AN INVESTIGATION OF GLOBAL NETWORK STRUCTURE IN BIPOLAR DISORDER

Introduction: Network analysis is a novel technique used to identify brain connectivity patterns. Metrics of integration and segregation allow for brain networks to be quantified into neurobiologically meaningful measures. Aim: This study utilises graph theory metrics to investigate properties of brain communication, as well as permutation testing to determine cluster based effects between groups. This analysis aims to elucidate disrupted anatomical wiring as an attribute of psychiatric illness. Methods: Participants were recruited as part of the Galway Bipolar Study (43 Healthy Controls & 42 subjects with Euthymic Bipolar Disorder). Diffusion MRI data was acquired on a 1.5 Tesla Scanner. Connectivity matrices were produced using ExploreDTI. Network metrics were generated using the Brain Connectivity Toolbox in MATLAB. The Network Based Statistic toolbox is a method to identify an experimental effect at the cluster level. FWER corrected p-values are calculated for each component using permutation testing. Results: Properties of integration and segregation revealed between group differences in metrics of Characteristic Path Length [p=0.017], Global Efficiency [p=0.015] and Clustering Coefficient [p=0.047]; with greater brain network disorganization in patients relative to controls. Network analysis was carried out through the NBS with M= 5000 permutations at p< 0.05, revealing a contrast in patients relative to controls across varying (t-statistic) thresholds[(t=2, p=0.015); (t=2.5, p=0.017); (t=3, p=0.020)], in which a single disconnected sub-network comprising multiple dysconnections was identified for each threshold. Conclusion: Metrics that characterize brain communication revealed greater disorganization in patients relative to controls. The NBS findings demonstrated consistency across t-statistic thresholds among occipital and default mode network regions. This study, applying novel network based statistics to MRI and DTI data, indicates that disrupted neuranatomical connectivity is a trait based feature of bipolar disorder.status: publishe

Recent advances in psychoneuroimmunology: inflammation in psychiatric disorders

Psychiatric disorders are common and complex and their precise biological underpinnings remain elusive. Multiple epidemiological, molecular, genetic and gene expression studies suggest that immune system dysfunction may contribute to the risk for developing psychiatric disorders including schizophrenia, bipolar disorder, and major depressive disorder. However, the precise mechanisms by which inflammation-related events confer such risk are unclear. In this review, we examine the peripheral and central evidence for inflammation in psychiatric disorders and the potential molecular mechanisms implicated including inhibition of neurogenesis, apoptosis, the HPA-axis, the role of brain-derived neurotrophic factor and the interplay between the glutamatergic, dopaminergic and serotonergic neurotransmitter systems

Progressive brain atrophy and cortical thinning in schizophrenia after commencing clozapine treatment

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity

Anatomical integration and rich-club connectivity in euthymic bipolar disorder

Background. Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses. Method. We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks. Results. Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus. Conclusions. This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.status: publishe

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity