Cognitive Behavioral Program for the Prevention of Depression in At-Risk Adolescents: Isolating the Effects of Dose.

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFD) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multi-site randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13-17. Youth were randomly assigned to the CBP program plus usual care (n=159) or to usual care alone (n=157). The CBP program involved 8 weekly acute sessions and 6 monthly continuation sessions. Results showed that higher CBP program dose predicted more DFDs, with a key threshold of approximately 75% of a full dose in analyses employing instrumental variable methodology to control multiple channels of bias. Specifically, attending at more than 75% of acute phase sessions led to 45.3 more DFDs over the 9-month period post randomization, which accounted for over 12% of the total follow-up days. Instrument sets were informed by study variables and external data including weather and travel burden. In contrast, conventional analysis methods failed to find a significant dose-outcome relation. Application of the instrumental variable approach, which better controls the influence of confounding, demonstrated that higher CBP program dose resulted in more DFDs.

Zero Suicide Quality Improvement: Developmental and Pandemic-Related Patterns in Youth at Risk for Suicide Attempts.

The Zero Suicide (ZS) approach to health system quality improvement (QI) aspires to reduce/eliminate suicides through enhancing risk detection and suicide-prevention services. This first report from our randomized trial evaluating a stepped care for suicide prevention intervention within a health system conducting ZS-QI describes 1) our screening and case identification process, 2) variation among adolescents versus young adults; and 3) pandemic-related patterns during the first COVID-19 pandemic year. Between April 2017 and January 2021, youths aged 12-24 with elevated suicide risk were identified through an electronic health record (EHR) case-finding algorithm followed by direct assessment screening to confirm risk. Eligible/enrolled youth were evaluated for suicidality, self-harm, and risk/protective factors. Case finding, screening, and enrollment yielded 301 participants showing suicide risk-indicators: 97% past-year suicidal ideation, 83% past suicidal behavior; 90% past non-suicidal self-injury (NSSI). Compared to young adults, adolescents reported: more past-year suicide attempts (47% vs 21%, p<.001) and NSSI (past 6-months, 64% vs 39%, p<.001); less depression, anxiety, posttraumatic stress, and substance use; and greater social connectedness. Pandemic-onset was associated with lower participation of racial-ethnic minority youths (18% vs 33%, p<.015) and lower past-month suicidal ideation and behavior. Results support the value of EHR case-finding algorithms for identifying youths with potentially elevated risk who could benefit from suicide-prevention services, which merit adaptation for adolescents versus young adults. Lower racial-ethnic minority participation after the COVID-19 pandemic-onset underscores challenges for services to enhance health equity during a period with restricted in-person health care, social distancing, school closures, and diverse stresses.

Sleep Characteristics are Associated with Risk of Treated Diabetes Among Postmenopausal Women.

OBJECTIVE: The purpose of this study was to determine whether sleep characteristics are associated with incidence of treated diabetes in postmenopausal individuals. METHODS: Postmenopausal participants ages 50-79 years reported sleep duration, sleep-disordered breathing, or insomnia at baseline and again in a subsample 3 years later. The primary outcome was self-reported new diagnosis of diabetes treated with oral drugs or insulin at any time after baseline. Multivariable Cox proportional hazards models were used. RESULTS: In 135,964 participants followed for 18.1 (± 6.3) years, there was a nonlinear association between sleep duration and risk of treated diabetes. Participants sleeping ≤5 hours at baseline had a 21% increased risk of diabetes compared with those sleeping 7 hours (adjusted hazard ratio [aHR] 1.21; 95% confidence interval [CI], 1.00-1.47). Those who slept for ≥9 hours had a nonsignificant 6% increased risk of diabetes compared with those sleeping 7 hours (aHR 1.06; 95% CI, 0.97-1.16). Participants whose sleep duration had decreased at 3 years had a 9% (aHR 1.09; 95% CI, 1.02-1.16) higher risk of diabetes than participants with unchanged sleep duration. Participants who reported increased sleep duration at 3 years had a risk of diabetes (HR 1.01; 95% CI, 0.95-1.08) similar to those with no sleep duration change. Participants at high risk of sleep-disordered breathing at baseline had a 31% higher risk of diabetes than those without (aHR 1.31; 95% CI, 1.26-1.37). No association was found between self-reported insomnia score and diabetes risk. CONCLUSIONS: Sleep-disordered breathing and short or long sleep duration were associated with higher diabetes risk in a postmenopausal population.

Predicting suicide attempts and suicide deaths among adolescents following outpatient visits.

BACKGROUND: Few studies report on machine learning models for suicide risk prediction in adolescents and their utility in identifying those in need of further evaluation. This study examined whether a model trained and validated using data from all age groups works as well for adolescents or whether it could be improved. METHODS: We used healthcare data for 1.4 million specialty mental health and primary care outpatient visits among 256,823 adolescents across 7 health systems. The prediction target was 90-day risk of suicide attempt following a visit. We used logistic regression with least absolute shrinkage and selection operator (LASSO) and generalized estimating equations (GEE) to predict risk. We compared performance of three models: an existing model, a recalibrated version of that model, and a newly-learned model. Models were compared using area under the receiver operating curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The AUC produced by the existing model for specialty mental health visits estimated in adolescents alone (0.796; [0.789, 0.802]) was not significantly different than the AUC of the recalibrated existing model (0.794; [0.787, 0.80]) or the newly-learned model (0.795; [0.789, 0.801]). Predicted risk following primary care visits was also similar: existing (0.855; [0.844, 0.866]), recalibrated (0.85 [0.839, 0.862]), newly-learned (0.842, [0.829, 0.854]). LIMITATIONS: The models did not incorporate non-healthcare risk factors. The models relied on ICD9-CM codes for diagnoses and outcome measurement. CONCLUSIONS: Prediction models already in operational use by health systems can be reliably employed for identifying adolescents in need of further evaluation.

Augmenting usual care SSRIs with cognitive behavioral therapy for insomnia to improve depression outcomes in youth: Design of a randomized controlled efficacy-effectiveness trial.

IMPORTANCE: Extant treatments for youth depression are only modestly effective. Alternative approaches are needed to improve health outcomes. A novel approach to improve depression outcomes is suggested by epidemiological studies finding that insomnia often predates and may contribute to depression risk. We test whether treating insomnia among youth starting a new course of SSRI antidepressants improves depression outcomes. This paper describes our study design. DESIGN: 2-arm randomized controlled efficacy-effectiveness trial. SETTING: A large non-profit health maintenance organization. PARTICIPANTS: 165 adolescents aged 12-19 with research-confirmed depression and insomnia diagnoses, starting a new episode of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment prescribed by their usual care provider. INTERVENTIONS: Two sleep interventions, each 6-7 sessions, both overlaying "treatment as usual" (TAU) SSRIs: a sleep hygiene (SH) attention control condition, and cognitive-behavioral therapy for insomnia (CBTI). CONCLUSIONS AND RELEVANCE: If CBT-I improved sleep is shown to improve depression-related outcomes, this may provide an additional, easily tolerated intervention for an important public health target. TRIAL REGISTRATION: clinicaltrials.gov, NCT02290496, https://clinicaltrials.gov/ct2/show/NCT02290496.

Cognitive-behavioral treatment of insomnia and depression in adolescents: A pilot randomized trial.

We tested whether augmenting conventional depression treatment in youth by treating sleep issues with cognitive behavioral therapy for insomnia (CBT-I) improved depression outcomes. We randomized youth 12-20 years of age to 10 weekly sessions of a sleep hygiene control condition (SH) combined with CBT for depression (CBT-D) (n = 20), or an experimental condition consisting of CBT-I combined with CBT-D (n = 21). We assessed outcomes through 26 weeks of follow-up and found medium-large effects favoring the experimental CBT-I arm on some sleep outcomes (actigraphy total sleep time and Insomnia Severity Index "caseness") and depression outcomes (higher percentage recovered, faster time to recovery), but little effect on other measures. Total sleep time improved by 99 min from baseline to week 12 in the CBT-I arm, but not in the SH arm. In addition, our pilot yielded important products to facilitate future studies: the youth-adapted CBT-I program; the study protocol; estimates of recruitment, retention, and attrition; and performance and parameters of candidate outcome measures. ClinicalTrials.gov Identifier NCT00949689.

Collaborative care for adolescents with depression in primary care: a randomized clinical trial.

IMPORTANCE: Up to 20% of adolescents experience an episode of major depression by age 18 years yet few receive evidence-based treatments for their depression. OBJECTIVE: To determine whether a collaborative care intervention for adolescents with depression improves depressive outcomes compared with usual care. DESIGN: Randomized trial with blinded outcome assessment conducted between April 2010 and April 2013. SETTING: Nine primary care clinics in the Group Health system in Washington State. PARTICIPANTS: Adolescents (aged 13-17 years) who screened positive for depression (Patient Health Questionnaire 9-item [PHQ-9] score ≥10) on 2 occasions or who screened positive and met criteria for major depression, spoke English, and had telephone access were recruited. Exclusions included alcohol/drug misuse, suicidal plan or recent attempt, bipolar disorder, developmental delay, and seeing a psychiatrist. INTERVENTIONS: Twelve-month collaborative care intervention including an initial in-person engagement session and regular follow-up by master's-level clinicians. Usual care control youth received depression screening results and could access mental health services through Group Health. MAIN OUTCOMES AND MEASURES: The primary outcome was change in depressive symptoms on a modified version of the Child Depression Rating Scale-Revised (CDRS-R; score range, 14-94) from baseline to 12 months. Secondary outcomes included change in Columbia Impairment Scale score (CIS), depression response (≥50% decrease on the CDRS-R), and remission (PHQ-9 score <5). RESULTS: Intervention youth (n = 50), compared with those randomized to receive usual care (n = 51), had greater decreases in CDRS-R scores such that by 12 months intervention youth had a mean score of 27.5 (95% CI, 23.8-31.1) compared with 34.6 (95% CI, 30.6-38.6) in control youth (overall intervention effect: F2,747.3 = 7.24, P < .001). Both intervention and control youth experienced improvement on the CIS with no significant differences between groups. At 12 months, intervention youth were more likely than control youth to achieve depression response (67.6% vs 38.6%, OR = 3.3, 95% CI, 1.4-8.2; P = .009) and remission (50.4% vs 20.7%, OR = 3.9, 95% CI, 1.5-10.6; P = .007). CONCLUSIONS AND RELEVANCE: Among adolescents with depression seen in primary care, a collaborative care intervention resulted in greater improvement in depressive symptoms at 12 months than usual care. These findings suggest that mental health services for adolescents with depression can be integrated into primary care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01140464.

Evidence for the management of adolescent depression.

Adolescent depression is a prevalent and disabling condition resulting in emotional suffering and social and educational dysfunction. Care for adolescent depression is suboptimal and could be improved through the development and use of quality indicators (QIs). This article reports on the development of a care pathway and QIs for the primary and specialty care management of adolescent depression from case identification through symptom remission. It presents evidence from a review of adolescent clinical practice guidelines and research literature to support QIs at critical nodes in the pathway, and describes implications for practice based on existing evidence. Barriers to measure development are identified, including gaps in empirical evidence, and a research agenda is suggested.

Evaluating the promise of health IT to enhance/expand the reach of mental health services.

OBJECTIVE: A growing number of health information technologies (HIT) are being developed and tested to address mental health conditions. HIT includes Internet and smartphone programs or apps, text messaging protocols and telepsychiatry. We reviewed the promise and evidence that HIT can expand access to mental health care and reduce disparities in use of services across groups in need. CONCLUSIONS: Limited reach of mental health services is a pervasive problem in the United States, and solving it will require innovations that enable us to extend our clinical reach into underserved populations without significantly expanding our workforce. In theory, HIT can extend access to mental health care in several ways: by enhancing the reach to priority populations, addressing system capacity issues, supporting training, improving clinical decision making, lowering the "consumer's threshold" for treatment, delivering preventive mental health services, speeding innovation and adoption and reducing cost barriers to treatment. At present, evidence is limited, and research is needed, focusing on consumer engagement strategies, the benefits and harms of HIT for the therapeutic relationship and the comparative effectiveness of various HIT alternatives.

Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression.

OBJECTIVE: To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial. METHOD: Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models. RESULTS: Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms. CONCLUSION: The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine. Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.

The complex role of sleep in adolescent depression.

Psychological and pharmacologic treatments for youth depression yield post-acute response and remission rates that are modest at best. Improving these outcomes is an important long-term goal. The authors examine the possibility that a youth cognitive behavioral therapy insomnia intervention may be an adjunct to traditional depression-focused treatment with the aim of improving depression outcomes. This "indirect route" to improving youth depression treatment outcomes is based on research indicating that the risk of depression is increased by primary insomnia and that sleep problems interfere with depression treatment success and on emerging adult depression randomized controlled trial results. The authors describe the protocol they developed.

Trends in youth antidepressant dispensing and refill limits, 2000 through 2009.

BACKGROUND: Antidepressant (AD) dispensing for depression in youth declined in the years following the 2003-04 Food and Drug Administration actions regarding increased risk of suicidal behavior. OBJECTIVE: To extend observation of youth AD dispensing and associated characteristics through 2009 to determine if AD dispensing continues to decline, has stabilized, or has rebounded. DESIGN: Retrospective time series design. SAMPLE: Youth (n=57,782) ages 10 to 17 inclusive. RESULTS: Both new (incident) and refill AD dispensing continued to decline through 2009, with no sign of leveling off. However, among youth who started AD treatment the cumulative supply of AD medication remained consistent across the pre- and postperiods, suggesting that cumulative treatment episode duration has not been degraded--possibly as a function of greater days supply with each new refill in the postperiod. Prescribers dramatically curtailed preauthorized refills in the postwarning period. CONCLUSION: Declines in AD dispensing to depressed youth may not reflect less intensive treatment for those youth who persist beyond the initial dispense. Lower rates of preauthorized refills may have been an attempt by prescribers to encourage return visits to evaluate response and adverse consequences.

Suicide attempts and nonsuicidal self-injury in the treatment of resistant depression in adolescents: findings from the TORDIA study.

OBJECTIVE: To evaluate the clinical and prognostic significance of suicide attempts (SAs) and nonsuicidal self-injury (NSSI) in adolescents with treatment-resistant depression. METHOD: Depressed adolescents who did not improve with an adequate SSRI trial (N = 334) were randomized to a medication switch (SSRI or venlafaxine), with or without cognitive-behavioral therapy. NSSI and SAs were assessed at baseline and throughout the 24-week treatment period. RESULTS: Of the youths, 47.4% reported a history of self-injurious behavior at baseline: 23.9% NSSI alone, 14% NSSI+SAs, and 9.5% SAs alone. The 24-week incidence rates of SAs and NSSI were 7% and 11%, respectively; these rates were highest among youths with NSSI+SAs at baseline. NSSI history predicted both incident SAs (hazard ratio [HR]= 5.28, 95% confidence interval [CI] = 1.80-15.47, z = 3.04, p = .002) and incident NSSI (HR = 7.31, z = 4.19, 95% CI = 2.88-18.54, p < .001) through week 24, and was a stronger predictor of future attempts than a history of SAs (HR = 1.92, 95% CI = 0.81-4.52, z = 2.29, p = .13). In the most parsimonious model predicting time to incident SAs, baseline NSSI history and hopelessness were significant predictors, adjusting for treatment effects. Parallel analyses predicting time to incident NSSI through week 24 identified baseline NSSI history and physical and/or sexual abuse history as significant predictors. CONCLUSIONS: NSSI is a common problem among youths with treatment-resistant depression and is a significant predictor of future SAs and NSSI, underscoring the critical need for strategies that target the prevention of both NSSI and suicidal behavior. CLINICAL TRIAL REGISTRATION INFORMATION: Treatment of SSRI-Resistant Depression in Adolescents (TORDIA). URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00018902.

Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA trial.

OBJECTIVE: Nonadherence to antidepressant treatment may contribute to poor outcome and to suicidal adverse events in adolescent depression. We examine the relationship between adherence and both clinical response and suicidal events in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) study. METHOD: The relationship between adherence to medication and clinical outcome was assessed in 190 treatment-resistant depressed adolescents who were randomized to one of four cells: switch to another selective serotonin reuptake inhibitor (SSRI), switch to venlafaxine, or either of these two medication switches plus cognitive behavioral therapy. Plasma levels of antidepressant drug and metabolites were determined after 6 and 12 weeks of treatment. A twofold or greater variation in the dose-adjusted concentration of drug plus metabolites (level/dose ratio [LDR]) was defined as nonadherence. Nonadherence was also determined by clinician pill counts (CPC) of the proportion of prescribed pills that were unused and was defined as having greater than 30% of the prescribed pills remaining. RESULTS: LDR and CPC showed low concordance. LDR was unrelated to clinical response. CPC adherence was related to a higher response rate overall (adherent, 63.0% versus nonadherent, 47.2%, p = .03). Approximately half (50.8%) of the sample surveyed showed evidence of nonadherence by CPC. Neither measure of adherence was related to the occurrence of suicidal events or to the pace of decline in suicidal ideation. CONCLUSIONS: Clinician pill counts may be a relevant measure of adherence that is related to outcome under formal clinical trial conditions in depressed adolescents. Nonadherence appears to be a common and significant source of treatment nonresponse. Clinical Trial Registration Information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.

Incremental cost-effectiveness of combined therapy vs medication only for youth with selective serotonin reuptake inhibitor-resistant depression: treatment of SSRI-resistant depression in adolescents trial findings.

CONTEXT: Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective. OBJECTIVE: To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI. DESIGN: Randomized controlled trial. SETTING: Six US academic and community clinics. PATIENTS: Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression. INTERVENTION: Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy. MAIN OUTCOME MEASURES: Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs (DFD-QALYs). Costs of intervention, nonprotocol services, and families were included. RESULTS: Combined treatment achieved 8.3 additional DFDs (P = .03), 0.020 more DFD-QALYs (P = .03), and 11.0 more DIDs (P = .04). Combined therapy cost $1633 more (P = .01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER] = $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78,948 per DFD-QALY (ICER = $78,948; 95% CI, -$9261 to $677,448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100,000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions. CONCLUSIONS: For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00018902.

Defensive startle response to emotional social cues in social anxiety.

Potentiation of fear-related defense behaviours coordinated by the amygdala in response to environmental threat characterizes several anxiety disorders. We compared eye-blink startle responses to startle probes delivered during the presentation of emotional and neutral social cues in high and low generalized social anxiety. Socially anxious individuals exhibited larger startle responses to emotional (positive and negative) relative to neutral social cues, compared to non-anxious individuals.

Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes.

OBJECTIVE: The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome. METHOD: Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator. RESULTS: Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3%) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24. CONCLUSIONS: Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among nonresponders could be important.

Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study.

OBJECTIVE: The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents. METHOD: A subsample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures. RESULTS: No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91). CONCLUSIONS: The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment.

Effective components of TORDIA cognitive-behavioral therapy for adolescent depression: preliminary findings.

In this report, we conducted a secondary analysis of the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study to explore the impact of specific cognitive-behavioral therapy (CBT) treatment components on outcome. In TORDIA, 334 youths (ages 12 to 18 years) with major depressive disorder who had failed to respond to an adequate course of selective serotonin reuptake inhibitor (SSRI) medication were randomized to a medication switch (either to an alternative SSRI or venlafaxine) with or without 12 weeks of adjunctive CBT. Participants who had more than 9 CBT sessions were 2.5 times more likely to have adequate treatment response than those who had 9 or fewer sessions. CBT participants who received problem-solving and social skills treatment components, controlling for number of sessions and other confounding variables, were 2.3 and 2.6 times, respectively, more likely to have a positive response. These preliminary findings underscore the importance of receiving an adequate number of sessions to attain an adequate clinical response. Finally, social skills and problem solving may be active elements in CBT for adolescent depression and should be considered in treatment by those working with seriously depressed youths.