No abstract

Our capacity to measure diverse aspects of human biology in vivo has developed rapidly in the past decades, but the rate at which these techniques have generated translatable insights into the biology of psychopathological conditions has lagged far behind. This slow progress is partly due to the poor sensitivity, specificity, and replicability of many findings in the literature, which have in turn been attributed to small effect sizes, small sample sizes, and low statistical power. A commonly proposed solution is to rely on large, consortia-sized samples to facilitate discovery of replicable findings. Here, we argue that increasing sample sizes will have limited impact unless a more fundamental issue is addressed: the precision with which target behavioral phenotypes are measured. We discuss key problems and outline several ways forward, largely centered on the use of appropriate statistical models with deep, transdiagnostic assessment of hierarchically organized and homogeneous psychopathology dimensions across the full range of the severity spectrum. We provide worked examples to demonstrate key problems and potential solutions. Arguably, a precision phenotyping approach can enhance the discovery and replicability of associations between biology and behavior, thereby facilitating insights into the pathophysiological mechanisms underlying psychiatric disorders.

Evidence suggests that individuals with schizophrenia (SZ) report anticipatory pleasure deficits compared to controls and that these deficits are linked to decreased motivation to engage socially. However, these deficits have been identified via self-report measures of hypothetical pleasant stimuli, leaving it unclear whether they exist in reference to actual social situations. To address this issue, we created a live social interaction that minimized the reliance of higher-order cognitive processes. SZ and control participants were told that they would be playing an "enjoyable sharing game" with another study participant (who was actually a confederate) that involved asking and answering questions (36 interpersonal closeness generation questions; Aron et al., 1997). Participants then reported their current mood and the emotions they anticipated experiencing during the pleasant social interaction. Immediately following the interaction, they reported their experienced emotions. We found that the SZ group anticipated more negative emotion ( d = 1.0), but were less accurate in forecasting negative emotion ( d = .81), than controls, and these effects were large. There were small, non-significant group differences in anticipation, experience, and accuracy in forecasting of positive emotion (all d s < .29). Also, social anhedonia was positively correlated with anticipated negative affect and negatively associated with experienced positive emotion. At the same time, controls reported finding the interaction to be a more positive emotional experience overall, d = 0.75. This is the first study to show that "anticipatory pleasure deficits" in SZ might actually be heightened anticipated negative emotion and that inaccurate forecasting could be linked to decreased social motivation.

Marek et al. analyzed three very large magnetic resonance imaging (MRI) datasets and concluded that thousands of participants are necessary to ensure replicable results in “brain-wide associations studies,” which they defined as “studies of the associations between common inter-individual variability in human brain structure/function and cognition or psychiatric symptomatology.” This conclusion overgeneralizes the implications of their findings and is likely to have an unwarranted chilling effect on neuroimaging research focused on individual differences, preventing good research with samples in the hundreds from being funded and conducted. To fend off these negative consequences, we explain why their conclusion is not fully justified, discuss methods that can yield larger effects, and suggest practical guidelines for sample size, recognizing the potential utility of samples in the hundreds.

Objective Previous research suggests people with social anhedonia (SocAnh) exhibit deficits in anticipated pleasure for social stimuli relative to controls. However, previous research has relied on hypothetical social stimuli and has focused on anticipated pleasure without examining negative affect. Method Participants were informed that they would complete an “enjoyable” sharing task with a peer and were asked to forecast positive and negative affect during the interaction. After the interaction, participants reported their experienced emotions. Results We found SocAnh and controls anticipated and experienced similar levels of positive affect and that both groups underpredicted positive affect. The SocAnh group anticipated and experienced more negative affect than controls and was more accurate in forecasting negative affect. Conclusion This is the first study to show that SocAnh is associated with the heightened anticipation of negative affect and that experiencing heightened negative affect during social interactions could drive reduced motivation and desire to engage in future social interaction.