Behavioral Health

Schizophrenia: Ensuring an accurate Dx, optimizing treatment

J Fam Pract. 2018 February;67(2):82-87

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Washington, DC: American Psychiatric Publishing; 2013.

2. McGrath J, Saha S, Chant D, et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67-76.

3. Henry LP, Amminger GP, Harris MG, et al. The EPPIC follow-up study of first-episode psychosis: longer-term and clinical and functional outcome 7 years after index admission. J Clin Psychiatry. 2010;71:716-728.

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7. Crismon L, Argo TR, Buckley PF. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, New York: McGraw-Hill; 2014:1019-1046.

8. Viron M, Baggett T, Hill M, et al. Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population. Am J Med. 2012;125:223-230.

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14. Jones PB, Barnes TRE, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006;63:1079-1087.

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CHARACTERISTICS AND SCOPE OF SCHIZOPHRENIA

Schizophrenia is a psychotic illness in which the individual loses contact with reality and often experiences hallucinations, delusions, or thought disorders. Criteria for schizophrenia described in the Diagnostic and Statistical Manual of Mental Disorders 5^th edition (DSM-5) include signs and symptoms of at least 6 months’ duration, as well as at least one month of active-phase positive and negative symptoms.¹

Delusions, hallucinations, disorganized speech, and disorganized behavior are examples of positive symptoms. Negative symptoms include a decrease in the range and intensity of expressed emotions (ie, affective flattening) and a diminished initiation of goal-directed activities (ie, avolition).

Approximately 7 in 1000 people will develop the disorder in their lifetime.² Schizophrenia is considered a “serious mental illness” because of its chronic course and often poor long-term social and vocational outcomes.^3,4 Symptom onset is generally between late adolescence and the mid-30s.⁵

Getting closer to understanding its origin

Both genetic susceptibility and environmental factors influence the incidence of schizophrenia.⁴ Newer models of the disease have identified genes (ZDHHC8 and DTNBP1) whose mutations may increase the risk of schizophrenia.⁶ Physiologic insults during fetal life—hypoxia, maternal infection, maternal stress, and maternal malnutrition—account for a small portion of schizophrenia cases.⁶

Abnormalities in neurotransmission are the basis for theories on the pathophysiology of schizophrenia. Most of these theories center on either an excess or a deficiency of neurotransmitters, including dopamine, serotonin, and glutamate. Other theories implicate aspartate, glycine, and gamma-aminobutyric acid as part of the neurochemical imbalance of schizophrenia.⁷

ESTABLISHING A DIAGNOSIS

Although psychotic symptoms may be a prominent part of schizophrenia, not all psychoses indicate a primary psychiatric disorder such as schizophrenia. Broadly, psychoses can be categorized as primary or secondary.

Primary psychoses include schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, delusional disorder, and mood disorders (major depressive disorder and borderline personality disorder) with psychotic features.¹ Difficulty in distinguishing between these entities can necessitate referral to a psychiatrist.

Secondary psychoses arise from a precursor such as delirium, dementia, medical illness, or adverse effects of medications or illicit substances. Medical illnesses that cause psychotic symptoms include:^5,8

seizures (especially temporal lobe epilepsy),
cerebrovascular accidents,
intracranial space-occupying lesions,
neuropsychiatric disorders (eg, Wilson’s or Parkinson’s disease),
endocrine disorders (eg, thyroid or adrenal disease),
autoimmune disease (eg, systemic lupus erythematosus, Hashimoto encephalopathy),
deficiencies of vitamins A, B₁, B₁₂, or niacin,
infections (eg, human immunodeficiency virus [HIV], encephalitis, parasites, and prion disease),
narcolepsy, and
metabolic disease (eg, acute intermittent porphyria, Tay-Sach’s disease, Niemann-Pick disease).

Several recreational drugs can cause psychotic symptoms: cocaine, amphetamines, cannabis, synthetic cannabinoids, inhalants, opioids, and hallucinogens. Psychotic symptoms can also appear during withdrawal from alcohol (delirium tremens) and from sedative hypnotics such as benzodiazepines. Prescribed medications such as anticholinergics, corticosteroids, dopaminergic agents (L-dopa), stimulants (amphetamines), and interferons can also induce psychotic symptoms.

First rule out causes of secondary psychosis

Rule out causes of secondary psychosis by conducting a detailed history and physical examination and ordering appropriate lab tests and imaging studies. If the patient’s psychosis is of recent onset, make sure the laboratory work-up includes a complete blood count (CBC), renal function testing, urine culture and sensitivity and urine toxicology, and measures of electrolytes, blood glucose, thyroid-stimulating hormone (TSH), vitamin B₁₂, folic acid, erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANA), HIV antibody, and serum fluorescent treponemal antibody absorption (FTA-ABS).⁹

All antipsychotic agents are comparably effective, but adverse effects differ.

Consider cranial computed tomography or magnetic resonance imaging if there are focal neurologic deficits or if the patient’s presentation is atypical (eg, new onset psychosis in old age).⁹ Clinical presentation may also indicate a need for electroencephalography, ceruloplasmin measurement, a dexamethasone suppression test, a corticotropin stimulation test, 24-hour urine porphyrin and copper assays, chest radiography, or cerebrospinal fluid analysis.⁹