Neuropharmacological Interventions for Cognitive Dysfunction in Schizophrenia

Abstract

Mental retardation remains one of the most devastating facts about schizophrenia as it significantly impairs functional outcome even though there is an improvement in antipsychotic treatment.  This paper methodically evaluated the neuropharmacological efficacy of certain modulatory substances such as NMDA receptor enhancers, dopamine D1 agonists, 6-nicotinic acetylcholine receptor agonists and GABAergic modulators on the critical cognitive domains such as working memory, attention, executive functioning and processing speed.  Mixed-method experimental design, using randomized controlled trials, cognition tests, serum biomarker profiling and neuroimaging measures was used.  These results showed that the greatest consistent improvements in working memory and cognitive flexibility were observed with NMDA-enhancing drugs with a mean improvement of 1825% compared to baseline.  Dopamine D1 agonist stimulants significantly boosted performance and processing speed in attentional tasks, whereas 7-nAChR agonists stimulated language learning and long-term attention, in a mild but sustained manner.  There was a heterogeneous responses of GABAergic modulators, which were correlated with substantial negative symptom burden reduction in cognitive domains.  The findings of the neuroimaging data revealed increased prefrontal cortex activity after treatment with a strong correlation (r = 0.64, p < 0.001) with cognitive score improvements.  The combined results support a multimodal neuropharmacological strategy as more useful than mono-mechanistic therapies, with a prospective therapeutic approach to the improvement of the cognitive impairment in schizophrenia.