Jared Van Snellenberg
Columbia University, Psychiatry, Faculty Member
Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive... more
Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ. We randomized 49 clinically stable individuals with SCZ to three weeks of intermittent treatment with 0.5 mg or 15 mg of DAR-0100A, or placebo (normal saline). Functional magnetic resonance imaging (fMRI) BOLD was used to evaluate the effects of drug administration on brain activity during a working memory (WM) task. Effects on cognition were also assessed usin...
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Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a... more
Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine-grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing correct trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the classic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity. We also observed a relative increase in activity in medial anterior prefrontal cortex, posterior cingulate/precuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predominantly subcortical and prefrontal r...
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We investigated judgements of agency in participants with schizophrenia and healthy controls. Participants engaged in a computer game in which they attempted to touch downward falling Xs and avoid touching Os. On some trials, participants... more
We investigated judgements of agency in participants with schizophrenia and healthy controls. Participants engaged in a computer game in which they attempted to touch downward falling Xs and avoid touching Os. On some trials, participants were objectively in perfect control. On other trials, they were objectively not in complete control because the movement of the cursor on the screen was distorted with respect to the position of the mouse by random noise (turbulence), or it was lagged by 250 or 500 ms. Participants made metacognitive judgements of agency as well as judgements of performance. Control participants' judgements of agency were affected by the turbulence and lag variables-indicating that they knew they were objectively not in control in those conditions, and they were also influenced by their assessments of performance. The patients also used their assessments of performance but neither turbulence nor lag affected their judgements of agency. This indicated an impair...
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This meta-analytic review examines the efficacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients... more
This meta-analytic review examines the efficacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients treated (a) with atypical versus typical antipsychotic medications, or (b) with various atypical treatments. In 17 atypical versus typical trials aggregating 939 participants, superior overall (verbal and nonverbal) LTM was detected in patients assigned to atypical trials. However, this difference was small (effect size estimate (ES) 0.17; 95% Confidence Interval (CI) 0.04 to 0.31) and specific to certain atypical treatments. Relative to typical antipsychotic trials, LTM superiority was marginally significant for risperidone trials (ES 0.20; 95% CI -0.03 to 0.44) and significant for olanzapine trials (ES 0.29; 95% CI 0.08 to 0.49). In contrast, clozapine trials did not produce a LTM advantage over typical trials (ES -0.06; 95% CI -0.35 to 0.23). Due to the lack of available studies, the effect of quetiapine was indeterminate. Direct comparison between atypical trials revealed a similar effect pattern. A marginally significant superiority in overall LTM was detected for risperidone and olanzapine compared to clozapine (ES 0.28; 95% CI -0.04 to 0.59), which reached significance for verbal LTM (ES 0.36; 95% CI 0.04 to 0.67). Finally, the beneficial impact of antipsychotic medications emerged as a function of differences in the anticholinergic properties of the treatment arms being compared.