Whole-exome sequencing in a Chinese sample provides preliminary evidence for the link between rare/low-frequency immune-related variants and early-onset schizophrenia.

Rare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing. The AAO variable was ascertained in the majority of SCZ participants for identify the early-onset (EOS, AAO<=18) and adult-onset (AOS, AAO>18) subgroups. We examined the overall association of rare/low-frequency, damaging variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels using Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was conducted. Resampling was used to obtain empirical p-values and to control for family-wise error rate (FWER). In binary-trait association tests, we identified 5 potential candidate risk genes and 10 gene ontology biological processes (GOBP) terms, among which PADI2 reached FWER-adjusted significance. In quantitative rare-variant association tests, we found marginally significant correlations of AAO with alterations in 4 candidate risk genes, and 5 GOBP pathways. Together, the biological and functional profiles of these genes and gene sets supported the involvement of perturbations of neural systems in SCZ, and altered immune functions in EOS.

Early-onset schizophrenia is associated with immune-related rare variants in a Chinese sample.

Background: Rare variants are likely to contribute to schizophrenia (SCZ), given the large discrepancy between the heritability estimated from twin and GWAS studies. Furthermore, the nature of the rare-variant contribution to SCZ may vary with the "age-at-onset" (AAO), since early-onset has been suggested as being indicative of neurodevelopment deviance. Objective: To examine the association of rare deleterious coding variants in early- and adult-onset SCZ in a Chinese sample. Method: Exome sequencing was performed on DNA from 197 patients with SCZ spectrum disorder and 82 healthy controls (HC) of Chinese ancestry recruited in Hong Kong. We also gathered AAO information in the majority of SCZ samples. Patients were classified into early-onset (EOS, AAO<18) and adult-onset (AOS, AAO>18). We collapsed the rare variants to improve statistical power and examined the overall association of rare variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels by Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was also conducted. We focused on variants which were predicted to have a medium or high impact on the protein-encoding process as defined by Ensembl. We applied a 100000-time permutation test to obtain empirical p-values, with significance threshold set at p < 1e -3 to control family-wise error rates. Moreover, we compared the burden of targeted rare variants in significant risk genes and gene sets in cases and controls. Results: Based on several binary-trait association tests (i.e., SCZ vs HC, EOS vs HC and AOS vs HC), we identified 7 candidate risk genes and 20 gene ontology biological processes (GOBP) terms, which exhibited higher burdens in SCZ than in controls. Based on quantitative rare-variant association tests, we found that alterations in 5 candidate risk genes and 7 GOBP pathways were significantly correlated with AAO. Based on biological and functional profiles of the candidate risk genes and gene sets, our findings suggested that, in addition to the involvement of perturbations in neural systems in SCZ in general, altered immune responses may be specifically implicated in EOS. Conclusion: Disrupted immune responses may exacerbate abnormal perturbations during neurodevelopment and trigger the early onset of SCZ. We provided evidence of rare variants increasing SCZ risk in the Chinese population.

Pathway-Specific Polygenic Scores Improve Cross-Ancestry Prediction of Psychosis and Clinical Outcomes.

Psychotic disorders are debilitating conditions with disproportionately high public health burden. Genetic studies indicate high heritability, but current polygenic scores (PGS) account for only a fraction of variance in psychosis risk. PGS often show poor portability across ancestries, performing significantly worse in non-European populations. Pathway-specific PGS (pPGS), which restrict PGS to genomic locations within distinct biological units, could lead to increased mechanistic understanding of pathways that lead to risk and improve cross-ancestry prediction by reducing noise in genetic predictors. This study examined the predictive power of genome-wide PGS and nine pathway-specific pPGS in a unique Chinese-ancestry sample of deeply-phenotyped psychosis patients and non-psychiatric controls. We found strong evidence for the involvement of schizophrenia-associated risk variants within "nervous system development" (p=2.5e-4) and "regulation of neuron differentiation" pathways (p=3.0e-4) in predicting risk for psychosis. We also found the "ion channel complex" pPGS, with weights derived from GWAS of bipolar disorder, to be strongly associated with the number of inpatient psychiatry admissions a patient experiences (p=1.5e-3) and account for a majority of the signal in the overall bipolar PGS. Importantly, although the schizophrenia genome-wide PGS alone explained only 3.7% of the variance in liability to psychosis in this Chinese ancestry sample, the addition of the schizophrenia-weighted pPGS for "nervous system development" and "regulation of neuron differentiation" increased the variance explained to 6.9%, which is on-par with the predictive power of PGS in European ancestry samples. Thus, not only can pPGS provide greater insight into mechanisms underlying genetic risk for disease and clinical outcomes, but may also improve cross-ancestry risk prediction accuracy.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

