Altered inhibition of negative emotions in subjects at family risk of major depressive disorder

Lisiecka, Danuta; Carballedo, Angela; Fagan, Andrew; Connolly, Gerald; Meaney, James; Frodl, Thomas

doi:10.1016/j.jpsychires.2011.10.010

Cited by 28 publications

(24 citation statements)

References 45 publications

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“…10 In our recent study, the unaffected healthy first-degree relatives of patients with MDD experienced more activation in the left caudate nucleus and the right middle cingulate cortex (MCC) during inhibition of emotional information; we hypothesized that changes in activation may be the result of a mechanism of compensation. 11 Our findings suggested that areas responsible for executive function and emotional processing may be altered in individuals with family history of MDD. 11 However, the pathophysiology of the role that family history of MDD plays in the development and diagnosis of MDD is not yet entirely understood.…”

Section: Introductionmentioning

confidence: 57%

“…11 Our findings suggested that areas responsible for executive function and emotional processing may be altered in individuals with family history of MDD. 11 However, the pathophysiology of the role that family history of MDD plays in the development and diagnosis of MDD is not yet entirely understood. The behavioural data suggest that the key skills impaired in individuals with a family history of MDD are emotion processing [12][13][14] and attention shifting from emotional content, 15,16 neural correlates of which have been previously verified in healthy individuals.…”

Section: Introductionmentioning

confidence: 57%

“…The HC-FHN participants were volunteers recruited through advertisements. Whereas both groups of healthy controls participated in our previous study, 11 this new sample was extended by including patients with MDD, and our data analysis focused on emotion processing and attention shifting.…”

Section: Participantsmentioning

confidence: 99%

“…We hypothesized that the HC-FHP group had elevated neural activation relative to the MDD-FHP group in frontal, premotor and parietal areas as markers for relative resilience and elevated activation compared with the HC-FHN group in the cingulate cortex and subcortical areas based on our previous study. 11 Furthermore, it was necessary to verify how emotion processing and attention shifting were altered by an acute depressive episode when the risk caused by family history of MDD was absent. We tested the question by comparing the HC-FHN with the MDD-FHN group.…”

Section: Introductionmentioning

confidence: 99%

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Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Lisiecka

Carballedo

Fagan

et al. 2013

J Psychiatry Neurosci

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IntroductionIndividuals with a first-degree relative who has major depressive disorder (MDD) are at a 2-to 3-fold greater risk for depression than those without a family history of MDD. 1 Rela tives of depressed patients, compared with individuals without family history of psychiatric disorders, are characterized by elevated neuroticism, depressive cognitions and rigidity 2 and by stability of these traits over time.3 Patients with MDD who had relatives with an affective disorder display greater neuroticism 4 and have an earlier age of onset of MDD. 5 Evidently, family history of MDD alters susceptibility to depression and to an acute MDD episode. The factor is clinically important since it involves mechanisms of elevated risk for MDD (relatives of patients with MDD compared with healthy controls), suggests relative resilience to the disease (relatives of patients with MDD compared with the patients themselves) and points to different endophenotypes of healthy controls and patients with MDD. A good understanding of these mechanisms should not be underestimated if diagnosis, therapy and prevention of the disorder are to be enhanced. Background: Family history of major depressive disorder (MDD) increases individuals' vulnerability to depression and alters the way depression manifests itself. Emotion processing and attention shifting are functions altered by MDD and family history of the disease; therefore, it is important to recognize the neural correlates of these functions in association with both factors. Methods: Our study determines neural correlates of emotion processing and attention shifting for healthy individuals and patients with MDD with and without family history of depression. We compared the performance and neural activity in a functional magnetic resonance imaging experiment examining emotion processing and attention shifting in all participants. Results: Our sample included 4 study groups: healthy controls without family history of depression (n = 25), patients with MDD without family history of the disease (n = 20), unaffected healthy first-degree relatives of patients with MDD (n = 21) and patients with MDD with family history of MDD (n = 30). Compared with healthy controls, unaffected first-degree relatives overactivate the somatosensory cortex and the attention controlling areas during both emotion processing and attention shifting. Patients with family history of MDD have stronger neural activation in subcortical areas during shifting attention from negative stimuli. Patients without family history of MDD have less activation in the paralimbic regions and more activation in core limbic areas, especially during emotion processing. Limitations: The conclusions about the intergroup differences in activation can be drawn only about neural areas engaged in the task. Conclusion: Unaffected first-degree relatives of patients with MDD overreact to external emotional cues and compensate for the vulnerability with increased involvement of executive control. Patients with a family history of MDD have le...

