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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.

Cognitive biases are systematic tendencies in the processing, selection and remembering of information. They are prevalent in schizophrenia-spectrum disorders (SSD) and are particularly associated with positive symptoms. The bias against disconfirmatory evidence (BADE) refers to a reluctance to integrate information that contradicts one’s beliefs and is associated with delusions. There is also some evidence of a link between BADE and formal thought disorder (FTD), though this relationship remains to be fully explored. FTD can be objectively quantified through speech via computerized processing of speech transcripts in both clinical and non-clinical samples. We sought to examine the relationship between BADE and speech connectedness in SSD patients (n = 30) and non-clinical controls (n = 15). We hypothesized that lower speech connectedness would be associated with greater severity of BADE. Speech graphs assessing language connectedness were generated from manually transcribed speech samples acquired during semi-structured interviews. The results supported previous findings of a greater BADE in patients relative to controls. While speech connectedness did not differ between patient and control groups, it was associated with positive symptoms (delusions, conceptual disorganization, and hallucinations) in patients. The link between BADE and FTD differed depending on whether patients had a non-affective or an affective SSD. In non-affective patients, higher BADE was associated with higher conceptual disorganization, measured via symptoms interviews, whereas higher BADE was associated with lower speech connectedness in affective patients. These findings support the notion that cognitive biases are linked to FTD, but suggest that non-affective versus affective diagnosis may affect the way in which this link is manifested.

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.

Cognitive impairments and abnormal immune activity are both associated with various clinical disorders. The association between C-Reactive protein (CRP), a marker associated with inflammation, and cognitive performance remains unclear. Further, mechanisms potentially linking CRP to cognition are not yet established. Brain structure may well mediate this relationship: immune processes play crucial roles in shaping and maintaining brain structure, and brain structure and function drive cognition. The UK Biobank is a large cohort study with extensive assessments, including high-sensitivity serum CRP levels, brain imaging, and various cognitive tasks. With data from 39,200 UK Biobank participants, we aimed first to determine the relationship between CRP and cognitive performance, and second, to assess metrics of brain morphology as potential mediators in this relationship. Participants were aged 40 to 73 at initial assessment and were mostly Caucasian. After accounting for potential covariates (e.g., age, sex, medical diagnoses, use of selective-serotonin reuptake inhibitors), we found CRP levels to have small, negative associations with fluid intelligence (b = -0.03, 95%CI[-0.05,-0.02], t(14381) = -3.62, pcor = .004), and numeric memory (b = -0.03, 95%CI[-0.05,-0.01], t(14366) = -3.31, pcor = .007). We found no evidence of brain morphology mediating these relationships. Our findings from this large sample suggest that serum-assessed CRP is of marginal importance for cognitive performance in mid-to-late aged Caucasians; the small effect sizes of statistically significant associations provide context to previous inconsistent results. The seeming lack of involvement of brain morphology suggests that other brain metrics (e.g., connectivity, functional activation) may be more pertinent to this relationship. Future work should also consider CRP levels measured in the central nervous system and/or other cytokines that may better predict cognitive performance in this population.

There is robust evidence for sex differences in domain-specific cognitive performance in the general population, where females typically show an advantage for verbal memory (VM), while males tend to perform better on tasks of spatial memory (SM). Sex differences in brain structure and connectivity are also well-documented and may provide insight into sex differences in cognition. In this study, we examined sex differences in cognition and morphometric brain connectivity of a large healthy sample (N = 31,180) from the UK Biobank dataset. Using T1-weighted magnetic resonance imaging (MRI) scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of morphometric brain connectivity, hypothesizing that sex-related differences in brain network global efficiency, or overall connectivity, would underlie observed cognitive differences. As predicted, females demonstrated better VM performance and males showed an advantage in SM. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males tended to have higher global efficiency, as well as higher regional connectivity (nodal strengths) in both the left and right hemispheres relative to females.Furthermore, higher global efficiency in males was found to mediate observed sex differences in cognition, predicting poorer verbal memory performance, better spatial memory, and slower processing speed in males. These findings contribute to an improved understanding of the way biological sex and differences in cognitive performance are related to morphometric brain connectivity as derived from graph-theoretic methods.

Episodic memory research in schizophrenia has a long history already which has clearly established significant impairments and strong associations with brain measures and functional outcome. The purpose of this chapter is not to make an exhaustive review of the recent literature but to highlight some relatively recent developments in the cognitive neuroscience field of episodic memory and schizophrenia. Hence, we present a contemporary view focusing specifically of relational memory which represents a form of episodic memory that refers to associations or binding among items or elements presented together. We describe the major tasks used and illustrate how their combination with brain imaging has: (1) favored the use of experimental memory tasks to isolate specific processes with specific neural correlates, (2) led to a distributed view of the neural correlates of memory impairments in schizophrenia where multiple regions are contributing, and (3) made possible the identification of fMRI biomarkers specific to episodic memory. We then briefly propose what we see as the next steps for memory research in schizophrenia so that the impact of this work can be maximized.

Verbal memory (VM) dysfunction is prevalent in first-episode psychosis (FEP) and has major impacts on long-term functional and clinical outcomes. Nevertheless, a substantial proportion of FEP patients have VM performance in the norm, called normal-range (NR) VM, and only a few studies have explored its relation to outcomes. Moreover, probable decrements between estimated premorbid and current cognitive performance could confuse the relationship between VM and clinical or functional outcomes in FEP patients. These potential interactions have not yet been considered in FEP, thus, we examined 1) the longitudinal relationship between VM performance (NR vs. below NR (BNR)) in FEP and clinical and functional outcomes over 24 months following admission to treatment, and 2) compared the clinical and functional status of NR patients with and without cognitive decrement at baseline and 12 months. A total of 271 patients (BNR = 114, NR = 157; 81 out of 105 NR with decrement) completed measures of psychosocial functioning and clinical symptoms at baseline, month 12, and month 24. Generalized Estimating Equations and unpaired t-tests were used to address the first and second aim, respectively. NR demonstrated better functioning and fewer negative symptoms when compared to BNR. Interestingly, NR patients with decrement reported significantly more negative symptoms at baseline compared to their counterparts without decrement. These findings document that a large proportion (57.9 %) of FEP patients have NR VM that appear to be functionally advantageous but that NR VM is nuanced by the presence or absence of a potential decrement early in the developmental course of the disorder.

Cognitive biases affecting evidence integration contribute to delusions and delusional ideation in the psychosis continuum. In previously published work we observed hyperactivity in a visual attention network (VsAN) during confirmatory evidence integration, and hypoactivity in a cognitive evaluation network (CEN) during disconfirmatory evidence integration in schizophrenia patients with delusions, suggesting that a task-specific imbalance of these networks may contribute to delusion maintenance. In the current study, we investigated whether patterns of aberrant functional connectivity observed in past work were associated with delusional ideation in 41 healthy individuals by examining associations between cognitive biases, subclinical schizotypal traits, and functional brain activity during evidence integration. Behaviourally, we replicated positive associations between schizotypal traits and cognitive biases and further showed that this association was driven by delusional ideation specifically. Constrained principal component analysis for fMRI (fMRI-CPCA) revealed recruitment of the brain networks observed in our previous clinical and non-clinical evidence integration studies: default-mode network (DMN); cognitive evaluation network (CEN); and visual attention (VsAN) network. Moreover, as with clinically-significant delusions, delusional ideation was associated with decreased CEN activity during the processing of disconfirmatory evidence and increased VsAN activity during the processing of confirmatory evidence. These findings suggest that this altered pattern of activation across networks during evidence integration may underlie delusional ideation and delusions in the psychosis continuum.

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.

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms.

