Background Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. Methods One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Results Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p <.001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Conclusions Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology.

Objective Alcoholism is associated with gray matter volume deficits in frontal and other brain regions. Whether persistent brain volume deficits in abstinence are predictive of subsequent time to alcohol relapse has not been established. The authors measured gray matter volumes in healthy volunteers and in a sample of treatment-engaged, alcohol-dependent patients after 1 month of abstinence and assessed whether smaller frontal gray matter volume was predictive of subsequent alcohol relapse outcomes. Method Forty-five abstinent alcohol-dependent patients in treatment and 50 healthy comparison subjects were scanned once using high-resolution (T1-weighted) structural MRI, and voxel-based morphometry was used to assess regional brain volume differences between the groups. A prospective study design was used to assess alcohol relapse in the alcohol-dependent group for 90 days after discharge from 6 weeks of inpatient treatment. Results Significantly smaller gray matter volume in alcohol-dependent patients relative to comparison subjects was seen in three regions: the medial frontal cortex, the right lateral prefrontal cortex, and a posterior region surrounding the parietal-occipital sulcus. Smaller medial frontal and parietal-occipital gray matter volumes were each predictive of shorter time to any alcohol use and to heavy drinking relapse. Conclusions These findings are the first to demonstrate that gray matter volume deficits in specific medial frontal and posterior parietal-occipital brain regions are predictive of an earlier return to alcohol use and relapse risk, suggesting a significant role for gray matter atrophy in poor clinical outcomes in alcoholism. Extent of gray matter volume deficits in these regions could serve as useful neural markers of relapse risk and alcoholism treatment outcome.

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Structural neuroimaging studies have provided evidence of differences in local brain volume between cocaine-dependent and healthy control individuals. While sex differences in aetiology, course and brain dysfunction associated with chronic cocaine abuse have been previously documented, evidence of sex-specific differences in brain volume has not been examined thus far. This study examined sex-related differences in grey matter volume between cocaine-dependent and healthy control subjects using voxel-based morphometry. High-resolution T1 structural scans were obtained from 36 inpatient, treatment-engaged 3-week abstinent cocaine-dependent (CD) individuals. Fifty healthy control subjects were also scanned. Segmentation and registration were performed in SPM8, using New Segment and DARTEL, respectively. The whole-brain statistical analysis was conducted in SPM8 using random field-based cluster-size testing and family-wise error rate correction for multiple comparisons. CD patients were found to have less grey matter volume in anterior prefrontal cortex, including frontopolar and orbitofrontal cortices, and a posterior region surrounding the parietal-occipital sulcus. Female CD patients had less grey matter volume than female controls in left inferior frontal gyrus, insula, superior temporal gyrus and hippocampus. Male CD patients had less grey matter in a superior cortical region that included the precentral gyrus and the mid-cingulate. These sex differences in lower grey matter volume add to the evidence from functional neuroimaging for sex-specific differences in the neurophysiological changes associated with chronic cocaine use.

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