The Prodrome and Clinical Risk for Psychotic Disorders

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Key points

  • Clinical high-risk (CHR) syndromes are associated with milder versions of psychological deficits and biological abnormalities observed in psychotic disorders, with those manifesting greater severity of deficits and abnormalities appearing to be at higher risk for conversion to psychosis.

  • Evidence of changes in brain structure during the prodromal phase indicates a neuropathologic process that may be the focus of future preventive intervention efforts to target neural mechanisms involved in the

General and Social Cognitive Functioning

Cognitive deficits, particularly in memory and attentional functions, are among the most extensively documented aspects of psychosis.14, 15 Likewise, a recent meta-analysis concluded that CHR individuals have significant cognitive deficits relative to matched HCs, and that CHR participants who convert to psychosis have greater baseline impairment than nonconverters.16 The severity of processing speed and verbal memory deficits also discriminates converters from nonconverters, with verbal memory

Neuroanatomy

A wide range of abnormalities in brain structure are associated with psychotic disorders. A recent review indicates decreases in intracranial and total brain volume, with the largest reductions in gray matter volume within cortical and subcortical regions.34 White matter reduction has also been observed in both medication-naive and medicated groups, and has been linked with severity of illness progression. A review of research involving CHR groups similarly indicates cortical and hippocampal

Neurotransmitters: Dopaminergic and Glutamatergic Systems

Theories of dopamine (DA) activity in psychosis have been prominent for decades, and substantial evidence indicates heightened DA in subcortical regions. Patients with psychosis manifest increased striatal DA activity and DA receptor density, and the extent of DA receptor occupancy (eg, D2 receptor) is associated with effectiveness of antipsychotics.52 Dysregulated presynaptic DA activity results in excessive DA release from areas projecting to the striatum, especially in the associative

Diagnostic dilemmas

Significant controversies and challenges surround diagnoses of CHR syndromes.67 With regard to inclusion of Attenuated Positive Syndrome (APS) as a formal diagnosis in diagnostic taxonomies, arguments in favor have included benefits for research and the observation that individuals who meet CHR syndrome criteria are typically seeking help and in distress. Arguments against involve concerns of overdiagnosis, stigmatization, and excessive medication of those who are false-positives. After

Summary

Significant progress has been made in the characterization of CHR syndromes, and findings indicate that they are associated with milder versions of many psychological deficits and biological abnormalities observed in psychotic disorders. Moreover, those at CHR who manifest the most severe deficits and abnormalities seem to be at greatest risk for psychosis conversion. Findings indicating prodromal changes in brain structure suggest that this stage is characterized by neuroplasticity that can

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    Disclosures: This research was supported in part by grant U01MHMH081988 from the National Institute of Mental Health awarded to Dr Walker.

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