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Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Background A domain of cognition that has been found to be impaired in bipolar disorder across mood states is working memory. Working memory can be separated into two components, maintenance and manipulation. Bipolar patients also demonstrate structural brain abnormalities in prefrontal and parietal regions, which are regions associated with working memory processes. Despite the understanding that working memory consists of multiple separable cognitive processes, no study to date has differentiated maintenance and manipulation, and associated them with underlying structural brain regions in bipolar disorder. Methods Twenty-six bipolar patients and 24 controls completed a visuospatial working memory task and structural neuroimaging. Prefrontal and parietal gray matter volume, surface area, and cortical thickness were obtained using FreeSurfer. The relationship between working memory performance, structural integrity, symptoms, and functioning were investigated. Results Bipolar patients were less accurate on the working memory task compared to controls, without a greater deficit in the manipulation condition. Controls had thicker prefrontal and parietal cortices than bipolar patients. In bipolar patients, thicker prefrontal cortices had a small association with greater accuracy on the maintenance condition, as well as greater depression. Limitations This study could have benefitted from a larger sample size. Conclusions Bipolar patients demonstrated both poorer accuracy on the visuospatial working memory task compared to controls and thinner cortices in areas associated with working memory, namely the prefrontal and parietal cortices. This demonstrates an underlying relationship between brain and behavior in bipolar disorder.

Background Schizophrenia is associated with poor cognitive function and elevated cardiometabolic disease risk. These health concerns may exacerbate neurocognitive dysfunction associated with hippocampal abnormalities, particularly hippocampal volume reductions. Regular exercise is thought to improve symptom severity, reduce depression, and improve cognition in schizophrenia, and may trigger exercise-mediated hippocampal growth. The potential for the benefits of exercise for treatment-resistant schizophrenia patients has not been clearly assessed. This study aims to assess the effect of exercise on hippocampal plasticity and clinical outcomes in chronic schizophrenia. Methods Seventeen DSM-IV criteria schizophrenia or schizoaffective disorder patients completed a customized moderate intensity 12-week aerobic or weight-bearing exercise program. Adherence rates were 83% ± 9.4%) with 70% of participants completing the entire exercise program. Concomitant neuroimaging, clinical and cognitive assessments were obtained at baseline and 12-weeks. Results At follow-up, symptom severity scores (t(16) = −16.8, p. ≤ 0.0001) and social functioning (t(16) = 4.4, p. = 0.0004) improved. A trend for improved depression scores (t(16) = −2.0, p. = 0.06) with no change in anxiety, or extrapyramidal symptoms were seen. Hippocampal volume increased (t(16) = −2.54, p. = 0.02), specifically in the left CA-1 field (F(16) = −2.33, p. = 0.03). Hippocampal vascular volume was unchanged. Change in hippocampal volume and vascular volume was not significantly correlated with change in symptom severity or affect scores. Conclusions Adjunct exercise may accelerate symptom improvement in treatment-resistant psychosis patients. While the underlying mechanism remains unclear, these results indicate that chronic schizophrenia patients experience hippocampal plasticity in response to exercise. Study registration Clinical Trials.gov NCT01392885 .

The health sciences have a public calling to provide socially responsive health care for all of society, particularly those most in need. This call is reverberating in universities and has particular relevance for health science professions. Despite universities' public mission, admissions practices in the health sciences exhibit a fundamental tension between excellence and access, with excellence defined by rankings and research productivity, and access defined by broader public access both to universities themselves and to the knowledge created there. Health science programs' popularity among students intensifies the exclusivity of admissions processes, at the expense of access. This paper presents both a psychometric and social justice critique of existing admissions criteria and processes. A psychometric perspective demonstrates that admissions processes have inherent bias and fairness issues not limited to reliance on standardized test scores, but extending to measures such as interviews, grade point averages, personal statements, recommendation letters, and CVs. Evaluating admissions criteria using a social justice lens focuses attention on procedural, background, and stake fairness, as well as practices that tend to exclude underrepresented groups. Potential improvements to admissions include applying promising practices from holistic approaches, reducing applicants' financial burden, instituting admissions criteria that more broadly represent all groups, involving underrepresented groups in adjudicating candidate applications, implementing equitable educational strategies, and evaluating the degree to which programs' climate and theoretical underpinnings are conducive to recruiting from underrepresented groups. Finally, to fulfill our public call for social responsiveness, it is essential to frame admissions to health science programs in terms of serving the public good by training candidates from underrepresented groups and by positioning excellence as access.

