Effects of Psychosocial Treatment On the Brain in Schizophrenia: Results From a Two-Year Trial of Cognitive Enhancement Therapy

Background and Purpose: Schizophrenia is a chronic and disabling disorder that places profound burden on the individuals who suffer from it, their families, and society. For many decades social work researchers have been developing psychosocial interventions that can be used in combination with pharmacotherapies to improve recovery in schizophrenia. Such interventions have been remarkably effective at reducing psychiatric relapse and symptomatology, as well as improving functional outcome in people who live with the illness. The repeatedly observed benefits of psychosocial intervention in a condition with such a strong neurobiologic basis as schizophrenia, combined with increasing evidence of the plasticity of the brain, has raised the intriguing possibility of the potential beneficial effects of psychosocial treatment on the brain in schizophrenia. To date, however, rigorous controlled studies integrating psychosocial interventions with neuroscientific methods in the treatment of schizophrenia have yet to be conducted. In this research, we sought to examine the potential neurobiologic and neuroprotective effects of a psychosocial cognitive rehabilitation program, Cognitive Enhancement Therapy (CET; www.CognitiveEnhancementTherapy.com), in individuals with early course schizophrenia.

Methods: Stabilized, early course outpatients with schizophrenia or schizoaffective disorder were randomly assigned to CET (n = 30) or an active Enriched Supportive Therapy (EST) control (n = 23) and treated for two years. CET is an integrated approach to the remediation of social and non-social cognitive deficits in schizophrenia that makes use of computer-assisted cognitive training and group-based experiential exercises focusing on the development of social cognition. EST is an individual treatment approach that focuses on illness management and stress reduction. Structural magnetic resonance imaging and cognitive assessments were completed prior to treatment and then annually for two years. Broad areas of frontal and temporal brain change were analyzed using longitudinal voxel-based morphometry methods employing mixed-effects models to examine the differential effects of CET compared to EST on brain change.

Results: Individuals receiving CET demonstrated significantly greater preservation of gray matter volume over the course of two years in the left hippocampus, parahippocampal gyrus, and fusiform gyrus, and significantly greater gray matter growth in the left amygdala (all corrected P < .040), compared with those receiving EST. All of these areas of the brain have been previously implicated in cognitive impairment in schizophrenia, and results from a series of growth models indicated that less gray matter loss in the left parahippocampal and fusiform gyrus, and greater gray matter increases in the left amygdala were significantly related to improved cognition and mediated the previously reported beneficial cognitive effects of CET.

Conclusions and Implications: CET, a psychosocial cognitive rehabilitation intervention, may offer neurobiologic protective and enhancing effects in early schizophrenia that are associated with improved long-term cognitive outcomes. The possibility of positively affecting the brain in schizophrenia with psychosocial treatment is real, and such findings lend support to the social work view of the reciprocal biopsychosocial nature of human behavior and disease. The continued elucidation of the capacity of psychosocial interventions to alter neurobiologically-based disease processes is an important direction for interdisciplinary social work and neuroscience research.