All Publications

  • Pregnancy during the pandemic: The impact of COVID-19-related stress on risk for prenatal depression. Psychological medicine King, L. S., Feddoes, D. E., Kirshenbaum, J. S., Humphreys, K. L., Gotlib, I. H. 2021: 1–32

    View details for DOI 10.1017/S003329172100132X

    View details for PubMedID 33781354

  • Default mode and salience network alterations in suicidal and non-suicidal self-injurious thoughts and behaviors in adolescents with depression. Translational psychiatry Ho, T. C., Walker, J. C., Teresi, G. I., Kulla, A., Kirshenbaum, J. S., Gifuni, A. J., Singh, M. K., Gotlib, I. H. 2021; 11 (1): 38


    Suicidal ideation (SI) and non-suicidal self-injury (NSSI) are two distinct yet often co-occurring risk factors for suicide deaths in adolescents. Elucidating the neurobiological patterns that specifically characterize SI and NSSI in adolescents is needed to inform the use of these markers in intervention studies and to develop brain-based treatment targets. Here, we clinically assessed 70 adolescents-49 adolescents with depression and 21 healthy controls-to determine SI and NSSI history. Twenty-eight of the depressed adolescents had a history of SI and 29 had a history of NSSI (20 overlapping). All participants underwent a resting-state fMRI scan. We compared groups in network coherence of subdivisions of the central executive network (CEN), default mode network (DMN), and salience network (SN). We also examined group differences in between-network connectivity and explored brain-behavior correlations. Depressed adolescents with SI and with NSSI had lower coherence in the ventral DMN compared to those without SI or NSSI, respectively, and healthy controls (all ps<0.043, uncorrected). Depressed adolescents with NSSI had lower coherence in the anterior DMN and in insula-SN (all ps<0.030, uncorrected), and higher CEN-DMN connectivity compared to those without NSSI and healthy controls (all ps<0.030, uncorrected). Lower network coherence in all DMN subnetworks and insula-SN were associated with higher past-month SI and NSSI (all ps<0.001, uncorrected). Thus, in our sample, both SI and NSSI are related to brain networks associated with difficulties in self-referential processing and future planning, while NSSI specifically is related to brain networks associated with disruptions in interoceptive awareness.

    View details for DOI 10.1038/s41398-020-01103-x

    View details for PubMedID 33436537

  • Heart rate variability moderates the effects of COVID-19-related stress and family adversity on emotional problems in adolescents: Testing models of differential susceptibility and diathesis stress. Development and psychopathology Miller, J. G., Chahal, R., Kirshenbaum, J. S., Ho, T. C., Gifuni, A. J., Gotlib, I. H. 2021: 1-12


    The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents' mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13-19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.

    View details for DOI 10.1017/S095457942100033X

    View details for PubMedID 34099071

  • Sex Differences in Pubertal Associations with Fronto-accumbal White Matter Morphometry: Implications for Understanding Sensitivity to Reward and Punishment NeuroImage Chahal, R., Delevich, K., Kirshenbaum, J. S., Borchers, L. R., Ho, T. C., Gotlib, I. H. 2020
  • Smaller caudate gray matter volume is associated with greater implicit suicidal ideation in depressed adolescents. Journal of affective disorders Ho, T. C., Teresi, G. I., Ojha, A. n., Walker, J. C., Kirshenbaum, J. S., Singh, M. K., Gotlib, I. H. 2020; 278: 650–57


    Objective biomarkers of cognitive vulnerabilities related to suicidal ideation (SI) may assist in early prevention in adolescents. Previously, we found that smaller gray matter volumes (GMVs) of the dorsal striatum prospectively predicted implicit SI, measured using a computerized implicit association test (IAT) assessing associations between "self" and "death," in a community sample of adolescents. Here, we sought to replicate these findings in an independent sample of depressed adolescents.53 depressed adolescents who varied in severity of suicidal thoughts and behaviors completed high-resolution structural MRI. Caudate, putamen, and nucleus accumbens GMVs were estimated using FreeSurfer 6.0. Robust linear regressions were used to examine associations between striatal GMVs and implicit and explicit SI, covarying for sex, age, total intracranial volume, medication use, and depression severity. Significance was determined using Bonferroni correction. Finally, LASSO regression was used to identify which striatal GMV contributed most to prediction of implicit SI.Smaller bilateral caudate and right nucleus accumbens GMVs were associated with higher IAT scores (all ps<0.001). Smaller putamen and nucleus accumbens GMVs were not associated with implicit or explicit SI. Our LASSO analysis indicated that right caudate GMV contributed most to the prediction of IAT scores.This study is the first to demonstrate that caudate GMVs are significantly associated with implicit self-associations with death in a sample of depressed adolescents. When considered with our previous work, smaller caudate GMVs may be a robust biomarker of implicit SI in adolescents, with clinical implications for early identification of youth at risk for engaging in suicidal behaviors.

