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Theory of mind (ToM), the cognitive capacity to attribute mental states to self and others, is robustly affected in schizophrenia. The neural substrates of ToM impairment have been largely studied with functional imaging, but little is known about structural abnormalities. We compared structural covariance (between-subjects correlations of brain regional measures) of magnetic resonance imaging-based cortical surface area between patients with schizophrenia and healthy control subjects and between schizophrenia subgroups based on the patients' ToM ability to examine ToM-specific effects on structural covariance in schizophrenia.T1-weighted structural images were acquired on a 3T magnetic resonance imaging scanner, and ToM was assessed with the Hinting Task for 104 patients with schizophrenia and 69 healthy control subjects. The sum of surface area was computed for 12 regions of interest selected and compared between groups to examine structural covariance within the often reported mentalizing network: rostral and caudal middle frontal gyrus, inferior parietal lobule, precuneus, and middle and superior temporal gyrus. High and low ToM groups were defined using a median split on the Hinting Task.Cortical surface contraction was observed in the schizophrenia group, predominantly in temporoparietal regions. Patients with schizophrenia also exhibited significantly stronger covariance between the right rostral middle frontal gyrus and the right superior temporal gyrus than control subjects (r = 4.015; p.001). Direct comparisons between high and low ToM subgroups revealed stronger contralateral frontotemporal covariances in the low ToM group.Our results provide evidence for structural changes underlying ToM impairments in schizophrenia that need to be confirmed to develop new therapeutic perspectives.

Objectives Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients’ verbal memory performance would improve but would remain inferior to controls. Methods Patients ( n = 311; low anticholinergic burden [ n = 241] and high anticholinergic burden [ n = 70], defined by a Drug Burden Index cut-off of 1) and healthy controls ( n = 128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. Results Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430) = 52.33, P Conclusion These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease.

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner.

Background: Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia. Aims: We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis. Method: Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations. Results: In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS. Conclusions: The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions.

Childhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development℠ (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (β = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (β = -0.0525, 95%CI:-0.100,-0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (β = 0.079, 95%CI:0.016,0.141), other reported psychopathology (β = 0.101, 95%CI:0.030,0.170), cognition (β = -0.052, 95%CI:0.-0.099,-0.002), and environmental adversity (β = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e. total surface area, mean cortical thickness) using a genetically-informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, among which 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recounted loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant overlap of global and regional genetic modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.

To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca’s area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.

Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N = 35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study (R). This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.

Description, The first genome-wide study of sulcal depth shows that it is highly genetically discoverable, associated with neurodevelopment., The folding of the human cerebral cortex is a highly genetically regulated process that allows for a much larger surface area to fit into the cranial vault and optimizes functional organization. Sulcal depth is a robust yet understudied measure of localized folding, previously associated with multiple neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the multivariate omnibus statistical test (MOSTest) applied to vertex-wise measures from 33,748 U.K. Biobank participants (mean age, 64.3 years; 52.0% female), we identified 856 genome-wide significant loci (P < 5 × 10−8). Comparisons with cortical thickness and surface area indicated that sulcal depth has higher locus yield, heritability, and effective sample size. There was a large amount of genetic overlap between these traits, with gene-based analyses indicating strong associations with neurodevelopmental processes. Our findings demonstrate sulcal depth is a promising neuroimaging phenotype that may enhance our understanding of cortical morphology.

Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia.We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis.Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations.In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS.The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions.

The molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discovered 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% were validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during development were found to significantly impact the measured variations in tissue-specific imaging features. Our results shed new light on the biological determinants of brain tissue composition and their potential overlap with the genetic basis of neuropsychiatric disorders.

There is growing evidence that psychosis is characterized by brain network abnormalities. Analyzing morphological abnormalities with T1-weighted structural MRI may be limited in discovering the extent of deviations in cortical associations. We assess whether structural associations of either cortical white–gray contrast (WGC) or cortical thickness (CT) allow for a better understanding of brain structural relationships in first episode of psychosis (FEP) patients. Principal component and structural covariance analyses were applied to WGC and CT derived from T1-weighted MRI for 116 patients and 88 controls, to explore sets of brain regions that showed group differences, and associations with symptom severity and cognitive ability in patients. We focused on 2 principal components: one encompassed primary somatomotor regions, which showed trend-like group differences in WGC, and the second included heteromodal cortices. Patients’ component scores were related to general psychopathology for WGC, but not CT. Structural covariance analyses with WGC revealed group differences in pairwise correlations across widespread brain regions, mirroring areas derived from PCA. More group differences were uncovered with WGC compared with CT. WGC holds potential as a proxy measure of myelin from commonly acquired T1-weighted MRI and may be sensitive in detecting systems-level aberrations in early psychosis, and relationships with clinical/cognitive profiles.

