Reduction of prefrontal thickness in military police officers with post-traumatic stress disorder

Abstract Background Brain-imaging studies in post-traumatic stress disorder (PTSD) have consistently revealed alterations in brain structure and function and this is correlated to symptomatology. However, few studies have investigated the role of biomarkers in PTSD some specific groups, as police officers. Objective To evaluate prefrontal and limbic volumes, and cortical thickness of police officers exposed to trauma during work who developed post-traumatic stress disorder, resilient matched controls (without PTSD), and compared to healthy civilians. Methods Prefrontal and limbic volumes, and cortical thickness of 12 police officers with PTSD, 12 resilient police officers, and 12 healthy civilians who underwent brain MRI were analyzed. Results Differences in limbic structures volume were not significative after Bonferroni correction. A significant reduction in cortical thickness on right rostral cingulate, right and left middle frontal gyrus, left superior frontal, left lingual, calcarine and cuneus were observed in PTSD group in comparison to controls was observed. Discussion Although preliminary, our results suggested not only the association between cortical thickness and PTSD, but also indicated that patients and controls have anatomical differences.

Structural covariance in schizophrenia and first-episode psychosis: An approach based on graph analysis.

Schizophrenia is a neurodevelopmental disorder that produces abnormalities across different brain regions. Measuring structural covariance with MRI is a well-established approach to investigate common changes in distinct systems. We investigated structural covariance in schizophrenia in a large Brazilian sample of individuals with chronic schizophrenia (n = 143), First Episode Psychosis (n = 32), and matched healthy controls (n = 82) using a combination of graph analysis and computational neuroanatomy. Firstly, we proposed the connectivity-closeness and integrity-closeness centrality measures and them compared healthy controls with chronic schizophrenia regarding these metrics. We then conducted a second analysis on the mapped regions comparing the pairwise difference between the three groups. Our results show that compared with controls, both patient groups (in pairwise comparisons) had a reduced integrity-closeness in pars orbitalis and insula, suggesting that the relationship between these areas and other brain regions is increased in schizophrenia. No differences were found between the First Episode Psychosis and Schizophrenia groups. Since in schizophrenia the brain is affected as a whole, this may mirror that these regions may be related to the generalized structural alteration seen in schizophrenia.

PRODH polymorphisms, cortical volumes and thickness in schizophrenia.

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia.

BACKGROUND: Treatment resistance affects up to one third of patients with schizophrenia (SCZ). A better understanding of its biological underlying processes could improve treatment. The aim of this study was to compare cortical thickness between non-resistant SCZ (NR-SCZ), treatment-resistant SCZ (TR-SCZ) patients and healthy controls (HC). METHODOLOGY: Structural MRI scans were obtained from 3 groups of individuals: 61 treatment resistant SCZ individuals, 67 non-resistant SCZ and 80 healthy controls. Images were analyzed using cortical surface modelling (implemented in freesurfer package) to identify group differences in cortical thickness. Statistical significant differences were identified using Monte-Carlo simulation method with a corrected p-cluster<0.01. RESULTS: Patients in the TR-SCZ group showed a widespread reduction in cortical thickness in frontal, parietal, temporal and occipital regions bilaterally. NR-SCZ group had reduced cortex in two regions (left superior frontal cortex and left caudal middle frontal cortex). TR-SCZ group also showed decreased thickness in the left dorsolateral prefrontal cortex (DLPFC) when compared with patients from NR-SCZ group. CONCLUSIONS: The reduction in cortical thickness in DLPFC indicates a more severe form of the disease or a specific finding for this group. Alterations in this region should be explored as a putative marker for treatment resistance. Prospective studies, with individuals being followed from first episode psychosis until refractoriness is diagnosed, are needed to clarify these hypotheses.

ZDHHC8 gene may play a role in cortical volumes of patients with schizophrenia.

ZDHHC8 rs175174 polymorphism is located in 22q11.2 region and its role in brain volume has not been fully addressed. A total of 282 schizophrenia patients and 379 controls were genotyped. A sample of 138 patients underwent brain MRI scan. No association was found between schizophrenia and genotypes. Nevertheless, GG-genotype carriers presented gray matter volume (GMV) reduction in frontal lobe compared to A-allele carriers, and cerebellar hemispheres GMV reductions were found in G-allele carriers compared to AA-genotype. Moreover, A-allele carriers presented posterior brain GMV reductions when compared to GG-genotype. These data suggest that ZDHHC8 may play a role in cortical volumes.