Background. Psychosis, social anxiety, and autism are clinical constructs that share important phenotypic features, particularly social dysfunction. A critical determinant of social functioning is an individual’s ability to recognize when social cues, like eye gaze, are meant for them. Emerging computational modeling data in psychosis suggest that altered perception of gaze direction stems from deficits in evidence accumulation – the process of gathering and integrating information – when processing social cues. Here, we investigated whether aberrant evidence accumulation during eye gaze processing are associated with social functioning or, as a secondary aim, with other measures of psychopathology, in a transdiagnostic sample enriched for psychotic, socially anxious, or autistic characteristics. Methods. We examined gaze perception in a sample of 111 adolescents and young adults (ages 14-30) with varying levels of social dysfunction and enriched for psychosis proneness, social anxiety, and autistic traits. We used drift diffusion models (DDM) to characterize key processes driving perceptual judgements in a self-directed gaze discrimination task, including the efficiency of evidence accumulation. We tested whether evidence accumulation was associated with social functioning, social cognition, and these different psychopathology dimensions. Results. Impaired evidence accumulation during gaze processing showed strong associations with impaired social cognition and modest associations with diminished social functioning and elevated psychosis and social anxiety symptoms. However, evidence accumulation sensitivity was not associated with autism traits. Conclusions. Evidence accumulation for subtle social cues relates to social cognition—a key determinant of social functioning. It may also be relevant to real-world social functioning and multiple psychopathology dimensions, including psychosis and social anxiety. Therefore, evidence accumulation should be investigated as a mechanism supporting social difficulties and related psychopathology.

The ability to accurately perceive gaze direction is an essential social skill but is impaired across psychopathologies exhibiting social dysfunction (e.g., schizophrenia, social anxiety disorder, autism spectrum disorder). Disrupted sensory processing and self-referential processing may both lead to aberrant gaze perception, but their respective contributions in different psychopathologies are unclear. A general population sample of 106 participants completed an online psychophysical gaze perception task and a battery of psychopathology trait questionnaires. Participants viewed face images with 9 gaze angles, superimposed with 3 levels (no, low, high) of sensory noise and in 2 (forward, deviated) head orientations, and indicated perceived self-directed gaze (yes/no) for each face. Psychophysical properties of the gaze perception curve (width, threshold) were used to index perceptual imprecision and self-referential bias, respectively. Decreased precision was associated with higher autism traits but lower social anxiety, supporting differential contributions of sensory processing among psychopathology dimensions. Subjects showed decreased precision and increased self-referential bias, when viewing stimuli with added visual noise or incongruent gaze-head directions, resembling performance previously observed in patients with schizophrenia. Additionally, higher levels of social anxiety statistically predicted a greater decrease in precision when sensory noise was added. Findings are discussed in relation to the experimental psychopathology literature and in the context of self-referential gaze perception as an adaptive default in ambiguous contexts. Overall, this work enhances our basic scientific understanding of the cognitive components that contribute to gaze perception, while advancing our knowledge of how these components are disrupted as a function of subclinical psychopathology.

Accurate gaze detection is fundamental to social interactions and is impaired in individuals with higher levels of autistic traits. One mechanism is reduced attention to the eyes, but the reasons behind this atypical behavior remain debated. This study investigated whether reduced attention to the eyes associated with autistic traits stems from aversion or indifference. One hundred and twenty-seven adolescents and young adults with varying levels of autistic traits completed a gaze direction task while their eye position and pupil size were recorded. Higher levels of autistic traits were associated with reduced dwell time on the eye region after, but not before, gaze direction judgments, indicating reduced attention when it was not task-relevant. Autistic traits were associated with more frequent exits and re-entries from/to the eye region after judgments, indicating less stable social engagement. Additionally, autistic traits were not associated with enlarged pupillary responses, indicating no heightened arousal expected with aversion. These findings demonstrate reduced sustained engagement with the eyes among individuals with higher levels of autistic traits, consistent with indifference rather than aversion. The temporal specificity-emerging primarily after task completion-helps reconcile contradictory literature findings. Results suggest interventions should focus on enhancing sustained social engagement rather than addressing aversion.