Background The relationship between poor insight and less favorable outcomes in schizophrenia has promoted research efforts to understand its neurobiological basis. Thus far, research on neural correlates of insight has been constrained by small samples, incomplete insight assessments, and a focus on frontal lobes. The purpose of this study was to examine associations of cortical thickness and subcortical volumes, with a comprehensive assessment of clinical insight, in a large sample of enduring schizophrenia patients. Methods Two dimensions of clinical insight previously identified by a factor analysis of 4 insight assessments were used: Awareness of Illness and Need for Treatment (AINT) and Awareness of Symptoms and Consequences (ASC). T1-weighted structural images were acquired on a 3 T MRI scanner for 110 schizophrenia patients and 69 healthy controls. MR images were processed using CIVET (version 2.0) and MAGeT and quality controlled pre and post-processing. Whole-brain and region-of-interest, vertex-wise linear models were applied between cortical thickness, and levels of AINT and ASC. Partial correlations were conducted between volumes of the amygdala, thalamus, striatum, and hippocampus and insight levels. Results No significant associations between both insight factors and cortical thickness were observed. Moreover, no significant associations emerged between subcortical volumes and both insight factors. Conclusions These results do not replicate previous findings obtained with smaller samples using single-item measures of insight into illness, suggesting a limited role of neurobiological factors and a greater role of psychological processes in explaining levels of clinical insight.

Childhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development℠ (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (β = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (β = -0.0525, 95%CI:-0.100,-0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (β = 0.079, 95%CI:0.016,0.141), other reported psychopathology (β = 0.101, 95%CI:0.030,0.170), cognition (β = -0.052, 95%CI:0.-0.099,-0.002), and environmental adversity (β = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments.

Genome-Wide Association studies have typically been limited to single phenotypes, given that high dimensional phenotypes incur a large multiple comparisons burden: ~1 million tests across the genome times the number of phenotypes. Recent work demonstrates that a Multivariate Omnibus Statistic Test (MOSTest) is well powered to discover genomic effects distributed across multiple phenotypes. Applied to cortical brain MRI morphology measures, MOSTest has resulted in a drastic improvement in power to discover loci when compared to established approaches (min-P). One question that arises is how well these discovered loci replicate in independent data. Here we perform 10 times cross validation within 35,644 individuals from UK Biobank for imaging measures of cortical area, thickness and sulcal depth (>1,000 dimensionality for each). By deploying a replication method that aggregates discovered effects distributed across multiple phenotypes, termed PolyVertex Score (PVS), we demonstrate a higher replication yield and comparable replication rate of discovered loci for MOSTest (# replicated loci: 348-845, replication rate: 94-95%) in independent data when compared with the established min-P approach (# replicated loci: 31-68, replication rate: 65-80%). An out-of-sample replication of discovered loci was conducted with a sample of 8,336 individuals from the Adolescent Brain Cognitive Development® (ABCD) study, who are on average 50 years younger than UK Biobank individuals. We observe a higher replication yield and comparable replication rate of MOSTest compared to min-P. This finding underscores the importance of using well-powered multivariate techniques for both discovery and replication of high dimensional phenotypes in Genome-Wide Association studies.

Negative symptoms are present at the onset of psychosis and their persistence is significantly associated with poor psychosocial functioning and lower quality of life. Persistent negative symptoms (PNS) may be idiopathic or secondary to other factors such as depression, positive symptoms, and medication side-effects. Several studies have examined neurocognitive functions in early psychosis patients with PNS relative to non-PNS, but have not systematically controlled for secondary PNS (sPNS). The latter may have a distinct neurocognitive profile that could obscure differences between PNS and non-PNS. Using a large (n = 425) sample, we examined neurocognitive functions in PNS, sPNS, and non-PNS and hypothesized that PNS would be associated with greater impairments relative to non-PNS. Following admission to an early intervention program, a neurocognitive battery was administered after at least 3 months of treatment, and symptom data collected during a subsequent 6-month period were used to classify patients as PNS, sPNS and non-PNS. At month 12, both PNS and sPNS groups had significantly lower level of functioning relative to the non-PNS group but the sPNS group experienced higher levels of depressive and positive symptoms and were on a higher dose of antipsychotics. Relative to non-PNS, PNS patients exhibited significant impairments in verbal memory and working memory, whereas sPNS patients exhibited a trend towards greater impairments in verbal memory. This study confirms that the presence of PNS or sPNS negatively influences functioning with more selective cognitive impairments found in PNS, providing evidence that these groups of patients could benefit from different personalised interventions.

