Frontostriatal salience network expansion in individuals in depression.

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset1. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals2-4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Research-Practice Partnership to Develop and Implement Routine Mental Health Symptom Tracking Tool Among Older Adults During COVID-19.

OBJECTIVE: Older adults are disproportionally impacted by the COVID-19 pandemic, causing a mental health crisis in late life, due to physical restrictions (e.g., quarantine), limited access to services, and lower literacy and access to technology. Despite established benefits, systematic screening of mental health needs of older adults in community and routine care settings is limited and presents multiple challenges. Cross-disciplinary collaborations are essential for identification and evaluation of mental health needs and service delivery. METHODS: Using a research-practice partnership model, we developed and implemented a routine mental health needs identification and tracking tool at a community-based social services organization. Repeated screenings were conducted remotely over 5 months and included depression, anxiety, perceived loneliness, social support, and related domains such as sleep quality, resilience, and trauma symptoms linked to COVID-19. We examined symptomatic distress levels and associations between different domains of functioning. RESULTS: Our project describes the process of establishing a research-practice partnership during the COVID-19 pandemic. We collected 292 screenings from 124 individuals; clients were mildly to moderately depressed and anxious, reporting large amounts of time alone and moderate levels of loneliness. Those reporting higher depressive symptoms reported higher anxiety symptoms, poorer sleep quality, lower quality of life, lower capacity to adapt to challenging situations, and greater trauma symptoms due to COVID-19. CONCLUSION: Our routine screening tool can serve as a blueprint for case management agencies and senior centers nationwide, beyond the pressing mental health crisis due to COVID-19, to continue identifying needs as they emerge in the community.

Strength-based methods - a narrative review and comparative multilevel meta-analysis of positive interventions in clinical settings.

OBJECTIVE: In psychotherapy, strength-based methods (SBM) represent efforts to build on patients' strengths while addressing the deficits and challenges that led them to come to therapy. SBM are incorporated to some extent in all major psychotherapy approaches, but data on their unique contribution to psychotherapy efficacy is scarce. METHODS: First, we conducted a systematic review and narrative synthesis of eight process-outcome psychotherapy studies that investigated in-session SBM and their relation to immediate outcomes. Second, we conducted a systematic review and multilevel comparative meta-analysis contrasting strength-based bona fide psychotherapy vs. other bona fide psychotherapy at post-treatment (57 effect sizes nested in 9 trials). RESULTS: Despite their methodological variability, the pattern of results in the process-outcome studies was generally positive, such that SBM were linked with more favorable immediate, session-level patient outcomes. The comparative meta-analysis found an overall weighted average effect size of g = 0.17 (95% CIs [0.03, 0.31], p < .01) indicating a small but significant effect in favor of strength-based bona fide psychotherapies. There was non-significant heterogeneity among the effect sizes (Q(56) = 69.1, p = .11; I2 = 19%, CI [16%, 22%]). CONCLUSION: Our findings suggest that SBMs may not be a trivial by-product of treatment progress and may provide a unique contribution to psychotherapy outcomes. Thus, we recommend integration of SBM to clinical training and practice across treatment models.

Improved outcomes for depressed elder abuse victims with video-delivered psychotherapy during COVID-19.

OBJECTIVE: There is a lack of evidence-based scalable therapies for elder abuse victims, with no current remotely delivered tailored psychotherapy. The purpose of this manuscript is to (a) examine the effectiveness of a brief therapy for depression for elder abuse victims, and (b) to compare remote intervention delivery via phone or video to the traditional in-person delivery. METHOD: PROTECT, Providing Options to Elderly Clients Together, is a brief therapy developed in collaboration with partners at the Department for the Aging (DFTA) of New York City. During the COVID-19 outbreak, PROTECT delivery shifted from in-person to phone or video delivery. Depression severity was tracked using the Patient Health Questionaire-9 (PHQ-9). Reduction in depression severity was evaluated using a linear mixed effects model with non-inferiority test to compare the effectiveness of video vs in-person delivery of PROTECT. RESULTS: PROTECT reduced depression (average 5.15 PHQ-9 points). Video and phone delivery were non-inferior to in-person delivery. The video group completed therapy more quickly than the in-person group and had a more rapid improvement in depression symptoms. CONCLUSIONS: PROTECT therapy delivered remotely reduces depression among diverse elder abuse victims. Video delivery of PROTECT could increase reach and scalability to serve more vulnerable older depressed victims.

