Background Neuroimaging studies of emotion in schizophrenia have reported abnormalities in amygdala and other regions, although divergent results and heterogeneous paradigms complicate conclusions from single experiments. To identify more consistent patterns of dysfunction, a meta-analysis of functional imaging studies of emotion was undertaken. Methods Searching Medline and PsycINFO databases up through January of 2011, 88 potential articles were identified, of which 26 met inclusion criteria, comprising 450 patients with schizophrenia and 422 healthy comparison subjects. Contrasts were selected to include emotion perception and emotion experience. Foci from individual studies were subjected to a voxel-wise meta-analysis using multi-level kernel density analysis. Results For emotional experience, comparison subjects showed greater activation in the left occipital pole. For emotional perception, schizophrenia subjects showed reduced activation in bilateral amygdala, visual processing areas, anterior cingulate cortex (ACC), dorsolateral frontal cortex, medial frontal cortex and subcortical structures. Schizophrenia subjects showed greater activation in the cuneus, parietal lobule, precentral gyrus and superior temporal gyrus. Combining across studies and eliminating studies that did not balance on effort and stimulus complexity eliminated most differences in visual processing regions as well as most areas where schizophrenia subjects showed a greater signal. Reduced reactivity of the amygdala appeared primarily in implicit studies of emotion, whereas deficits in ACC activity appeared throughout all contrasts. Conclusions Processing emotional stimuli, schizophrenia patients show reduced activation in areas engaged by emotional stimuli, although in some conditions, schizophrenia patients exhibit increased activation in areas outside those traditionally associated with emotion, possibly representing compensatory processing.

Objective In the current issue, Cannon and colleagues, as part of the second phase of the North American Prodrome Longitudinal Study (NAPLS2), report on a risk calculator for the individualized prediction of developing a psychotic disorder in a 2-year period. The present study represents an external validation of the NAPLS2 psychosis risk calculator using an independent sample of subjects at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP). Methods 176 subjects with follow-up (from the total EDIPPP sample of 210) rated as clinical high-risk (CHR) based on the Structured Interview for Prodromal Syndromes were used to construct a new prediction model with the 6 significant predictor variables in the NAPLS2 psychosis risk calculator (unusual thoughts, suspiciousness, Symbol Coding, verbal learning, social functioning decline, baseline age, and family history). Discrimination performance was assessed with the area under the receiver operating curve (AUC). The NAPLS2 risk calculator was then used to generate a psychosis risk estimate for each case in the external validation sample. Results The external validation model showed good discrimination, with an AUC of 79% (95% CI 0.644–0.937). In addition, the personalized risk generated by the NAPLS calculator provided a solid estimation of the actual conversion outcome in the validation sample. Conclusions In the companion papers in this issue, two independent samples of CHR subjects converge to validate the NAPLS2 psychosis risk calculator. This prediction calculator represents a meaningful step towards early intervention and personalized treatment of psychotic disorders.

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.

Accurately perceiving self-referential social signals, particularly eye contact, is critical to social adaptation. Schizophrenia is often accompanied by deficits in social cognition, but it is unclear whether this includes gaze discrimination deficits. This study investigated whether eye-contact perception is preserved or impaired and if it is related to symptoms and broader socioemotional functioning in schizophrenia. Twenty-six participants with schizophrenia (SCZ) and 23 healthy controls (HC) made eye-contact judgments for faces in varying gaze direction (from averted to direct in ten 10% increments), head orientation (forward, 30° averted), and emotion (neutral, fearful). Psychophysical analyses for forward faces showed that SCZ began endorsing eye contact with weaker eye-contact signal and their eye-contact perception was less of a dichotomous function, as compared with HC. SCZ were more likely than HC to endorse eye contact when gaze was ambiguous, and this overperception of eye contact was modulated by head orientation and emotion. Overperception of eye contact was associated with more severe negative symptoms. Decreased categorical gaze perception explained variance of socioemotional deficits in schizophrenia after taking basic neurocognition into consideration, suggesting the relationship was not solely due to a general deficit problem. These results were discussed in relation to the nature of categorical gaze perception and its significance to clinical and functional presentations of schizophrenia.

Highlights Strict social distancing, implemented widely to curb the spread of COVID-19, has the unintended consequences of prolonged social isolation and adverse impact on mental health. We conducted an online survey to examine the impact of loneliness on mental health during COVID-19 in hong Kong, a model case for the population-wide practice of effective social distancing. An astonishing 65.6% of the respondents reported clinical levels of depression, anxiety, and/or stress, and 22.5% were showing signs of psychosis risk. Loneliness, but not social network size, explained 12.0% to 29.2% of variance in these psychiatric symptoms. To mitigate the potential epidemic of mental illness in the near future, there is an urgent need to prepare clinicians, caregivers and stakeholders to focus on loneliness.