The Management of Major Depressive Disorder: Synopsis of the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations. METHODS: Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis. RECOMMENDATIONS: The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on pharmacologic management, pharmacogenomics, psychotherapy, complementary and alternative therapies, and the use of telemedicine.

Maternal Bonding Predicts Actigraphy-Measured Sleep Parameters in Depressed and Nondepressed Adults.

Associations between subjective maternal bonding recalled from the first 16 years of life and current sleep indices were investigated in a clinical sample of 34 adults with major depressive disorder and 36 normal controls (n = 70) using the self-report parental bonding instrument and wrist actigraphy. Results of multiple linear regression analyses indicated that reports of maternal bonding indices were associated with several sleep indices in adulthood independent of depression status. Higher levels of maternal care were associated with greater time in bed and total sleep time. Higher levels of maternal overprotection were associated with fewer awakenings. Findings indicate that reported maternal bonding characteristics in childhood are related to objectively measured sleep characteristics in adulthood, independent of mood state.

A Virtual Reality Intervention for the Treatment of Phantom Limb Pain: Development and Feasibility Results.

OBJECTIVE: To describe the development of a virtual reality (VR) treatment for phantom limb pain (PLP) and phantom sensations and provide feasibility data from testing the treatment in a population of veterans. DESIGN & SUBJECTS: Fourteen participants completed a baseline visit evaluating their amputation, PLP, and phantom sensations. Subsequently, participants completed a VR treatment modeled after mirror therapy for PLP, navigating in a VR environment with a bicycle pedaler and motion sensor to pair their cadence to a VR avatar. The VR avatar enabled visualization of the participant's intact phantom limb in motion, a hypothesized mechanism of mirror therapy. SETTING: Laboratory. METHODS: Participants completed pre- and post-treatment measures to evaluate changes in PLP, phantom sensations, and rate helpfulness, realism, immersion, adverse experiences, and treatment satisfaction. RESULTS: Eight of 14 participants (57.1%) reported PLP pre-VR treatment, and 93% (13/14) reported one or more unpleasant phantom sensations. After treatment, 28.6% (4/14) continued to report PLP symptoms (t[13] = 2.7, P = 0.02, d = 0.53) and 28.6% (4/14) reported phantom sensations (t[13] = 4.4, P = 0.001, d = 1.7). Ratings of helpfulness, realism, immersion, and satisfaction were uniformly high to very high. There were no adverse experiences. Four participants completed multiple VR treatments, showing stable improvements in PLP intensity and phantom sensations and high user ratings. CONCLUSIONS: This feasibility study of a novel VR intervention for PLP was practical and was associated with significant reductions in PLP intensity and phantom sensations. Our findings support continued research in VR-based treatments in PLP, with a need for direct comparisons between VR and more established PLP treatments.

Long-term effects of executive function training among veterans with chronic TBI.

Objective: To investigate long-term effects of GOALS executive function training in Veterans with chronic TBI. In a recently completed study Veterans with chronic TBI showed improvement immediately post-GOALS but not control training on measures of executive function, functional task performance, and emotion regulation. We now examine the long-term maintenance of post-GOALS training changes in the same sample. Setting: San Francisco VA Health Care System (SFVAHCS), and VA Northern California Health-Care System (VANCHS) in Martinez. Participants and Design: 24 Veterans with chronic TBI were assessed at baseline, post-GOALS training, and long-term follow-up 6+ months following completion of training with a structured telephone interview, neuropsychological and complex functional performance measures, and self-report measures of daily and emotional functioning. Results: Participants reported an increased likelihood of involvement in competitive employment/volunteering at follow-up (61%) compared to baseline (26%; χ2 = 5.66, p < .01, ѱ = .35). Repeated measures MANOVAS indicated improvement on attention/executive function (F = 13.85, p < .01, partial η2 = .42), complex functional task performance (GPS Total: F = 9.12, p < .01, partial η2 = .38) and daily functioning (MPAI Total: F = 3.23, p < .05, partial η2 = .21), and reduction in overall mood disturbance (POMS Total: F = 3.42, p < .05, partial η2 = .22) at follow-up relative to baseline. Discussion: Training in attention regulation applied to participant-defined goals is associated with meaningful long-term improvement in cognitive skills, emotion regulation, and daily functioning in Veterans with chronic TBI.

Randomized controlled trial of cognitive behavioral social skills training for older consumers with schizophrenia: defeatist performance attitudes and functional outcome.

