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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.

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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.

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