There is converging evidence that brain serotonin and dopamine may selectively modulate learning and memory in humans. However, this has not been directly demonstrated. In the current study, we used the method of amino acid precursor depletion to explore the effects of low serotonin and catecholamine function on memory in healthy female volunteers. Participants completed three experimental sessions: (i) tryptophan depletion (TD to lower 5-HT); (ii) tyrosine and phenylalanine depletion (TPD to lower catecholamines); and (iii) a balanced control condition (Bal). All testing was conducted in a double-blind, placebo-controlled, crossover design. Cognitive and mood assessments were performed at baseline and 5 h after ingesting the amino acid mixture. Consistent with previous studies, TD impaired declarative memory consolidation on a structured word-learning task, while TPD, acting to lower brain dopamine availability, impaired spatial working memory. No secondary deficits were observed on measures of attention, short-term memory or subjective mood state. These findings suggest that low brain serotonin versus dopamine selectively impairs memory performance in humans. This may shed light on the role of these neurotransmitters in disorders that are characterized by significant memory impairment.

This study examined the criterion and construct validity of a brief computerized cognitive test battery (CogState Schizophrenia Battery) compared to a conventional cognitive test battery recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus. The CogState and MATRICS batteries yielded comparable effect sizes in comparing patients with schizophrenia to healthy controls (Cohen's ds = -1.50 for both batteries). Moderate to large correlations were observed between CogState and MATRICS measures of processing speed, attention/vigilance, working memory, verbal and visual learning, reasoning/problem solving, and social cognition (rs = .56-.79). CogState and MATRICS composite scores also correlated strongly with scores on the University of California at San Diego (UCSD) Performance-Based Skills Assessment (UPSA; rs = .76 and .79, respectively) in patients with schizophrenia. Results of this study suggest that the CogState Schizophrenia Battery provides valid measurement of the cognitive domains nominated by the MATRICS consensus group as being important to consider in the context of pharmacological treatments for cognitive impairment in schizophrenia.

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