Elevated schizotypal traits are a risk factor for developing schizophrenia and other forms of psychopathology. Because schizophrenia is marked by social functioning difficulties, examining how schizotypal traits shape everyday interactions can clarify early risk processes. Although ecological momentary assessment (EMA) has been used to examine social interaction likelihood (how often people interact), depth (complexity of content in interactions), and enjoyment (pleasure derived from interactions) in people with schizophrenia, few have explored differences in social interactions across schizotypal traits (positive, negative, and disorganized). This study used EMA to evaluate how positive, negative, and disorganized schizotypal traits in college students (n = 185) relate to social interaction likelihood, depth, and enjoyment in daily life. Given their established role in social functioning and their complex relationships with schizotypal traits, we also investigated whether affect and stress predict individuals' concurrent likelihood, depth, and enjoyment of social interactions. Results revealed that negative traits more strongly predicted reduced social interaction likelihood (B = -0.02, p = .04) and enjoyment (B = -0.06, p < .01) compared to positive (likelihood: B = 0.01, p = .37; enjoyment: B = 0.03, p = .02) and disorganized (likelihood: B = 0.00, p = .85; enjoyment: B = -0.04, p = .04) traits. Contrary to hypotheses, positive affect emerged as the strongest predictor of social interaction outcomes, surpassing negative affect and stress. Additionally, we observed a significant interaction between positive schizotypal traits and negative affect (B = -0.01, p = .03), such that individuals higher in positive traits showed a stronger reduction in enjoyment when experiencing negative affect. These findings enhance our understanding of how schizotypal traits and affect impact daily social interactions and may inform future personalized interventions designed to improve social functioning deficits in at-risk individuals.

BACKGROUND AND HYPOTHESIS:Perception integrates sensory input with prior knowledge. Alterations in how both information sources are combined may lead to the departures from consensus reality that characterize schizophrenia (SZ). One source of prior knowledge is recent experience. Visual aftereffects-perceptions of the "opposite" of previously viewed stimulus-are driven by neuronal adaptation and demonstrate how recent experience influences perception. Our recent work revealed stronger tilt (orientation) aftereffects, but not negative afterimages (luminance aftereffects) in people with SZ relating to negative symptom severity, suggesting altered adaptation is more prominent in cortical than subcortical visual systems and may be an important illness mechanism. Because different aftereffects depend differentially on adaptation at different levels of the visual hierarchy, we sought to extend findings and probe where in the cortical hierarchy neuronal adaptation is most pronounced in SZ. STUDY DESIGN:Two types of motion aftereffects were measured in SZ (n = 55) and healthy controls (HC; n = 43): "first-order" aftereffects caused by luminance-defined motion that elicits strong adaptation in early visual cortex, and "higher-order" aftereffects caused by non-luminance-feature-defined motion (eg, texture) that is primarily represented in extrastriate motion-sensitive areas. STUDY RESULTS:Relative to HC, SZ showed stronger first-order but not higher-order motion aftereffects. Differences were not explained by task sensitivity, response bias, visual acuity, blinks, or fixation deviations. CONCLUSIONS:Altered neuronal adaptation in SZ is likely more pronounced at earlier (eg, V1) versus later (eg, V5/MT) stages of the visual hierarchy. Consequently, findings potentially implicate early visual cortical processing alterations in illness pathophysiology and/or clinical presentation.

In this Comment, we discuss how visual system abnormalities in schizophrenia can provide mechanistic insights and aid prognosis. We also highlight the importance of coordinated efforts to harmonize the field of vision and oculomics in psychiatry.

Background Social cognitive deficits are common across many psychiatric conditions and contribute to broader social dysfunction. One hypothesized mechanism involves altered basic visual processing, which may disrupt the perception of low-level social cues and, in turn, compromise broader social cognitive processes. Here, we examined relations between basic visual processing and different levels of social cognition in a transdiagnostic youth sample. Methods A sample of 148 youth, ranging from healthy individuals to individuals with neuropsychiatric diagnoses and significant social dysfunction, completed two measures of basic visual processing (contrast sensitivity and visual integration) and a battery of social cognition tasks spanning lower-level (gaze perception) to mid-level (emotion recognition) to higher-level (theory of mind) social cognition. We used a four-level path model to test whether basic visual processing predicts gaze perception, which in turn predicts emotion recognition, which predicts theory of mind. Results Poorer contrast sensitivity and visual integration were associated with less precise gaze perception, which was, in turn, associated with worse emotion recognition, which was associated with worse theory of mind. This four-level path model demonstrated good fit and showed superior fit compared to alternative models. Conclusion These findings suggest that basic visual processing influences the perception of basic social cues (e.g., gaze direction), which subsequently impairs more complex social perception and inference. Notably, this study extends prior observations from individuals with chronic schizophrenia to a transdiagnostic youth sample, indicating that altered basic visual processing may be a shared mechanism contributing to social cognitive deficits across psychiatric disorders and illness stages.