From the onset of schizophrenia, verbal memory (VM) deficits and negative symptoms are strongly associated, and both additively predict functional outcomes. Emotion recognition (ER) and theory of mind (ToM; the ability to infer others' mental states), two components of social cognition, are also particularly affected in schizophrenia. Explanatory models of negative symptoms have integrated these cognitive impairments as potential precursors and previous studies revealed relationships between ER and/or ToM and VM, as well as with negative symptoms, but the organization of these associations remains unclear. We aimed to determine whether impairments in VM and social cognition sequentially pave the way for negative symptoms in schizophrenia. To this end, we used mediation analyses. One hundred and forty participants with a diagnosis of schizophrenia or schizoaffective disorder were recruited. First, correlational analyses were conducted between our variables of interest. The mediating effect of social cognition between VM and negative symptoms was then examined using the PROCESS macro. Variables of interest were significantly correlated (r = |0.166| to |0.391|), except for ER and negative symptoms. Only the serial multiple mediation model with 2 mediators (ER followed by ToM) revealed a significant indirect effect of VM on negative symptoms (β = - 0.160, 95% CI = -.370 to -.004). This relationship was selective for expressive negative symptoms (e.g., blunted affect and alogia). This study illustrates the richness of the relationship between cognitive deficits and negative symptoms and provides additional information for the involvement of social cognition in negative symptoms’ etiology.

Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a scoping review of remote cognitive assessment in severe mental illness to provide an overview of available measures and guide best practices. Overall, 34 studies (n = 20,813 clinical participants) were reviewed and remote measures, psychometrics, facilitators, barriers, and future directions were synthesized using a logic model. We identified 82 measures assessing cognition in severe mental illness across 11 cognitive domains and four device platforms. Remote measures were generally comparable to traditional versions, though psychometric properties were infrequently reported. Facilitators included standardized procedures and wider recruitment, whereas barriers included imprecise measure adaptations, technology inaccessibility, low patient engagement, and poor digital literacy. Our review identified several remote cognitive measures in psychiatry across all cognitive domains. However, there is a need for more rigorous validation of these measures and consideration of potentially influential factors, such as sex and gender. We provide recommendations for conducting remote cognitive assessment in psychiatry and fostering high-quality research using digital technologies.

Integrating evidence that contradicts a belief is a fundamental aspect of belief revision and is closely linked to delusions in schizophrenia. In a previous functional magnetic resonance imaging (fMRI) study on healthy individuals, we identified functional brain networks underlying evidence integration as visual attention network (VsAN; dorsal anterior cingulate cortex, insula, occipital regions), default-mode network (DMN), and cognitive evaluation network (CEN; orbitofrontal cortex, inferior frontal gyrus, parietal cortex). In the current clinical fMRI study, we compared network-based activity during evidence integration between healthy controls (n = 41), nondelusional (n = 37), and delusional (n = 33) patients with schizophrenia, and related this activity to cognitive processing involved in evidence integration measured outside the scanner. Task-induced coordinated activation was measured using group-constrained principal component analysis for fMRI. Increased VsAN activation, reduced DMN deactivation, and reduced CEN activation were observed for schizophrenia, with this pattern being most pronounced for the delusional group. Importantly, poor evidence integration comprehensively measured outside the scanner was significantly associated with increased VsAN activation and reduced DMN deactivation when processing confirmatory evidence, and with reduced CEN activation when processing disconfirmatory evidence. This is the first comprehensive study of the functional brain networks associated with evidence integration in schizophrenia and highlights how an imbalance of functional brain networks responding to confirmatory and disconfirmatory evidence may underlie delusions in schizophrenia.

Severe cognitive impairments and cognitive distortions are core to schizophrenia-spectrum disorders (SSDs) and are associated with deteriorated social functioning. Despite well-established efficacy of group psychosocial therapies targeting cognitive health in SSDs, dissemination of these programs remains limited. Remote delivery offers a promising strategy for increasing the programs' accessibility. Yet, little research has evaluated group therapies for cognitive health delivered in this way. Thus, we aimed to assess, from participants' and therapists' perspectives, the

