Brain structural correlates of irritability: Findings in a large healthy cohort.

Irritability and nonviolent aggression are common behavioral features across the population, yet there is limited neurobiological research into subclinical phenotypes representing the lower edge of a symptom continuum ranging from slight irritability to criminal violence. We studied brain structural correlates of irritability in a large healthy cohort to test the hypothesis of associations with fronto-limbic brain structures implicated in mood regulation. In a large multicenter effort, we recruited 409 mentally healthy adults from the community, who received T1-weighted high-resolution 3 T MRI scans. These structural scans were automatically preprocessed for voxel- and surface-based morphometry measurements with the CAT 12 toolbox implemented in SPM 12. Subclinical aggressive symptoms were assessed using the SCL-90-R aggression/hostility subscale and then correlated with cortical volume (VBM), and cortical thickness and gyrification. VBM analysis showed significant (P < 0.05, FDR-corrected at peak-level) positive correlations of cortical volume with SCL-90-R aggression subscale values in large clusters spanning bilateral anterior cingulate and orbitofrontal cortices and left lingual and postcentral gyri. Surface-based morphometry yielded mostly uncorrected positive correlations with cortical thickness in bilateral precentral gyri and with gyrification in left insula and superior temporal gyrus. Our findings imply an association of subclinical aggressive symptoms with cortical volume in areas important for emotion awareness and regulation, which might also be related to cortical adaptation to mental stress. These results overlap with several findings on impulsive aggression in patients suffering from affective and disruptive behavior disorders. They also suggest a biological symptom continuum manifesting in these brain areas. Hum Brain Mapp 38:6230-6238, 2017. © 2017 Wiley Periodicals, Inc.

Hippocampal Volume as a Putative Marker of Resilience or Compensation to Minor Depressive Symptoms in a Nonclinical Sample.

Case-control studies in major depression have established patterns of regional gray matter loss, including the hippocampus, which might show state-related effects dependent on disease stage. However, there is still limited knowledge on compensation effects that might occur in people resilient to depression showing only subclinical symptoms. We used voxel-based morphometry on a multicenter data set of 409 healthy nonclinical subjects to test the hypothesis that local hippocampal volume would be inversely correlated with subclinical depressive symptoms [Symptom Checklist 90-Revised (SCL-90-R) depression scores]. Our region-of-interest results show a significant (p = 0.042, FWE cluster-level corrected) positive correlation of SCL-90-R scores for depression and a left hippocampus cluster. Additionally, we provide an exploratory finding of gyrification, a surface-based morphometric marker, correlating with a right postcentral gyrus cluster [p = 0.031, family-wise error (FWE) cluster-level corrected]. Our findings provide first preliminary evidence of an inverse relationship for subjects in the absence of clinical depression and might thus point to processes related to compensation. Similar effects have been observed in remission from major depression and thus deserve further study to evaluate hippocampal volume not only as a state-dependent marker of disease but also of resilience.

Effects of a neurodevelopmental genes based polygenic risk score for schizophrenia and single gene variants on brain structure in non-clinical subjects: A preliminary report.

We tested whether a polygenic risk score integrating the effects of genes affecting neurodevelopment is associated to brain structural variation in healthy subjects. We acquired magnetic resonance imaging and genetic data of 167 healthy adults and computed a neurodevelopmental polygenic risk score (nPRS). We correlated the nPRS with local gyrification, cortical thickness and grey matter density and explored effects of single nucleotide polymorphisms included in the score. We did not find significant correlations of this nPRS with either measure. Individuals with the risk allele at rs11139497 show increases in cortical thickness (p < 0.05, FWE corrected) of the left superior temporal gyrus.

Altered gyrification in schizophrenia and its relation to other morphometric markers.

Schizophrenia is modelled as a neurodevelopmental disease with high heritability. However, established markers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies. Gyrification on the other side is assumed to be more specifically determined by genetic and early developmental factors. Here, we compare T1 weighted 3 Tesla MRI scans of 51 schizophrenia patients and 102 healthy controls (matched for age and gender) using a unified processing pipeline with the CAT12 toolbox. Our study provides a direct comparison between 3D gyrification, cortical thickness, and grey matter volume. We demonstrate that significant (p < 0.05, FWE corrected) results only partially overlap between modalities. Gyrification is altered in bilateral insula, temporal pole and left orbitofrontal cortex, while cortical thickness is additionally reduced in the prefrontal cortex, precuneus, and occipital cortex. Grey matter volume (VBM) was reduced in bilateral medial temporal lobes including the amygdala as well as medial and dorsolateral prefrontal cortices and cerebellum. Our results lend further support for altered gyrification as a marker of early neurodevelopmental disturbance in schizophrenia and show its relation to other morphological markers.

Subclinical Agoraphobia Symptoms and Regional Brain Volumes in Non-clinical Subjects: Between Compensation and Resilience?

Background: Symptoms of anxiety are present not only in panic disorder or other anxiety disorders, but are highly prevalent in the general population. Despite increasing biological research on anxiety disorders, there is little research on understanding subclinical or sub-threshold symptoms relating to anxiety in non-clinical community samples, which could give clues to factors relating to resilience or compensatory changes. Aims:This study focused on brain structural correlates of subclinical anxiety/agoraphobia symptoms from a multi-center imaging study. Methods: We obtained high-resolution structural T1 MRI scans of 409 healthy young participants and used the CAT12 toolbox for voxel-based morphometry (VBM) analysis. Subjects provided self-ratings of anxiety using the SCL-90-R, from which we used the phobia subscale, covering anxiety symptoms related to those of panic and agoraphobia spectrum. Results: We found significant (p < 0.05, FDR-corrected) correlations (mostly positive) of cortical volume with symptom severity, including the right lingual gyrus and calcarine sulcus, as well as left calcarine sulcus, superior, middle, and inferior temporal gyri. Uncorrected exploratory analysis also revealed positive correlations with GMV in orbitofrontal cortex, precuneus, and insula. Conclusions: Our findings show brain structural associations of subclinical symptoms of anxiety, which overlap with those seen in panic disorder or agoraphobia. This is consistent with a dimensional model of anxiety, which is reflected not only functionally but also on the structural level.

Associations between urban upbringing and cortical thickness and gyrification.

Urbanicity has been linked to several psychiatric disorders, especially schizophrenia. Recent studies suggest effects of urban upbringing and stress on brain structure and function. Here, we used surface-based and voxel-based morphometry to study the effects of urban upbringing in different environments on variation in brain structure in a non-clinical sample. We recruited 85 young and healthy individuals from the community and recorded urban vs. rural background in their first 15 years of live. All participants underwent T1-weighted 3T MRI, which were then processed via CAT12 toolbox (in SPM12) to analyse cortical volume, thickness and gyrification. These parameters were correlated with an established measure of cumulative childhood and adolescence exposure to urban environments. We found significant (p < 0.05, FWE-corrected) negative correlations of cortical thickness with higher index of urban upbringing in the left dorsolateral prefrontal cortex, bilateral medial prefrontal cortices, as well as temporal cortices including the left superior temporal and left parahippocampal cortex. In contrast, results for volume and gyrification (incl. left posterior cingulate cortex) did not survive correction for multiple comparisons. We show a strong association of early-life urbanicity with cortical thickness in several areas, which are also impaired in schizophrenia patients. Along with other findings, these results converge on the dorsolateral prefrontal cortex as an area mediating this environmental risk.