INTRODUCTION:Subjective visual disturbances and objective visual deficits are common across the psychosis spectrum. Few investigations have tested them in the same sample to ask whether subjective disturbances may arise from low-level visual processing deficits. This study assessed whether reduced contrast sensitivity (CS), a low-level visual processing deficit in people with schizophrenia (PSZ), may contribute to subjective visual disturbances across the psychosis spectrum. METHODS:PSZ (n = 54) and controls (n = 54) matched for gender, age, and race/ethnicity, together with High PLE (n = 55) and Low PLE (n = 45) matched for gender, age, race/ethnicity, education, and IQ completed a CS task and the Bonn Scale, a structured interview assessing visual distortions. Group differences in CS and Bonn scores as well as their correlations with social risk factors were evaluated. In addition, the Bonn Scale's factor structure was examined. RESULTS:PSZ and High PLE endorsed more distortions than controls. In PSZ, distortion severity, but not CS, correlated with social risk factors and clinical symptoms. Only PSZ showed reduced CS, and no associations between distortions and CS were observed. CONCLUSIONS:Findings do not support a bottom-up account of visual distortions; instead, they may arise from higher-order processes.

BACKGROUND:Mentalizing-our ability to make inferences about the mental states of others-is impaired across psychiatric disorders and robustly associated with functional outcomes. Mentalizing deficits have been prominently linked to aberrant activity in cortical regions considered to be part of the "social brain network" (e.g., dorsomedial prefrontal cortex, temporoparietal junction), yet emerging evidence also suggests the importance of cerebellar dysfunction. In the present study-using a transdiagnostic, clinical psychiatric sample spanning the psychosis-autism-social anxiety spectrums-we examined the role of the cerebellum in mentalizing and its unique contributions to broader social functioning. METHODS:Sixty-two participants (38 with significant social dysfunction secondary to psychiatric illness and 24 nonclinical controls without social dysfunction) completed a mentalizing task during functional magnetic resonance imaging. General linear model analysis, latent variable modeling, and regression analyses were used to examine the contribution of cerebellum activation to the prediction of group status and social functioning. RESULTS:Mentalizing activated a broad set of social cognitive brain regions, including cerebral mentalizing network (MN) nodes and posterior cerebellum. Higher posterior cerebellum activation significantly predicted clinical status (i.e., individuals with psychiatric disorders versus nonclinical controls). Finally, cerebellar activation accounted for significant variance in social functioning independent of all other cerebral MN brain regions identified in a whole-brain analysis. CONCLUSIONS:Findings add to an accumulating body of evidence establishing the unique role of the posterior cerebellum in mentalizing deficits and social dysfunction across psychiatric illnesses. Collectively, our results suggest that the posterior cerebellum should be considered - alongside established cerebral regions - as part of the mentalizing network.

OBJECTIVE:Researchers are increasingly interested in exploring the role of the menopausal transition in eating disorder risk. We recently embarked on studies of this critical life phase and encountered significant challenges in assessing menopausal status that limited our ability to test study hypotheses. This Research Forum describes these challenges and presents descriptive data on staging accuracy as well as recommendations for improving assessments that can advance research in this critical area of women's health. METHOD:Data come from 207 women (ages 40-58) assessed in an ongoing study from the MSU Twin Registry. Menopausal status (premenopause, perimenopause, postmenopause) was measured with the Perimenopause Evaluation Questionnaire assessing women's self-identified stage as well as the regularity of menstrual cycles and medical history. Staging accuracy was evaluated by comparing the self-identified stage with results from individual case analyses of questionnaire responses. RESULTS:Many more women self-identified as premenopausal (62%), perimenopausal (27%), and postmenopausal (11%) than we identified in case analyses (20%, 7%, 8%, respectively). These discrepancies appeared to be due to women failing to account for medications or medical conditions that would cause premature cessation of menses and/or insufficient questionnaire items and information for staging women with complicated reproductive histories. DISCUSSION:Findings highlight significant limitations of self-identified status or questionnaire responses alone in determining menopausal status. We provide recommendations for improving stage assessments, drawn from the challenges and lessons learned in our own studies, thereby allowing others to better explore this critical stage and advance women's health in our field.

Background and Hypothesis Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS.Study Design Here, we modeled fMRI data using dynamic causal modeling (DCM) to examine patient-control differences in effective connectivity evoked by a double-step (DS) task (30 SZ, 29 HC). The interrogated network was formed from a combination of (1) functionally identified FEF and IPS regions that robustly responded on DS trials and (2) anatomically identified thalamic regions involved in CD transmission. We also examined the relationship between clinical symptoms and effective connectivity parameters associated with task modulation of network pathways.Study Results Network connectivity was indeed modulated by the DS task, which involves CD transmission. More importantly, we found reduced effective connectivity from thalamus to IPS in SZ, which was further correlated with passivity symptom severity.Conclusions These results reaffirm the importance of IPS and thalamocortical connections in oculomotor CD signaling and provide mechanistic insights into CD alterations and consequently agency disturbances in schizophrenia.