BACKGROUND: Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia. This study aimed to clarify whether these three constructs influence clinical and functional outcome of schizophrenia. METHOD: At baseline, 127 first-episode schizophrenia patients completed a behavioural paradigm for emotion-behaviour decoupling, and self-report scales for experiential pleasure and emotion expressivity deficits. Cluster-analysis was applied to characterize schizophrenia subgroups based on these three constructs. At end-point (mean follow-up = 5.37 years, SD = 1.03 years), 85 schizophrenia patients were reassessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and a clinician-rated social functioning scale. RESULTS: Cluster 1 (n = 74) did not show emotion-behaviour decoupling, and had intact experiential pleasure and emotion expressivity. Cluster 2 (n = 29) showed emotion-behaviour decoupling and experiential pleasure deficits. Cluster 3 (n = 24) showed emotion expressivity deficits. At endpoint, the three clusters differed significantly in CAINS MAP factor (p = 0.016) and social functioning (p = 0.019), but not CAINS EXP factor. Specifically, Cluster 2 (n = 18) showed more severe negative symptoms of CAINS MAP factor (p = 0.046) and poorer social functioning (p = 0.022) than Cluster 1 (n = 49). Cluster 3 (n = 18) did not differ from Cluster 1 and Cluster 2 in negative symptoms and social functioning. DISCUSSION: Emotion-behaviour decoupling and experiential pleasure deficits predicted clinical and functional outcome of schizophrenia.

Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study.

BACKGROUND: Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown. METHODS: Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group. RESULTS: We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls. CONCLUSIONS: Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Revisiting the latent structure of negative symptoms in schizophrenia: Evidence from two second-generation clinical assessments.

BACKGROUND: Negative symptoms are core symptom of schizophrenia, and many previous research studied the latent structure of negative symptoms based on a single measurement scale. Applying two second-generation negative symptom scales to the same sample can address measurement-invariance of latent structure. METHODS: Three-hundred-and-five schizophrenia patients were assessed using the CAINS and the BNSS. Confirmatory Factor Analysis (CFA) tested four competing factor-models: (1) a 1-factor model; (2) a 2-factor model comprising the motivation and pleasure (MAP) domain and the diminished expression (EXP) domain; (3) a 5-factor model comprising anhedonia, avolition, asociality, blunted affect and alogia; (4) a hierarchical model comprising the "first-order" 5-domain factors and the "second-order" MAP & EXP factors. RESULTS: The CFA results for the data of the CAINS showed that the 2-factor model had the best data fit over the other competing models. The CFA using the BNSS data in the same sample also supported the superiority of the 2-factor model. Lastly, after combining the items of the BNSS and CAINS together in the same sample for CFA, the 2-factor model prevailed over the other competing models. CONCLUSIONS: The 2-factor model appears to be measurement-invariant latent structure of negative symptoms. The novel method of combining the items of the CAINS and BNSS might have circumvented the possible imperfect construct of a single scale. Our findings support the MAP and EXP factors as the latent structure for negative symptoms.

The Important Role of Motivation and Pleasure Deficits on Social Functioning in Patients With Schizophrenia: A Network Analysis.

