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Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

ABSTRACT: Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, known as imaging gene x environment interaction (iGxE), is beginning to contribute to our understanding of the neural mechanisms through which genetic variation and stress increase psychopathology risk. Although awaiting replication, evidence suggests that genetic variation within the canonical neuroendocrine stress hormone system, the hypothalamic-pituitary-adrenal axis, contributes to variability in stress-related corticolimbic structure and function, which, in turn, confers risk for psychopathology. For iGxE research to reach its full potential it will have to address many challenges, of which we discuss: (i) small effects, (ii) measuring the environment and neural phenotypes, (iii) the absence of detailed mechanisms, and (iv) incorporating development. By actively addressing these challenges, iGxE research is poised to help identify the neural mechanisms underlying genetic and environmental associations with psychopathology.

SUBMITTER: Bogdan R

PROVIDER: S-EPMC4677127 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

Bogdan Ryan R Pagliaccio David D Baranger David Aa DA Hariri Ahmad R AR

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150720 1

Stress exposure is associated with individual differences in corticolimbic structure and function that often mirror patterns observed in psychopathology. Gene x environment interaction research suggests that genetic variation moderates the impact of stress on risk for psychopathology. On the basis of these findings, imaging genetics, which attempts to link variability in DNA sequence and structure to neural phenotypes, has begun to incorporate measures of the environment. This research paradigm, ...[more]

PMID: 26189450

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Project description:Introduction:Adequate sleep is essential for cognitive and emotion-related functioning, and 9 to 12 hr of sleep is recommended for children ages 6 to 12 years and 8 to 10 hr for children ages 13 to 18 years. However, national survey data indicate that older youth sleep for fewer hours and fall asleep later than younger youth. This shift in sleep duration and timing corresponds with a sharp increase in onset of emotion-related problems (e.g., anxiety, depression) during adolescence. Given that both sleep duration and timing have been linked to emotion-related outcomes, the present study tests the effects of sleep duration and timing, and their interaction, on resting-state functional connectivity (RS-FC) of corticolimbic emotion-related neural circuitry in children and adolescents. Methods:A total of 63 children and adolescents (6-17 years, 34 females) completed a weekend overnight sleep journal and a 10-min resting-state functional magnetic resonance imaging scan the next day (Sunday). Whole-brain RS-FC of the amygdala was computed, and the effects of sleep duration, timing (i.e., midpoint of sleep), and their interaction were explored using regression analyses. Results:Overall, we found that older youth tended to sleep later and for fewer hours than younger youth. Controlling for age, shorter sleep duration was associated with lower RS-FC between the amygdala and regions implicated in emotion regulation, including ventral anterior cingulate cortex, precentral gyrus, and superior temporal gyrus. Interestingly, midpoint of sleep was associated with altered connectivity in a distinct set of brain regions involved in interoception and sensory processing, including insula, supramarginal gyrus, and postcentral gyrus. Our data also indicate widespread interactive effects of sleep duration and midpoint on brain regions implicated in emotion regulation, sensory processing, and motor control. Conclusion:These results suggest that both sleep duration and midpoint of sleep are associated with next-day RS-FC within corticolimbic emotion-related neural circuitry in children and adolescents. The observed interactive effects of sleep duration and timing on RS-FC may reflect how homeostatic and circadian process interact in the brain and explain the complex patterns observed with respect to emotional health when considering sleep duration and timing. Sleep-related changes in corticolimbic circuitry may contribute to the onset of emotion-related problems during adolescence.

Project description: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.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.

Dataset Information

Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

Publications

Genetic Moderation of Stress Effects on Corticolimbic Circuitry.

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