ACortical circuit dysfunction and cognitive deficits in
schizophrenia – implications for preemptive interventions
Abstract
Schizophrenia is a devastating disorder that is common, usually chronic, frequently associated with substantial co-morbidity for
addictive and medical disorders and, as a consequence, very costly in both personal and economic terms. At present, no proven
means for preventing or modifying the course of the illness exist. This review discusses evidence supporting the ideas that: (i)
impairments in certain cognitive processes are the core feature of schizophrenia; (ii) these cognitive impairments reflect
abnormalities in specific cortical circuits; and (iii) these circuitry abnormalities arise during childhood–adolescence. The implications
of these findings for the development and implementation of safe, preemptive, disease-modifying interventions in individuals at high
risk for a clinical diagnosis of schizophrenia are considered.
Introduction
The identification of individuals at high risk for a major psychiatric
illness, and the development of novel interventions that can change the
course of the illness before its debilitating signs and symptoms
emerge, represent critical current challenges in public health. This
article considers these challenges for schizophrenia, a leading cause of
years of life lost to disability and premature mortality in developed
countries (Lopez et al., 2006). Schizophrenia is now considered to be
a neurodevelopmental disorder in which psychosis actually represents
a late, and potentially preventable, outcome of the illness (Insel,
2010); that is, the appearance of the diagnostic clinical features of
schizophrenia (psychosis) represents not the onset of the illness, but
the downstream product of years of pathogenic processes at work.
From this perspective, the development of effective preemptive
treatments for schizophrenia (i.e. interventions that modify disease
pathogenesis in order to prevent or delay the appearance of psychosis)
requires knowledge of: (i) the abnormalities in brain circuitry that
underlie the core functional disturbances of the illness; (ii) when
during the course of development these abnormalities in brain circuitry
arise; and (iii) a means to detect these abnormalities in brain circuitry
when their functional impact is still subclinical.