ObjectiveA potential distinguishing factor between more benign and transient psychotic-like experiences (PLEs) versus PLEs that predict risk for psychiatric disorders is whether the PLEs are sustained and distressing (sustained dPLEs). The current study examined associations of both sustained and transient dPLEs with relevant risk factors (e.g., cognition), use of mental health services, and functional correlates (e.g., school performance) in school-age children.MethodThe current study used three Adolescent Brain Cognitive Development℠ study data waves to create sustained dPLE (n=272), transient dPLE (n=244), and control (n=272) groups. Hierarchical linear models examined whether these groups differed in terms of use of mental health services, functional correlates, family history of mental disorders, other symptoms (e.g., parent-rated psychotic symptoms, internalizing, externalizing symptoms), environmental factors (e.g., adverse childhood events [ACEs]), cognitive functioning, developmental milestone delays, and neuroimaging indices.ResultsSeveral factors were more strongly associated with sustained versus transient dPLEs, including use of mental health services (for sustained vs. controls: d=0.38), drop in grades (d=--.30), other symptoms (i.e., parent-rated psychotic, bipolar, internalizing, externalizing, suicidality; 0.33>dsdsConclusionsThese results have implications for understanding the pathogenesis of dPLEs, including indicating that several factors may distinguish transient from persisting dPLEs in children, including higher symptoms and ACEs, lower executive functioning scores, greater use of mental health services, and worsening school performance.

Widespread structural brain abnormalities have been consistently reported in schizophrenia, but their relation to the heterogeneous clinical manifestations remains unknown. In particular, it is unclear whether anatomical abnormalities in discrete regions give rise to discrete symptoms or whether distributed abnormalities give rise to the broad clinical profile associated with schizophrenia. Here, we apply a multivariate data-driven approach to investigate covariance patterns between multiple-symptom domains and distributed brain abnormalities in schizophrenia. Structural magnetic resonance imaging and clinical data were derived from one discovery sample (133 patients and 113 controls) and one independent validation sample (108 patients and 69 controls). Disease-related voxel-wise brain abnormalities were estimated using deformation-based morphometry. Partial least-squares analysis was used to comprehensively map clinical, neuropsychological, and demographic data onto distributed deformation in a single multivariate model. The analysis identified 3 latent clinical-anatomical dimensions that collectively accounted for 55% of the covariance between clinical data and brain deformation. The first latent clinical-anatomical dimension was replicated in an independent sample, encompassing cognitive impairments, negative symptom severity, and brain abnormalities within the default mode and visual networks. This cognitive-negative dimension was associated with low socioeconomic status and was represented across multiple races. Altogether, we identified a continuous cognitive-negative dimension of schizophrenia, centered on 2 intrinsic networks. By simultaneously taking into account both clinical manifestations and neuroanatomical abnormalities, the present results open new avenues for multi-omic stratification and biotyping of individuals with schizophrenia.

Background To examine whether the duration of unremitted psychotic symptoms after the onset of a first episode of psychosis (FEP) is associated with cortical thickness and hippocampal volume, as well as structural covariance of these measures. Method Longitudinal MRI scans were obtained for 80 FEP patients shortly after entry to FEP clinic (baseline), and then 12 months and 24 months later. The proportion of time patients experienced unremitted positive symptoms for 2 interscan intervals (baseline to 12 mo, 12 mo to 24 mo) was calculated. Changes in cortical thickness and hippocampal volumes were calculated for each interscan interval and associated with duration of unremitted psychotic symptoms. Significant regions were then used in seed-based structural covariance analyses to examine the effect of unremitted psychotic symptoms on brain structural organization. Importantly, analyses controlled for antipsychotic medication. Results Cortical thinning within the left medial/orbitofrontal prefrontal cortex and superior temporal gyrus were significantly associated with the duration of unremitted psychotic symptoms during the first interscan interval (ie, baseline to 12 mo). Further, changes in cortical thickness within the left medial/orbitofrontal cortex positively covaried with changes in thickness in the left dorsal and ventrolateral prefrontal cortex during this period. No associations were observed during the second interscan interval, nor with hippocampal volumes. Conclusions These results demonstrate that cortical thickness change can be observed shortly after an FEP, and these changes are proportionally related to the percentage of time spent with unremitted psychotic symptoms. Altered structural covariance in the prefrontal cortex suggests that unremitted psychotic symptoms may underlie reorganization in higher-order cortical regions.

Verbal memory (VM) is one of the most affected cognitive domains in first-episode psychosis (FEP) and is a robust predictor of functioning. Given that healthy females demonstrate superior VM relative to males and that female patients show less-severe illness courses than male patients, this study examined whether normative sex differences in VM extend to FEP and influence functioning. Four hundred and thirty-five patients (299 males, 136 females) with affective or nonaffective psychosis were recruited from a catchment-based specialized FEP intervention service and 138 nonclinical controls (96 males, 42 females) were recruited from the same community. One of the two neurocognitive batteries comprising six cognitive domains (VM, visual memory, working memory, attention, executive function, processing speed) were administered at baseline. In patients, positive and negative symptoms were evaluated at baseline and functioning was assessed at 1-year follow-up. Patients were more impaired than controls on all cognitive domains, but only VM showed sex differences (both patient and control males performed worse than females), and these results were consistent across batteries. In patients, better baseline VM in females was related to better functioning after 1 year, mediated through fewer baseline negative symptoms. Supplemental analyses revealed these results were not driven by affective psychosis nor by age and parental education. Thus, normative sex differences in VM are preserved in FEP and mediate functioning at 1-year follow-up via negative symptoms. This study highlights the importance of investigating sex effects for understanding VM deficits in early psychosis and suggests that sex may be a disease-modifying variable with important treatment implications.

