David Brent - US grants

suicide; bereavement; mental health epidemiology; adolescence (12-20); psychological stressor; pathology; family structure /dynamics; peer group; human subject;

The proposed project is a four year family study of the familial aggregation of suicide and suicidal behavior among the families of adolescents. The rates of suicide, suicidal behavior, Axis I and Axis II psychiatric disorders will be compared among the relatives of three groups: 75 adolescent suicide completers ("completers"), 75 hospitalized adolescents who have made at least one suicide attempt ("attempters), and 75 psychiatrically hospitalized never- suicidal adolescents ("controls"). The two hospitalized groups will be frequency-matched on age, race, sex, and broad-band psychiatric diagnosis to the completers. Lifetime history of psychiatric disorder (Axis I and II) and tendency to impulsive violence will be assessed in the probands and by direct interview (Family Study) in the first-degree relatives and designated grandparents, aunts, and uncles of the probands. The remainder of the second-degree relatives and those first-degree relatives unavailable for direct interview will be assessed indirectly by the Family History Method. The specific aims of the study are to test the following hypotheses: (1) The families of completers will show higher rates of suicide than the families of attempters, but both the relatives of completers and attempters will show higher rates of suicide and suicidal behavior than the relatives of controls: (2) The families of completers and attempters will show similar rates of Axis I disorders, but will show higher rates and earlier ages of onset of bipolar disorder and substance abuse, when compared with families of controls: (3) The families of completers and attempters will show higher prevalence of antisocial, borderline, and histrionic personality disorders, and a greater tendency to impulsiveviolence and sensation seeking when compared with families of controls; (4) Among the families of completers and attempters, higher rates of suicide and suicidal behavior will be observed among the families of those probands: (a) with affective disorder, (b) who have made high intent attempts/completions, and (c) who have made violent attempts/completions. This is a revision of grant 1 R01 MH43366-01.

The proposed project is a clinical trial of three different psychotherapeutic interventions for adolescent suicide attempters with RDC major depression. One hundred twenty (120) nonpsychotic, non-bipolar depressed suicide attempters aged 13-18, will be randomly assigned to one of three treatments: (1) cognitive-behavioral therapy (CBI); (2) systemic-behavioral family therapy (SBFT); or (3) non-directive supportive therapy. Treatment will be 12-16 sessions in length to be delivered over a 12 week period, and will be monitored for integrity with the therapeutic model through intensive training and supervision, use of therapy manual, and monitoring a rating of videotaped sessions. The aims of the study are to test the following hypotheses: (1) Patients treated with CBT and SBFR relative to patients treated with NST will show greater improvements in the prevalence and severity of depression and suicidality and in social competence, (2) At 3, 6, 9, and 12 month follow-up, CBT- and SBFr-treated patients will continue to show decreased prevalence and severity of depression and suicidality and superior social competency compared to NST-treated patients. Those factors predictive of responses to CBT vs. SBFR will also be explored.

The proposed study is an integrated psychosocial and neurobiologic approach to the problem of youthful suicide. Over a four year period, 20 suicide victims, aged 13-19 and 20 matched controls dying of accidents, homicides or sudden natural deaths will be systematically investigated with regard to both neurobiological and psychosocial indices. The controls will be matched to the suicides on age, sex, Tanner Stage, postmortem interval, season of death, and side of the brain (left versus right) studied. Cases with positive brain, blood, or urine toxicologies for illicit or psychotropic drugs or alcohol will be excluded from this study. A psychosocial profile on each subject will be developed by use of psychological autopsy interviews with key informants targeting: (a) Axis I and II disorders, current and lifetime; (b) history of impulsive violence, and (c) family history of Axis I and II disorders, impulsive violence, and suicidality. A neurobiological profile of youthful suicide victims will be developed through serotonergic and other probes using postmortem brain material of victims and controls. (1) The serotonergic system will be assessed by measuring: (a) absolute levels of serotonin (5- HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific brain regions; (b) 5-HT1A, paroxetine, and 5-HT2 binding indices in the above-noted brain regions; and (c) parallel autoradiographic studies related to (b). (2) Additionally, (a) regional levels of norepinephrine (NE), dopamine (DA), and homovanillic acid (HVA) will be assayed, as well as (b) binding for low- and high-affinity beta-adrenergic receptors by quantitative receptor autoradiography. It is predicted that: (1) youthful suicide victims, compared to psychopathological and normal controls, will show decreased 3H-paroxetine, increased 5-HT2, and increased beta-adrenergic binding in the prefrontal cortex; (2) differences between suicides and controls will cut across Axis I psychiatric diagnoses; and (3) changes in serotonergic function will be correlated with history of impulsive violence, Axis II personality disorder and family history of Axis II disorder, impulsive violence, and suicidal behavior.

