Bipolar Disorder Workup

Updated: Feb 11, 2022
  • Author: Stephen Soreff, MD; Chief Editor: Glen L Xiong, MD  more...
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Approach Considerations

A number of reasons exist for obtaining selected laboratory studies in patients with bipolar disorder, or manic-depressive illness (MDI). An extensive range of tests is indicated, because bipolar disorder encompasses both depression and mania and because a significant number of medical causes for each state exists. The basic principle remains, "Do not miss a treatable medical cause for the mental status."

Second, the condition necessitates use of a number of medications that require certain body systems to be working properly. For example, lithium requires an intact genitourinary (GU) system and can affect certain other systems, and certain anticonvulsants can suppress bone marrow.

Third, because bipolar illness is a lifelong disorder, performing certain baseline studies is important to establish any long-term effects of the medications.

A number of infections, especially chronic infections, can produce a presentation of depression in the patient. An encephalitis can dramatically manifest as changes in mental status and, in rare situations, present with bipolar features.



Blood Studies

Complete blood count

A complete blood count (CBC) with differential is used to rule out anemia as a cause of depression in bipolar disorder, or manic-depressive illness (MDI). Treatment, especially with certain anticonvulsants, may depress the bone marrow—hence the need to check the red blood cell (RBC) and white blood cell (WBC) counts for signs of bone marrow suppression.

Lithium may cause a reversible increase in the WBC count.

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate (ESR) is determined to look for any underlying disease process such a lupus or an infection. An elevated ESR often indicates an underlying disease process.

Fasting glucose

In some cases, a fasting glucose level is indicated to rule out diabetes. In addition, atypical antipsychotics have been associated with weight gain and problems with blood glucose regulation in patients with diabetes, therefore, a baseline fasting glucose should be obtained.


Serum electrolyte concentrations are measured to help diagnose electrolyte problems, especially with sodium, that are related to depression. Treatment with lithium can lead to renal problems and electrolyte problems, and low sodium levels can lead to higher lithium levels and lithium toxicity. Hence, in screening candidates for lithium therapy as well as those on lithium therapy, checking electrolytes is indicated.

Serum calcium is assessed to diagnose hypercalcemia and hypocalcemia associated with mental status changes (eg, hyperparathyroidism). An elevated calcium blood level can cause depression or mania. Hyperparathyroidism, as evidenced by an elevated calcium blood level, produces depression. Certain antidepressants, such as nortriptyline, affect the heart; therefore, checking calcium levels is important.


Low serum protein levels found in patients who are depressed may be a result of not eating. Such low levels increase the availability of certain medications, because these drugs have less protein to which to bind.


Researchers and clinicians have long sought biological indicators for mental disorders, particularly for affective disorders. Frye and colleagues took an important first step in this process by analyzing 7.5 ml blood samples from patients diagnosed with unipolar depression (n=52), bipolar II disorder (n=49), and bipolar I disorder (n=46) as well as 141 control subjects. They found six proteins significantly associated with mood disorders including unipolar and bipolar depression. Growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls; MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls; and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. These findings suggest that proteomic panels may be helpful in identifying and distinguishing mood disorders. [72]

Thyroid hormones

Thyroid tests are performed to rule out hyperthyroidism (mania) and hypothyroidism (depression). Treatment with lithium can cause hypothyroidism, and hypothyroidism may cause rapid cycling of mood, especially in women.

In a study to assess the relationship between bipolar disorder and thyroid dysfunction, Krishna et al found that elevated T3 hormone had a statistically significantly association with bipolar disorder. [73] In fact, patients with bipolar disorder were 2.55 times more commonly associated with thyroid dysfunction than individuals without bipolar disorder. [73]

Creatinine and blood urea nitrogen

Kidney failure can present as depression. Treatment with lithium can affect urinary clearances, and serum creatinine and blood urea nitrogen (BUN) levels can increase; however, other signs and symptoms of kidney failure will appear first. Carefully and regularly monitor renal function.

Liver and lipid panel

Antipsychotics agents have also been associated with changes in patients’ lipid profiles, potentially resulting in dyslipidemia (eg, hypertriglyceridemia), as well as liver damage/dysfunction.

Other laboratory tests

Although not a routine screening test in bipolar disorder and unnecessary in patients with normal liver function test results, urine copper level testing may be performed to rule out Wilson disease, which produces mental changes. Wilson disease is a rare condition that is easily missed.

Antinuclear antibody testing is used to rule out lupus.

Testing for human immunodeficiency virus (HIV) may be helpful. Acquired immunodeficiency syndrome (AIDS) causes changes in mental status, including dementia and depression.

Obtaining a Venereal Disease Research Laboratory (VDRL) test may be indicated in selected patients. Syphilis, especially in its later stage, alters mental status.


Substance and Alcohol Screening

Alcohol abuse and abuse of a wide variety of drugs can present as either mania or depression. For example, speed (ie, amphetamines) and cocaine abuse can present as a manialike disorder, and barbiturate abuse can present as a depressionlike disorder.

A number of patients with bipolar disorder, or manic-depressive illness (MDI), also have a drug or alcohol addiction; that is, they have dual diagnoses. Indeed, relative to other mental illnesses, individuals with bipolar disorder have a disproportionately high rate of substance use disorders, a co-occurrence that is associated with significant morbidity and mortality. [74]

Performing a substance screen helps to make this dual diagnosis. If the patient has a dual diagnosis, addiction-focused treatment should be coordinated with the treatment of bipolar disorder. [3]


Magnetic Resonance Imaging

The total value of performing magnetic resonance imaging (MRI) in a patient with bipolar disorder, or manic-depressive illness (MDI), remains unclear; however, a couple of reasons do exist for performing an imaging study. Because manic-depressive illness is a lifelong disease, a strong battery of studies rules out any other medical etiology and establishes a baseline. Some investigators report that patients with mania demonstrate hyperintensity in their temporal lobes.



Many of the antidepressants, especially the tricyclic agents and some of the antipsychotics, can affect the heart and cause conduction problems. Lithium also can lead to changes such as reversible flattening or inversion of T waves on electrocardiography (ECG). In older patients with bipolar disorder, or manic-depressive illness (MDI), on lithium or tricyclic antidepressant therapy, a pretreatment ECG is important.



Generally, routine electroencephalography (EEG) is unnecessary in the evaluation of bipolar disorder, or manic-depressive illness (MDI). However, some reasons for ordering EEG in patients with bipolar illness may be appropriate and include the following:

  • EEG provides a baseline and helps to rule out any neurologic problems; use this test to rule out a seizure disorder and brain tumor

  • If electroconvulsive therapy (ECT) is contemplated, an EEG may be helpful; EEG monitoring during ECT is used to determine the occurrence and duration of seizure

  • Some studies have shown that abnormalities in EEG findings have been indicative of anticonvulsant effectiveness; specifically, an abnormal EEG finding may predict the response to valproate

  • Some patients may have seizures when on medications, especially antidepressants; in addition, lithium can cause diffuse slowing throughout the brain