Widespread structural brain abnormalities have been consistently reported in schizophrenia, but their relation to the heterogeneous clinical manifestations remains unknown. In particular, it is un-clear whether anatomical abnormalities in discrete regions give rise to discrete symptoms, or whether distributed abnormalities give rise to the broad clinical profile associated with schizophrenia. Here we apply a multivariate data-driven approach to investigate covariance patterns between multiple symptom domains and distributed brain abnormalities in schizophrenia. Structural MRI, and clinical data were derived from one discovery sample (133 patients, 113 controls) and one independent validation sample (108 patients, 69 controls). Disease-related voxel-wise brain abnormalities were estimated using deformation based morphometry. Partial least squares analysis was used to comprehensively map clinical, neuropsychological and demographic data onto distributed deformation in a single multivariate model. The analysis identified three latent clinical-anatomical dimensions that collectively accounted for 55% of the covariance between clinical data and brain deformation. The first latent clinical-anatomical dimension was replicated in an independent sample, encompassing cognitive impairments, negative symptom severity and brain abnormalities within the default mode and visual networks. This cognitive-negative dimension was associated with low socioeconomic status and was represented across multiple races. Altogether, we identified a continuous cognitive-negative dimension of schizophrenia, centered on two intrinsic networks. By simultaneously taking into account both clinical manifestations and neuroanatomical abnormalities, the present results open new avenues for multi-omic stratification and biotyping of individuals with schizophrenia.

BackgroundThere is growing recognition that connectome architecture shapes cortical and sub-cortical grey matter atrophy across a spectrum of neurological and psychiatric diseases. Whether connectivity contributes to tissue volume loss in schizophrenia in the same manner remains unknown.MethodsHere we relate tissue volume loss in patients with schizophrenia to patterns of structural and functional connectivity. Grey matter deformation was estimated in a sample of N = 133 individuals with chronic schizophrenia (48 female, 34.7 ± 12.9 years) and N = 113 controls (64 female, 23.5 ± 8.4 years). Deformation-based morphometry (DBM) was used to estimate cortical and subcortical grey matter deformation from T1-weighted MR images. Structural and functional connectivity patterns were derived from an independent sample of N = 70 healthy participants using diffusion spectrum imaging and resting-state functional MRI.ResultsWe find that regional deformation is correlated with the deformation of structurally- and functionally-connected neighbours. Distributed deformation patterns are circumscribed by specific functional systems (the ventral attention network) and cytoarchitectonic classes (limbic class), with an epicenter in the anterior cingulate cortex.ConclusionsAltogether, the present study demonstrates that brain tissue volume loss in schizophrenia is conditioned by structural and functional connectivity, accounting for 25-35% of regional variance in deformation.

Background: Social interactions require rapid, real-time information integration and performative application of dynamic social information, and can be especially difficult for patients with schizophrenia. Their difficulty processing social information could lie in challenges extracting the information or in updating their actions to accommodate the new information, resulting in behaviors that may appear rigid or inappropriate. Disruptions may emerge in the underlying, requisite behavioral or neural processes. Methods: Seventeen matched healthy controls and seventeen patients with schizophrenia participated in an fMRI study, which included a social interaction priming procedure wherein they met a friendly stranger who held opposite social values from their own. They answered self-judgement questions about their social values two days before the priming experiment and again during the fMRI scan. Results: Controls suppress social values when interacting with the stranger whereas patients with schizophrenia augment the opposite values, simultaneously holding two sets of social values. Compared to controls, patients display hyperactivity in dorsomedial prefrontal cortex and atypical activity in caudate, posterior cingulate and precuneus. Discussion: Patients appear to correctly extract social information but apply the information atypically. They display evidence of atypical social flexibility on both performative and neural measures, resulting in confusion between self and other.

