Chapter 6: Biological Assessment of Patients with Psychiatric Symptoms



Biological abnormalities, unidentified medical illnesses, and substance abuse can cause psychiatric symptoms in otherwise mentally healthy individuals and can exacerbate such symptoms in persons already diagnosed with psychiatric illnesses. For example, hypo- or hyperglycemia can present with symptoms of anxiety, while depression may be an early sign of pancreatic carcinoma. To identify and treat the underlying medical problem, physical examination and specific biological tests and procedures are used in the clinical evaluation of patients who exhibit behavioral symptoms.

Physical Examination

A complete physical examination is essential when evaluating individuals with psychiatric symptoms. Of particular importance in the physical examination is the assessment of neurological function, particularly of sensory systems such as vision and hearing. In certain people, particularly the elderly, sensory impairment can result in psychiatric symptoms such as depression (see Chapter 4).

Physical abnormalities also can result from behavioral problems. For example, skin lesions identified in the physical examination can indicate illegal drug use or unreported domestic abuse.

Laboratory Studies

Screening tests

Basic laboratory screening studies, such as urinalysis and blood studies, can help rule out physiological causes of psychiatric symptoms. Blood studies include complete blood count, erythrocyte sedimentation rate, and the metabolic screening battery (serum electrolyte level, glucose level, and hepatic and renal function tests).

Tests of endocrine function are particularly important in patients with behavioral symptoms. Patients with depression may have endocrine irregularities, including abnormalities in growth hormone, melatonin, gonadotropin, and thyroid hormone. Patients with adrenal disorders such as Addison’s disease and Cushing’s syndrome classically demonstrate psychiatric symptoms (see Chapter 25).

Thyroid function tests are used to screen for hypothyroidism and hyperthyroidism, which can mimic depression and anxiety, respectively. Although no clear association exists between primary depressive illness and abnormal thyroid function, about one-third of depressed patients show decreased thyrotropin response to thyrotropin-releasing hormone. Clearly, thyroid function should be evaluated in depressed patients who also show physical symptoms of hypothyroidism. In a similar way, anxious, agitated patients who also show tremor and weight loss should be evaluated for hyperthyroidism (Joffe 2000).

Table 6-1 provides a summary of laboratory test results for patients with psychiatric symptoms that may be related to physical illnesses. Analysis of blood B12 and folate levels and a toxicology screen to identify substance abuse (Table 6-2) should also be conducted for these patients.

Table 6.1Laboratory Testing of Patients with Psychiatric Symptoms

Major Psychiatric Symptom Suspected Physical Condition Physical Symptoms Laboratory Test Results

  • Hypothyroidism (myxedema)

  • Fatigue
  • Weight gain
  • Constipation
  • Edema
  • Hair loss
  • Decreased cold tolerance

  • Increased thyroid stimulating hormone (TSH)
  • Decreased T3
  • Decreased free T4

  • Addison’s disease (adrenocortical insufficiency)

  • Skin hyperpigmentation
  • Hypotension
  • Weakness/fatigue

  • Decreased Na+
  • Increased K+
  • Eosinophilia

  • Cushing’s syndrome (adrenocortical excess)

  • Purple stripes on skin (stria)
  • Central (abdominal) obesity
  • Bruising
  • Muscle weakness

  • Positive DST
  • Poor glucose tolerance

  • Pancreatic carcinoma

  • Weight loss
  • Abdominal pain

  • Increased amylase

  • Hyperthyroidism (thyrotoxicosis)

  • Flushing
  • Weight loss
  • Diarrhea

  • Decreased TSH
  • Increased T3
  • Increased free T4

  • Pheochromocytoma (adrenal medullary tumor)

  • Hypertension
  • Headache
  • Tachycardia
  • Tremor

  • Elevated VMA

  • Hypoglycemia

  • Sweating
  • Tachycardia
  • Somnolence

  • Low blood sugar

  • Hyperglycemia

  • Polyuria
  • Nausea and vomiting
  • Anorexia

  • High blood sugar
  • Ketones in blood and urine
  • Anion gap acidosis
Psychosis or personality changes  