OBJECTIVES: To determine whether Cognitive Behavioral Social Skills Training (CBSST) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia, and whether defeatist performance attitudes are associated with change in functioning in CBSST. DESIGN: An 18-month, single-blind, randomized controlled trial. SETTING: Outpatient clinic at a university-affiliated Veterans Affairs hospital. PARTICIPANTS: Veteran and non-veteran consumers with schizophrenia or schizoaffective disorder (N = 79) age 45-78. INTERVENTIONS: CBSST was a 36-session, weekly group therapy that combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning. The comparison intervention, goal-focused supportive contact (GFSC), was supportive group therapy focused on achieving functioning goals. MEASUREMENTS: Blind raters assessed functioning (primary outcome: Independent Living Skills Survey), CBSST skill mastery, positive and negative symptoms, depression, anxiety, defeatist attitudes, self-esteem, and life satisfaction. RESULTS: Functioning trajectories over time were significantly more positive in CBSST than in GFSC, especially for participants with more severe defeatist performance attitudes. Greater improvement in defeatist attitudes was also associated with better functioning in CBSST, but not GFSC. Both treatments showed comparable significant improvements in amotivation, depression, anxiety, positive self-esteem, and life satisfaction. CONCLUSIONS: CBSST is an effective treatment to improve functioning in older consumers with schizophrenia, and both CBSST and other supportive goal-focused interventions can reduce symptom distress, increase motivation and self-esteem, and improve life satisfaction. Participants with more severe defeatist performance attitudes may benefit most from cognitive behavioral interventions that target functioning. TRIAL REGISTRY: ClinicalTrials.Gov #NCT00237796 (http://clinicaltrials. gov/show/NCT00237796).

12-step affiliation and attendance following treatment for comorbid substance dependence and depression: a latent growth curve mediation model.

Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD.

Improvement in executive functioning after Goal-Oriented Attentional Self-Regulation training is associated with reduction in PTSD hyperarousal symptoms among veterans with comorbid PTSD and mild TBI.

Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that combines mindfulness-based attention regulation with individualized goal management strategies to improve functioning in daily life after traumatic brain injury (TBI). While not a specific target of GOALS training, previous research has indicated improvements in emotional functioning following GOALS training, specifically symptoms related to depression and posttraumatic stress disorder (PTSD). The current study is based on the hypothesis that improvements in cognitive control processes related to executive functioning and attention after GOALS training generalize to improvements in emotional functioning, thereby resulting in reductions in emotional distress. The current study analyzed archival data from 33 Veteran participants with a confirmed diagnosis of PTSD and a history of mild TBI who received either GOALS training or a psychoeducational intervention matched for time, therapist attention, and participation format. Regression analysis was used to assess the strength of the relationship between improvements in Overall Attention/Executive Functioning and decreases in hyperarousal symptoms associated with PTSD. Results from the regression analysis revealed that improvements in Overall Attention/Executive Functioning after GOALS was significantly associated with reductions in hyperarousal symptoms associated with PTSD (R2 = 0.26, F(1,15) = 5.01, ß = -.51, p < .05). The current findings suggest that cognitive improvements after GOALS training may lead to changes in emotional functioning, resulting in decreased emotional distress. This is important, particularly in VA settings, because the results potentially highlight additional areas of research and focus on the treatment of comorbid mild TBI and PTSD among Veterans.

Alpha Event-Related Desynchronization During Reward Processing in Schizophrenia.

BACKGROUND: Alterations in the brain's reward system may underlie motivation and pleasure deficits in schizophrenia (SZ). Neuro-oscillatory desynchronization in the alpha band is thought to direct resource allocation away from the internal state, to prioritize processing salient environmental events, including reward feedback. We hypothesized reduced reward-related alpha event-related desynchronization (ERD) in SZ, consistent with less externally focused processing during reward feedback. METHODS: Electroencephalography was recorded while participants with SZ (n = 54) and healthy control participants (n = 54) played a simple slot machine task. Total alpha band power (8-14 Hz), a measure of neural oscillation magnitude, was extracted via principal component analysis and compared between groups and reward outcomes. The clinical relevance of hypothesized alpha power alterations was examined by testing associations with negative symptoms within the SZ group and with trait rumination, dimensionally, across groups. RESULTS: A group × reward outcome interaction (p = .018) was explained by healthy control participants showing significant posterior-occipital alpha power suppression to wins versus losses (p < .001), in contrast to participants with SZ (p > .1). Among participants with SZ, this alpha ERD was unrelated to negative symptoms (p > .1). Across all participants, less alpha ERD to reward outcomes covaried with greater trait rumination for both win (p = .005) and loss (p = .002) outcomes, with no group differences in slope. CONCLUSIONS: These findings demonstrate alpha ERD alterations in SZ during reward outcome processing. Additionally, higher trait rumination was associated with less alpha ERD during reward feedback, suggesting that individual differences in rumination covary with external attention to reward processing, regardless of reward outcome valence or group membership.