Background and Hypothesis:Unpacking the pathophysiological mechanisms of schizophrenia is necessary for advancing prediction, prevention, and treatment efforts. Mechanisms can be identified using easy-to-use and scalable clinical biomarkers, which reflect illness processes. Pupillometry is one such biomarker. Blunted dilation related to cognitive demand has been interpreted as a metric of diminished effort in schizophrenia, while blunted constriction to light has been interpreted as a metric of altered autonomic balance in schizophrenia. However, these 2 sets of findings may also reflect a common mechanism of schizophrenia. Therefore, this study aimed to explore the association between blunted cognitive dilation and blunted constriction to light to provide a parsimonious mechanism of autonomic and effort disturbances experienced by individuals with schizophrenia. Study Design:We assessed light-induced constriction and cognitive dilation during a double-step task in individuals with schizophrenia (n = 84) and demographically matched healthy controls (HC, n = 69), compared these metrics between groups, and computed their correlation within each group. Study Results:Replicating prior findings, dilation and constriction were blunted in schizophrenia relative to HC. Blunted constriction and dilation were positively correlated in schizophrenia but not HC (although the 2 correlations did not differ significantly). Conclusions:Findings provide, for the first time, preliminary support of a common mechanism linking blunted pupil constriction to light and dilation to cognitive demands in schizophrenia. We propose that individuals with schizophrenia may exhibit impaired top-down modulation of autonomic control. Future studies are needed to validate this proposed mechanism.

BACKGROUND AND HYPOTHESIS:Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis.STUDY DESIGN:We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements.STUDY RESULTS:SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site.CONCLUSIONS:These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.

An altered use of context and experience to interpret incoming information has been posited to explain schizophrenia symptoms. The visual system can serve as a model system for examining how context and experience guide perception and the neural mechanisms underlying putative alterations. The influence of prior experience on current perception is evident in visual aftereffects, the perception of the “opposite” of a previously viewed stimulus. Aftereffects are associated with neural adaptation and concomitant change in strength of lateral inhibitory connections in visually responsive neurons. In a previous study, we observed stronger aftereffects related to orientation (tilt aftereffects) but not luminance (negative afterimages) in individuals diagnosed with schizophrenia, which we interpreted as potentially suggesting altered cortical (but not subcortical) adaptability and local changes in excitatory-inhibitory interactions. Here, we tested whether stronger tilt aftereffects were specific to individuals with schizophrenia or extended to individuals with bipolar disorder. We measured tilt aftereffects and negative afterimages in 32 individuals with bipolar disorder, and compared aftereffect strength to a previously reported group of 36 individuals with schizophrenia and 22 healthy controls. We observed stronger tilt aftereffects, but not negative afterimages, in individuals with schizophrenia as compared to both controls and individuals with bipolar disorder, who did not differ from each other. These results mitigate concerns that stronger tilt aftereffects in schizophrenia are a consequence of medication or of the psychosocial consequences of a severe mental illness.

The ability to accurately perceive gaze direction is an essential social skill but is impaired across psychopathologies exhibiting social dysfunction (e.g., schizophrenia, social anxiety disorder, autism spectrum disorder). Disrupted sensory processing and self-referential processing may both lead to aberrant gaze perception, but their respective contributions in different psychopathologies are unclear. A general population sample of 122 participants completed an online psychophysical gaze perception task and a battery of psychopathology traits questionnaires. Participants viewed face images with 9 gaze angles, superimposed with 3 levels (no, low, high) of sensory noise and in 2 (forward, deviated) head orientations, and indicated perceived self-directed gaze (yes/no) to each face. Psychophysical properties of the gaze perception curve (width, threshold) indexed perceptual imprecision and self-referential bias, respectively. Decreased precision was associated with higher autism traits but with lower social anxiety, supporting differential contributions of sensory processing among psychopathology dimensions. Subjects showed decreased precision and increased self-referential bias, when viewing stimuli with added visual noise or incongruent gaze-head directions, resembling the performance observed in patients with schizophrenia in the literature. Additionally, higher levels of social anxiety statistically predicted a greater decrease in precision when sensory noise was added. Experimental findings are discussed in relation to the experimental psychopathology literature and in the context of self-referential gaze perception as an adaptive default in ambiguous contexts. Overall, this work enhances our basic scientific understanding of the cognitive components that contribute to gaze perception, while advancing our knowledge of how these components are disrupted as a function of subclinical psychopathology.