Accurate automated quantification of subcortical structures is a greatly pursued endeavour in neuroimaging. In an effort to establish the validity and reliability of these methods in defining the striatum, globus pallidus, and thalamus, we investigated differences in volumetry between manual delineation and automated segmentations derived by widely used FreeSurfer and FSL packages, and a more recent segmentation method, the MAGeT-Brain algorithm. In a first set of experiments, the basal ganglia and thalamus of thirty subjects (15 first episode psychosis [FEP], 15 controls) were manually defined and compared to the labels generated by the three automated methods. Our results suggest that all methods overestimate volumes compared to the manually derived "gold standard", with the least pronounced differences produced using MAGeT. The least between-method variability was noted for the striatum, whereas marked differences between manual segmentation and MAGeT compared to FreeSurfer and FSL emerged for the globus pallidus and thalamus. Correlations between manual segmentation and automated methods were strongest for MAGeT (range: 0.51 to 0.92; p0.01, corrected), whereas FreeSurfer and FSL showed moderate to strong Pearson correlations (range 0.44-0.86; p0.05, corrected), with the exception of FreeSurfer pallidal (r=0.31, p=0.10) and FSL thalamic segmentations (r=0.37, p=0.051). Bland-Altman plots highlighted a tendency for greater volumetric differences between manual labels and automated methods at the lower end of the distribution (i.e. smaller structures), which was most prominent for bilateral thalamus across automated pipelines, and left globus pallidus for FSL. We then went on to examine volume and shape of the basal ganglia structures using automated techniques in 135 FEP patients and 88 controls. The striatum and globus pallidus were significantly larger in FEP patients compared to controls bilaterally, irrespective of the method used. MAGeT-Brain was more sensitive to shape-based group differences, and uncovered widespread surface expansions in the striatum and globus pallidus bilaterally in FEP patients compared to controls, and surface contractions in bilateral thalamus (FDR-corrected). By contrast, after using a recommended cluster-wise thresholding method, FSL only detected differences in the right ventral striatum (FEPControl) and one cluster of the left thalamus (ControlFEP). These results suggest that different automated pipelines segment subcortical structures with varying degrees of variability compared to manual methods, with particularly pronounced differences found with FreeSurfer and FSL for the globus pallidus and thalamus.

Among individuals with psychosis, those with poor cognitive insight (lower Self-Reflectiveness, higher Self-Certainty) show volumetric reductions in cortical structure. We evaluated whether changes in cognitive insight are associated with progressive changes in cortical structure in first-episode psychosis (FEP) and control subjects. Beck Cognitive Insight Scale ratings and magnetic resonance imaging scans were acquired at baseline for 130 FEP and 52 controls, 59 FEP and 28 controls at 1-year, and 53 FEP and 20 controls at 2-years. Cortical thickness was computed across scans and analyzed with linear mixed models. At baseline, groups did not differ on Self-Reflectiveness or Self-Certainty. At baseline, higher Self-Reflectiveness significantly correlated with thinner right occipital cortex in FEP, and higher Self-Certainty was significantly negatively correlated with cortical thickness in left posterior cingulate in controls. Longitudinal analysis showed that Self-Reflectiveness and Self-Certainty did not change over time in either group. Interestingly, the lack of change in cognitive insight aligned with longitudinal cortical thickness results, where no interaction effects were seen with cortical thickness between time and either Self-Reflectiveness or Self-Certainty. Exploratory analyses with a reduced threshold found that in FEP, across all time-points, higher Self-Certainty associated with thinner cortex in left posterior cingulate/precuneus. Results suggest that the posterior cingulate may be a common neural correlate for Self-Certainty in FEP and non-clinical subjects.

People with psychosis show deficits recognizing facial emotions and disrupted activation in the underlying neural circuitry. We evaluated associations between facial emotion recognition and cortical thickness using a correlation-based approach to map structural covariance networks across the brain. Fifteen people with an early psychosis provided magnetic resonance scans and completed the Penn Emotion Recognition and Differentiation tasks. Fifteen historical controls provided magnetic resonance scans. Cortical thickness was computed using CIVET and analyzed with linear models. Seed-based structural covariance analysis was done using the mapping anatomical correlations across the cerebral cortex methodology. To map structural covariance networks involved in facial emotion recognition, the right somatosensory cortex and bilateral fusiform face areas were selected as seeds. Statistics were run in SurfStat. Findings showed increased cortical covariance between the right fusiform face region seed and right orbitofrontal cortex in controls than early psychosis subjects. Facial emotion recognition scores were not significantly associated with thickness in any region. A negative effect of Penn Differentiation scores on cortical covariance was seen between the left fusiform face area seed and right superior parietal lobule in early psychosis subjects. Results suggest that facial emotion recognition ability is related to covariance in a temporal-parietal network in early psychosis.