Negative symptoms, particularly the motivation and pleasure (MAP) deficits, are associated with impaired social functioning in patients with schizophrenia (SCZ). However, previous studies seldom examined the role of the MAP on social functioning while accounting for the complex interplay between other psychopathology. This network analysis study examined the network structure and interrelationship between negative symptoms (at the "symptom-dimension" and "symptom-item" levels), other psychopathology and social functioning in a sample of 269 patients with SCZ. The psychopathological symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Positive and Negative Syndrome Scale (PANSS). Social functioning was evaluated using the Social and Occupational Functioning Assessment Scale (SOFAS). Centrality indices and relative importance of each node were estimated. The network structures between male and female participants were compared. Our resultant networks at both the "symptom-dimension" and the "symptom-item" levels suggested that the MAP factor/its individual items were closely related to social functioning in SCZ patients, after controlling for the complex interplay between other nodes. Relative importance analysis showed that MAP factor accounted for the largest proportion of variance of social functioning. This study is among the few which used network analysis and the CAINS to examine the interrelationship between negative symptoms and social functioning. Our findings supported the pivotal role of the MAP factor to determine SCZ patients' social functioning, and as a potential intervention target for improving functional outcomes of SCZ.

Prospective Memory Influences Social Functioning in People With First-Episode Schizophrenia: A Network Analysis and Longitudinal Study.

Background: Prospective memory (PM) impairment is associated with impaired social functioning, but evidence is limited to chronic schizophrenia samples and cross-sectional design. The aim of this study was to utilize network analysis to address the complex interplay between PM, psychopathology, and functional outcome.Methods: This longitudinal study recruited 119 people with first-episode DSM-IV schizophrenia and followed up with them for 2 to 6 years. PM and working memory were assessed at baseline (in 2010-2015) using valid computerized tasks and the Letter-Number Span Test, respectively. Psychopathology and social functioning were assessed at endpoint (in 2016-2017) using the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively. Network analysis examined the effect of baseline PM on SOFAS while accounting for the effects of psychopathology.Results: The resultant network showed that social functioning, PANSS positive symptoms, and PANSS general symptoms clustered together, whereas time-based and event-based PM and working memory formed another cluster. Time-based PM linked event-based PM and working memory with social functioning. Time-based PM (expected influence [EI] = 0.69), event-based PM (EI = 0.65), and working memory (EI = 0.83) demonstrated high values of expected influence, but social functioning (variance explained = 0.685) and PANSS negative (variance explained = 0.657) and general (variance explained = 0.583) subscales demonstrated high values of predictability.Conclusions: Time-based PM is the central node linking neurocognitive functions with social functioning. PM and working memory are "target" nodes for interventions bringing changes to the network, whereas social functioning and psychopathology are "malleable" nodes. PM and working memory are promising intervention targets for functional recovery in schizophrenia.

Shared and distinct reward neural mechanisms among patients with schizophrenia, major depressive disorder, and bipolar disorder: an effort-based functional imaging study.

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.

Subclinical psychopathology and affective forecasting: Role of in-the-moment feelings.

It is important for positive well-being and social engagement to understand how people predict future emotions, an ability known as affective forecasting. However, mechanisms underpinning the change to affective forecasting are not well understood in people with subclinical psychiatric symptoms. The current study differentiated components that comprise affective forecasting and investigated how non-clinical features relate to these. We recruited 319 participants to complete the social affective forecasting task and respond to questionnaires that captured schizotypal and autistic traits as well as depressive symptoms. Associations between affective forecasting and subclinical features were investigated using correlations, regression, and structure equation modeling. Results showed that interpersonal features of schizotypal traits negatively predicted anticipated emotions in positive social conditions via in-the-moment feelings but not via mental simulation. Findings highlight that in-the-moment feelings may be an intervention target to help people who have difficulties with social interactions to anticipate more pleasure for future social events.

Structural network alterations and their association with neurological soft signs in schizophrenia: Evidence from clinical patients and unaffected siblings.

