Omega-3 fatty acids also have been investigated, based on evidence that their levels might be deficient in schizophrenia patients, leading to alterations in neurotransmission among other processes.
In a randomized, double-blind placebo-controlled trial, 81 adolescents and young adults with subthreshold psychosis received 1.2 g/d of omega-3 polyunsaturated fatty acids (PUFAs) for 12 weeks, followed by a 40-week monitoring period. At 12 months, 2 of 41 in the omega-3 group (4.9%) and 11 of 40 (27.5%) in the placebo group had transitioned to psychotic disorder, a significant difference (Arch. Gen. Psychiatry 2010;67:146-54).
The omega-3s also significantly reduced positive symptoms, negative symptoms, general symptoms, and improved functioning, compared with placebo, with no difference in the incidence of adverse effects between the treatment groups. "This finding suggests that the omega-3s prevented the transition to psychosis. If this is the case, it would be significant for young people at high risk of developing schizophrenia or other psychotic disorders," Dr. Keshavan said.
Antiviral agents also might have prevention potential. In an unpublished study by Dr. Konasale M. Prasad in Dr. Keshavan’s Pittsburgh group, valacyclovir in patients with schizophrenia produced a trend toward improvement in working memory.
And finally, evidence suggests that an integrated neurocognitive and social-cognitive rehabilitation program using cognitive enhancement therapy (CET) can positively affect cognitive and functional outcomes. A total of 58 early-course outpatients with schizophrenia or schizoaffective disorder were randomly assigned to CET or enriched supportive therapy, an illness management intervention using psychoeducation and applied coping strategies. After 2 years, CET moderately enhanced neurocognitive function. Strong differential effects on social cognition, cognitive style, and social adjustment composites remained at year 2 and also extended to measures of symptomatology, particularly negative symptoms (Psychiatr. Serv. 2009;60:1468-76).
The University of Pittsburgh authors, of whom Dr. Keshavan was again the principal investigator, concluded "CET appears to be an effective approach to the remediation of cognitive deficits in early schizophrenia that may help reduce disability in this population. The remediation of such deficits should be an integral component of early intervention programs treating psychiatrically stable schizophrenia outpatients."
Another study, currently in press, showed that gray matter density increased with CET compared to enriched supportive therapy at 1 year, Dr. Keshavan said.
"The summary is that there are many promising hypotheses and more research is needed to develop proof of concept," he concluded.
Dr. Keshavan disclosed that he receives grant/research support from GlaxoSmithKline.