    View details for DOI 10.1016/j.jad.2020.09.046

    View details for PubMedID 33039875

  • Higher Executive Control Network Coherence Buffers Against Puberty-Related Increases in Internalizing Symptoms During the COVID-19 Pandemic. Biological psychiatry. Cognitive neuroscience and neuroimaging Chahal, R. n., Kirshenbaum, J. S., Miller, J. G., Ho, T. C., Gotlib, I. H. 2020


    Early pubertal maturation has been posited to be a biopsychosocial risk factor for the onset of internalizing psychopathology in adolescence; further, early-maturing youths exhibit heightened reactivity to stressful events. School closures and enforced social distancing, as well as health and financial uncertainties, during the COVID-19 pandemic are expected to adversely affect mental health in youths, particularly adolescents who are already at risk for experiencing emotional difficulties. The executive control network (ECN) supports cognitive processes required to successfully navigate novel challenges and regulate emotions in stressful contexts.We examined whether functional coherence of the ECN, measured using resting-state functional magnetic resonance imaging 5 years before the pandemic (T1), is a neurobiological marker of resilience to increases in the severity of internalizing symptoms during COVID-19 in adolescents who were in more advanced stages of puberty at T1 relative to their same-age peers (N = 85, 49 female).On average, participants reported an increase in symptoms from the 3 months before pandemic to the 2 most recent weeks during the pandemic. We found that early-maturing youths exhibited greater increases in internalizing symptoms during the pandemic if their ECN coherence was low; in contrast, relative pubertal stage was not associated with changes in internalizing symptoms in adolescents with higher ECN coherence at T1.These findings highlight the role of the functional architecture of the brain that supports executive functioning in protecting against risk factors that may exacerbate symptoms of internalizing psychopathology during periods of stress and uncertainty.

    View details for DOI 10.1016/j.bpsc.2020.08.010

    View details for PubMedID 33097469

  • Lithium continuation therapy following ketamine in patients with treatment resistant unipolar depression: a randomized controlled trial NEUROPSYCHOPHARMACOLOGY Costi, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Wade, E., Welch, A., Collins, K. A., Feder, A., Iosifescu, D. V., Charney, D. S., Murrough, J. W. 2019; 44 (10): 1812–19
  • Longitudinal Decreases in Suicidal Ideation are Associated With Increases in Salience Network Coherence in Depressed Adolescents Schwartz, J., Ho, T., Ordaz, S., Gotlib, I. ELSEVIER SCIENCE INC. 2019: S77
  • Sensitive Periods of Stress and Adolescent Amygdala-Ventromedial Prefrontal Cortex Connectivity: A Longitudinal Investigation Ho, T., Humphreys, K., King, L., Colich, N., Schwartz, J., Ohashi, K., Teicher, M., Gotlib, I. ELSEVIER SCIENCE INC. 2019: S100
  • Lithium continuation therapy following ketamine in patients with treatment resistant unipolar depression: a randomized controlled trial. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Costi, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Wade, E., Welch, A., Collins, K. A., Feder, A., Iosifescu, D. V., Charney, D. S., Murrough, J. W. 2019


    The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is associated with rapid but transient antidepressant effects in patients with treatment resistant unipolar depression (TRD). Based on work suggesting that ketamine and lithium may share overlapping mechanisms of action, we tested lithium compared to placebo as a continuation strategy following ketamine in subjects with TRD. Participants who met all eligibility criteria and showed at least an initial partial response to a single intravenous infusion of ketamine 0.5mg/kg were randomized under double-blind conditions to lithium or matching placebo before receiving an additional three infusions of ketamine. Subsequent to the ketamine treatments, participants remained on lithium or placebo during a double-blind continuation phase. The primary study outcome was depression severity as measured by the Montgomery-Asberg Depression Rating Scale compared between the two groups at Study Day 28, which occurred ~2 weeks following the final ketamine of four infusions. Forty-seven participants with TRD were enrolled in the study and underwent an initial ketamine infusion, of whom 34 participants were deemed to have at least a partial antidepressant response and were eligible for randomization. Comparison between treatment with daily oral lithium (n=18) or matching placebo (n=16) at the primary outcome showed no difference in depression severity between groups (t32=0.11, p=0.91, 95% CI [-7.87, 8.76]). There was no difference between lithium and placebo in continuing the acute antidepressant response to ketamine. The identification of a safe and effective strategy for preventing depression relapse following an acute course of ketamine treatment remains an important goal for future studies.