Cognitive insight is described as a balance between one's self-reflectiveness (recognition and correction of dysfunctional reasoning), and self-certainty (overconfidence). Neuroimaging studies have linked the ventrolateral prefrontal cortex (VLPFC) to cognitive insight in people with psychosis. However, the relationship between cognitive insight and structural connectivity between the VLPFC and other brain areas is unknown. Here, we investigated the modulation of cognitive insight on structural covariance networks involving the VLPFC in a first-episode psychosis sample. Fifteen patients with a first-episode psychosis provided magnetic resonance (MR) scans and completed the Beck Cognitive Insight Scale (BCIS). MR scans were also available for 15 historical controls. Seed-based analysis of structural covariance was conducted using the Mapping Anatomical Correlations Across the Cerebral Cortex (MACACC) methodology, whereby Pearson correlation coefficients were extracted between seed regions in left and right VLPFC and cortical thickness across the brain. Structural covariance maps between groups were compared at each vertex. In first-episode subjects, we evaluated the modulation of BCIS scores on cortical covariance between VLPFC and every other vertex. Findings showed no significant group difference between first-episode psychosis subjects and controls in thickness covariance seeded from left or right VLPFC. However, in first-episode psychosis subjects, a positive association with self-certainty was found in networks seeded from both left and right VLPFC with thickness in medial frontal cortex and right pars triangularis. No significant associations were found for self-reflectiveness. These results suggest that self-certainty, but not self-reflectiveness, positively modulated cortical covariance in a frontal network in patients with a first-episode psychosis.

Individuals with sub-threshold psychotic symptoms (STPS) are considered at clinical high risk for psychosis (CHR). Imaging studies comparing CHR and patients shortly after a first episode of psychosis (FEP) support progressive cortical thinning by illness stage. However, at least 30% of FEP patients deny pre-onset STPS, suggesting no history of CHR. This calls into question the generalizability of previous imaging findings. To better understand the physiology of early psychosis symptomology, we investigated the relationship between pre-onset STPS and cortical thickness (CT) among FEP patients, examining regional CT and structural covariance (SC). Patients (N = 93) were recruited from PEPP-Montreal, a FEP clinic at the Douglas Mental Health University Institute. The Circumstances of Onset and Relapse Schedule was administered to retrospectively identify patients who recalled at least one of nine expert-selected STPS prior to their FEP (STPS+, N = 67) and to identify those who did not (STPS-, N = 26). Age and sex-matched healthy controls (HC) were recruited (N = 84) for comparison. Participants were scanned between one and three times over the course of two years. CT values of 320 scans (143 HC, 123 STPS+, 54 STPS-) that passed quality control were extracted for group analysis. Linear mixed effects models accounting for effects of age, sex, education, and mean thickness were applied for vertex-wise, group comparisons of cortical thickness and SC. Multiple comparison corrections were applied with Random Field Theory (p-cluster = 0.001). Compared to controls, only STPS- patients exhibited significantly reduced CT in a cluster of the right ventral lateral prefrontal cortex. The vertex with the highest t-statistic within this cluster was employed as a seed in the subsequent SC analysis. After RFT-correction, STPS+ patients exhibited significantly stronger SC between the seed and right pars orbitalis compared to STPS- patients, and HC exhibited significantly stronger SC between the seed and right middle temporal gyrus compared to STPS- patients. Our results revealed patterns of SC that differentiated patient subgroups and patterns of cortical thinning unique to STPS- patients. Our study demonstrates that the early course of sub-threshold psychotic symptoms holds significance in predicting patterns of CT during FEP.

