Over the last decade or so, our field has experienced a radical shift in our understanding of schizophrenia and other serious psychotic disorders, such as schizoaffective disorder and bipolar disorder with psychosis. We now understand that these are neurocognitive disorders (ie, how neural systems in the brain represent and process information). We also understand that they are neurodevelopmental disorders with genetic components and antecedents during gestation. The developmental course unfolds with increasing signs, symptoms, and cognitive dysfunction, until the onset of the first episode of psychosis during adolescence or early adulthood. Cognitive deficits are more significant determinants of functional outcome than are symptoms, although most current psychiatric treatments focus only (or mostly) on symptom management.
Accumulating evidence indicates that psychotic disorders constitute syndromes rather than diseases per se. Groups of patients can show a common clinical phenotype with multiple different etio-pathogenic factors that contribute to illness onset and expression. Patients with different clinical diagnostic phenotypes (such as schizophrenia rather than bipolar disorder with psychosis) can show similar underlying patterns of cognitive dysfunction and neurobiological abnormalities. New insights into the pathogenesis of psychotic disorders has spurred research focused on key domains of neural system dysfunction and on how brain plasticity mechanisms can be harnessed to drive healthier neural system functioning, improve cognition, and support functional recovery.
Cognitive and neural system dysfunction in psychotic disorders
Although the clinical symptoms of psychotic disorders are dramatic and are what most clinicians focus on as their treatment targets, impairments in a wide range of cognitive function are observed in these illnesses, ranging from the earliest stages of information processing in the brain, to higher-level abilities to abstract, to read social cues, to self-reflect, and to engage in meta-cognition. These various areas of cognitive dysfunction are accompanied by abnormalities in their neural system correlates. Moreover, patients exhibit a fair amount of cognitive and neural system heterogeneity, both within and across traditional diagnostic groupings—different patients will often have different patterns of impairment. Nonetheless, the following general categories of findings are commonly observed:
• Sensory and perceptual processing abnormalities: A range of subtle deficiencies in representing and processing auditory and visual information, including socially relevant information, that can show functional consequences.
• Learning and memory deficits: Impairments in how the brain encodes, learns, and makes decisions based on new information, including socially relevant information; responds to changes in rewarding or punishing contingencies in the environment; encodes and remembers autobiographical events (episodic memory); and learns associations and meanings (semantic memory).
• Executive dysfunction (ie, impaired cognitive control): Deficits in attention and working memory; problems with inhibitory control; impaired abstraction, reasoning, planning, sequencing.
In psychotic disorders, the emergent picture is one of a brain that has undergone aberrant patterns of neurodevelopment, with reduced functional connectivity among key neural systems and reduced efficiency in its cognitive and socio-affective operations.1 This suggests that to improve cognition and functioning, it is essential to begin treatment as early as possible in the course of illness. Interventions designed to correct or compensate for abnormal neural system functioning must be started before irreversible maladaptive changes in the cortical and subcortical representational systems have taken root. Cognitive remediation and cognitive training approaches are used to improve cognition and are increasingly being studied in individuals who are in the early phases of illness.
Dr Vinogradov is Professor and Department Head, Donald W. Hastings Endowed Chair, Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN. Dr Vinogradov reports that she is on the Speakers’ Bureau for Alkermes and Mindstrong.
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