  • AIDS dementia

  • Ataxia
  • Weight loss
  • Low-grade fever

  • Positive HIV test
  • Low B12 level

  • Acute intermittent porphyria

  • Peripheral neuropathy
  • Abdominal pain, nausea, and vomiting
  • Red/purple urine

  • Elevated d-aminolevulinic acid
  • Elevated porphobilinogen
  • Leukocytosis

  • Connective tissue disorders (e.g., SLE, rheumatoid arthritis)

  • Skin, nail, and mucous membrane changes
  • Joint pain
  • Fever
  • Headache

  • Anemia
  • Positive antiphospholipid
  • Positive ANA
  • Positive rheumatoid factor

  • Hypoparathyroidism

  • Muscle spasm
  • Laryngeal spasm
  • Paresthesias

  • Decreased Ca2

  • Hyperparathyroidism

  • Bone pain
  • Polydipsia
  • Chronic fatigue
  • Kidney stones

  • Variable PTH levels
  • Increased Ca2

  • Wilson’s disease

  • Gait abnormalities
  • Rigidity
  • Kayser-Fleischer rings (copper deposition in the cornea)

  • Increased urinary copper
  • Decreased serum ceruloplasmin

Table 6.2Laboratory Findings for Selected Drugs of Abuse

Class of Substance Elevated Levels in Body Fluids Length of Time After use that Substance can be Detected
Sedatives Alcohol (legal intoxication is 0.08%–0.15% BAC, depending on state laws; coma occurs at BAC of 0.40%–0.50% in nonalcoholics) Hours
Gamma-glutamyltransferase Hours
Specific barbiturate or benzodiazepine or its metabolite 7 days or less
Opioids Opiate other than methadone 12–36 hours
Methadone 2–3 days
Stimulants Cotinine (nicotine metabolite) 1–2 days
Amphetamine 1–2 days
Benzoylecgonine (cocaine metabolite) 1–3 days in occasional users; longer in heavy users
Hallucinogens and related agents Cannabinoid metabolites 7–28 days
Serum glutamic-oxaloacetic transaminase level and creatinine phosphokinase (reflecting muscle damage associated with PCP use) ;7 days

Pharmacotherapy patients

Laboratory tests are used to monitor patients for biological complications of pharmacotherapy (see Chapter 19). Some psychoactive agents are more likely to cause physical difficulties than others. Specifically, the mood-stabilizing agents, carbamazepine (Tegretol) and valproic acid (Depakene, Depakote) are associated with abnormal liver function. Carbamazepine and the antipsychotic agent clozapine (Clozaril) are associated with blood abnormalities such as agranulocytosis (decreased number of granulocytic white blood cells). These abnormalities usually become apparent within the first few months of treatment.

Because they can develop hypothyroidism and kidney problems, patients being treated with the antimanic agent lithium should have regular T3, T4, and TSH, and kidney function (blood urea nitrogen, creatinine, and urinalysis) tests. Because of the drug’s narrow therapeutic range, lithium levels also should be monitored regularly. Plasma concentrations of some antipsychotic and antidepressant agents (e.g., imipramine, desipramine, and nortriptyline) also may be measured to evaluate patient compliance or to determine whether therapeutic blood levels of the agent have been reached in nonresponding patients.

Case 6.1

The Patient

The wife of a retired 73-year-old man tells the doctor that her husband has been acting differently over the past few months. She reports that he no longer does the crossword puzzles he formerly enjoyed and shows little interest in the television shows he looked forward to weekly. His wife is convinced that he is either depressed or developing Alzheimer’s disease. Physical and neurological examinations are essentially normal, but ocular examination reveals bilateral central lens opacities (cataracts).


