Adolescents With Major Depression Demonstrate Increased Amygdala Activation

Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido; Max, Jeffrey E.; Bischoff‐Grethe, Amanda; Lansing, Amy E.; Brown, Gregory G.; Strigo, Irina A.; Wu, Jing; Paulus, Martin P.

doi:10.1016/j.jaac.2009.09.004

Cited by 78 publications

(43 citation statements)

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“…Previous and current fMRI studies from our group and others consistently show that depressed adolescents demonstrate increased hyperactivation of the amygdala, a key limbic structure involved in emotion generative processing (18) and aberrant functional connectivity between the amygdala and other emotional regulation areas (19, 23, 24). This may be related to sustained increase of stress levels with autonomic dysregulation, including a sympathetic overdrive and a decreased parasympathetic tone (25, 26).…”

Section: Introductionmentioning

confidence: 54%

“…This has been specifically addressed in the DSM5, which states “ in terms of genetic risk, family, twin, and high-risk transmission studies all indicate that Generalized Anxiety Disorder (GAD) and MDD share some, if not most, of their genetic risk factors ” and a new diagnostic entity of mixed depression and anxiety has been introduced. In the RDoC matrix, it is also evident that generalized and social anxiety and depression symptomatology are linked to dysfunction in the same neurocircuitry, such as sustained limbic hyperreactivity (18–20) and reduced adaptive flexibility of the default mode network (DMN) (20–22). Consequently, we chose to include participants with symptoms of depression and/or generalized and social anxiety in this study and hypothesized that the TARA intervention should impact both depressive symptomatology and symptoms of generalized and social anxiety.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: “Training for Awareness Resilience and Action” (TARA)—A Pilot Study

et al. 2017

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BackgroundThe novel group treatment program Training for Awareness, Resilience, and Action (TARA) was developed to target specific mechanisms based on neuroscience findings in adolescent depression and framed within the National Institute of Mental Health Research Domain Criteria. TARA contains training of autonomic and emotional self-regulation, interoceptive awareness, relational skills, and value-based committed action.MethodsWe performed a single-arm trial to test the feasibility and preliminary efficacy of TARA in reducing depression and anxiety levels and assessed whether the specific targeted domains of function reflected the hypothesized symptom change. Twenty-six adolescents (14–18 years old, 7 males and 19 females) participated in the 12-week group program. Assessment was performed before (T0), immediately after (T1), and 3 months after the end of TARA (T2).ResultsSignificant improvement was seen in depression symptoms (Reynolds Adolescent Depression Scale Second Edition) between T0–T1 (t-value = −3.56, p = 0.002, CI = −6.64, −1.77) and T0–T2 (t-value = −4.17, p < 0.001, CI = −11.20, −3.75) and anxiety symptoms (Multidimensional Anxiety Scale for Children) between T0–T1 (t-value = −2.26, p = 0.033, CI = −4.61, −0.21) and T0–T2 (t-value = −3.06, p = 0.006, 95% confidence interval = −9.02, −1.73). Significant improvements in psychological flexibility, sleep, and mindfulness skills were also found between T0 and T2.LimitationsThe sample size was small without a control condition. The pilot design did not allow for testing the hypothesized brain changes and effect of TARA on relevant systemic biomarkers.ConclusionTARA is feasible in a sample of clinically depressed and/or anxious adolescents and preliminary efficacy was demonstrated by reduced depression and anxiety symptoms. The specific symptom and behavioral outcomes corresponded well with the hypothesized mechanisms of change.

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Section: Introductionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: “Training for Awareness Resilience and Action” (TARA)—A Pilot Study

et al. 2017

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“…The insula is thought to be critical to the integration and awareness of autonomic, visceral, and hedonic information (Craig, 2009) and it has been implicated in depression-relevant processes such as interoception, emotional self-awareness, decision making and cognitive control (Craig, 2009). A growing body of literature has identified insular dysfunction in adolescents at-risk for (Gotlib et al, 2010) and with depression (Ho et al, 2015; 2013; 2014; Perlman et al, 2012; Yang et al, 2010). Additionally, resting-state studies showed altered patterns of insular connectivity in both adults (Jacobs et al, 2016; Tahmasian et al, 2013; Veer et al, 2010) and adolescents (Connolly et al, 2013; Cullen et al, 2009; Jin et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Increased amygdala activation to emotional stimuli has been linked to adult (Drevets, 2000) and adolescent depression (Hulvershorn et al, 2011; Yang et al, 2010). Normalization of amygdala activation to emotional stimuli has also been associated with successful pharmacological and psychotherapeutic interventions for depression in both adults (Arnone et al, 2012; Fu et al, 2008; Godlewska et al, 2012; Sheline et al, 2001) and adolescents (Straub et al, 2015; Tao et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression

Connolly

Blom

et al. 2017

Journal of Affective Disorders

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Background The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents. Method We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24). Results Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. Limitations Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized. Conclusions Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.

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“…Importantly, heightened amygdala and hippocampus response to threat-related stimuli has also been observed in children, adolescents, and adults with depression (e.g. Barch et al, 2012; Beesdo et al, 2009; Bishop et al, 2004; Etkin et al, 2004; Ewbank et al, 2009; Gaffrey et al, 2011; Thomas et al, 2001b; Yang et al, 2010). Amygdala hyper-responsivity is similarly present in unaffected children at risk for depression (based on parental history of depression; Monk et al, 2008), suggesting that these differences may precede the development of psychopathology and that genetic risk and/or early environmental factors may play a key role.…”

Section: Introductionmentioning

confidence: 94%

HPA axis genetic variation, pubertal status, and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children

et al. 2015

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Accumulating evidence suggests a role for stress exposure, particularly during early life, and for variation in genes involved in stress response pathways in neural responsivity to emotional stimuli. Understanding how individual differences in these factors predict differences in emotional responsivity may be important for understanding both normative emotional development and for understanding the mechanisms underlying internalizing disorders, like anxiety and depression, that have often been related to increased amygdala and hippocampus responses to negatively valenced emotional stimuli. The present study examined whether stress exposure and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predict individual differences in amygdala and hippocampus responses to fearful vs. neutral faces in school-age children (7–12 year olds; N=107). Experience of more stressful and traumatic life events predicted greater left amygdala responses to negative emotional stimuli. Genetic profile scores interacted with sex and pubertal status to predict amygdala and hippocampus responses. Specifically, genetic profile scores were a stronger predictor of amygdala and hippocampus responses among pubertal vs. prepubertal children where they positively predicted responses to fearful faces among pubertal girls and positively predicted responses to neutral faces among pubertal boys. The current results suggest that genetic and environmental stress-related factors may be important in normative individual differences in responsivity to negative emotional stimuli, a potential mechanism underlying internalizing disorders. Further, sex and pubertal development may be key moderators of the effects of stress-system genetic variation on amygdala and hippocampus responsivity, potentially relating to sex differences in stress-related psychopathology.

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Adolescents With Major Depression Demonstrate Increased Amygdala Activation

Cited by 78 publications

References 42 publications

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: “Training for Awareness Resilience and Action” (TARA)—A Pilot Study

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: “Training for Awareness Resilience and Action” (TARA)—A Pilot Study

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression

HPA axis genetic variation, pubertal status, and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children

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