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  • Schizophrenia is characterized by positive symptoms (eg, delusions, disorganized speech [association disturbance], hallucinations, behavior disturbance [disorganized or catatonic], and illusions); negative symptoms (eg, alogia [poverty of speech], avolition, flat affect, anhedonia, and social isolation); and cognitive dysfunction (eg, impaired attention, working memory, and executive function) all leading to impaired psychosocial functioning.


  • Schizophrenia causation theories include genetic predisposition, obstetric complications with hypoxia, increased neuronal pruning, neurodevelopmental disorders, neurodegenerative theories, dopamine receptor defect, and regional brain abnormalities including hyper- or hypoactivity of dopaminergic processes in specific brain regions. Increased ventricular size and decreased gray matter have been reported.

  • Alterations in glutamatergic neurotransmission resulting in increased neuronal pruning have also been implicated in schizophrenia pathogenesis. Genes controlling N-methyl-D-aspartate (NMDA) receptor activity are hypothesized to be part of this process.

  • Studies have also shown increased susceptibility to immune/autoimmune disorders in schizophrenia, as well as abnormalities of autoantibodies and cytokine functioning.

  • Positive symptoms may be closely associated with dopamine receptor hyperactivity in the mesocaudate, whereas negative and cognitive symptoms may be most closely related to dopamine receptor hypofunction in the prefrontal cortex.


  • Symptoms of the acute episode may include being out of touch with reality; hallucinations (especially hearing voices); delusions (fixed false beliefs); ideas of influence (actions controlled by external influences); disconnected thought processes (loose associations); illogical conversation; ambivalence (contradictory thoughts); flat, inappropriate, or labile affect; autistic thinking (withdrawn and inwardly directed thinking); uncooperativeness, hostility, and verbal or physical aggression; impaired self-care skills; and disturbed sleep and appetite.

  • After the acute psychotic episode has resolved, typically there are residual features (eg, anxiety, suspiciousness, lack of motivation, poor insight, impaired judgment, social withdrawal, difficulty in learning from experience, and poor self-care skills).

  • Comorbid psychiatric and medical disorders (eg depression, anxiety disorders, substance abuse, and general medical disorders such as respiratory disorders, cardiovascular disorders, and metabolic disturbances) can also occur. Medication nonadherence is also common.


  • The Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), specifies the following diagnostic criteria:

    • ✔ Continuous symptoms that persist for at least 6 months with at least 1 month of active phase symptoms (Criterion A) and may include prodromal or residual symptoms.

      • Criterion A: For at least 1 month, there must be at least two of the following present for a significant portion of time: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms. At least one symptom must be delusions, hallucinations, or disorganized speech.

      • Criterion B: Significantly impaired functioning.

  • Before treatment, perform a mental status examination, physical (vitals including height and weight) and neurologic examination, complete family and social history, psychiatric diagnostic interview, and laboratory workup (complete blood count [CBC], electrolytes, hepatic function, renal function, electrocardiogram [ECG], fasting serum glucose, serum lipids, thyroid function, and urine drug screen).



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