Sex-Dependent Association of Perigenual Anterior Cingulate Cortex Volume and Migration Background, an Environmental Risk Factor for Schizophrenia

Abstract

Migration status is one of the best-established risk factors for schizophrenia. An increase in risk is observed in both first- and second-generation immigrants, with a varying magnitude depending on the ethnic background of the individuals. The underlying mechanisms for the increased risk are only recently coming into focus. A causal role for social stress has been widely proposed, and recent work indicated altered neural stress processing in the perigenual anterior cingulate cortex (pACC) in migrants. Since previous work shows that social stress may lead to enduring changes in the gray matter volume of vulnerable brain regions, we investigated the impact of migration background on brain structure. We studied healthy young adults (N = 124), native Germans and second-generation migrants, using whole-brain structural magnetic resonance imaging. Groups were matched for a broad range of sociodemographic characteristics including age, gender, urban exposure, and education. We found a significant group by sex interaction effect in pACC gray matter volume, which was reduced in males with migration background only. This mirrors previous findings in urban upbringing, another risk factor for schizophrenia. Our results provide convergent evidence for an impact of environmental risk factors linked to schizophrenia on gray matter volume and extend prior data by highlighting the possibility that the pACC structure may be particularly sensitive to the convergent risk factors linked to schizophrenia.

Keywords: environmental risk; gray matter volume; magnetic resonance imaging; minority status; schizophrenia risk.

Fig. 1.

Migrant status and sex interaction on ACC GM volume. (A) T-map of interaction effects between migrant status and sex on GM volume. A significant interaction effect is seen in the pACC (T = 4.17, P = .004, FWE-corrected within ROI). A significant decrease in pACC GM volume in migrant males compared with females and nonmigrants is observed. (B) Mean GM volumes of the most significant voxel (MNI: x = −6, y = 52, z = 7). Error bars indicate standard error of the mean. Coordinates refer to the MNI standard space. T-maps are displayed at P < .005 uncorrected for presentation purposes. The color bar represents T-values. GM, gray matter; pACC, perigenual anterior cingulate cortex; MNI, Montreal Neurological Institute; FWE, family-wise error correction for multiple comparisons; ROI, region of interest.

Fig. 2.

Early life urbanicity and sex interaction on ACC GM volume. (A) T-map of interaction effects between early-life urbanicity and sex on GM volume. A significant interaction effect is seen in the pACC (T = 3.49, P = .033, FWE-corrected within ROI). (B) Scatterplots of early-life urbanicity and adjusted GM volumes of the most significantly correlated voxel for the interaction effect (MNI: x = −12, y = 40, z = 7) illustrate a negative correlation in males and no correlation in females. The scatter plot is adjusted for demographic covariates. Coordinates refer to the MNI standard space. T-maps are displayed at P < .005 uncorrected for presentation purposes. The color bar represents T-values. GM, gray matter; pACC, perigenual anterior cingulate cortex; MNI, Montreal Neurological Institute; FWE, family-wise error correction for multiple comparisons; ROI, region of interest.