Psychosis is often characterized by global and regional brain structure alterations as well as general and domain-specific cognitive deficits. Previous brain structure-cognition findings in psychosis typically involve brain regions of interest or individual cognitive domains, with findings that may reflect general rather than specific effects. Here, we systematically examined whether global cortical thickness and/or general cognition drive thickness-cognition associations in two first-episode psychosis (FEP) samples to assess generalizability. Magnetic resonance imaging, cognitive, and sociodemographic data were acquired in two samples (sample 1: 97 FEP, 81 control; sample 2: 77 FEP, 53 control). Multivariate global thickness-general cognition associations were examined in patients using partial least squares to optimize brain-cognition associations. Widespread cortical thinning was associated with a general cognitive impairment, higher symptom severity, lower education, female sex, and older age. After covarying mean thickness, a general cognitive impairment was associated with bidirectional regional alterations (decreased motor, inferior temporal, and increased frontal thickness), which related to more severe negative symptoms, lower education, and younger age, and generalized out-of-sample. Domain-specific effects in verbal memory and processing speed also emerged and were related to bidirectional cortical thickness in overlapping regions, negative symptoms, lower education, and male sex in both samples. Thus, examining brain regions-of-interest and/or individual cognitive domains may capture global/general deficits rather than region- or domain-specific associations. Bidirectional thickness alterations point to inefficient cortical reorganization rather than unidimensional decline. Domain-specific associations may represent subgroups of patients with distinct sociodemographic, clinical, and cognitive profiles, who might benefit from more personalized interventions.

Schizophrenia is characterized by cognitive impairments and widespread structural brain alterations (e.g., decreased volume, thickness, surface area). Brain structure-cognition associations have been extensively studied in schizophrenia, typically involving individual cognitive domains or brain regions of interest. Findings in overlapping and diffuse brain regions may point to structural alterations in large-scale brain networks. We performed a systematic review and meta-analysis examining whether brain structure-cognition associations can be explained in terms of biologically meaningful brain networks. Of 7,621 screened articles, 88 were included in a series of meta-analyses assessing publication bias, heterogeneity, and study quality. Significant associations were found between overall brain structure and eight cognitive domains (speed of processing, attention/vigilance, working/verbal/visual memory, executive function, social cognition, and verbal fluency). Brain structure within functionally defined networks (default, dorsal/ventral attention, frontoparietal, limbic, somatosensory, visual) and external structures (amygdala, hippocampus and cerebellum) typically showed associations with conceptually related cognitive domains, with higher-level domains (e.g., executive function, social cognition) associated with more networks. These findings suggest brain structure- cognition associations in schizophrenia may follow network architecture.

Schizophrenia is characterized by cognitive impairments and widespread structural brain abnormalities. Brain structure-cognition associations have been extensively studied in schizophrenia, typically involving individual cognitive domains or brain regions of interest. Findings in overlapping and diffuse brain regions may point to structural alterations in large-scale brain networks. We performed a systematic review and meta-analysis examining whether brain structure-cognition associations can be explained in terms of biologically meaningful brain networks. Of 7,261 screened articles, 88 were included in a series of meta-analyses assessing publication bias, heterogeneity, and study quality. Significant associations were found between overall brain structure and eight MATRICS-inspired cognitive domains. Brain structure mapped onto the seven Yeo functionally defined networks and extraneous structures (amygdala, hippocampus, and cerebellum) typically showed associations with conceptually related cognitive domains, with higher-level domains (e.g., executive function, social cognition) associated with more networks. These findings synthesize the extensive literature on brain structure and cognition in schizophrenia from a contemporary network neuroscience perspective and suggest that brain structure-cognition associations in schizophrenia may follow functional network architecture.

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.

Research informed by dual process models of addictions has clearly demonstrated an association between automatic and controlled alcohol-related cognitions and alcohol use. However, the literature is limited with respect to examination of the cognitive abilities that may moderate these associations across populations. This study examined executive abilities, automatic and controlled alcohol-related cognitions, and alcohol use and problems in sample of college students. It was hypothesized that the executive abilities of working memory and response inhibition would moderate relations between alcohol-related cognitions and involvement. Specifically, it was anticipated that individuals with weaker abilities in these areas would demonstrate stronger relations between automatic cognitions and use, while individuals with stronger abilities in these areas would demonstrate more robust relations between controlled cognitions and use. Research participants completed two Implicit Association Tasks measuring alcohol-related arousal and relaxation associations. In addition, participants completed questionnaires regarding alcohol expectancies, alcohol consumption and problems, and various measures of neuropsychological functioning. We tested study hypotheses using structural equation modeling and probed significant interactions using simple slope analyses. Support for a moderating effect of inhibition abilities on relations between implicit relaxation associations and alcohol involvement was observed. Findings from this study contribute to our understanding of cognitive and neuropsychological factors that contribute to alcohol misuse with important implications for preventive interventions

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.