Psychological Dimensions Relevant to Motivation and Pleasure in Schizophrenia.

Motivation and pleasure deficits are common in schizophrenia, strongly linked with poorer functioning, and may reflect underlying alterations in brain functions governing reward processing and goal pursuit. While there is extensive research examining cognitive and reward mechanisms related to these deficits in schizophrenia, less attention has been paid to psychological characteristics that contribute to resilience against, or risk for, motivation and pleasure impairment. For example, psychological tendencies involving positive future expectancies (e.g., optimism) and effective affect management (e.g., reappraisal, mindfulness) are associated with aspects of reward anticipation and evaluation that optimally guide goal-directed behavior. Conversely, maladaptive thinking patterns (e.g., defeatist performance beliefs, asocial beliefs) and tendencies that amplify negative cognitions (e.g., rumination), may divert cognitive resources away from goal pursuit or reduce willingness to exert effort. Additionally, aspects of sociality, including the propensity to experience social connection as positive reinforcement may be particularly relevant for pursuing social goals. In the current review, we discuss the roles of several psychological characteristics with respect to motivation and pleasure in schizophrenia. We argue that individual variation in these psychological dimensions is relevant to the study of motivation and reward processing in schizophrenia, including interactions between these psychological dimensions and more well-characterized cognitive and reward processing contributors to motivation. We close by emphasizing the value of considering a broad set of modulating factors when studying motivation and pleasure functions in schizophrenia.

Psychiatric residents' interest in psychotherapy and training stage: a multi-site survey.

BACKGROUND: Most psychiatric residents enter training intent on learning both psychopharmacologic and psychotherapeutic interventions. After graduation, however, many emphasize pharmacotherapy over psychotherapy. METHODS: A multisite survey of psychiatry residents queried psychotherapy interests, attitudes, and practice intentions. Factors associated with self-reported decreased interest in psychotherapy since beginning residency were examined. RESULTS: Although 11.8% of the entire sample (n = 229 PGY1-PGY4 residents) reported decreased interest in psychotherapy during training, among PGY4s the corresponding figure was 16.4%. Positive attitudes towards psychotherapy, and self-perceived competence in cognitive-behavioral and psychodynamic psychotherapy were most highly correlated with maintained interest in psychotherapy. Dissatisfaction with the quality of psychotherapy faculty and curriculum, and viewing departmental leadership as unsupportive of psychotherapy training were correlated with decreased interest during training. CONCLUSIONS: Maintaining residents' interest in psychotherapy requires improvements in curriculum, teaching, and supervision throughout training. Our data underscore the crucial role that departmental leadership must play in supporting trainees' goals of becoming comprehensively trained psychiatrists.

VA Academic Affiliations Matter in the Era of Community Care: A Model From California.

BACKGROUND: The Veterans Health Administration (VHA), 1 of 3 administrative branches in the US Department of Veterans Affairs (VA), is the largest integrated health care system in the United States. The VHA has 4 missions: providing health care to eligible veterans; supporting research to benefit veterans and the larger society; providing education for health care trainees; and supporting emergency response. OBSERVATIONS: In service of these goals, the VA has academic affiliations with training institutions throughout the country, offering unique and extensive training and research opportunities. These affiliations are a 2-way street where both the VA and the affiliate provide and gain from their partnership. For example, VA affiliations with University of California (UC) medical schools benefit veteran care and are a major contributor to the UC academic mission. This article explores the history of the VA, current veteran demographics and needs, academic affiliations, and the integrated care model of training in all VHA facilities. The VA and UC academic affiliation system is described further with regard to shared research and educational functions. CONCLUSIONS: We identify risks to academic affiliations if a shift occurs from VHA care to VA-managed community-based care following the implementation of recent legislation. We also provide suggestions for VA academic affiliates to help assess and guide the potential impact of increased VA-managed community care.

