As psychiatrists well know, psychotropic medications are of only limited value in improving cognition in people with schizophrenia. So scientists have been working diligently to develop effective cognitive remediation programs for such individuals—for example, drill-and-practice exercises or computer-based neurocognitive training.

And it looks as if such programs can lead to moderate cognitive improvement, a meta-analysis published in the December 2007 American Journal of Psychiatry showed.

As the lead investigator, Susan McGurk, Ph.D., of the Dartmouth Psychiatric Research Center, and colleagues wrote: "The effects of cognitive remediation on cognitive performance were remarkably similar across the 26 studies included in the analysis despite differences in length and training methods between cognitive remediation programs, inpatient/outpatient setting, patient age, and provision of adjunctive psychiatric rehabilitation."

But what is it that makes such programs effective? They prevent or reverse schizophrenia-induced damage to the brain, a study by Matcheri Keshavan, M.D., a professor of psychiatry at Harvard Medical School, and colleagues suggested. The report of their findings was published May 3 in the Archives of General Psychiatry.

The researchers selected as their subjects 53 symptomatically stabilized but cognitively disabled outpat ients fairly early in the course of schizophrenia or schizoaffective disorder. That is, most had experienced their first psychotic symptoms within the previous five years. Subjects' average age was 26.

The subjects were randomized to receive, over the next two years, either a cognitive remediation program called cognitive enhancement therapy (CET) or a control regimen called enriched supportive therapy (EST).

CET included 60 hours of weekly computer-based neurocognitive training in attention, memory, and problem solving as well as 45 weekly sessions designed to address key social-cognitive deficits that can limit functional recovery from schizophrenia, such as difficulties in managing emotions, trouble communicating nonverbally, a lack of foresight, or a lack of perspective. The researchers had previously found that CET could produce strong and lasting improvements in cognition in subjects who had had schizophrenia for many years.

Subjects in the EST group met individually with a therapist to learn and practice a variety of stress-reduction and illness-management techniques designed to forestall relapse and enhance adjustment to their illness.

The researchers used structural MRI scans to evaluate the brain topography of all subjects at the start of the study, a year later, and at the end of the study two years later. They then compared subjects' brain-scan results.

By the end of the study, the cognitive-therapy group had a significantly greater preservation of gray matter in several brain regions known to be impaired by schizophrenia—the hippocampus, parahippocampal gyrus, and fusiform gyrus—than the control group did.

Moreover, by the end of the study, the cognitive-therapy group had experienced significantly greater gray-matter increases in the amygdala than the control group had. This brain area, too, is known to be impaired by schizophrenia.

And crucially, the researchers noted, "These differential effects of CET on gray-matter change were significantly related to improved cognitive outcome, with patients who experienced less gray-matter decline and greater gray-matter increases also demonstrating significantly greater cognitive improvement over the two years of the study."

Thus cognitive remediation may benefit cognition in people with schizophrenia by preventing or reversing gray-matter loss.

True, "overall structural changes in regional brain volumes were not large," the researchers wrote, "but were reliably detectable and may reflect functional changes."

"Our observations are of clinical relevance on three counts," Keshavan told Psychiatric News. "First, our observations provide a neurobiological basis of understanding how psychosocial treatments such as cognitive remediation work. Second, these findings suggest that monitoring brain function with neuroimaging techniques may eventually offer the psychiatrist a way to evaluate therapeutic benefits, as well as to identify patients who might be the best candidates for these treatments. Finally, the neuroprotective effects of cognitive remediation in schizophrenia, if confirmed, offer therapeutic optimism in regard to cognitive deficits in this illness, especially since currently there are few medications shown to benefit these deficits."

The study was funded by the National Institute of Mental Health.

An abstract of "Neuroprotective Effects of Cognitive Enhancement Therapy Against Gray Matter Loss in Early Schizophrenia" is posted at <http://archpsyc.ama-assn.org/cgi/content/short/2010.63>.