Common and distinct structural features of schizophrenia and bipolar disorder: The European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT) study

INTRODUCTION: Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach. METHODS: The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions. RESULTS: The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients. CONCLUSION: Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus.Funding: PB was partially funded by grants from the Ministry of Health (RF-2011-02352308). Grant support of EM was provided by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602450 (IMAGEMEND Project). Part of the present study was conducted at the Hospital Universitario MarqueÂs de Valdecilla, University of Cantabria (Santander, Spain), under the following grant support: Carlos III Health Institute PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005- Orden sco/3246/2004, SENY Fundacio Research Grant CI 2005-0308007 and FundacioÂn MarqueÂs de Valdecilla API07/011. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement and analysis. Part of the study was conducted at the Ospedale San Raffaele, Milano, supported by the European Union EU-FP7-HEALTH-F2-2008-222963 “MOODINFLAME” and by the Italian Ministry of Health RF-2011-02350980 projects. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Twin MRI studies on genetic and environmental determinants of brain morphology and function in the early lifespan

Neurodevelopment represents a period of increased opportunity and vulnerability, during which a complex confluence of genetic and environmental factors influences brain growth trajectories, cognitive and mental health outcomes. Recently, magnetic resonance imaging (MRI) studies on twins have increased our knowledge of the extent to which genes, the environment and their interactions shape inter-individual brain variability. The present review draws from highly salient MRI studies in young twin samples to provide a robust assessment of the heritability of structural and functional brain changes during development. The available studies suggest that (as with many other traits), global brain morphology and network organization are highly heritable from early childhood to young adulthood. Conversely, genetic correlations among brain regions exhibit heterogeneous trajectories, and this heterogeneity reflects the progressive, experience-related increase in brain network complexity. Studies also support the key role of environment in mediating brain network differentiation via changes of genetic expression and hormonal levels. Thus, rest- and task-related functional brain circuits seem to result from a contextual and dynamic expression of heritability

Disordered cortico-limbic interactions during affective processing in children and adolescents at risk for schizophrenia revealed by fMRI and Dynamic Causal Modeling Archives f General Psychiatry

Disordered functional architecture of brain networks may contribute to the well-documented increased risk for psychiatric disorders in offspring of patients with schizophrenia.To investigate aberrant interactions between regions associated with affective processing in children and adolescent offspring of patients with schizophrenia (HR-SCZ group) and healthy control subjects using dynamic causal modeling of functional magnetic resonance imaging data.Subjects participated in a continuous affective processing task during which positive, negative, and neutral valenced faces were presented. Interactions between regions in the brain's face- and emotion-processing network were modeled using dynamic causal modeling. Multiple competing models were evaluated by a combinatorial approach and distinguished at the second level using Bayesian model selection before parameter inference.Participants were recruited from the community.Twenty-four controls with no family history of psychosis (to the second degree) and 19 children and adolescent offspring of a parent with schizophrenia (age range, 8 to 20 years).Bayesian model selection revealed a winning model, the architecture of which revealed bidirectional frontolimbic connections that were modulated by valence. Analyses of parameter estimates revealed that HR-SCZ group members were characterized by (1) decreased driving inputs to the visual cortex; (2) decreased intrinsic coupling, most robustly between frontolimbic regions; and (3) increased modulatory inhibition by negative valence of frontolimbic connections (all P < .01, Bonferroni corrected).These results are the first demonstration of network analyses techniques for functional magnetic resonance imaging data in children and adolescents at risk for schizophrenia. Dysfunctional interactions within the emotional processing network provide evidence of latent vulnerabilities that may confer risk for disordered adolescent development and eventually the emergence of the manifest disorder

Reduced intra-amygdala activity to positively valenced faces in adolescent schizophrenia offspring

Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the baso-lateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population

Chronological age and its impact on associative learning proficiency and brain structure in middle adulthood

The rate of biological change in middle-adulthood is relatively under-studied. Here, we used behavioral testing in conjunction with structural magnetic resonance imaging to examine the effects of chronological age on associative learning proficiency and on brain regions that previous functional MRI studies have closely related to the domain of associative learning

Using Realistic Virtual Environments in the Study of Spatial Encoding

Computer generated virtual environments have reached a level of sophistication and ease of production that they are readily available for use in the average psychology laboratory. The potential benefits include cue control, incorporation of interactivity and novelty of environments used. The draw-backs include limitations in realism and lack of fidelity. In this chapter we describe our use of virtual environments to study how 3D space is encoded in humans with special emphasis on realism and interactivity. We describe the computational methods used to implement this realism and give examples from studies concerning spatial memory for object form, spatial layout and scene recognition