Goal-Oriented Attention Self-Regulation Training Improves Executive Functioning in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury.

Difficulties in executive-control functions are common sequelae of both traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). The goal of this study was to assess whether a cognitive rehabilitation training that was applied successfully in civilian and military TBI would be effective for military Veterans with comorbid PTSD and mild TBI (mTBI). In the previous study, Veterans with a history of mild to severe TBI improved significantly after goal-oriented attentional self-regulation (GOALS) training on measures of attention/executive function, functional task performance, and emotional regulation. The objective of this study was to assess effects of GOALS training in Veterans with comorbid PTSD and mTBI. Forty Veterans with a current PTSD diagnosis and history of mTBI (6+ months post) were randomized to either five weeks of GOALS or Brain-Health Education (BHE) training matched in time and intensity. Evaluator-blinded assessments at baseline and post-training included neuropsychological and complex functional task performance, and self-report measures of emotional functioning/regulation. After GOALS but not BHE training, participants significantly improved from baseline on primary outcome measures of: overall complex attention/executive function neuropsychological performance composite (F = 12.35, p = 0.001; Cohen d = 0.48), and overall mood disturbance -POMS emotional regulation self-report (F = 4.29, p = 0.05, Cohen d = 0.41). In addition, GOALS but not BHE participants indicated a significant decrease in PTSD symptoms (PCL-M Total Score) (F = 4.80, p = 0.05, Cohen d = 0.60), and demonstrated improvement on complex functional task performance-GPS Learning and Memory (F = 5.06, p = 0.05, Cohen d = 0.56]. Training in attentional self-regulation applied to participant-defined goals may improve cognitive functioning in Veterans with comorbid PTSD and mTBI. Improving cognitive control functioning may also improve functioning in other domains such as emotional regulation and functional performance, potentially making it particularly relevant for Veterans with a history of mTBI and comorbid psychiatric symptoms.

A longitudinal investigation of the impact of life stress on HIV treatment adherence.

Suboptimal antiretroviral adherence is associated with poorer HIV outcomes. Psychosocial factors, including life stress, depression and coping, may influence adherence behavior. This prospective investigation sought to examine the impact of life stress (acute life events, chronic stress, and perceived stress), depression, and coping style on adherence to HIV treatment regimes over time. Participants were 87 treatment-seeking HIV-infected individuals recruited from an urban HIV clinic. They completed clinician-administered interviews and self-report questionnaires at baseline and 3-month follow-up. Acute life events and chronic stress prospectively predicted decreases in treatment adherence more strongly among individuals in a major depressive episode (n = 21) compared to non-depressed individuals (n = 66). Coping style did not appear to be the mechanism by which life stress influenced adherence among depressed HIV-infected individuals. These findings demonstrate that life stress has toxic effects for depressed individuals and suggest that treatment adherence interventions with depressed individuals could be enhanced via development of stress management skills.

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial.

Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. Prolonged Exposure (PE) therapy is one of the most widely used evidence-based treatments for PTSD, but there is substantial room for improvement in outcomes and retention rates. Accumulating data suggest that oxytocin offers a promising pharmacological approach towards achieving this goal. Therefore, the primary objective of this two-site Phase II study is to examine the ability of oxytocin (vs. placebo) administration combined with PE therapy to (1) reduce PTSD symptom severity, (2) accelerate the rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). Intranasal oxytocin (40 IU) will be administered directly prior to each PE therapy session. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the physiological mechanisms underlying PTSD and positive treatment response. ClinicalTrials.gov Identifier: NCT04228289.

Working with reactant patients: are we prescribing nonadherence?

OBJECTIVE: In spite of high levels of antidepressant nonadherence frequently observed among depressed samples, relatively little research has investigated psychosocial predictors of adherence. Fostering greater collaboration in depression treatment to increase adherence has been advocated, but this strategy has not been adequately studied. The aim of this study was to examine the interaction of provider collaboration and patient reactance in the prediction of antidepressant adherence during the acute treatment phase. METHOD: Fifty outpatients diagnosed with major depressive disorder beginning antidepressant treatment within psychiatry clinics of the VA San Diego Healthcare System comprised the study sample. Patients were administered questionnaires following their medication evaluations to measure predictor variables. Antidepressant adherence was assessed via brief telephone interviews 3, 6, 9, and 12 weeks after treatment initiation. The roles of provider collaboration, patient reactance, and their interaction in adherence were examined using multiple regression analyses. RESULTS: The interaction between provider collaboration and patient reactance accounted for 18.3% of the variance in 3-week adherence (P<.01). Among more reactant patients, greater levels of collaboration predicted better adherence, whereas among patients lower in reactance less collaboration predicted better adherence. No relationships were observed beyond the initial 3 weeks of treatment. CONCLUSIONS: This study demonstrates that interpersonal process variables are important in influencing antidepressant adherence and challenges the advocacy of more collaboration in antidepressant treatment as a "blanket strategy." Establishing a more collaborative set with reactant patients may ensure greater early treatment adherence, a critical period during which antidepressants have typically not yet taken effect.