BACKGROUND: Grey matter abnormalities and neurological soft signs (NSS) have been found in schizophrenia patients and their unaffected relatives. Evidence suggested that NSS are associated with grey matter morphometrical alterations in multiple regions in schizophrenia. However, the association between NSS and structural abnormalities at network level remains largely unexplored, especially in the schizophrenia and unaffected siblings. METHOD: We used source-based morphometry (SBM) to examine the association of structural brain network characteristics with NSS in 62 schizophrenia patients, 25 unaffected siblings, and 60 healthy controls. RESULTS: Two components, namely the IC-5 (superior temporal gyrus, inferior frontal gyrus and insula network) and the IC-10 (parahippocampal gyrus, fusiform, thalamus and insula network) showed significant grey matter reductions in schizophrenia patients compared to healthy controls and unaffected siblings. Further association analysis demonstrated separate NSS-related grey matter covarying patterns in schizophrenia, unaffected siblings and healthy controls. Specifically, NSS were negatively associated with IC-1 (hippocampus, caudate and thalamus network) and IC-5 in schizophrenia, but with IC-3 (caudate, superior and middle frontal cortices network) in unaffected siblings and with IC-5 in healthy controls. CONCLUSION: Our results confirmed the key cortical and subcortical network abnormalities and NSS-related grey matter covarying patterns in the schizophrenia and unaffected siblings. Our findings suggest that brain regions implicating genetic liability to schizophrenia are partly separated from brain regions implicating neural abnormalities.

Negative belief-updating bias for positive daily life events in individuals with schizophrenia and social anhedonia.

INTRODUCTION: Low-pleasure beliefs are found in both patients with schizophrenia (SZ) and individuals with high social anhedonia (SocAnh), and are associated with anhedonia. However, little is known about the development and maintenance of these low-pleasure beliefs in the clinical and subclinical populations. We investigated whether patients with SZ and individuals with high SocAnh have deficits in updating their beliefs, which may contribute to the understanding of the formation and maintenance of low-pleasure beliefs. METHODS: The Modified Belief Updating Task was administered to assess belief-updating patterns in a clinical sample (36 SZ patients and 30 matched controls) and a subclinical sample (27 individuals with high SocAnh and 30 matched controls). RESULTS: We found that compared with controls, SZ patients updated their beliefs to a greater extent and more frequently when receiving bad news for positive life events, but not for negative life events. Moreover, individuals with high SocAnh also exhibited similar patterns in updating their beliefs for positive life events after controlling depressive symptoms. CONCLUSIONS: Our findings suggest that negative belief-updating patterns for positive events may play an important role in the formation and maintenance of low-pleasure beliefs in patients with SZ and individuals with high SocAnh.

Altered empathy-related resting-state functional connectivity in patients with bipolar disorder.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people's emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal-parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

Co-occurrence of schizo-obsessive traits and its correlation with altered executive control network functional connectivity.

The prevalence of obsessive-compulsive symptoms (OCS) in schizophrenia patients is as around 30%. Evidence suggested that mild OCS could reduce symptoms of schizophrenia, supporting the presence of compensatory functions. However, severe OCS could aggravate various impairments in schizophrenia patients, supporting the "double jeopardy hypothesis". Patients with schizo-obsessive comorbidity, schizophrenia patients and obsessive-compulsive disorder patients have been found to have similarities in executive dysfunctions and altered resting-state functional connectivity within the executive control network (ECN). Executive functions could be associated with the ECN. However, little is known as to whether such overlap exists in the subclinical populations of individuals with schizo-obsessive traits (SOT), schizotypal individuals and individuals with high levels of obsessive-compulsive symptoms (OCS). In this study, we recruited 30 schizotypal individuals, 25 individuals with OCS, 29 individuals with SOT and 29 controls for a resting-state ECN-related functional connectivity (rsFC) and a go/shift/no-go task. We found that individuals with SOT exhibited increased rsFC within the ECN compared with controls, while schizotypal individuals exhibited the opposite. Individuals with OCS exhibited decreased rsFC within the ECN and between the ECN and the default mode network (DMN), relative to controls. No significant correlational results between altered rsFC related to the ECN with executive function performance were found after corrections for multiple comparisons in three subclinical groups. Our findings showed that individuals with SOT had increased rsFC within the ECN, while schizotypal individuals and individuals with OCS showed the opposite. Our findings provide evidence for possible neural substrates of subclinical comorbidity of OCS and schizotypy.