This case illustrates why physical examination is important for patients who are suspected of having a psychiatric illness. This patient shows symptoms of depression (e.g., decreased interest and lack of enjoyment in usual activities) in response to decreased sensory stimulation caused by his gradual loss of vision. In some patients, decreased vision or hearing can even result in symptoms resembling those of psychosis or dementia. For several reasons, including the fact that symptoms of sensory loss typically come on gradually, elderly patients may not identify the problem until it has caused significant social impairment.


When the cataracts are treated and his vision improves, the patient’s interest in his environment and day-to-day activities should return. If there is no significant improvement, other reasons for the patient’s depression, including the onset of dementia, should be identified and addressed.

Measurement of biogenic amines

Altered concentrations of monoamines in neural tissue are involved in the manifestations of major psychiatric disorders (see Chapter 5). Despite this close association, it is difficult to correlate directly or predict how changes in these concentrations are associated with changes in behavior. One reason for this is that for practical reasons, levels of monoamines cannot be measured in the brain tissue of living patients. Instead, metabolites of the monoamines, present in higher quantities than the actual monamines, are measured in body fluids such as cerebrospinal fluid, blood, and urine. Although not commonly used in diagnosis, measurement of these metabolites can provide useful clinical and research information about the patient (Table 6-3).

Case 6.2

The Patient

A 40-year-old female patient visits her family physician complaining of fatigue and feeling “cold all the time.” Her symptoms started about 1 year ago. The interview reveals that the patient feels that her job as a schoolteacher has become too “draining” and she wants to give it up. She also relates that her marriage is in trouble because her husband does not understand why she is too tired to go out in the evenings or on weekends. The patient says that these problems have made her feel sad and hopeless and that she cries frequently. Physical examination reveals that the patient has gained 8 lb (3.6 kg) in the past year. Her skin and hair appear dry, her voice is hoarse, and she shows slow return of deep tendon reflexes, i.e., slow return of the limb to its resting position after the deep tendon reflex is activated. Otherwise, the physical exam is unremarkable. Laboratory studies indicate that serum concentrations of TSH are increased, and those of triiodothyronine (T3) and free thyroxine (T4) are decreased.


Hypothyroid patients such as this woman can present with symptoms of depression. Thyroid status therefore must be evaluated in patients who show depression along with classic symptoms of hypothyroidism such as cold intolerance, weight gain, lethargy, or dryness of the skin and hair. Voice and hearing changes also may occur in hypothyroid patients because of edema of the larynx and middle ear. Other symptoms of hypothyroidism include constipation, menstrual irregularities, and slow return of deep tendon reflexes (see Table 5-4).


Treatment with l-thyroxine (Synthroid) starting with a low dose and titrating up to a maintenance dose of 0.1 to 0.15 mg per day is indicated for this patient. Within a few weeks, there should be normalization of serum thyroid hormone and TSH levels. Clinical improvement in her emotional and physical symptoms may take longer. Thyroid hormones also can be used to augment the effectiveness of antidepressant medication not only in hypothyroid patients like this one, but in euthyroid patients as well (Joffe, 2000).

Table 6.3 Monoamines: Metabolites, Brain Production, and Associated Psychopathology

Neurotransmitter (Primary Site of Production in Brain) Concentration of Metabolite in Blood Plasma, Cerebrospinal Fluid, or Urine (Increased [?] or Decreased [?]) Associated Psychopathology
Dopamine (substantia nigra, ventral tegmental area) (?) HVA ;

  • Schizophrenia
  • Other psychotic illnesses
(?) HVA ;

  • Parkinson’s disease
  • Patients treated with antipsychotic agents
  • Depression
Norepinephrine (locus ceruleus) (?) VMA  

  • Adrenal medullary tumor (pheochromocytoma)
(?) MHPG  

  • Severe depression
  • Attempted suicide
Serotonin (raphe nuclei) (?) 5-HIAA  

  • Severe depression
  • Attempted suicide
  • Aggressiveness and violence
  • Impulsiveness
  • Fire setting
  • Tourette’s syndrome
  • Alcohol abuse
  • Bulimia