Exploring valence bias as a metric for frontoamygdalar connectivity and depressive symptoms in childhood.
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ABSTRACT:
SUBMITTER: Petro NM
PROVIDER: S-EPMC8255333 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChildhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms.MethodsA longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression.ResultsTen functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings.ConclusionsThis study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms.
| S-EPMC10120398 | biostudies-literature
Project description:Childhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain's self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.
| S-EPMC8891292 | biostudies-literature
Project description:ObjectiveTo conduct an evidence-based review of adolescent self-report depression measures and to demonstrate how various measures can be rescored onto a harmonized metric.MethodSix widely used person-reported outcome measures (PROMs) were reviewed. Psychometric properties were evaluated using previously published guidance for PROMs. Next, two secondary data sources (from an outpatient behavioral health clinic and from the general population) were evaluated to harmonize scores across three of the measures. Both item response theory and equipercentile linking methods were used and compared.ResultsAll six PROMs demonstrated a high evidence base for widespread use depending on the purpose of the assessments. Adolescent involvement when developing the PROM for content validity and floor or ceiling effects were the least frequent available evidence. Three of the PROMs were linked to the PROMIS® Pediatric Depressive Symptoms v2.0 (PROMIS-PedDepSx) metric. The scales were highly correlated and essentially unidimensional when aggregated. All linking methods were broadly comparable. Group-level score conversions are recommended to minimize linking bias.ConclusionsThere are a number of strong, widely used PROMs for the evidence-based assessment (EBD) of adolescent depression. However, score comparability is a concern whenever there is a proliferation of measures. Harmonized score metrics support data aggregation and re-analysis. Using four PROMs, one of which served as the scoring metric, we demonstrated the possibility of harmonized depression scores. Future directions for EBD should evaluate whether harmonized PROMs for other pediatric health domains would be useful.
| S-EPMC7849937 | biostudies-literature
Project description:BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [(18)F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [(18)F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [(18)F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [(18)F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [(18)F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally.
| S-EPMC4918731 | biostudies-literature
Project description:Perinatal maternal depressive symptoms influence brain development of offspring. Such effects are particularly notable in the amygdala, a key structure involved in emotional processes. This study investigated whether the functional organization of the amygdala varies as a function of pre- and postnatal maternal depressive symptoms. The amygdala functional network was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) in 128 children at age of 4.4 to 4.8 years. Maternal depressive symptoms were obtained at 26 weeks of gestation, 3 months, 1, 2, 3, and 4.5 years after delivery. Linear regression was used to examine associations between maternal depressive symptoms and the amygdala functional network. Prenatal maternal depressive symptoms were significantly associated with the functional connectivity between the amygdala and the cortico-striatal circuitry, especially the orbitofrontal cortex (OFC), insula, subgenual anterior cingulate (ACC), temporal pole, and striatum. Interestingly, greater pre- than post-natal depressive symptoms were associated with lower functional connectivity of the left amygdala with the bilateral subgenual ACC and left caudate and with lower functional connectivity of the right amygdala with the left OFC, insula, and temporal pole. These findings were only observed in girls but not in boys. Early exposure to maternal depressive symptoms influenced the functional organization of the cortico-striato-amygdala circuitry, which is intrinsic to emotional perception and regulation in girls. This suggests its roles in the transgenerational transmission of vulnerability for socio-emotional problems and depression. Moreover, this study underscored the importance of gender-dependent developmental pathways in defining the neural circuitry that underlies the risk for depression.
| S-EPMC6866529 | biostudies-literature
Project description:BACKGROUND:Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. METHODS:Children were assessed for BI at multiple age points from infancy through age seven. On the basis of a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (n = 44). Participants completed an event-related functional magnetic resonance imaging attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. RESULTS:The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. CONCLUSIONS:Behavioral inhibition during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology.
| S-EPMC3725217 | biostudies-literature
Project description:Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient's subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis in a proof-of-concept study using fMRI functional connectivity neurofeedback. We targeted connectivity between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state-which results in a loss of this anticorrelation-is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, we found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Because these results look promising, this paradigm next needs to be examined with a greater sample size and with better controls. Nonetheless, here we provide preliminary evidence for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.Clinical trial registration: Both experiments reported here were registered clinical trials (UMIN000015249, jRCTs052180169).