Combining structural (sMRI) and functional magnetic resonance imaging (fMRI) data in schizophrenia patients with and without auditory hallucinations (9 SZ_AVH, 12 SZ_nAVH), 18 patients with bipolar disorder, and 22 healthy controls, we examined whether cortical thinning was associated with abnormal activity in functional brain networks associated with auditory hallucinations. Language-task fMRI data were combined with mean cortical thickness values from 148 brain regions in a constrained principal component analysis (CPCA) to identify brain structure-function associations predictable from group differences. Two components emerged from the multimodal analysis. The "AVH component" highlighted an association of frontotemporal and cingulate thinning with altered brain activity characteristic of hallucinations among patients with AVH. In contrast, the "Bipolar component" distinguished bipolar patients from healthy controls and linked increased activity in the language network with cortical thinning in the left occipital-temporal lobe. Our findings add to a body of evidence of the biological underpinnings of hallucinations and illustrate a method for multimodal data analysis of structure-function associations in psychiatric illness.

Additional file 1: Table S1. Characteristics of TNBC patients.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress – with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.

Additional file 2: Figure S1. Genomic and proteic analysis of PI3K-AKT-mTOR and RTK-MAPK pathways in PDX models.

Rationale & Objective Assessment of how patients feel and function is needed for clinical care and research for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The objective of this study was to develop a patient-reported outcome assessment appropriate for use in children and adults with FSGS and MCD. Study Design Qualitative study using semi-structured interviews. Setting & Participants 48 semi-structured interviews with children aged 8 to 17 years (n = 11) and adults (n = 10) with FSGS and children aged 8 to 17 (n = 11) and adults (n = 16) with MCD recruited from 3 academic medical centers. Analytical Approach Latent content analysis. Results FSGS and MCD have a pervasive and comparable impact on physical, social, and mental health-related quality of life regardless of age or diagnosis. Physical symptoms of swelling, fatigue, and pain were articulated by most participants. Disease management was also a frequent topic of discussion; participants described their experiences with medication and associated side effects, as well as lifestyle changes made to manage their disease (ie, dietary changes and frequent medical appointments). These discussions often identified a profound impact on physical abilities and life participation. In many instances, participants described the negative impact these symptoms had on their mood and sense of self, with most participants reporting feelings of anxiety. Limitations Participants were primarily non-Hispanic White and English speaking, which may limit generalizability. Conclusions Our results suggest that there are commonalities to the FSGS-MCD patient experience of health-related quality of life that will enable the generation of a disease-specific FSGS-MCD patient-reported outcomes instrument for use in children and adults. The development of this tool is intended to facilitate better care and support clinical research for these individuals., Graphical abstract

Background: Psychiatric disorders (e g , schizophrenia) present cognitive deficits and biases that greatly impact functional outcome Due to the COVID-19 pandemic, traditional in-person assessments and interventions must be adapted for remote delivery, but many clinicians and researchers are rapidly embarking on this path with little guidance We synthesized the literature on remote cognitive assessment in psychiatry to facilitate development of these guidelines Methods: We systematically reviewed the literature via OVID and EBSCO, and searched the grey literature, selecting peer-reviewed research articles reporting on remote cognitive assessment in individuals with mental illness We recorded study parameters, remote measure characteristics, psychometric properties, facilitators, barriers, and future directions Extracted data was synthesized using the logic model methodology Results: Of 25,374 retrieved articles, 32 articles were included Remote measures were available across several cognitive domains (e g , processing speed, attention, verbal/visual/working memory, executive function, social cognition, biases) through various digital platforms Psychometric validation was performed in fewer than half of reviewed articles Facilitators included standardized procedures and automated scoring, while barriers were limited digital literacy, low engagement, and imprecise measure adaptations Conclusions: Our scoping review identified several remote cognitive measures used in psychiatry;however, there is a need for more rigorous validation of these measures The development of open-source alternatives and consideration of potential influential factors, such as sex and gender differences, is encouraged Remote mental health is currently a necessity, yet also a rare opportunity to draw from and contribute to the growing psychiatry digital health literature as well as support more personalized remote interventions Supported By: CIHR Keywords: Neurocognition, Cognitive Bias, Systematic Review, Severe Mental Illness, Remote Assessment

Trace elemental ratios preserved in the calcitic skeleton of bamboo corals have been shown to serve as archives of past ocean conditions. The concentration of dissolved barium (BaSW), a bioactive nutrientlike element, is linked to biogeochemical processes such as the cycling and export of nutrients. Recent work has calibrated bamboo coral Ba/Ca, a new BaSW proxy, using corals spanning the oxygen minimum zone beneath the California Current System. However, it was previously unclear whether Ba/Cacoral records were internally reproducible. Here we investigate the accuracy of using laser ablation inductively coupled plasma mass spectrometry for Ba/Cacoral analyses and test the internal reproducibility of Ba/Ca among replicate radial transects in the calcite of nine bamboo corals collected from the Gulf of Alaska (643–720 m) and the California margin (870–2054 m). Data from replicate Ba/Ca transects were aligned using visible growth bands to account for nonconcentric growth; smoothed data were reproducible within ~4% for eight corals (n = 3 radii/coral). This intracoral reproducibility further validates using bamboo coral Ba/Ca for BaSW reconstructions. Sections of the Ba/Ca records that were potentially influenced by noncarbonate bound Ba phases occurred in regions where elevated Mg/Ca or Pb/Ca and coincided with anomalous regions on photomicrographs. After removing these regions of the records, increased Ba/Cacoral variability was evident in corals between ~800 and 1500 m. These findings support additional proxy validation to understand BaSW variability on interannual timescales, which could lead to new insights into deep sea biogeochemistry over the past several centuries.

Delusions of reference in schizophrenia are thought to result from misattributions of self-relevance to neutral events. Activation of regions within the cortical midline structures (CMS; e.g., medial prefrontal cortex, cingulate cortex, and precuneus) have been previously associated with self-referential processing in schizophrenia patients; however, the specificity of this pattern to individuals with current delusions of reference has yet to be determined. In the present study, we identified functional brain networks that underlie self-referential processing using task-based multivariate functional connectivity. Healthy control subjects (n=15) and schizophrenia patients with (n=14) and without (n=13) current delusions of reference were shown ambiguous statements while undergoing functional magnetic resonance imaging, and evaluated whether these statements were thought to be specifically about them. Our results revealed two functionally distinct CMS networks that differed between patients and controls during self-referential processing: a posterior CMS network, which showed muted deactivity in non-delusional patients; and an anterior CMS network, in which delusional patients demonstrated hyperactivity. Furthermore, activity within the anterior CMS network across the three groups showed a linear pattern of increasing activity associated with greater intensity of delusions of reference, suggesting that hyperactivity in this network may underlie delusions of reference.

This paper argues the need for consideration of both animal welfare and conservation when making management decisions regarding human activities that affect marine mammals. Population level effects may take a long time to be determined, whereas animal welfare metrics can be observed in the short term, enabling problems to be addressed more rapidly. In addition, implementing current legislation in many countries related to the management of impacts on marine mammals requires animal welfare to be taken into account. Such legislation reflects societal values and public concern for individual animals. Two case studies are discussed. These are: management measures related to incidental killing in commercial fisheries, and injury or disturbance from intense sources of underwater noise from seismic surveys. Both of these threats have welfare and conservation implications for marine mammals. An increased focus on welfare would better reflect societal values including requirements under various legal regimes and could also enable more targeted and effective conservation actions.