In this two year period, we plan to complete subject recruitment and interviewing, data analysis, and manuscript preparation. In all, the relatives of 60 adolescent suicide completers, 75 psychiatrically hospitalized suicide attempters, 75 psychiatrically hospitalized never-suicidal psychiatric controls, and 60 adolescent community controls will be assessed. On average, four relatives per family will be directly interviewed and assessed as to Axis I and II psychiatric disorder, history of suicidal behavior, and personality traits related to impulsive aggression and novelty-seeking. Two sets of comparisons are made: (a) between two non-referred samples - the relatives of suicide completers and community controls; and (b) between two clinically referred samples - relatives of hospitalized suicide attempters and never-suicidal psychiatric controls. The aims of this competitive renewal are to test the following hypotheses: (1). Higher familial rates of suicide and suicidal behavior, antisocial, borderline, and avoidant personality disorder, and greater tendency to impulsive violence, assaultive behavior, and novelty-seeking will be seen in the relatives of suicide completers vs. community controls, and in the relatives of suicide attempters vs. psychiatric controls. (2). The association between suicidality in the proband and familial rates of suicidal behavior will persist after controlling for proband and family differences in Axis I diagnosis, but will be explained by the excess in certain personality disorders and traits (specifically, tendency to impulsive violence, antisocial disorder, borderline disorder, and avoidant disorders). (3). For both suicide attempters and suicide completers, suicidality in the proband that is violent or of high intent will be associated with higher familial rates of suicide and suicidal behavior, history of assaultive behavior, antisocial disorder, and greater tendency to impulsive violence,.

In this two year period, we plan to complete subject recruitment and interviewing, data analysis, and manuscript preparation. In all, the relatives of 60 adolescent suicide completers, 75 psychiatrically hospitalized suicide attempters, 75 psychiatrically hospitalized never-suicidal psychiatric controls, and 60 adolescent community controls will be assessed. On average, four relatives per family will be directly interviewed and assessed as to Axis I and II psychiatric disorder, history of suicidal behavior, and personality traits related to impulsive aggression and novelty-seeking. Two sets of comparisons are made: (a) between two non-referred samples - the relatives of suicide completers and community controls; and (b) between two clinically referred samples - relatives of hospitalized suicide attempters and never-suicidal psychiatric controls. The aims of this competitive renewal are to test the following hypotheses: (1). Higher familial rates of suicide and suicidal behavior, antisocial, borderline, and avoidant personality disorder, and greater tendency to impulsive violence, assaultive behavior, and novelty-seeking will be seen in the relatives of suicide completers vs. community controls, and in the relatives of suicide attempters vs. psychiatric controls. (2). The association between suicidality in the proband and familial rates of suicidal behavior will persist after controlling for proband and family differences in Axis I diagnosis, but will be explained by the excess in certain personality disorders and traits (specifically, tendency to impulsive violence, antisocial disorder, borderline disorder, and avoidant disorders). (3). For both suicide attempters and suicide completers, suicidality in the proband that is violent or of high intent will be associated with higher familial rates of suicide and suicidal behavior, history of assaultive behavior, antisocial disorder, and greater tendency to impulsive violence,.