    View details for PubMedID 30858518

  • Resting-state functional connectivity and inflexibility of daily emotions in major depression. Journal of affective disorders Schwartz, J., Ordaz, S. J., Kircanski, K., Ho, T. C., Davis, E. G., Camacho, M. C., Gotlib, I. H. 2019; 249: 26–34


    BACKGROUND: Major Depressive Disorder (MDD) is characterized by aberrant resting-state functional connectivity (FC) in anterior cingulate regions (e.g., subgenual anterior cingulate [sgACC]) and by negative emotional functioning that is inflexible or resistant to change.METHODS: MDD (N = 33) and control (CTL; N = 31) adults completed a resting-state scan, followed by a smartphone-based Experience Sampling Methodology (ESM) protocol surveying 10 positive and negative emotions 5 times per day for 21 days. We used multilevel modeling to assess moment-to-moment emotional inflexibility (i.e., strong temporal connections between emotions). We examined group differences in whole-brain FC analysis of bilateral sgACC, and then examined associations between emotional experiences and the extracted FC values within each group.RESULTS: As predicted, MDDs had inflexibility in sadness and avoidance (p<.001, FDR-corrected p<.05), indicating that these emotional experiences persist in depression. MDDs showed weaker FC between the right sgACC and pregenual/dorsal anterior cingulate (pg/dACC) than did CTLs (FWE-corrected, voxelwise p=.01). Importantly, sgACC-pg/dACC FC predicted sadness inflexibility in both MDDs (p = .046) and CTLs (p = .033), suggesting that sgACC FC is associated with day-to-day negative emotions.LIMITATIONS: Other maladaptive behaviors likely also affect the flexibility of negative emotions. We cannot generalize our finding of a positive relation between sgACC FC and inflexibility of sadness to individuals with more chronic depression or who have recovered from depression.CONCLUSIONS: Our preliminary findings suggest that connections between portions of the ACC contribute to the persistence of negative emotions and are important in identifying a brain mechanism that may underlie the maintenance of sadness in daily life.

    View details for PubMedID 30743019

  • Longitudinal decreases in suicidal ideation are associated with increases in salience network coherence in depressed adolescents. Journal of affective disorders Schwartz, J., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2018; 245: 545–52


    BACKGROUND: Suicidal ideation (SI) is an important predictor of suicide attempt, yet SI is difficult to predict. Given that SI begins in adolescence when brain networks are maturing, it is important to understand associations between network functioning and changes in severity of SI.METHODS: Thirty-three depressed adolescents were administered the Columbia-Suicide Severity Rating Scale to assess SI and completed resting-state fMRI at baseline (T1) and 6 months later (T2). We computed coherence in the executive control (ECN), default mode (DMN), salience (SN), and non-relevant noise networks and then examined the association between changes in brain network coherence and changes in SI severity from T1 to T2.RESULTS: A greater reduction in severity of SI was associated with a stronger increase in SN coherence from T1 to T2. There were no associations between the other networks and SI.LIMITATIONS: We cannot generalize our findings to more psychiatrically diverse samples. More time-points are necessary to understand the trajectory of SI and SN coherence change.CONCLUSIONS: Our finding that reductions in SI are associated with increases in SN coherence extends previous cross-sectional results documenting a negative association between SI severity and SN coherence. The SN is involved in coordinating activation of ECN and DMN in response to salient information. Given this regulatory role of the SN, the association between SN coherence and SI suggests that adolescents with reduced SN coherence might more easily engage in harmful thoughts. Thus, the SN may be particularly relevant as a target for treatment applications in depressed adolescents.

    View details for PubMedID 30439679

  • Differing Windows of Sensitivity to Stress in Amygdala-Ventromedial Prefrontal Cortex Structural and Functional Connectivity: Implications for the Neurobiology of Depression in Youth Ho, T., Humphreys, K., King, L., Colich, N., Schwartz, J., Leong, J., Ohashi, K., Teicher, M., Gotlib, I. ELSEVIER SCIENCE INC. 2018: S81