Introduction Since 2009, CBRAIN, a collaborative, web-based research platform, has served a broad international community of researchers in performing large-scale data and computational neuroscience (Sherif, 2014). With over 800 users at 193 sites in 32 different countries and hosting over 60 software pipelines, CBRAIN has provided over 35 million CPU hours on computing resources around the world, including Stampede2 at TACC, the world's largest supercomputer dedicated to academic research. CBRAIN is a central component in the Healthy Brains for Healthy Lives infrastructure (HBHL, 2018) and the Canadian Open Neuroscience Platform (CONP, 2018), which require new features connecting existing platforms (e.g. LORIS (Das, 2016), OpenNeuro (Gorgolewski, 2017), and BrainCode (Vaccarino, 2018), utilizing community-based standards (e.g. BIDS (Gorgolewski, 2016), Boutiques (Glatard, 2018), and CARMIN (Glatard, 2015)), and offering new usage modalities and interfaces. Methods CBRAIN's primary purpose is to provide an ecosystem that abstracts away the low-level details of data movement and computational execution on advanced research computing resources. CBRAIN provides an orchestration system consisting of a central control instrument, termed a Portal, which communicates and submit tasks to remote compute servers, called Bourreaux. Portals and Bourreaux access remote data resources through passive DataProviders.The CBRAIN platform provides a unifying service layer for access to remote computing resources around the world (e.g. Compute Canada, XSEDE, and the CCC-Axis). CBRAIN is a Ruby on Rails application, is completely open source (https://github.com/aces/cbrain) and provided as a service free of charge (https://portal.cbrain.mcgill.ca). Requirements from new national and international initiatives lead to developments increasing interoperability, functionality and usability supporting a wider community and integrating with a broader set of community-driven tools and standards. Results New features developed in the CBRAIN platform are: RESTful API: A fully documented and functional CBRAIN RESTful API is now available at https://app.swaggerhub.com/apis/prioux/CBRAIN/5.1.0 and allows projects to utilize CBRAIN as a backend technology. To promote a community standard, CBRAIN will support CARMIN, a common web API for remote pipeline execution, such that any CARMIN compliant tool can use CBRAIN as a backend without rewriting their package. Datalad and S3 Integration: A Datalad DataProvider provides an interface to move data from Datalad (Datalad, 2018) versioned resources into the CBRAIN ecosystem. A new S3 DataProvider provides data movement from cloud-based resources. BIDS Compatibility: Capitalizing on the BIDS standard, an automatic parallelization capability to ensure BIDSApps run efficiently. Provenance and error-handling are also available, and the user only needs to specify the BIDS-formatted input dataset and the pipeline to execute. Boutiques Integration: To enable computational pipelines to be discoverable and shareable, and ease the burden of integration and deployment, we have adopted the Boutiques JSON standard to define our computational pipelines and to pull new pipelines from the Boutiques Repository. New Interactive Interface: A user-focused, interactive and dynamic CBRAIN user-interface has been designed, built with React.js and GraphQL, interacting through the CBRAIN API to launch tasks and manage data, The UI is highly modular and can quickly be adapted to new user and visualization requirements over time. New modular visualizations have also been developed using React.js. Conclusions CBRAIN has for nearly a decade served as a platform for accomplishing large-scale, large-data neuroinformatics. The new implementations provide a connection to a larger community of neuroinformatics and scientific research and promote FAIR standards in computational science., {"references":["CONP (2018), Canadian Open Neuroscience Platform, https://conp.ca","Das, S. (2016), 'The MNI data-sharing and processing ecosystem', NeuroImage, vol. 124, pp. 1188–1195.","Datalad (2018), available at http://www.datalad.org.","Glatard, T. (2018). Boutiques: a flexible framework to integrate command-line applications in computing platforms. GigaScience, 7, giy016.","Glatard, T. (2015). CARMIN: a common web API for remote pipeline execution. Frontiers in Neuroscience, vol. 9, no. 00053.","Gorgolewski, K.J. (2016). The brain imaging data structure, a format for organizing and describing outputs of neuroimaging experiments. Scientific Data, vol. 3, 160044.","Gorgolewski, K.J. (2017). OpenNeuro—a free online platform for sharing and analysis of neuroimaging data. Organization for Human Brain Mapping. Vancouver, Canada, 1677.","HBHL (2018), Healthy Brains for Healthy Lives, http://www.mcgill.ca/hbhl","Sherif, T. (2014), 'CBRAIN: a web-based, distributed computing platform for collaborative neuroimaging research', Front Neuroinform, vol. 8, pp. 54.","Vaccarino, A. L. (2018). Brain-CODE: A Secure Neuroinformatics Platform for Management, Federation, Sharing and Analysis of Multi-Dimensional Neuroscience Data, vol. 12, pp. 28."]}

Background There is growing recognition that connectome architecture shapes cortical and subcortical gray matter atrophy across a spectrum of neurological and psychiatric diseases. Whether connectivity contributes to tissue volume loss in schizophrenia in the same manner remains unknown. Methods Here, we relate tissue volume loss in patients with schizophrenia to patterns of structural and functional connectivity. Gray matter deformation was estimated in a sample of 133 individuals with chronic schizophrenia (48 women, mean age 34.7 ± 12.9 years) and 113 control subjects (64 women, mean age 23.5 ± 8.4 years). Deformation-based morphometry was used to estimate cortical and subcortical gray matter deformation from T1-weighted magnetic resonance images. Structural and functional connectivity patterns were derived from an independent sample of 70 healthy participants using diffusion spectrum imaging and resting-state functional magnetic resonance imaging. Results We found that regional deformation is correlated with the deformation of structurally and functionally connected neighbors. Distributed deformation patterns are circumscribed by specific functional systems (the ventral attention network) and cytoarchitectonic classes (limbic class), with an epicenter in the anterior cingulate cortex. Conclusions Altogether, the present study demonstrates that brain tissue volume loss in schizophrenia is conditioned by structural and functional connectivity, accounting for 25% to 35% of regional variance in deformation.