Neuropsychological predictors of functional outcome in Cognitive Behavioral Social Skills Training for older people with schizophrenia.

Cognitive Behavioral Social Skills Training (CBSST) is a 24-session weekly group therapy intervention to improve functioning in people with schizophrenia. In our prior randomized clinical trial comparing treatment as usual (TAU) with TAU plus group CBSST (Granholm, E., McQuaid, J.R., McClure, F.S., Auslander, L., Perivoliotis, D., Pedrelli, P., Patterson, T., Jeste, D.V., 2005. A randomized controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am. J. Psychiatry 162, 520-529.), participants with schizophrenia in CBSST showed significantly better functional outcome than participants in TAU. The present study was a secondary analysis of neuropsychological predictors of functional outcome in our prior CBSST trial. We examined (1) whether neuropsychological impairment at baseline moderated functional outcome in CBSST relative to TAU, and (2) whether improvement in neuropsychological abilities mediated improvement in functional outcome in CBSST. Attention, verbal learning/memory, speed of processing, and executive functions were assessed at baseline, end of treatment, and 12-month follow-up. Greater severity of neuropsychological impairment at baseline predicted poorer functional outcome for both treatment groups (nonspecific predictor), but the interaction between severity of neuropsychological impairment and treatment group was not significant (no moderation). Effect sizes for the difference between treatment groups on functional outcome measures at 12-month follow-up were similar for participants with relatively mild (d=.44-.64) and severe (d=.29-.60) neuropsychological impairment. Results also did not support the hypothesis that improvement in neuropsychological abilities mediated improvement in functioning in CBSST. Adding CBSST to standard pharmacologic care, therefore, improved functioning relative to standard care alone, even for participants with severe neuropsychological impairment, and this improvement in functioning was not related to improvement in neuropsychological abilities in CBSST.

Comorbidity of substance dependence and depression: role of life stress and self-efficacy in sustaining abstinence.

The authors examined life stress and self-efficacy as predictors of time to relapse for 113 adults with comorbid major depressive disorder and alcohol and/or substance dependence in a randomized clinical trial comparing 2 psychotherapy interventions (integrated cognitive- behavioral therapy and 12-step facilitation therapy). Life stress, self-efficacy, and substance use were assessed at treatment entry, 12 weeks (mid-treatment), and 24 weeks (end of treatment). Time to relapse was defined as the number of days from treatment initiation until first alcohol and/or drug use. Half of the sample relapsed within the study period of 24 weeks. There was no significant difference between treatment groups. Individuals experiencing life stressors were more likely to relapse early than those not experiencing life stressors. Lower self-efficacy also predicted earlier relapse. Chronic stress levels and self-efficacy were stable across time for most individuals. In contrast, acute stress events occurred at differing times, and survival analyses provided evidence of heightened relapse risk in the month following acute stressors. The interaction of self-efficacy and life stress was not significant. The results highlight the significance of life stress and self-efficacy as predictors of early relapse.

A randomized controlled trial of cognitive-behavior therapy for tinnitus.

This study is a randomized, waitlist-controlled trial testing the effect of a brief, "manualized" cognitive-behavioral group therapy on distress associated with tinnitus, quality of well-being, psychological distress including depression, and internal focus. Cognitive-behavioral therapy (CBT) included training in activity planning, relaxation training and, primarily, cognitive restructuring. Sixty-five participants were recruited, and 41 completed treatment. Participants were randomly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period. Participants completed outcome measures at the time of their random assignment and at 8, 16, and 52 weeks later. Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression, indicating that CBT led to greater improvement in those symptoms. The current results suggest that CBT, applied in a group format using a manual, can reduce the negative emotional distress, including depression, associated with tinnitus.

Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse.

BACKGROUND: According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression. METHODS: Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed. RESULTS: Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state. CONCLUSIONS: These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.