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Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias.

ABSTRACT: BACKGROUND:Cortisol has potent effects on learning and neuroplasticity, but little is known about its effects on negative memory biases in depression. Animal models show that aversive caregiving alters effects of glucocorticoids (primarily corticosterone in rodents and cortisol in primates) on learning and neuroplasticity into adulthood. METHODS:We investigated whether history of childhood emotional abuse (EA) moderated effects of cortisol administration (CORT) versus placebo on emotional memory formation in depression. Participants included 75 unmedicated women with varying levels of depression severity and/or EA history. In a double-blind crossover investigation, we used functional magnetic resonance imaging to measure effects of CORT (vs. placebo) on neural function during emotional memory formation. RESULTS:CORT eliminated the well-known relationship between depression severity and negative memory bias, a finding explained by EA severity. For women with a history of severe EA, CORT reduced depression-related negative memory bias and normalized recall for pleasant stimuli. EA severity also moderated CORT effects on neural function: in women with history of severe EA, CORT increased activation in the supplementary motor area during viewing of unpleasant relative to pleasant pictures. Additionally, supplementary motor area activation predicted reduced negative bias for pictures encoded during CORT. CONCLUSIONS:These results suggest that increasing cortisol signaling may be neurocognitively beneficial in depressed women with a history of maltreatment. The findings corroborate prior research suggesting that presence or absence of adverse caregiving is etiologically important in depression. These findings suggest potential neurocognitive mechanisms of therapeutics targeting cortisol signaling, which show promise in treating affective disorders.

SUBMITTER: Abercrombie HC

PROVIDER: S-EPMC5833310 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias.

Abercrombie Heather C HC Frost Carlton P CP Walsh Erin C EC Hoks Roxanne M RM Cornejo M Daniela MD Sampe Maggie C MC Gaffey Allison E AE Plante David T DT Ladd Charlotte O CO Birn Rasmus M RM

Biological psychiatry. Cognitive neuroscience and neuroimaging 20171122 3

<h4>Background</h4>Cortisol has potent effects on learning and neuroplasticity, but little is known about its effects on negative memory biases in depression. Animal models show that aversive caregiving alters effects of glucocorticoids (primarily corticosterone in rodents and cortisol in primates) on learning and neuroplasticity into adulthood.<h4>Methods</h4>We investigated whether history of childhood emotional abuse (EA) moderated effects of cortisol administration (CORT) versus placebo on e ...[more]

PMID: 29486869

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Project description:Adverse caregiving during development can produce long-lasting changes to neural, endocrine, and behavioral responses to stress, and is strongly related to elevated risk of adult psychopathology. While prior experience of adversity is associated with altered sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis activity, the underlying neural pathways are not completely understood. In a double-blind crossover study, we used diffusion tensor imaging (DTI) to examine whether variation in white matter structure predicts differences in HPA-SNS interactions as a function of early adversity. Participants included 74 women who exhibited a wide range of depression severity and/or childhood emotional abuse (EA). Participants attended two experimental sessions during which they were administered 20 mg cortisol (CORT) or placebo and after 90 min, viewed emotionally laden pictures while undergoing MRI scanning. Immediately after emotional picture-viewing, we collected salivary alpha-amylase (sAA) to index SNS activation. We tested whether EA moderated the relation between fractional anisotropy (FA), a measure of white matter fiber structure, and sAA. In the placebo condition, for participants with minimal history of EA, higher FA in corticomotor projections was negatively correlated with sAA, whereas in participants with severe EA, the correlation was trending in the opposite direction. Following CORT administration, FA and sAA were not related, suggesting that SNS tone during acute cortisol elevation may depend on neural pathways other than corticomotor projections. The results suggest that at baseline-though not during cortisol elevation-increased FA in these tracts is associated with lower levels of SNS activity in women with minimal EA, but not in women with severe EA. These findings provide evidence that corticomotor projections may be a key component of altered neural circuitry in adults with history of maltreatment, and may be related to alterations in stress neuromodulators in psychopathology.

Project description:BackgroundCognitive disturbances in depression are pernicious and so contribute strongly to the burden of the disorder. Cognitive function has been traditionally studied by challenging subjects with modality-specific psychometric tasks and analysing performance using standard analysis of variance. Whilst informative, such an approach may miss deeper perceptual and inferential mechanisms that potentially unify apparently divergent emotional and cognitive deficits. Here, we sought to elucidate basic psychophysical processes underlying the detection of emotionally salient signals across individuals with melancholic and non-melancholic depression.MethodsSixty participants completed an Affective Go/No-Go (AGN) task across negative, positive and neutral target stimuli blocks. We employed hierarchical Bayesian signal detection theory (SDT) to model psychometric performance across three equal groups of those with melancholic depression, those with a non-melancholic depression and healthy controls. This approach estimated likely response profiles (bias) and perceptual sensitivity (discriminability). Differences in the means of these measures speak to differences in the emotional signal detection between individuals across the groups, while differences in the variance reflect the heterogeneity of the groups themselves.ResultsMelancholic participants showed significantly decreased sensitivity to positive emotional stimuli compared to those in the non-melancholic group, and also had a significantly lower discriminability than healthy controls during the detection of neutral signals. The melancholic group also showed significantly higher variability in bias to both positive and negative emotionally salient material.ConclusionsDisturbances of emotional signal detection in melancholic depression appear dependent on emotional context, being biased during the detection of positive stimuli, consistent with a noisier representation of neutral stimuli. The greater heterogeneity of the bias across the melancholic group is consistent with a more labile disorder (i.e. variable across the day). Future work will aim to understand how these findings reflect specific individual differences (e.g. prior cognitive biases) and clarify whether such biases change dynamically during cognitive tasks as internal models of the sensorium are refined and updated in response to experience.

Project description:BackgroundThe adverse childhood experience (ACE) study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age.Methods560 (223M/337F) young adults (18-25?years) were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0-4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depressive disorder (MDD) and current symptoms were evaluated by SCID, interview, and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity, or duration of maltreatment across childhood.ResultsThe most important predictors of lifetime history of MDD were non-verbal emotional abuse in males and peer emotional abuse (EA) in females at 14?years of age, and these were more important predictors across models than number of types of maltreatment (males: t 9?=?16.39, p?<?10(-7); females t 9?=?5.78, p?<?10(-4)). Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females.ConclusionThis study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption, and treatment of MDD.

Dataset Information

Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias.

Publications

Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias.

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