Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry

Abstract

Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent-offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain.

Significance statement: Parents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent-offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit-based female-specific intergenerational transmission patterns in depression.

Keywords: MRI; anxiety disorder; intergenerational imaging.

Figure 1.

GMV associations between parents and offspring. Top, Brain regions showing significantly greater positive correlations in mother–daughter pairs compared with mother–son pairs. Middle, Brain regions showing significantly greater positive correlations in mother–daughter pairs compared with father–daughter pairs. Bottom, Brain regions showing significantly greater positive correlations in mother–daughter pairs compared with father–son pairs. All comparisons showed similar morphometric association patterns. Axial view of Talairach coordinates: z, −27, −22, −17, −12, −7, −2. Sagittal view of Talairach coordinates: x, 29, 13, −3. Lt, Left; Rt, right. For all analyses, the statistical threshold is set at p = 0.05 corrected.

Figure 2.

Brain areas specific to mother–daughter relationships. Brain map representing voxels that overlap between three maps presented in Figure 1 to illustrate a specific positive association in mother–daughter pairs. Red circle represents amygdala. Blue circle represents the gyrus rectus. Green circle represents the OFC. Pink circle represents the ACC. Yellow circle represents the parahippocampus gyrus. Although the extent of brain regions are smaller compared with Figure 1 (because of the conservative nature of conjoint analysis), we still observed significant voxels in the same brain areas. Lt, Left; Rt, right. For all analyses, the statistical threshold is set at p = 0.05 corrected.