Psychotic Disorder

Psychosis is a syndrome embedded in several disorders, including schizophrenia and bipolar disorder with psychotic features. Individuals with psychotic disorders have increased mortality, overall mortality was 6.7 per 10 000 among health system outpatients. The clinical symptoms include positive symptoms (e.g., hallucinations, delusions, and disorganized thoughts and speech), negative symptoms (e.g., apathy, affective flattening, and social withdrawal), and cognitive dysfunction.

Causes of Psychotic Disorder

Epidemiologic studies strongly implicate heredity in the pathogenesis of idiopathic psychotic disorders. Although the specific genetic markers and modes of heritance of psychotic disorders have not been determined, two general hypotheses have been proposed: common allele hypothesis and rare allele hypothesis. The hippocampus, midbrain, corpus striatum, and prefrontal cortex, all regions that are implicated in psychotic symptoms and disorders. Several associations have been found between idiopathic psychosis and genes controlling synaptic neurotransmission, particularly genes involving pathways mediated by dopamine (DA) and glutamate.

Dopamine (DA) and Glutamate in Psychotic Disorder

Individuals at familial risk for psychosis display attenuated DA stress processing in ventromedial prefrontal cortex (vmPFC), a brain region previously identified to play a key role in human dopaminergic stress regulation. Evidence has emerged showing that, at least in part, the stress response is facilitated by DA release in the striatum and prefrontal cortex. Investigating stress-related DAergic activity in the context of psychotic disorder could thus provide new insights into the pathogenesis of the disorder.

Schizophrenia and affective psychosis were linked to a hypoglutamatergic state and hypofunction of energy metabolism, while bipolar disorder and major depressive disorder were linked to a hyperglutamatergic state and hyperfunction of energy metabolism. Glutamatergic system and ensuing adaptations of neuronal energy metabolism are linked to distinct psychiatric symptom dimensions, delivering novel evidence for targeted treatment approaches.

Fig.1 Pathophysiological model of psychotic disorders. (Lieberman, 2018)

Treatment Methods of Psychotic Disorder

Cognitive and behavioral rehabilitation has been used in the treatment of idiopathic psychotic disorders. The most widely studied of these techniques are social skills training and family psycho-education. Cognitive behavioral therapy (CBT), a treatment originally developed for mood and anxiety disorders, may also be useful for psychotic symptoms. CBT in patients with schizophrenia can also help to reduce the distress caused by hallucinations or delusional beliefs. It has been hoped that precision medicine will provide new targets such as the products of newly identified genes associated with psychotic disorders.

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Reference

1. Lieberman, J.A.; First, M.B. Psychotic disorders. New England Journal of Medicine. 2018, 379(3): 270-280.