Background: Impaired corollary discharge (CD) signalling disrupts the ability to predict the sensory consequences of one's own actions; impaired CD signalling may be specific to schizophrenia or it may also be a transdiagnostic mechanism of psychosis. We sought to assess whether disruptions in oculomotor CD signalling are equally present in schizophrenia and bipolar disorder (BD) with psychotic features, and whether these putative CD disruptions relate to anomalous self-experiences. Methods: We recruited patients with schizophrenia and patients with BD with psychotic features, as well as healthy controls, to complete a double-step saccade task. On each trial, 2 visual targets (T1 and T2) flashed in rapid succession. For half of the trials, participants could use visual information to look at T2. For the other half, looking correctly at T2 required CD. Results: We included 66 patients with schizophrenia, 43 patients with BD with psychotic features, and 37 healthy controls. On trials requiring CD, patient groups were significantly less accurate than controls in localizing T2 (F-2,F-131 = 8.40, p < 0.001). This reduced accuracy was related to difficulty in compensating for variability in the first saccade (F-2,F-131 = 9.11, p < 0.001). Among controls, anomalous self-experiences predicted worse performance (F-1,F- 57 = 14.23, p < 0.001). Limitations: Our sample comprised stable outpatients with relatively low symptom scores, which may limit the generalizability of our results. Conclusion: These results suggest CD impairments may be a marker of predisposition for psychosis. However, observed inconsistencies suggest that this relationship is nuanced.

AbstractIntroductionPathophysiological theories of schizophrenia (SZ) symptoms posit an abnormality in using predictions to guide behavior. One such prediction is based on imminent movements, via corollary discharge signals (CD) that relay information about planned movement kinematics to sensory brain regions. Empirical evidence suggests a reduced influence of sensorimotor predictions in individuals with SZ within multiple sensory systems, including in the visual system. One function of CD in the visual system is to selectively enhance visual sensitivity at the location of planned eye movements (pre‐saccadic attention), thus enabling a prediction of the to‐be‐foveated stimulus. We expected pre‐saccadic attention shifts to be less pronounced in individuals with SZ than in healthy controls (HC), resulting in unexpected sensory consequences of eye movements, which may relate to symptoms than can be explained in the context of altered allocation of attention.MethodsWe examined this question by testing 30 SZ and 30 HC on a pre‐saccadic attention task. On each trial participants made a saccade to a cued location in an array of four stimuli. A discrimination target that was either congruent or incongruent with the cued location was briefly presented after the cue, during saccade preparation. Pre‐saccadic attention was quantified by comparing accuracy on congruent trials to incongruent trials within the interval preceding the saccade.ResultsAlthough SZs were less accurate overall, the magnitude of the pre‐saccadic attention effect generally did not differ across groups nor show a convincing relationship with symptom severity. We did, however, observe that SZ had reduced pre‐saccadic attention effects when the discrimination target (probe) was presented at early stages of saccade planning, when pre‐saccadic attention effects first emerged in HC.ConclusionThese findings suggest generally intact pre‐saccadic shifts of attention in SZ, albeit slightly delayed. Results contribute to our understanding of altered sensory predictions in people with schizophrenia.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate ( g = −0.15, p = 0.03), higher thalamic glutamine ( g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls ( g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate ( z = −0.02, p < 0.001) and frontal white matter Glx ( z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG ( z = 0.01, p = 0.01) and temporal lobe ( z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

Interoception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but few studies have explored potential neural underpinnings. The current study aims to investigate the anatomical connectivity of a previously identified interoception network in individuals with schizophrenia, and the relationship between network structural connectivity and both emotional functioning and clinical symptoms. Thirty-five participants with schizophrenia (SZ) and 36 healthy control participants (HC) underwent diffusion tensor imaging (DTI) and performed tasks measuring emotional functioning. Probabilistic tractography was used to identify white matter tracts connecting key hubs in an interoception network. Microstructural integrity of these tracts was compared across groups and correlated with measures of emotional functioning and symptom severity. Compared with HC, SZ exhibited altered structural connectivity in the interoception network. In HC, the structural connectivity of the network was significantly correlated with emotion recognition, supporting a link between the interoception network and emotional functioning. However, this correlation was much weaker in SZ. These findings suggest that altered interoception may have implications for illness mechanisms of schizophrenia, especially in relation to emotional deficits.