Network analysis of executive function, emotion, and social anhedonia.

This study constructed the network structure of social anhedonia, emotion processing, and executive function in college students using network analysis. We calculated the strength of each node in the network. The results suggest that social anhedonia had negative effects on executive function, emotion experience, and emotion expression.

Altered brain structural and functional connectivity in schizotypy.

BACKGROUND: Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of 'brain disconnection' and 'brain connectivity compensation' to 'brain connectivity decompensation'. METHODS: In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated. RESULTS: We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network. CONCLUSIONS: These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.

The impact of childhood trauma on thalamic functional connectivity in patients with obsessive-compulsive disorder.

BACKGROUND: Childhood trauma is a vulnerability factor for the development of obsessive-compulsive disorder (OCD). Empirical findings suggest that trauma-related alterations in brain networks, especially in thalamus-related regions, have been observed in OCD patients. However, the relationship between childhood trauma and thalamic connectivity in patients with OCD remains unclear. The present study aimed to examine the impact of childhood trauma on thalamic functional connectivity in OCD patients. METHODS: Magnetic resonance imaging resting-state scans were acquired in 79 patients with OCD, including 22 patients with a high level of childhood trauma (OCD_HCT), 57 patients with a low level of childhood trauma (OCD_LCT) and 47 healthy controls. Seven thalamic subdivisions were chosen as regions of interest (ROIs) to examine the group difference in thalamic ROIs and whole-brain resting-state functional connectivity (rsFC). RESULTS: We found significantly decreased caudate-thalamic rsFC in OCD patients as a whole group and also in OCD_LCT patients, compared with healthy controls. However, OCD_HCT patients exhibited increased thalamic rsFC with the prefrontal cortex when compared with both OCD_LCT patients and healthy controls. CONCLUSIONS: Taken together, OCD patients with high and low levels of childhood trauma exhibit different pathological alterations in thalamic rsFC, suggesting that childhood trauma may be a predisposing factor for some OCD patients.

Neural mechanisms of prospection in individuals with schizotypal traits, autistic traits, or depressive symptoms.

Prospection refers to the ability to mentally construct future events, which is closely related to motivation and anhedonia. The neural underpinning of impaired prospection in psychiatric populations remains unclear. We recruited 34 individuals with autistic traits (AT), 27 individuals with schizotypal traits (ST), 31 individuals with depressive symptoms (DS), and 35 controls. Participants completed a prospection task while undergoing functional Magnetic Resonance Imaging (MRI). We found that regions of the "default mode network" including the medial frontal gyrus, the posterior cingulate cortex, the precuneus and the parahippocampus were activated; and regions of the "task-positive network" including the inferior parietal lobe, the inferior frontal gyrus and the precentral gyrus were deactivated during prospection in controls. Compared with controls, AT, ST, and DS showed comparable behavioral performance on prospection. However, reduced activation in anterior cingulate cortex and frontal gyrus was found in AT individuals relative to controls during prospection. ST individuals showed hyperactivation in the caudate relative to controls when processing positive emotion, while DS individuals and controls showed similar neural responses during prospection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Social brain network predicts real-world social network in individuals with social anhedonia.

Social anhedonia (SA) impairs social functioning in schizophrenia. Previous evidence suggested that certain brain regions predict longitudinal change of real-world social outcomes, yet previous study designs have failed to capture the corresponding functional connectivity among the brain regions involved. This study measured the real-world social network in 22 pairs of individuals with high and low levels of SA, and followed up them for 21 months. We further explored whether resting-state social brain network characteristics could predict the longitudinal variations of real-world social network. Our results showed that social brain network characteristics could predict the change of real-world social networks in both the high SA and low SA groups. However, the results differed between the two groups, i.e., the topological characteristics of the social brain network predicted real-world social network change in the high SA group; whereas the functional connectivity within the social brain network predicted real-world social network change in the low SA group. Principal component analysis and linear regression analysis on the entire sample showed that the functional connectivity component centered at the right orbital inferior frontal gyrus could best predict social network change. Our findings support the notion that social brain network characteristics could predict social network development.