| S-EPMC8850610 | biostudies-literature
Project description:Attrition from mortality is common in longitudinal studies of the elderly. Ignoring the resulting non-response or missing data can bias study results.1260 elderly participants underwent biennial follow-up assessments over 10 years. Many missed one or more assessments over this period. We compared three statistical models to evaluate the impact of missing data on an analysis of depressive symptoms over time. The first analytic model (generalized mixed model) treated non-response as data missing at random. The other two models used shared parameter methods; each had different specifications for dropout but both jointly modeled both outcome and dropout through a common random effect.The presence of depressive symptoms was associated with being female, having less education, functional impairment, using more prescription drugs, and taking antidepressant drugs. In all three models, the same variables were significantly associated with depression and in the same direction. However, the strength of the associations differed widely between the generalized mixed model and the shared parameter models. Although the two shared parameter models had different assumptions about the dropout process, they yielded similar estimates for the outcome. One model fitted the data better, and the other was computationally faster.Dropout does not occur randomly in longitudinal studies of the elderly. Thus, simply ignoring it can yield biased results. Shared parameter models are a powerful, flexible, and easily implemented tool for analyzing longitudinal data while minimizing bias due to nonrandom attrition.
| S-EPMC2733930 | biostudies-other
Project description:ObjectiveMaternal depression is a risk factor for adolescent depression; however, the effect of childhood exposure to maternal depression on adolescent engagement in health risk behaviors (eg, substance use, delinquency) is unclear.MethodsWe examined the relationship between maternal depressive symptoms (child's age 4-15) and engagement in health risk behaviors at age 16 to 17 by using data from 2910 mother-youth pairs in a nationally representative prospective Canadian cohort. Maternal depressive trajectories were estimated through finite mixture modeling, and multiple regression analyses examined the relationship between maternal depressive symptoms and engagement in various health risk behaviors (linear regression) and age of debut of various behaviors (Cox regression).ResultsFive trajectories of maternal depressive symptoms were found: recurrent maternal symptoms, midchildhood exposure to maternal symptoms, adolescent exposure to maternal symptoms, mild maternal symptoms, and low symptoms. Adolescents exposed to maternal depressive symptoms during middle childhood were more likely to use common substances (alcohol, cigarettes, marijuana), engage in violent and nonviolent delinquent behavior, and have an earlier debut ages of cigarette, alcohol, marijuana, and hallucinogen use.ConclusionsThe results of this study suggest that exposure to maternal depressive symptoms, particularly in middle childhood, is associated with greater and earlier engagement in health risk behaviors.
| S-EPMC4533251 | biostudies-literature
Project description:ImportanceChildhood intrafamilial aggression, a series of aggressive behaviors inflicted by family members, and adulthood mental health are associated with childhood peer bullying (eg, in the neighborhood or in school). However, few studies have been able to identify the contribution of childhood peer bullying to the association between childhood intrafamilial aggression and adult depression.ObjectiveTo examine the mediating role of childhood peer bullying in the association between childhood intrafamilial aggression and depression in adulthood.Design, setting, and participantsThis population-based cross-sectional study used data from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults (≥45 years) participated in a CHARLS wave from July 1 to September 30, 2015, and the CHARLS life history survey from June 1 to December 31, 2014, with complete data. A 4-step mediation model with logistic regression was run to test the mediating role of peer bullying. Data analysis was performed from October 1 to 30, 2019.ExposuresChildhood intrafamilial aggression, including parental physical maltreatment and sibling aggression, and peer bullying.Main outcomes and measuresDepressive symptoms measured by a categorical variable derived from the Center for Epidemiologic Studies Depression Scale, based on a cutoff score of 12.ResultsAmong the 15 450 respondents (mean [SD] age, 59.5 [9.9] years; 7987 women [51.7%]), 4422 (28.6%) were exposed to parental physical maltreatment; 986 (6.4%), to sibling aggression; and 2504 (16.2%), to peer bullying in childhood. Respondents experiencing intrafamilial aggression were more likely to be bullied by peers (parental physical maltreatment odds ratio [OR], 2.53 [95% CI, 2.25-2.83]; sibling aggression OR, 3.05 [95% CI, 2.46-3.78]). Children with these adverse experiences were at a higher risk of adult depression symptoms (parental physical maltreatment OR, 1.28 [95% CI, 1.15-1.42]; sibling aggression OR, 1.40 [95% CI, 1.13-1.74]; peer bullying OR, 1.78 [95% CI, 1.56-2.01]). Peer bullying mediated 30% (95% CI, 19%-42%) of the association between childhood parental maltreatment and adult depression and 35% (95% CI, 15%-54%) of the association between sibling aggression and depression symptoms in adulthood.Conclusions and relevanceThis study found that being bullied by peers was a mediator of the association between childhood intrafamilial aggression and depression in adulthood. The findings have important implications to mitigate the effect of early-life stress and promote life-course mental health through dealing with childhood intrafamilial aggression and peer bullying experiences coordinately.
| S-EPMC7403920 | biostudies-literature