BACKGROUND: Verbal memory is one of the most severely affected cognitive domains in schizophrenia and related psychoses and impairment in this domain is one of the strongest predictors of poor clinical and functional outcome. Verbal memory deficits in schizophrenia have been linked to alterations in various measures of brain structure (e.g., cortical thinning, decreased brain volume) and function (e.g., aberrant functional connectivity) within widespread cortical and subcortical areas, including the hippocampus, medial temporal lobes, and frontal regions. However, previous research generally employs mass-univariate analysis or multivariate techniques that relate verbal memory to networks derived from overall variance; thus, brain networks specifically optimized to explain patterns of verbal memory performance have yet to be determined. In the current study, we examined differences between first-episode psychosis (FEP) patients and healthy controls on a verbal memory-optimized structural brain network derived from partial least squares (PLS) regression, which maximizes the covariance between the dependent (cortical thickness) and independent (verbal memory) variables of interest. METHODS: Participants (81 FEP patients, 115 healthy controls, matched for age, sex, and handedness) underwent magnetic resonance imaging and completed one of two cognitive test batteries (Wechsler Memory Scale or CogState Research Battery). Composite verbal memory domain scores were calculated from the respective control z-scores for each battery and combined into a single verbal memory domain. Cortical thickness values (residualized for age, sex, and test battery) were derived using CIVET version 2.1.0 and parcellated into 78 regions of interest (ROIs) using the Automated Anatomical Labeling (AAL) atlas. PLS regression was used to identify a verbal memory-optimized cortical thickness network by maximizing covariance between these variables and significant ROIs were determined using permutation tests. Group differences on the PLS component-based cortical thickness and verbal memory scores (i.e., linear combinations of cortical thickness ROIs/verbal memory which have maximum covariance with predictor/response scores, respectively) were assessed with t-tests. RESULTS: The FEP group showed significantly impaired performance on verbal memory relative to healthy controls, t(194) = 7.29, p < .001, 95% CI = [0.87 - 1.51]. PLS revealed a right-dominant verbal memory-related network including significant contributions from right temporal cortex (inferior/middle temporal gyrus, parahippocampal gyrus, middle/superior temporal pole), bilateral sensorimotor regions, and left middle frontal gyrus (loadings: 0.21 - 0.53; all ps < 0.05). Significant group differences were observed on component-based cortical thickness scores, t(194) = 2.53, p < 0.05, 95% CI = [0.10 - 0.82], and verbal memory component scores, t(194) = 7.29, p < .001, CI = [0.49 - 0.85], indicating that FEP patients showed a significantly decreased contribution to this network than healthy controls. DISCUSSION: Using PLS to maximize covariance between region-based cortical thickness and verbal memory performance in a large sample of FEP patients and healthy controls, we identified a right-dominant frontotemporal network on which FEP patients showed decreased scores relative to controls. This suggests that decreased structural connectivity between regions within this network may underlie impaired verbal memory performance in FEP. Future research will further investigate network characteristics to determine the nature of these group differences and whether they are observable longitudinally through different stages of psychosis.

BACKGROUND: Verbal memory (VM) is one of the most affected cognitive domains in patients with schizophrenia and a robust predictor of functional outcome. There are well-documented sex differences in verbal memory in healthy individuals, which may be particularly pertinent to study in psychosis. For instance, in healthy individuals, women tend to have significantly better verbal memory performance relative to men. Given that male psychosis patients present with an earlier age of onset, more negative symptoms, and have poorer functional outcomes than women, consideration of sex differences may lead to a better understanding of VM impairment in psychosis and its wide-ranging effects on outcome. Studies of first-degree relatives of schizophrenia patients and those at clinical high-risk for psychosis demonstrate specific impairments in immediate but not delayed recall, suggesting that impaired immediate recall may be a marker for psychosis. Our aims were thus (1) to investigate sex differences in VM ability in first-episode psychosis (FEP) patients and controls, and (2) to distinguish between sub-domains of memory impairment in FEP in relation to sex differences, by examining both immediate and delayed recall performance. METHODS: 437 FEP patients (301 males, 136 females; age range 14–35) and 138 (96 males, 42 females matched on age, sex, handedness, and socioeconomic status) were included. VM was calculated from the Logical Memory Subscales of the Wechsler Memory Scale (n=324) or a computerized VM task from the CogState Research Battery (n=251). Performance of the matched control group was used as normative data to derive z-scores for VM, as well as for immediate and delayed recall separately. Main effects of sex (males, females) and diagnostic group (patients, controls), as well as group × sex interactions, on VM were examined, covarying for battery version. RESULTS: No significant group × sex interactions were found with respect to memory performance, F(1,570)=0.64, p=0.43. Significant main effects of group and sex on VM were observed, where FEP patients performed worse than controls, F(1,570)=75.69, p

Background Current neuroscience literature has related treatment with aripiprazole to improved memory performance and subcellular changes in the hippocampus. Aims To explore the volumetric changes in hippocampal grey matter in people with a first episode of psychosis (FEP) treated with second-generation antipsychotics. Method Baseline and 1-year follow-up magnetic resonance images were obtained. Hippocampal volumes were estimated by using FreeSurfer and MAGeT-Brain. Subgroups included: aripiprazole (n=13), olanzapine (n=12), risperidone/paliperidone (n=24), refused-antipsychotics (n=13) and controls (n=44). Results Aripiprazole subgroup displayed significant increases in bilateral hippocampal volume compared with all other subgroups (FreeSurfer: all P’s