Psychotic Disorders Increasingly Seen as Preventable

By Tucker, Miriam E. | Clinical Psychiatry News, February 2011 | Go to article overview

Psychotic Disorders Increasingly Seen as Preventable


Tucker, Miriam E., Clinical Psychiatry News


PITTSBURGH -- Emerging evidence is leading to optimism that early interventions could prevent the onset of schizophrenia or reduce its impact on cognitive function.

Among psychiatric disorders, schizophrenia tends to manifest later in life than most, typically not until late adolescence or early adulthood. Yet, evidence suggests that brain changes actually occur much earlier in life among those destined to develop the disease, said Dr. Matcheri S. Keshavan, the Stanley Cobb Professor of Psychiatry at Harvard Medical School and vice chair of public psychiatry at Beth Israel Deaconess Medical Center and the Massachusetts Mental Health Center, all in Boston.

Indeed, schizophrenia is increasingly being viewed as a neurodevelopmental disorder with psychosis as a late and potentially preventable stage of the illness (Nature 2010;468:187-93). Researchers are now investigating whether it is possible to detect these early signs and intervene before the onset of psychosis to minimize the impact of the disease, said Dr. Keshavan, who is also professor of psychiatry at the University of Pittsburgh.

The emergence of cognitive control and emotion regulation during adolescence are related to expansion of connectivity and fine-tuning of both excitatory and inhibitory neurotransmitter systems. At the same time, abstract thinking and executive function arise from increased efficiency at the expense of brain plasticity, or the ability of the brain to rewire itself in response to change.

These processes might go haywire in those at risk for schizophrenia, and a combination of genetic and environmental factors could lead to a failure of inhibitory processes resulting in psychosis, he explained.

"Psychosis begins in adolescence, but schizophrenia really begins in childhood or even earlier. ... The risk-plasticity model of development of schizophrenia suggests several windows of opportunity for primary, secondary, and tertiary prevention," he said.

Several signs mark the early stages of disease. In one recent meta-analysis of 18 studies, individuals with schizophrenia demonstrated mean IQ scores of approximately half a standard deviation below those of healthy comparison subjects, years before the onset of psychotic symptoms (Am. J. Psychiatry 2008;165:579-87).

Certain biomarkers might help to identify those at risk. In a study from Dr. Keshavan's work in Pittsburgh, at-risk relatives of schizophrenia patients who themselves had schizotypy performed less well on the Wisconsin Card Sort task, which assesses executive function, and showed age-related deficits on the oculomotor delayed-response task, compared with nonschizotypal relatives and healthy controls (Prog. Neuropsy-chopharmacol. Biol. Psychiatry 2006;30:230-8).

Two follow-up studies showed gray matter losses evolving during the premorbid phase among high-risk relatives, compared with control relatives, in areas mediating social cognition and overlapping with cognitive deficits (Neuroimage 2011;54S1:S272-9; Neuroimage 2011;54S1:S287-92).

Other data from Dr. Keshavan's group at the University of Pittsburgh indirectly suggest that neurons do not appear to be lost in schizophrenia, but that a reduction in synaptic connectivity occurs leading to reduced brain plasticity (Schizophr. Res. 2010;119:47-51). Such a process might be reversible, he noted.

A variety of environmental factors have been implicated in triggering schizophrenia among individuals who already are genetically predisposed. These include obstetric complications (Ann. NY Acad. Sci. 2003;1008:269-75), exposure to the herpes simplex virus (Mol. Psychiatry 2007;12:105-13), and cannabis use (Schizophr. Res. 2008;99:1-6).

In a longitudinal study of 291 prodromal individuals who sought treatment, the risk of conversion to psychosis was 35% over a period of 2.5 years. Five baseline features independently predicted conversion risk: A genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse. …

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