Dataset Information

Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress.

ABSTRACT: Hippocampal volume has been found to be smaller in individuals with stress-related disorders, but it remains unclear whether smaller volume is a consequence of stress or rather a vulnerability factor. Here, we examined this issue by relating stress levels to hippocampal volumes in healthy participants examined every 5 years in a longitudinal population-based study. Based on scores of 25- to 60-year-old participants on the perceived stress questionnaire, we defined moderately to high (n = 35) and low (n = 76) stress groups. The groups were re-examined after 5 years (at the 6th study wave). Historical data on subjective stress were available up to 10 years prior to Wave 5. At the first MRI session, the moderately to high stress group had a significantly smaller hippocampal volume, as measured by FreeSurfer (version 5.3), compared with the low-stress group. At follow-up, group differences in stress levels and hippocampal volume remained unchanged. In retrospective analyses of subjective stress, the observed group difference in stress was found to be stable. The long-term stability of group differences in perceived stress and hippocampal volume suggests that a small hippocampal volume may be a vulnerability factor for stress-related disorders.

SUBMITTER: Lindgren L

PROVIDER: S-EPMC4961026 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress.

Lindgren Lenita L Bergdahl Jan J Nyberg Lars L

Cerebral cortex (New York, N.Y. : 1991) 20160526 8

Hippocampal volume has been found to be smaller in individuals with stress-related disorders, but it remains unclear whether smaller volume is a consequence of stress or rather a vulnerability factor. Here, we examined this issue by relating stress levels to hippocampal volumes in healthy participants examined every 5 years in a longitudinal population-based study. Based on scores of 25- to 60-year-old participants on the perceived stress questionnaire, we defined moderately to high (n = 35) and ...[more]

PMID: 27230217

Similar Datasets

Project description:BackgroundSmaller hippocampal volume in patients with posttraumatic stress disorder (PTSD) represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features.MethodsCase-control cross-sectional studies of U.S. military veterans (n = 282) from the Iraq and Afghanistan era were grouped into PTSD (n = 142) and trauma-exposed controls (n = 140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3 T. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model.ResultsSignificantly lower subfield volumes were associated with PTSD in left CA1 (P = 0.01; d = 0.21; uncorrected), CA3 (P = 0.04; d = 0.08; uncorrected), and right CA3 (P = 0.02; d = 0.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD (F4, 221 = 3.32, P = 0.07) is present and the other subfield findings are nonsignificant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD-associated differences in global hippocampal shape were nonsignificant.ConclusionsThe present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.

Project description:BACKGROUND:Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. METHOD:Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-? messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. RESULTS:Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-? (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). CONCLUSIONS:Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF.

Project description:During exposure to chronic stress, some individuals engage in active coping behaviors that promote resiliency to stress. Other individuals engage in passive coping that is associated with vulnerability to stress and with anxiety and depression. In an effort to identify novel molecular mechanisms that underlie vulnerability or resilience to stress, we used nonbiased analyses of microRNAs in the ventral hippocampus (vHPC) to identify those miRNAs differentially expressed in active (long-latency (LL)/resilient) or passive (short-latency (SL)/vulnerable) rats following chronic social defeat. In the vHPC of active coping rats, miR-455-3p level was increased, while miR-30e-3p level was increased in the vHPC of passive coping rats. Pathway analyses identified inflammatory and vascular remodeling pathways as enriched by genes targeted by these microRNAs. Utilizing several independent markers for blood vessels, inflammatory processes and neural activity in the vHPC, we found that SL/vulnerable rats exhibit increased neural activity, vascular remodeling and inflammatory processes that include both increased blood-brain barrier permeability and increased number of microglia in the vHPC relative to control and resilient rats. To test the relevance of these changes for the development of the vulnerable phenotype, we used pharmacological approaches to determine the contribution of inflammatory processes in mediating vulnerability and resiliency. Administration of the pro-inflammatory cytokine vascular endothelial growth factor-164 increased vulnerability to stress, while the non-steroidal anti-inflammatory drug meloxicam attenuated vulnerability. Collectively, these results show that vulnerability to stress is determined by a re-designed neurovascular unit characterized by increased neural activity, vascular remodeling and pro-inflammatory mechanisms in the vHPC. These results suggest that dampening inflammatory processes by administering anti-inflammatory agents reduces vulnerability to stress. These results have translational relevance as they suggest that administration of anti-inflammatory agents may reduce the impact of stress or trauma in vulnerable individuals.

Dataset Information

Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress.

Publications

Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets