Bonnie Klimes-Dougan

A preliminary study of functional connectivity in comorbid adolescent depression

Major depressive disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n=12) and healthy adolescents (n=14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.

Neuropsychological Functioning in Adolescent Children of Mothers with a History of Bipolar or Major Depressive Disorders

BACKGROUND Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). METHODS Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. RESULTS Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. CONCLUSIONS Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions.

Abnormal Amygdala Resting-State Functional Connectivity in Adolescent Depression

IMPORTANCE Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

Fidelity at a Distance: Assessing Implementation Fidelity of the Early Risers Prevention Program in a Going-to-Scale Intervention Trial

The present study examined the feasibility of an innovative technology designed to assess implementation fidelity of the Early Risers conduct problems prevention program across 27 geographically dispersed school sites. A multidimensional construct of fidelity was used to assess the quantity of services provided (exposure), the degree to which program strategies conformed to the manual (adherence), and how well implementers delivered the program (quality of delivery). The measurement technology featured a fidelity monitoring system that required (a) weekly reporting on a web-based documentation system to assess program exposure and adherence, and (b) five annually administered telephone interviews with a technical assistant to assess quality of program implementation. The results showed that the fidelity monitoring system was feasible, with all sites achieving 100% compliance in completion of their required on-line reporting and on average over 80% of the required teleconference interviews. User feedback indicated satisfaction with the web-based program. The system was successful in measuring multiple indices of fidelity. The strengths and limitations of measuring fidelity at a distance with web-based and teleconferencing technologies are discussed.

Emotion socialization in adolescence: The roles of mothers and fathers

This chapter provides a review of the literature that examines the role of mothers and fathers in socializing emotion in their sons and daughters during adolescence. Within the context of this chapter, we focus on mother-father similarities, differences, and coordinated efforts in socializing the emotion of their adolescent children. Empirical data is presented that provides new evidence about the coordinated efforts of parents and its implications for the development of adolescent psychopathology. The authors emphasize the importance of both adolescent emotion capabilities and the role mothers and fathers play in supporting or deterring healthy emotional development in adolescence.

A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mothers functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability-stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.

Identifying Unmet Mental Health Needs in Children of Formerly Homeless Mothers Living in a Supportive Housing Community Sector of Care

This study reports psychosocial characteristics of a sample of 111 children (K to 2nd grade) and their mothers who were living in urban supportive housings. The aim of this study was to document the various types and degree of risk endemic to this population. First, we describe the psychosocial characteristics of this homeless sample. Second, we compared this homeless sample with a grade-matched, high-risk, school-based sample of children (n = 146) who were identified as showing early symptoms of disruptive behaviors. Third, we compared the parents in both samples on mental health, parenting practices, and service utilization. Results showed that children living in supportive housing were in the at-risk range and had comparable levels of externalizing problems, internalizing problems, school problems and emotional strengths with the school-based risk sample receiving prevention services at a family support community agency. Mothers in supportive housing reported significantly higher psychological distress, less optimal parenting practices and greater service utilization. These findings are among the first to provide empircal support for the need to deliver prevention interventions in community sectors of care.

Within-adolescent coupled changes in cortisol with DHEA and testosterone in response to three stressors during adolescence

It is hypothesized that hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes function together to maintain adaptive functioning during stressful situations differently in adolescence than the characteristic inverse relations found in adulthood. We examined within-person correlated changes (coupling) in cortisol, DHEA and testosterone in response to parent-adolescent conflict discussion, social performance, and venipuncture paradigms. Data are derived from two samples of boys and girls from the Northeastern US (213 adolescents aged 11-16, M=13.7, SD=1.5 years; 108 adolescents aged 9-14, M=11.99, SD=1.55) using different biological sampling vehicles (saliva and blood). Results consistently show that across samples, vehicles, and contexts, cortisol and DHEA and cortisol and testosterone are positively coupled in response to environmental stimuli. Findings underscore the importance of considering the effects of multiple hormones together in order to further our understanding of the biological underpinnings of behavior, especially during adolescence, as adolescence is a developmental transition period that may be qualitatively different from adulthood in terms of hormone functioning.

An fMRI study of emotional face processing in adolescent major depression

BACKGROUND Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). METHOD Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. RESULTS ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. LIMITATIONS Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. CONCLUSIONS Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment.

Suicide prevention public service announcements: perceptions of young adults.

BACKGROUND Determining optimal methods for preventing suicide continues to be an elusive goal. AIMS The study examines benefits and possible untoward effects of public service announcements (PSAs) for young adults. METHODS Young adult participants (N = 279) were randomly assigned to one of three conditions: (a) a billboard simulation, (b) a 30-s TV ad simulation, and (c) a no-information condition. RESULTS Largely replicating a study previously conducted with adolescents, the results provided some evidence of the benefit of the simulated TV ad (e. g., increased knowledge, perceived as useful), but it also provided some evidence of untoward effects for the billboard (e. g., viewers were less likely to endorse help-seeking strategies, normative beliefs were altered for high-risk participants). CONCLUSIONS These results are preliminary but nevertheless highlight the need for carefully researching existing messages prior to market diffusion, so that the well-intended efforts of preventionists can meet their desired goals.