Research indicates that people with schizophrenia often achieve similar levels of subjective well-being (SWB) compared to healthy controls despite prominent symptomatology and significant functional difficulties. Furthermore, compared to healthy controls, young-adult people with schizophrenia differ in the relative importance they place on values, or guiding life principles, associated with educational and occupational success (openness to change), suggesting that changing motivations may contribute to SWB and the apparent motivational deficits commonly reported in this population. The current study sought to better understand these relationships in middle-aged people with schizophrenia or schizoaffective disorder (n=29) versus a relatively healthy group of community controls (n=23). Participants completed measures of SWB and values. They also completed a cognitive battery and interviews concerned with mental and physical health. Patients reported similar levels of SWB compared to controls in the context of significant cognitive, social and vocational difficulties. Moreover, living consistently with values (valued living) predicted SWB in both groups. Lastly, internalized mental illness stigma was negatively associated with openness to change in the patient group. While encouraging from an emotional resiliency perspective, SWB and valued living in people with schizophrenia may hinder motivation towards treatment goals that could otherwise improve functional outcomes in this population., Highlights • Patients with schizophrenia reported similar levels of SWB compared to community controls. • Living consistently with values (i.e., valued living) predicted SWB in both groups. • Internalized mental illness stigma was negatively associated with openness to change values in the patient group. • Changing motivations may contribute to the apparent motivational deficits commonly reported in people with schizophrenia.

While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results.

Working memory (WM) and fluid intelligence ( Gf ) are thought to be highly related, though psychometrically distinct cognitive constructs. Both are important in a wide range of cognitively demanding tasks, and predictive of success in educational, occupational, and social domains. From a cognitive perspective, WM and Gf may share a capacity constraint due to the shared demand for attentional resources. Neuroimaging investigations of these two cognitive constructs have suggested similar shared frontal and parietal areas of neural activation as well, though to our knowledge the two have not been investigated in the same population. Here, we examine group level functional activations for tasks of WM (dual n-back), Gf (Raven's Standard Progressive Matrices; RSPM), as well as a theoretically unrelated comparison task of visual word/pseudoword decoding (lexical decision task) in a large sample of healthy young adults (N = 63) aged 18–40. Consistent with previous research, results indicate large areas of fronto-parietal activation in response to increasing task demands for the n-back task (dorsolateral, ventrolateral, and rostral prefrontal cortex, premotor cortex, and posterior parietal cortex), which largely subsume similar but more circumscribed regions of activation for the RSPM and lexical decision tasks. These results are discussed in terms of a task-general central network which may underlie performance of WM, Gf , and word decoding tasks alike, and perhaps even goal-directed behaviour more generally.

Studies have demonstrated that personality traits differ in schizophrenia patients and family members compared to controls, suggesting familial risk. This study evaluated personality traits in a family study of schizophrenia, as well as the relationship between personality traits and symptoms and social functioning in schizophrenia patients. Thirty-two schizophrenia patients, 28 adult non-psychotic relatives, and 27 community controls completed the Dimensional Assessment of Personality Pathology–Basic Questionnaire (DAPP-BQ). Schizophrenia patients differed on many dimensions of the DAPP-BQ compared to controls and/or relatives: affective lability, anxiousness, callousness, conduct problems, cognitive dysregulation, identity problem, intimacy, insecure attachment, low affiliation, narcissism, oppositionality, restricted expression, self-harm, submissiveness, and suspiciousness. No differences were found between relatives and controls. Furthermore, in schizophrenia patients, associations were found between personality and particularly general symptoms, as well as social functioning. Personality traits can be conceptualized as an extended phenotype in schizophrenia patients.

Numerous studies demonstrate that working memory training benefits cognitive performance; however, such findings are controversial and the field is polarized. Despite a multitude of behavioural studies, investigation into the neurobiological mechanisms underlying working memory training remains limited. Diffusion tensor imaging (DTI) allows for the visualization of white matter structure and is a promising approach to identify neurobiological change associated with working memory training. In this study, 25 healthy community dwelling adults (age 18–40 years) underwent neuroimaging before and after completing a 6-week home- and web-based complex working memory training program. An active control group (n = 24) completed 6-weeks of processing speed training using the same computerized platform and imaging protocol. Voxel-wise statistical analysis of the DTI data was conducted with FSL's Tract-Based Spatial Statistics (TBSS) to assess change in several metrics over the course of the intervention. Additionally, averaged whole-brain values (i.e., throughout all cerebral white matter) for each DTI metric were examined via one-way analysis of covariance (ANCOVA). The participants' scores on the training tasks significantly improved post-training. The training was not associated with improved scores on non-trained cognitive measures. The working memory training also did not alter regional or global white matter microstructure, as measured by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Consistent with our previous published findings on brain activity and grey matter structure in the same study sample, the present study does not suggest that home- and web-based complex working memory training alters white matter microstructure.