Modifiable predictors of nonresponse to psychotherapies for late-life depression with executive dysfunction: a machine learning approach.

The study aimed to: (1) Identify distinct trajectories of change in depressive symptoms by mid-treatment during psychotherapy for late-life depression with executive dysfunction; (2) examine if nonresponse by mid-treatment predicted poor response at treatment end; and (3) identify baseline characteristics predicting an early nonresponse trajectory by mid-treatment. A sample of 221 adults 60 years and older with major depression and executive dysfunction were randomized to 12 weeks of either problem-solving therapy or supportive therapy. We used Latent Growth Mixture Models (LGMM) to detect subgroups with distinct trajectories of change in depression by mid-treatment (6th week). We conducted regression analyses with LGMM subgroups as predictors of response at treatment end. We used random forest machine learning algorithms to identify baseline predictors of LGMM trajectories. We found that ~77.5% of participants had a declining trajectory of depression in weeks 0-6, while the remaining 22.5% had a persisting depression trajectory, with no treatment differences. The LGMM trajectories predicted remission and response at treatment end. A random forests model with high prediction accuracy (80%) showed that the strongest modifiable predictors of the persisting depression trajectory were low perceived social support, followed by high neuroticism, low treatment expectancy, and low perception of the therapist as accepting. Our results suggest that modifiable risk factors of early nonresponse to psychotherapy can be identified at the outset of treatment and addressed with targeted personalized interventions. Therapists may focus on increasing meaningful social interactions, addressing concerns related to treatment benefits, and creating a positive working relationship.

Comparing the streamlined psychotherapy "Engage" with problem-solving therapy in late-life major depression. A randomized clinical trial.

Effective psychotherapies for late-life depression are underutilized, mainly because of their complexity. "Engage" is a novel, streamlined psychotherapy that relies on neurobiology to identify core behavioral pathology of late-life depression and targets it with simple interventions, co-designed with community therapists so that they can be delivered in community settings. Consecutively recruited adults (≥60 years) with major depression (n = 249) were randomly assigned to 9 weekly sessions of "Engage" or to the evidence-based Problem-Solving Therapy (PST) offered by 35 trained community social workers and assessed by blind raters. "Engage" therapists required an average of 30% less training time to achieve fidelity to treatment than PST therapists and had one-third of the PST therapists' skill drift. Both treatments led to reduction of HAM-D scores over 9 weeks. The mixed effects model-estimated HAM-D ratings were not significantly different between the two treatments at any assessment point of the trial. The one-sided 95% CI for treatment-end difference was (-∞, 0.07) HAM-D points, indicating a non-inferiority margin of 1.3 HAM-D points or greater; this margin is lower than the pre-determined 2.2-point margin. The two treatment arms had similar response (HR = 1.08, 95% CI (0.76, 1.52), p = 0.67) and remission rates (HR = 0.89, 95% CI (0.57, 1.39), p = 0.61). We conclude that "Engage" is non-inferior to PST. If disseminated, "Engage" will increase the number of therapists who can reliably treat late-life depression and make effective psychotherapy available to large numbers of depressed older adults.

How does hostile resistance interfere with the benefits of cognitive-behavioral therapy for panic disorder? The role of therapist adherence and working alliance.

Objective Although clients' hostile behavior directed at therapists (hostile resistance) predicts worse outcomes in cognitive-behavioral therapy (CBT) for panic disorder, the process by which this happens remains unknown. This study examines two putative mechanisms: working alliance and therapist adherence. Method: Seventy-one adults with primary panic disorder received CBT in a larger trial. Hostile resistance and adherence in Sessions 2 and 10 were reliably coded using observer-rated measures; client- and therapist-rated questionnaires assessed working alliance. Outcome measures were attrition and symptomatic improvement, assessed at multiple timepoints with the Panic Disorder Severity Scale. Results: Hostile resistance was significantly related to both preexisting (r = -.36, p = .04) and subsequent declines (r = -.58, p < .0001) in the working alliance. Nevertheless, hierarchical linear modeling revealed that neither a declining alliance nor therapist adherence (whether treated as linear or curvilinear) was independently predictive of symptom change, nor did these factors mediate hostile resistance's association with worse symptomatic improvement. Exploratory logistic regressions similarly indicated that neither adherence nor alliance moderated whether hostilely resistant clients dropped out. Conclusion: This is the first study to establish a bidirectional association between hostile resistance and a declining working alliance. Findings also add to a mixed literature on the adherence-outcome relationship.

Perceived Social Support and Interpersonal Functioning as Predictors of Treatment Response Among Depressed Older Adults.

OBJECTIVE: Social isolation is highly common in late life and is associated with devastating mental health and physical outcomes. This study investigated whether components of social isolation (marital status, perceived social support, and interpersonal problems) predict change in depression severity over the course of a brief adherence intervention delivered in a primary care setting. METHOD: A sample of 189 older adults with major depressive disorder were randomized to either an adherence intervention, "Treatment Initiation Program," or treatment as usual. Marital status, perceived social support and interpersonal problems were assessed at baseline. A mixed-effects regression was used to test whether these factors predicted the change trajectory in depression severity over 24 weeks. RESULTS: Being married (F(2,176) = 6.60; p = 0.001), reporting higher perceived social support (F(2,177) = 4.70; p = 0.01), and fewer interpersonal problems (F(2, 176) = 4.34; p = 0.01) predicted lower depression severity on average over the course of 24 weeks. CONCLUSION: Social variables such as living in partnership, perceiving others as supportive, and reporting few interpersonal problems may reduce older adults' vulnerability to depression and enhance their ability to benefit from treatment. These findings can guide development of interventions that will target these social factors early in treatment to increase efficacy.

Cortical Thickness of the Salience Network and Change in Apathy Following Antidepressant Treatment for Late-Life Depression.

OBJECTIVE: Apathy is common in late-life depression and is associated with poor response to antidepressant drugs. In depressed older adults, apathy may be characterized by neuroanatomical abnormalities of the salience network. The current study examined whether cortical thickness of select salience network structures predicted change in apathy following a 12-week treatment with escitalopram. METHODS: A sample of 46 older adults with major depressive disorder received 12 weeks of escitalopram treatment at a daily target dose of 20 mg. All participants underwent a structural brain MRI scan at baseline, and cortical thickness was estimated in key cortical nodes of the salience network: the caudal anterior cingulate cortex and the insula. We measured baseline and post-treatment symptoms using the Apathy Evaluation Scale and the Hamilton Depression Rating Scale. RESULTS: A thicker insula at baseline predicted reduction in apathy symptoms following 12 weeks of treatment with escitalopram, even when controlling for age, baseline depression severity and change in depressive symptoms. CONCLUSION: Reduced insular thickness predicted residual apathetic symptoms following escitalopram treatment. These results converge with our previous findings of abnormal functional connectivity of the insular cortex in older depressed individuals with apathy. Older depressed adults with apathy may benefit from alternative treatment approaches or augmentative interventions that target abnormalities of the salience network.

PROTECT: a novel psychotherapy for late-life depression in elder abuse victims.

Elder abuse is prevalent, and victims have high rates of depression and low quality of life. We established an academic-community partnership to test the feasibility, acceptability, and impact of a brief psychotherapy for depression (PROTECT) among elder abuse victims with capacity to make decisions. Elder abuse service providers referred depressed (Patient Health Questionnaire-9 [PHQ-9] ≥ 10) older victims (age ≥ 55 years) for potential pilot study participation. Forty eligible victims who consented were randomized to PROTECT psychotherapy (N = 25) or a Usual Care (N = 15) condition involving a community psychotherapy referral. Follow-up research assessments were conducted at 6 weeks (mid-treatment) and 9 weeks (end of treatment) after study initial assessment. We used mixed-effects regression models to examine treatment effects on depression severity and quality of life over time. Most victims (75%) reported two or more types of abuse. The a priori acceptability benchmark was met at the end of PROTECT therapy. All PROTECT participants initiated therapy; this engagement rate is greater than the a priori 75% standard set for feasibility. We found a significant reduction in depression severity (Montgomery-Åsberg Depression Rating Scale [MADRS]), with PROTECT leading to greater benefits compared to Usual Care. Both study groups had a similar improvement in quality of life. The pilot project results found that PROTECT psychotherapy is feasible, acceptable, and effective in reducing depression. With the support of our partnership, we found that PROTECT could be delivered alongside elder abuse services with victims willing to initiate therapy that leads to meaningful treatment effects.