The proposed project is a clinical trial of three different psychotherapeutic interventions for adolescent suicide attempters with RDC major depression. One hundred twenty (120) nonpsychotic, non-bipolar depressed suicide attempters aged 13-18, will be randomly assigned to one of three treatments: (1) cognitive-behavioral therapy (CBI); (2) systemic-behavioral family therapy (SBFT); or (3) non-directive supportive therapy. Treatment will be 12-16 sessions in length to be delivered over a 12 week period, and will be monitored for integrity with the therapeutic model through intensive training and supervision, use of therapy manual, and monitoring a rating of videotaped sessions. The aims of the study are to test the following hypotheses: (1) Patients treated with CBT and SBFR relative to patients treated with NST will show greater improvements in the prevalence and severity of depression and suicidality and in social competence, (2) At 3, 6, 9, and 12 month follow-up, CBT- and SBFr-treated patients will continue to show decreased prevalence and severity of depression and suicidality and superior social competency compared to NST-treated patients. Those factors predictive of responses to CBT vs. SBFR will also be explored.

A treatment core is proposed with specific aims for infrastructure/quality improvement, scientific development, and training. Specific to the area of scientific development is a series of pilot studies which includes treatment protocols during year 01 for assessment of the pharmacokinetics of the SSRIs and a dose-ranging study of SRRIs in depression. Documentation analytical methods is provided along with data supporting their quality control.

DESCRIPTION (provided by applicant): This 5-year, two-site R0l proposal, based in New York and in Pittsburgh, is a competitive renewal of a high-risk study of the familial transmission of early-onset suicidal behavior. By the end of the first funding period, we will have recruited the offspring of two groups of probands-approximately 334 offspring of 167 mood disordered suicide attempters and a comparison group of 168 offspring of 83 mood disordered non-attempters. Probands, biological offspring over the age of 10, and the biological co-parent were characterized as to psychopathology, suicide attempt history, tendency to impulsive aggression and family environment, and were genotyped with polymorphic markers for serotonin pathway genes. Results of cross-sectional analyses indicate clear evidence of the familial transmission of suicidal acts and its relationship to both transmission of mood disorders and other psychopathology such as aggression/impulsivity and family adversity including sexual abuse. Offspring of multiplex families have the highest risk for attempt and earliest age of onset. We now propose to follow up offspring, as they move through the age of risk for a first suicide attempt. Probands will also be reassessed, as their clinical status can affect offspring outcome. Subjects will be re-assessed with respect to psychopathology, impulsive aggression, and suicidal behavior. In addition, laboratory-based measures of impulsivity and executive function, and more detailed assessment of trauma history and family adversity will be obtained. Direct sequencing of candidate genes will be conducted in families multiplex for suicide attempt. The prospective tracking of offspring will permit detection of the evolution of psychopathology and development of a predictive and explanatory model for the familial transmission of suicidal behavior. This study should lead to an empirical basis for the prevention and treatment of suicidal behavior.

Early onset affective and anxiety disorders are frequent and recurrent psychiatric disorders associated with significant morbidity and mortality. Anxiety disorders in children and adolescents are one of the most prevalent forms of psychopathology affecting as many as 10 percent of children. Estimates of the prevalence of Major Depressive Disorder (MDD) is 2 percent in pre-adolescent school aged children and 5 percent in adolescents. Increased risk for MDD is conferred by childhood anxiety disorders and a history of trauma (e.g. abuse). Within five years of the onset of MDD, up to 70 percent of children and adolescents with depression will experience a recurrence, and as many as 20-40 percent of the children will develop Bipolar I disorder. in addition, it is estimated that close to 5 percent of depressed adolescents will complete suicide within 10 years of their initial episode of MDD. Early onset affective and anxiety disorders frequently persist into adulthood, and functional impairment is greatest in adults who experienced the onset of these disorders in childhood. The Clinical Core is the gateway to the Center. It supports the overall goal of the Center of improving the life course of children, adolescents, and families with early-onset affective and anxiety disorders through research on assessment, phenomenology, correlates, and course. Specific foci of research supported in this Core include: improved assessment of risk factors for early onset affective and anxiety disorders (e.g. trauma); identification of factors associated with onset, course, recurrence, and transition to other disorders (e.g. pre-existing and comorbid anxiety disorders); and examination of predictors of treatment response (e.g. parental psychopathology, life events).

behavioral /social science research tag; disease /disorder proneness /risk; family structure /dynamics; medical outreach /case finding

The center is organized to enable a focus on longitudinal studies, treatment development, and services research targeted at effective and anxiety disorders in adolescents. The clinical Core will serve the other cores by providing standardized recruitment, assessment and quality control for patients treated and followed by the Treatment Core and Services Research Core. The development of new assessment methods in this Core will also serve all CRC projects, particularly through the development of a more useful method of assessing anxiety (the SCARED) and traumatic events specific to adolescents. The thrust within the center as a whole, is the attention to minority group issues in the development and validation of these instruments and procedures. The Treatment Core and Services Research Core will collaboratively be responsible for treatment, maintenance, outcome, and follow-up assessment. The Statistics Core has been conceived now as a distinct Core to emphasize the importance of its services and use of its consultation by all components of the CRC.