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Section: Introductionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 57%

Section: Participantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Lisiecka

Carballedo

Fagan

et al. 2013

J Psychiatry Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 Accordingly, other groups have shown altered frontal and subcortical reward-related neural processes in healthy individuals at familial risk for affective disorders. [6][7][8] Prospective longitudinal studies may provide valuable insights into the association between risk factors and disorder onset. By following healthy high-risk individuals for 7 years before the onset of any affective disorder, we were able to show that discrete subclinical symptoms predict subsequent disorder onset.…”

Section: Introductionmentioning

confidence: 99%

Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

Macoveanu

Miskowiak

Kessing

et al. 2016

jpn

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IntroductionHeritable genetic traits and environmental components both contribute to the etiology of affective disorders. While the specific contribution of these 2 factors to disorder onset remains elusive, family and twin studies have consistently identified a family history of affective disorders as a major risk factor.1 First-degree relatives of patients with depression have a 2-fold to 4-fold increased risk for depression than individuals with no psychiatric history in first-degree relatives.2 Yet the specific neurobiological correlates mediating this vulnerability to affective disorders, which are transmitted in affected families, remain to be identified.Recent studies in high-risk individuals have revealed that healthy individuals at familial risk for affective disorders show a range of neurobiological abnormalities. Two studies from our group showed lower serotonin (5-HT) transporter binding in the prefrontal cortex 3 and decreased hippocampal volume. 4 We recently observed altered neural response in the hippocampus and orbitofrontal cortex to monetary gains and losses in healthy first-degree relatives of patients with depression.5 Accordingly, other groups have shown altered frontal and subcortical reward-related neural processes in healthy individuals at familial risk for affective disorders. [6][7][8] Prospective longitudinal studies may provide valuable insights into the association between risk factors and disorder onset. By following healthy high-risk individuals for 7 years before the onset of any affective disorder, we were able to show that discrete subclinical symptoms predict subsequent disorder onset. 9 The personality trait neuroticism, which refers to emotional instability, vulnerability to stress and anxiety disorders, 10 was also found to predict subsequent disorder Background: Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals. Methods: We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain. Results: We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this e...

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Cognitive Performance in First-Degree Relatives of Individuals With vs Without Major Depressive Disorder

2019

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IMPORTANCE Findings of cognitive impairment in major depressive disorder (MDD), including remitted MDD, raise the question whether impaired cognition is part of preexisting vulnerability rather than a consequence of MDD or its treatment. To our knowledge, no meta-analyses have been published on cognitive impairment in first-degree relatives of individuals with MDD.OBJECTIVE To compare cognitive performance between individuals with and without family history of MDD.STUDY SELECTION Original articles that reported data on cognition in first-degree relatives of individuals with MDD compared with controls with no family history of major mental illness.DATA EXTRACTION AND SYNTHESIS Means and SDs were extracted, and standardized mean differences (SMD) between relatives and controls were calculated for each measure of cognitive performance. The relative-control differences in overall cognition and in specific cognitive domains were synthesized in random-effects meta-analyses with robust variance estimation that allows including multiple correlated measures of cognition within each study. Heterogeneity was quantified with τ 2 . Publication bias was assessed with funnel plots and Egger intercept. MAIN OUTCOMES AND MEASURES Performance on cognitive tests.RESULTS Across 284 measures of cognition in 54 nonoverlapping samples including 3246 relatives of people with MDD (mean age 15.38 years, 57.68% females) and 5222 controls (mean age 14.70 years, 55.93% females), relatives of people with MDD performed worse than controls across all measures of cognition (SMD = −0.19; 95% CI, −0.27 to −0.11; P < .001). Domain-specific meta-analyses showed similar size of relative-control difference in most domains of cognition, including Full-Scale IQ (SMD = −0.19), verbal intelligence (SMD = −0.29), perceptual intelligence (SMD = −0.23), memory (SMD = −0.20), academic performance (SMD = −0.40), and language (SMD = −0.29). Study characteristics were not significantly associated with observed between-group differences. There was no evidence of publication bias. CONCLUSIONS AND RELEVANCEA general impairment in cognition is a feature of familial disposition for MDD. Cognition may contribute to early identification of risk for depression and may be examined as potential target for early intervention. 11. Rasic D, Hajek T, Alda M, Uher R. Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies.

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Altered inhibition of negative emotions in subjects at family risk of major depressive disorder

Cited by 28 publications

References 45 publications

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

Cognitive Performance in First-Degree Relatives of Individuals With vs Without Major Depressive Disorder

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