Rheumatoid arthritis (RA) is a chronic inflammatory condition with variable clinical presentation and disease progression. Importantly, animal models of RA are widely used to examine disease pathophysiology/treatments. Here, we exploited known vendor colony-based differences in endocrine/immune responses to gain insight into inflammatory modulators in arthritis, utilizing the adjuvant-induced arthritis (AA) model. Our previous study found that Sprague-Dawley (SD) rats from Harlan develop more severe AA, have lower corticosteroid binding globulin, and have different patterns of cytokine activation in the hind paw, compared to SD rats from Charles River. Here, we extend these findings, demonstrating that Harlan rats show reduced hypothalamic cytokine responses to AA, compared to Charles River rats, and identify colony-based differences in cytokine profiles in hippocampus and spleen. To go beyond individual measures, probing for networks of variables underlying differential responses, we combined datasets from this and the previous study and performed constrained principal component analysis (CPCA). CPCA revealed that with AA, Charles River rats show activation of chemokine and central cytokine networks, whereas Harlan rats activate peripheral immune/hypothalamic-pituitary-adrenal networks. These data suggest differential underlying disease mechanism(s), highlighting the power of evaluating multiple disease biomarkers, with potential implications for understanding differential disease profiles in individuals with RA.

Background Verbal memory is one of the most affected cognitive domains in patients with schizophrenia and related psychoses. Several studies have found associations between cognitive abilities and white matter fractional anisotropy (FA) in schizophrenia; however, only a few tractography studies have investigated FA relative to verbal memory in patients with a first episode of psychosis (FEP) compared with healthy controls (HC). Although white matter tractography differences have been well established between chronic patients and HC, the direction of findings from FEP studies has been inconsistent. Thus, the present study aims to examine whole-brain white matter differences and its association with verbal memory in individuals with a FEP relative to HC using tractography. Methods Diffusion-weighted images were acquired on a 1.5T scanner for patients (n=65) and controls (n=54) at baseline. The Wechsler Memory Scale was used as a measure of verbal memory. Pre-processing was performed on a subject-by-subject basis using MRtrix. Diffusion tractography was generated using a probabilistic anatomically-constrained tractography algorithm, which constrains the reconstruction to specific biological priors. Furthermore, the spherical-deconvolution informed filtering of tractograms (SIFT) tool will be used to ensure the tractogram is biologically meaningful. This results in subject-specific connectomes defining the mean FA between two regions of interest that were defined using the Desikan- Killiany atlas. A linear model was used to test for main effect of group and main effect of verbal memory on white matter tract FA, covarying for age and sex. For both sets of analyses, results were corrected for multiple comparisons using false discovery rate (FDR). Results A significant main effect of group on whole-brain average FA was observed, with patients displaying lower average FA compared to healthy controls (Patients=0.291, controls=0.300, p Discussion Findings from this study suggest there are some significant differences in whole-brain average FA between individuals experiencing a FEP and healthy controls. However, when analyzing whole-brain tract FA, none of the connections survived corrections for multiple comparisons. These findings might be limited by the scanner resolution included in this study, which may not capture more subtle differences. Nonetheless, these results are consistent with a cross-sectional study comparing healthy individuals to chronic and first-episode patients suggesting that modest differences are present early in the disease and increase as the disease progresses. We suggest that future studies analyze white matter tract using a longitudinal design to identify disease progression.

To characterise children presenting with hot beverage scalds versus scalds caused by starchy water.Retrospective survey of prospectively collected database of all children presenting over a two-year period.There were 138 starch scalds and 262 hot beverage injuries. Children with hot beverage injuries were significantly younger (18.2 months; IQR 14.1, 27.8) than those suffering starch scald injuries (51.4 months; 18.7, 102.3; p0.001). Perineal burns were more common in the starch group than the hot beverage scald group (10.9% vs. 2.4%, p0.001). Chest/breast and abdominal burns were more common in the hot beverage group than the starch group (60.7% vs. 36.9%, p0.001). Children under three years of age in both groups are significantly less likely to receive adequate first aid at the scene (p0.001). There are no differences in the need for skin grafting or scar management when comparing hot beverage scalds and scalds caused by starchy liquids.Scald injuries caused by starchy liquids do not appear to cause a more severe injury than hot beverage scalds. There is a different pattern of injury from starchy liquids in older children. Children under three years old are less likely to receive appropriate first aid at the scene.

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.