condition

Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms. It can occur in the context of bipolar disorder or major depressive disorder. It can be difficult to distinguish from schizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Unipolar psychotic depression requires that psychotic symptoms occur during severe depressive episodes, although residual psychotic symptoms may also be present in between episodes. Diagnosis using the DSM-5 involves meeting the criteria for a major depressive episode, along with the criteria for "mood-congruent or mood-incongruent psychotic features" specifier.

Treatment-resistant depression (TRD) is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment-resistant depression vary, and they do not include a resistance to psychotherapy. Inadequate response has most commonly been defined as less than 50% reduction in depressive symptoms following treatment with at least one antidepressant medication, although definitions vary widely. Some other factors that may contribute to inadequate treatment are: a history of repeated or severe adverse childhood experiences, early discontinuation of treatment, insufficient dosage of medication, patient noncompliance, misdiagnosis, cognitive impairment, low income and other socio-economic variables, and concurrent medical conditions, including comorbid psychiatric disorders. Cases of treatment-resistant depression may also be referred to by which medications people with treatment-resistant depression are resistant to. In treatment-resistant depression adding further treatments such as psychotherapy, lithium, or aripiprazole is weakly supported as of 2019.

Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder (BP-I).

Pseudodementia is a condition where mental cognition can be temporarily decreased. The term pseudodementia is applied to the range of functional psychiatric conditions such as depression, schizophrenia and other psychosis, mania, dissociative disorder and conversion disorder that may mimic organic dementia, but are essentially reversible on treatment. Pseudodementia typically involves three cognitive components: memory issues, deficits in executive functioning, and deficits in speech and language. Specific cognitive symptoms might include trouble recalling words or remembering things in general, decreased attentional control and concentration, difficulty completing tasks or making decisions, decreased speed and fluency of speech, and impaired processing speed. People with pseudodementia are typically very distressed about the cognitive impairment they experience. Two treatments found to be effective for the treatment of depression may also be beneficial in the treatment of pseudodementia: Cognitive behavioral therapy (CBT) which identifies behaviors that positively and negatively impact mood, and Interpersonal therapy which focuses on identifying ways in which interpersonal relationships contribute to depression.

Late-life depression refers to depression occurring in older adults and has diverse presentations, including as a recurrence of early-onset depression, a new diagnosis of late-onset depression, and a mood disorder resulting from a separate medical condition, substance use, or medication regimen. Research regarding late-life depression often focuses on late-onset depression, which is defined as a major depressive episode occurring for the first time in an older person.

<span class="mw-page-title-main">Selective serotonin reuptake inhibitor</span> Class of antidepressant medication

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.

The differential diagnoses of anorexia nervosa (AN) includes various types of medical and psychological conditions, which may be misdiagnosed as AN. In some cases, these conditions may be comorbid with AN because the misdiagnosis of AN is not uncommon. For example, a case of achalasia was misdiagnosed as AN and the patient spent two months confined to a psychiatric hospital. A reason for the differential diagnoses that surround AN arise mainly because, like other disorders, it is primarily, albeit defensively and adaptive for, the individual concerned. Anorexia Nervosa is a psychological disorder characterized by extremely reduced intake of food. People with anorexia nervosa tend to have a low self-image and an inaccurate perception of their body.

Borderline personality disorder (BPD) is a personality disorder characterized by a pervasive, long-term pattern of significant interpersonal relationship instability, a distorted sense of self, and intense emotional responses, which can be misdiagnosed. Misdiagnosis may involve erroneously assigning a BPD diagnosis to individuals not meeting the specific criteria or attributing an incorrect alternate diagnosis in cases where BPD is the accurate condition.

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