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  • Schizophrenia is characterized by psychotic symptoms such as hallucinations and delusions (often referred to as “positive” symptoms), negative or deficit symptoms such as lack of motivation and social withdrawal, and cognitive impairments affecting attention, working memory, declarative memory, language fluency, and diverse aspects of social cognition.

  • Bipolar disorder is characterized by extreme mood swings between mania (characterized by euphoria or irritability, grandiosity, increased energy, and decreased need for sleep) and depression (characterized by sadness, loss of interest, decreased energy, disturbed sleep and appetite, ideas of worthlessness, guilt, and suicidal ideation). Affected individuals may return to normal mood states (euthymia) between acute episodes, but many have residual symptoms. Psychotic symptoms may occur in either manic or depressed episodes, most often congruent with mood. Bipolar patients with psychosis may have cognitive deficits similar to those seen in individuals with schizophrenia.

  • A milder form of the illness, bipolar II disorder is also recognized in which hypomania (mild mania) alternates with depression. Such patients do not generally suffer psychotic symptoms.

  • Some individuals experience a mixture of symptoms characteristic of schizophrenia and bipolar disorder and are currently given the diagnosis of schizoaffective disorder.

  • The heritability of schizophrenia and bipolar disorder is estimated to be very high, in the range of 65% to 80%. In contrast, the heritability of unipolar depression is less, approximately 35%, with greater environmental influence.

  • Despite their high heritabilities, the genetic risk of schizophrenia and bipolar disorder is highly polygenic, with many hundreds of genetic variants each contributing small increments of risk in the population, with different combinations of loci acting in different individuals. Genetic studies have found significant sharing of genetic risk variants between schizophrenia and bipolar disorder.

  • Schizophrenia is characterized by loss of gray matter in frontal and temporal regions of the cerebral cortex. Unaffected first-degree relatives may have milder gray matter loss with similar spatial patterns.

  • First-degree relatives of individuals with schizophrenia may have attenuated symptoms such as suspiciousness, social isolation, eccentric beliefs, and mild cognitive impairments without psychosis. This condition is currently diagnosed as schizotypal disorder.

  • Antipsychotic drugs are effective for the positive (psychotic) symptoms of schizophrenia, for acute manic episodes, and when combined with an antidepressant for psychotic depression. They are also efficacious in preventing acute relapses in schizophrenia, and often in combination with mood-stabilizing drugs in bipolar disorder. They lack efficacy for the negative and cognitive symptoms of schizophrenia.

  • The therapeutic action of antipsychotic drugs depends on their ability to antagonize D2 dopamine receptors. This mechanism of action can also cause significant Parkinson-like motor side effects. Second-generation antipsychotic drugs partly mitigate motor side effects by blocking other neurotransmitter receptors (most significantly 5HT2A receptors) but have their own significant side effects, in particular, weight gain and elevation of serum glucose and lipids.

  • Lithium is effective both for acute mania and for mood stabilization in bipolar disorder. Certain anticonvulsant drugs, such as valproate, are also effective. However, which of these drugs’ many pharmacological actions is responsible ...

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