Little research has examined the association between disordered gambling and psychosis. In addition, clinicians treating schizophrenia or schizoaffective disorders rarely screen for or treat comorbid gambling problems due to diagnostic overshadowing. Thus, the effects of disordered gambling on symptoms of schizophrenia and vice versa remain largely unexplored and unidentified in research and clinical practice. The goal of the present study was to explore qualitatively the reciprocal associations between schizophrenia/schizoaffective disorder and disordered gambling through content and functional analyses from the perspective of the affected individual. Eight participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder and disordered gambling participated in a qualitative interview examining key antecedents associated with their gambling, as well as perceived functional consequences of gambling. Content analysis revealed unique patterns of responses specific to individuals with schizophrenia or schizoaffective disorder that are not typically observed in individuals with disordered gambling alone. Specifically, gambling as filling a need for activity, and gambling as a means of connecting with society/world were the notable reasons for engaging in problematic gambling. Furthermore, some, but not all participants described a direct exacerbation of their psychosis by gambling and a greater involvement in gambling due to their symptoms of schizophrenia.

Schizophrenia is associated with deficits in face perception and emotion recognition. Despite consistent behavioural results, the neural mechanisms underlying these cognitive abilities have been difficult to isolate, in part due to differences in neuroimaging methods used between studies for identifying regions in the face processing system. Given this problem, we aimed to validate a recently developed fMRI-based dynamic functional localizer task for use in studies of psychiatric populations and specifically schizophrenia. Previously, this functional localizer successfully identified each of the core face processing regions (i.e. fusiform face area, occipital face area, superior temporal sulcus), and regions within an extended system (e.g. amygdala) in healthy individuals. In this study, we tested the functional localizer success rate in 27 schizophrenia patients and in 24 community controls. Overall, the core face processing regions were localized equally between both the schizophrenia and control group. Additionally, the amygdala, a candidate brain region from the extended system, was identified in nearly half the participants from both groups. These results indicate the effectiveness of a dynamic functional localizer at identifying regions of interest associated with face perception and emotion recognition in schizophrenia. The use of dynamic functional localizers may help standardize the investigation of the facial and emotion processing system in this and other clinical populations.

Diffusion tensor imaging (DTI) studies suggest abnormalities in the white matter microstructure of the fornix in schizophrenia patients. Research evaluating schizophrenia patient and relatives also suggests that the white matter microstructure of the fornix is heritable. However, previous studies have been hindered by limited DTI methodology. Therefore, the goal of this study was to assess whether fornix abnormalities were related to the genetic liability for schizophrenia using the novel methodological approach of assessing multiple metrics of along-tract measurements, in addition to whole-tract means. Twenty-five schizophrenia patients, 24 adult non-psychotic first-degree biological relatives, and 27 community controls underwent neuroimaging. No group differences were found for any of the DTI metrics using the classical whole-tract measures of the fornix. Along-tract analysis detected local increases in fractional anisotropy (FA) in the right fimbria of the fornix for relatives compared to patients and controls corrected for false discovery rate. No significant associations were found between symptoms, global functioning, or IQ and whole-tract FA means in schizophrenia patients or relatives. Increased FA in non-psychotic relatives could represent a compensatory mechanism to guard against psychosis or an abnormality associated with the genetic liability for the disorder. These findings underscore the importance of obtaining along-tract measurements, in addition to whole-tract measurements to fully understand white matter abnormalities in schizophrenia.

Background Previous literature has indicated abnormalities in facial emotion recognition abilities, as well as deficits in basic visual processes in major depression. However, the literature is unclear on a number of important factors including whether or not these abnormalities represent deficient or enhanced emotion recognition abilities compared to control populations, and the degree to which basic visual deficits might impact this process. Methods The present study investigated emotion recognition abilities for angry versus neutral facial expressions in a sample of undergraduate students with Beck Depression Inventory-II (BDI-II) scores indicative of moderate depression (i.e. ≥20), compared to matched low-BDI-II score (i.e. ≤2) controls via the Bubbles Facial Emotion Perception Task. Results Results indicated unimpaired behavioural performance in discriminating angry from neutral expressions in the high depressive symptoms group relative to the minimal depressive symptoms group, despite evidence of an abnormal pattern of visual facial information usage. Limitations The generalizability of the current findings is limited by the highly structured nature of the facial emotion recognition task used, as well as the use of an analog sample undergraduates scoring high in self-rated symptoms of depression rather than a clinical sample. Conclusions Our findings suggest that basic visual processes are involved in emotion recognition abnormalities in depression, demonstrating consistency with the emotion recognition literature in other psychopathologies (e.g. schizophrenia, autism, social anxiety). Future research should seek to replicate these findings in clinical populations with major depression, and assess the association between aberrant face gaze behaviours and symptom severity and social functioning.

