Larger grey matter volume of the inferior frontal gyrus (IFG) is among the most replicated biomarkers of genetic risk for bipolar disorders (BD). However, the IFG is a heterogeneous prefrontal region, and volumetric findings can be attributable to changes in cortical thickness (CT), surface area (SA) or gyrification. Here, we investigated the morphometry of IFG in participants at genetic risk for BD.

We quantified the IFG cortical grey matter volume in 29 affected, 32 unaffected relatives of BD probands, and 42 controls. We then examined SA, CT, and cortical folding in subregions of the IFG.

We found volumetric group differences in the right IFG, with the largest volumes in unaffected high-risk and smallest in control participants (F2,192 = 3.07, p = 0.01). The volume alterations were localized to the pars triangularis of the IFG (F2,97 = 4.05, p = 0.02), with no differences in pars opercularis or pars orbitalis. Pars triangularis volume was highly correlated with its SA [Pearson r(101) = 0.88, p < 0.001], which significantly differed between the groups (F2,97 = 4.45, p = 0.01). As with volume, the mean SA of the pars triangularis was greater in unaffected (corrected p = 0.02) and affected relatives (corrected p = 0.05) compared with controls. We did not find group differences in pars triangularis CT or gyrification.

These findings strengthen prior knowledge about the volumetric findings in this region and provide a new insight into the localization and topology of IFG alterations. The unique nature of rIFG morphology in BD, with larger volume and SA early in the course of illness, could have practical implications for detection of participants at risk for BD.

Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD.

A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs.

Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed.

Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.

We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).

The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.

The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.

The risk of developing bipolar disorder (BD) has been linked to structural brain abnormalities. The degree to which genes and environment influence the association of BD with cortical surface area remains to be elucidated. In this twin study, genetic and environmental contributions to the association between liability to develop BD and surface area, thickness and volume of the cortex were examined.

The study cohort included 44 affected monozygotic (nine concordant, 12 discordant) and dizygotic (four concordant, 19 discordant) twin pairs, and seven twins from incomplete discordant monozygotic and dizygotic discordant twin pairs. In addition, 37 monozygotic and 24 dizygotic healthy control twin pairs, and six twins from incomplete monozygotic and dizygotic control pairs were included.

Genetic liability to develop BD was associated with a larger cortical surface in limbic and parietal regions, and a thicker cortex in central and parietal regions. Environmental factors related to BD were associated with larger medial frontal, parietal and limbic, and smaller orbitofrontal surfaces. Furthermore, thinner frontal, limbic and occipital cortex, and larger frontal and parietal, and smaller orbitofrontal volumes were also associated with environmental factors related to BD.

Our results suggest that unique environmental factors play a prominent role in driving the associations between liability to develop BD and cortical measures, particularly those involving cortical thickness. Further evaluation of their influence on the surface and thickness of the cortical mantle is recommended. In addition, cortical volume appeared to be primarily dependent on surface and not thickness.