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Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing.

ABSTRACT: Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.

SUBMITTER: Opmeer EM

PROVIDER: S-EPMC4014098 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing.

Opmeer Esther M EM Kortekaas Rudie R van Tol Marie-José MJ van der Wee Nic J A NJ Woudstra Saskia S van Buchem Mark A MA Penninx Brenda W J H BW Veltman Dick J DJ Aleman André A

Social cognitive and affective neuroscience 20130311 5

Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional mag ...[more]

PMID: 23482625

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Project description:The gene expressing the FK506 binding protein 51 (FKBP5) is involved in the regulation of glucocorticoid receptor sensitivity. The rs1360780 SNP in this gene (T allele vs C homozygous) has been found to be associated with major depressive disorder (MDD). The aim of our study was to investigate whether this polymorphism might be associated with altered brain structure and function in a cohort of 40 patients with MDD and 43 healthy controls. A functional magnetic resonance imaging (fMRI) emotional attention task was employed. Diffusion tensor imaging (DTI) was also conducted, extracting mean diffusivity (MD) and fractional anisotropy (FA) from brain areas that showed functional differences between patients expressing the two alleles of the rs1360780 SNP. Finally, the effect of the interaction of childhood adversity as measured by the Childhood trauma Questionnaire (CTQ) and rs1360780 allele status was analyzed in relation to DTI measures using a general linear model. All results presented are family-wise error (FWE) corrected. Functional interactions were found between genotype and diagnosis (p<0.01). Patients carrying the high-risk allele, compared with patients not carrying it, showed reduced activity in the rolandic operculum, Heschl gyrus, insula, parahippocampal gyrus, posterior cingulate cortex, inferior frontal gyrus (p<0.05 for all measures); and increased MD and reduced FA measures in many of these regions (p<0.05). An interaction between CTQ scores and allele status was associated with DTI changes in the insula, rolandic operculum, and inferior frontal gyrus. Here, the presence of both the high-risk allele and higher CTQ scores was associated with higher MD and lower FA values (p<0.05). In conclusion, MDD patients expressing the T allele of rs1360780, compared with C homozygous patients, exhibit functional and structural differences in areas involved in emotional perception and inhibition. The interaction between the T allele and childhood maltreatment explained our structural findings in these regions, suggesting that their altered maturation and function might be influenced by early chronic stress in the presence of this genetic trait.

Project description:Accumulating evidence suggests that childhood maltreatment (CM) confers risk for psychopathology later in life by inducing hypervigilance to social threat cues such as fearful faces. However, it remains unclear whether the modulatory impact of CM extents to the olfactory domain of social communication in humans. To address this question, we examined whether CM modulates the neural processing of chemosensory threat signals in sweat and whether CM affects the stress-reducing effects of oxytocin (OXT) in this context. In a randomized, double-blind within-subject functional MRI study design, 58 healthy participants (30 females) received intranasal OXT (40 IU) or placebo (PLC) and completed a forced-choice emotion recognition task with faces of varying emotion intensities (neutral to fearful) while exposed to sweat stimuli and a non-social control odor. Axillary sweat samples were collected from 30 healthy male donors undergoing an acute psychosocial stressor (stress) and ergometer training (sport) as control in a pre-study. CM was assessed by the 25-item Childhood Trauma Questionnaire (CTQ). The final fMRI analysis included 50 healthy participants (26 females). Regression analysis showed a stress-specific association of CTQ scores with amygdala hyperreactivity, hippocampal deactivation, and increased functional connectivity between the amygdala and the hippocampus, medial orbitofrontal cortex, and the anterior cingulate cortex (ACC) under PLC. Furthermore, we observed a positive association of CTQ scores and the dampening effects of OXT on stress-related amygdala responses. Our findings suggest that CM may induce hypervigilance to chemosensory threat cues in a healthy sample due to inefficient frontolimbic inhibition of amygdala activation. Future studies should investigate whether increased recruitment of the intralimbic amygdala-hippocampus complex reflects a compensatory mechanism that prevents the development of psychopathology in those who have experienced CM. Furthermore, the results reveal that the stress-specific effects of OXT in the olfactory domain are more pronounced in participants with increasing levels of CM exposure.

Dataset Information

Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing.

Publications

Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing.

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