Diffuse structural abnormalities in the prefrontal cortex have been reported in both schizophrenia patients and their nonpsychotic biological relatives. Additionally, working memory difficulties have long been documented in schizophrenia patients and have been associated with the genetic liability for the disorder. The present analysis investigated the relationship between prefrontal regional grey matter volumes and two facets of working memory in schizophrenia using a family study. Structural neuroimaging scans provided measurements of rostral middle, superior, and inferior prefrontal cortical grey matter volumes. Participants also completed a spatial working memory task that measured both short-term maintenance and manipulation of material in memory. Both schizophrenia patients and relatives had reduced superior and inferior frontal grey matter volumes. Schizophrenia patients demonstrated a spatial working memory deficit compared to both controls and relatives, with no greater impairment when required to manipulate material. Smaller prefrontal volumes in schizophrenia patients were associated with worse working memory performance. These relationships were absent in the nonpsychotic relatives and controls. Despite normative behavioural performance, nonpsychotic relatives demonstrated abnormalities in brain structure similar to those found in schizophrenia patients. Manipulation abilities were not more impaired than maintenance in schizophrenia patients. Consistent with other neuroimaging research, our results suggest that direct measures of the underlying biology may be more sensitive to the effects of the genetic liability for schizophrenia than behavioural measures.

article i nfo Atypical antipsychotic medications generally maintain or increase gray matter amount and functioning. First- episode psychosis patients have lower gray matter volume in the middle frontal gyrus, as well as worse performance on spatial working memory tasks compared to controls. This study investigated the effects of short-term four- and eight-week atypical treatment on middle frontal thickness and spatial working memory in first-episode psychosis patients. Nineteen drug-naive first-episode psychosis patients treated with risperidone or quetiapine and 26 controls completed structural magnetic resonance imaging, a spatial working memory task, and clinical assessment at three intervals (baseline, four weeks, and eight weeks; all patients and 23 controls completed all three assessments). Caudal and rostral middle frontal thicknesses were measured using the automated program Freesurfer. Positive, negative, and general symptoms of the Positive and Negative Syndrome Scale (PANSS) decreased significantly in patients, with most of the change occurring in the first four weeks of treatment. Patients demonstrated an increase in rostral middle frontal thickness over eight weeks of treatment compared to controls. There was a medium effect size relationship between reduction in negative symptoms at four and eight weeks, and a change in rostral middle frontal thickness over eight weeks. No changes were found in spatial working memory ability. Short-term atypical treatment with risperidone or quetiapine can increase prefrontal cortical thickness in psychosis. These find- ings are notable given the role of the rostral middle frontal region in cognition and the relationship between better cognitive functioning and better functional outcome in psychosis.

Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether the COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COMT genotype for lifetime symptomatology. The COMT Val allele was associated with greater positive symptomatology in schizophrenia, whereas Met homozygosity was associated with greater positive symptomatology in bipolar disorder. Findings support the COMT Val158Met polymorphism conferring vulnerability for different clinical phenotypes in schizophrenia and bipolar disorder. Lifetime symptomatology may be particularly useful in determining the relationship between genes and clinical phenotypes across mental disorders.

Neuropsychological and neurophysiological studies provide evidence for abnormal interhemispheric communication in schizophrenia. These abnormalities may have a substrate in structural irregularities of the corpus callosum. This study investigated schizophrenia patients (n=27) and healthy comparison subjects (n=31). Global and regional measurements of the corpus callosum were acquired from one midsagittal SPGR slice. Eight subregions were approximately matched to fiber pathways from cortical regions. Overall effects of diagnosis [Wilks' Lambda F(8,46)=2.45, p=0.03] and diagnosis by age interaction [Wilks' Lambda F(8,46)=2.58, p=0.02] were found in a MANCOVA of the eight functionally specific subregions. Specifically, chronic schizophrenia was associated with a smaller rostral body [lower by 6.9%, F(1,53)=9.70, p=0.003] and anterior midbody [lower by 9.7%, F(1,53)=4.89, p=0.03] subregions. The rostral body and anterior midbody subregions of the corpus callosum primarily have premotor, supplementary motor, and motor cortical fibers transversing through them. Functional abnormalities of the associated cortical regions are reported in schizophrenia. These novel findings suggest that structural abnormalities of the corpus callosum exist in schizophrenia, with perhaps the motor-specific subregions affected more than others. Structural differences in the corpus callosum may be a substrate for interhemispheric functional dysconnectivity in schizophrenia.