Dataset Information

Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.

ABSTRACT:

Importance

The neural systems that confer risk or vulnerability for developing familial depression, and those that protect against or confer resilience to becoming ill, can be disentangled from the effects of prior illness by comparing brain imaging measures in previously ill and never ill persons who have either a high or low familial risk for depression.

Objective

To distinguish risk and resilience endophenotypes for major depression from the effects of prior lifetime illness.

Design, setting, and participants

We used functional magnetic resonance imaging to measure and compare brain function during performance of an attentional, self-regulatory task across a large sample of multigenerational families ascertained specifically to be at either high or low risk for developing major depression. Study procedures were performed in a university setting. A total of 143 community participants were followed up prospectively for more than 20 years in a university setting. The sample was enriched with persons who were at higher or lower familial risk for developing depression based on being biological offspring of either a clinical sample of persons with major depression or a community control sample of persons with no discernible lifetime illness.

Main outcomes and measures

Task-related change in blood oxygen level-dependent functional magnetic resonance imaging signal.

Results

A risk endophenotype included greater activation of cortical attention circuits. A resilience endophenotype included greater activation of the dorsal anterior cingulate cortex. The effects of prior lifetime illness were common to both risk groups and included greater deactivation of default-mode circuits.

Conclusions and relevance

These findings identify neural systems that increase risk for depression, those that protect from illness, and those that endure following illness onset, and they suggest circuits to target for developing novel preventive and therapeutic interventions.

SUBMITTER: Peterson BS

PROVIDER: S-EPMC3965257 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.

Peterson Bradley S BS Wang Zhishun Z Horga Guillermo G Warner Virginia V Rutherford Bret B Klahr Kristin W KW Graniello Barbara B Wickramaratne Priya P Garcia Felix F Yu Shan S Hao Xuejun X Adams Phillip B PB Qian Ming M Liu Jun J Gerber Andrew A Weissman Myrna M MM

JAMA psychiatry 20140201 2

<h4>Importance</h4>The neural systems that confer risk or vulnerability for developing familial depression, and those that protect against or confer resilience to becoming ill, can be disentangled from the effects of prior illness by comparing brain imaging measures in previously ill and never ill persons who have either a high or low familial risk for depression.<h4>Objective</h4>To distinguish risk and resilience endophenotypes for major depression from the effects of prior lifetime illness.<h ...[more]

PMID: 24369340

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Project description:ImportanceAdolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development.ObjectiveTo examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder.Design, setting, and participantsA longitudinal study was conducted at Stanford University from October 1, 2003, to January 31, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression developed (converted), and 25 at low risk with no history of psychopathology (control).Main outcomes and measuresWe compared functional connectivity between resilient and converted, and between resilient and control, adolescent females using voxelwise 2-sided t tests to examine neural markers of resilience to depression as the main outcomes of interest. Specifically, we assessed differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, implicated in emotion regulation. We also examined the association between functional connectivity and life events.ResultsOf the 65 participants (mean [SD] age, 18.9 [2.5] years), adolescent females in the resilient group had greater connectivity between the amygdala and orbitofrontal cortex (z score = 0.23; P < .001) and between the dorsolateral prefrontal cortex and frontotemporal regions (z score = 0.24; P < .001) than did converted adolescent females. In adolescent females in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity was correlated with positive life events (r18 = 0.48; P = .03). Resilient adolescent females had greater connectivity within frontal (z score = 0.07; P < .001) and limbic (z score = 0.21; P < .001) networks than did control individuals. Both high-risk groups had greater salience network connectivity: the converted group had greater intranetwork connectivity than did the resilient (z score = 0.13; P < .001) and control (z score = 0.10; P < .001) groups, and the adolescent females in the resilient group had greater salience network connectivity with the superior frontal gyrus than did the converted (z score = 0.24; P < .001) adolescent females.Conclusions and relevanceResilient adolescent females have compensatory functional connectivity patterns in emotion regulatory networks that correlate with positive life events, suggesting that experience-dependent plasticity within these networks may confer resilience to depression. Further studies are warranted concerning connectivity-associated targets for promoting resilience in high-risk individuals.

Project description:BackgroundCognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.MethodsAssociations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457-14,836, age 45-81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.ResultsLifetime MDD was robustly associated with a lower g-factor (β = -0.10, PFDR = 4.7 × 10-5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = -0.18, PFDR = 7.5 × 10-5).ConclusionsFindings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

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Project description:Adopting a personalized medicine approach beyond genetic/epigenetic profiling within psychiatric diagnostic and treatment is challenging. For the first time, we studied the influence of two patient resources (resilience and illness representation) on the success of an inpatient treatment of major depressive disorder (MDD). Using a 5-week observational real-world-study, the treatment- success was measured by the difference between the subjective depression- severity (according to the German short form of Beck's Depression-Inventory) at baseline (i.e., days four to six post-admission) and study- endpoint. In the intention-to-treat sample (n = 60, 47.3 ± 12.8 years old; 58% females), the patients' illness representation [measured by the "Krankheitskonzeptskala" (KK)] did not predict their treatment- success. The KK-dimension 'trust-in-doctors' was associated with resilience but not with the treatment-success. Albeit, the patients' resilience (determined by Resilience- Scale, 11-item-version (RS-11)) negatively predicted their positive treatment- success (b = - 0.09, p = 0.017, f2 = 0.11). This influence of resilience on treatment- success was completely mediated by the baseline-depression- severity. This means, patients with low resilience reported high baseline-depression- levels which predicted a significant positive treatment- success. And, patients with high resilience reported low baseline-depression-levels which predicted no relevant or even negative inpatient treatment-success. The latter "high-resilience"- group (n = 27) was especially interesting. Remarkably, these patients appeared to have experienced within the first four-to-six inpatient treatment-days an "early sudden gain" against their considerable MDD- burden that initially had led to their admission. Thus, a stronger resilience might serve as a proxy of the development of an early MDD-relief as well as of lower baseline-depression- levels. Further studies are warranted to support the value of a patient's resilience to predict his treatment response and inpatient treatment duration.

Dataset Information

Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.

Importance

Objective

Design, setting, and participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.

Similar Datasets

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