A 5-year, 6-site study, consisting of o interlocking R01 applications is proposed to study the treatment of SSRI-resistant depression in 400 adolescents. Subjects will be those with DSM- IV MDD, currently in treatment, and still depressed despite at least 4 weeks of treatment at an adequate dosage (20mg) and at least 2 weeks of treatment at a higher dosage (40mg) of either paroxetine or fluoxetine. We focus on these two SSRIs because they are most commonly used drugs in this class, and the only two for which efficacy has been demonstrated in the treatment of adolescent depression. After an initial assessment, the adolescents will be observed at the higher dosage of SSRI for an additional 2 weeks and then be reassessed. Those who show no significant response over that time (decrease in CDRS-R less than 20 percent) will be tapered from their current regimen and entered into the protocol. These 400 subjects will be assigned to one of four conditions to be delivered over 12 weeks. The rate of clinically acceptable response to treatment (defined as a CGI less than or equal to 2 and greater than or equal to 50 percent decrease in the CDRS-R) will be compared across the 4 cells in a 2x2 factorial design: (1) switch within SSRI class (those on paroxetine switch to fluoxetine; those on fluoxetine switch to paroxetine); (2) switch to a different class of agent (venlafaxine); (3) switch within SSRI class plus receive cognitive behavior therapy (CBT), and; (4) switch to a different class of agent (venlafaxine) plus CBT. Subjects who show a clinically acceptable response will receive 12 additional weeks of continuation treatment with the same intervention as in the acute phase. Non-responders will be offered 12 weeks of open treatment. All subjects will be followed up for 12 months after the continuation phase, regardless of treatment compliance. We hypothesize that there will be a medication effect (venlafaxine superior to SSRI switch) and a CBT effect (CBT + medication superior to medication alone), and that CBT + venlafaxine superior to the other 3 cells. In addition, we hypothesize that the rate of relapse and recurrence will be lower in the CBT treated cells. The six sites participating and the number of subjects to be enrolled are: Brown (n=40), Dallas (n=80), Galveston (n=80), Oregon (n=80), UCLA (n=40), and Pittsburgh (n=80), with the latter being the site of this application and the coordinating site for the overall study.

DESCRIPTION (provided by applicant): This competitive renewal of the Center for Early-Onset Mood arid Anxiety Disorders MH55123) is submitted an ACISR in order to develop, test, and disseminate effective treatments for children and adolescents with mood and anxiety disorders and comorbid conditions. Since 1997, the Center has supported the development of 15 new NIMH grants, supplements, and subcontracts, including 4 new career awards. The work of Center investigators has helped to identify efficacious treatments for early-onset mood and anxiety disorders. We now propose to: (1) improve the outcome of youth who fail to respond to first-Iine interventions; (2) develop and test treatments for which there are no established first-Iine treatments; (3) adapt and disseminate efficacious first-Iine treatments to practice-based settings; and (4) prevent the onset of disorder and the complications thereof. The Center has four cores: the Operations Core (OC) coordinates and integrate the efforts of the Center, providing infrastructure support and quality assurance for subject recruitment, retention, and follow-up; data-entry, management, and statistical analysis. The OC facilitates the development of young investigators through salary and infrastructure support, pilot funds and mentoring. The Research Methods Core complements the activities of the OC by addressing methodological issues that impede treatment development and dissemination in 3 key areas: assessment development, data management and analysis, and the study of factors that impede or promote dissemination of effective treatments to practice settings. The Principal Research Core provides quality assurance over pharmacological and psychosocial treatments for clinical trials, develops and tests treatments for complex refractory disorders, adapts treatments to the needs of practice-based research, and develops treatments to prevent the onset of disorder or the complications thereof. The Research Network Development Core develops a practice-based research network based in primary care to support studies of practice variation and outcome, as well as dissemination studies. The Center will enhance the development of the next generation of intervention and services researchers and will disseminate new research information to families, practitioners, and researchers.

DESCRIPTION (provided by applicant) : This U10 proposal, RUPP-PI in Pittsburgh is to establish an NIMH Research Unit for Pediatric Psychopharmacology-Psychosocial Intervention in Pittsburgh. The proposed unit builds on the strengths of the Pittsburgh site in clinical epidemiology of mood disorders and suicidal behavior, psychosocial treatment development, pharmacokinetics of SSRI's, and participation in numerous success- fully performed, single and multi-site clinical trials involving CBT, antidepressants, and their combination for mood and anxiety disorders. Resources to support this program of research and training include a T32 postdoctoral training grant in child psychiatry research, an Intervention Research Center on early-onset mood and anxiety disorders, a RUPP devoted to pharmacokinetics of antidepressants, and a state-supported specialty clinic for mood disorders and suicidal behavior. The exemplar research protocol, "Treatment of Adolescent Suicide Attempters" (TASA), targets a major public health issue: although adolescents in this country suffer 2 million suicide attempts annually, no large scale, multimodal controlled intervention studies for this condition have been conducted. The proposed 5-year study will determine the effectiveness of a multi-modal treatment intervention to prevent further reattempts in 480 depressed adolescents attempters, ages 12 to 18, at 8 sites. The Experimental Treatment Group will receive a 24-week course of antidepressant medication management (MM), and cognitive behavioral therapy. The Control Treatment Group will be referred to a community provider for standard clinical care plus enhanced clinical monitoring and case management to encourage treatment adherence. Both groups will be assessed at baseline 2, 4, 8, 12, 24, 36 and 48 weeks by an independent evaluator blind to treatment assignment. We hypothesize that the experimental treatment will result in fewer suicide attempts, diminished depression and severity of suicidal ideation, and greater global improvement scores differ between the 2 groups over a one-year period of observation. The expertise and experience at this RUPP-PI site also will be directed to train new investigators. In creating TASA, a collaborative group of 8 applicants forged the ability to work together.

DESCRIPTION (provided by applicant): A 5-year, population-based, longitudinal study of the impact of parental suicide on surviving children and their families is proposed. We will (1) recruit the families of parents who have either committed suicide (n=100), died by accident (n=100), or are neighborhood controls (n=l00), matched by neighborhood, age, race, and sex to the suicides; (2) assess the suicide and accident victims by psychological autopsy, and the control parent by direct interview; (3) assess the surviving spouse (or in the case of the living control, simply the spouse) and biological offspring of the index parents aged 8-17 at 3 months after the death; and (4) follow the surviving spouse and offspring annually over the course of the project. The main goals of the project are to: (1) identify possible adverse sequelae of parental suicide, namely an increased incidence of psychopathology such as depression, suicide attempt, and PTSD, and increased incidence of traumatic grief and (2) identify factors that either increase risk or increase protection against the development of these sequelae. Offspring and the surviving spouse will be assessed with regard to outcome (current and incident psychopathology, suicidal behavior, grief, other risk behaviors, and functional status); vulnerability factors (traumatic exposure to the death; relationship with the deceased; previous personal and family history of psychopathology, ongoing mental health status of surviving parent, exposure to family adversity, and intercurrent life events), and protective factors (social support, connectedness to family and school, religious involvement, involvement in organized activities, coping style, personality traits [e.g., self-esteem, locus of control], and involvement with informal and formal bereavement services). This study would be the first large-scale, population-based investigation of the sequelae of parental suicide to have comprehensive coverage of domains of outcome, risk and protective factors. The results of this study should be very useful in the design of preventive interventions for bereaved children and their families.

[unreadable] DESCRIPTION (provided by applicant): This application is one of four interlocking R01's to assess the impact of a group cognitive behavioral program (CBP) on the prevention of depression in adolescents at risk for depression. Eligible teens must have a parent with active depression; teens themselves must have either a past depressive episode or current subsyndromal depressive symptoms. In this 5-year study, 320 at-risk adolescents (80 at each site) drawn from managed care organizations will be randomized to either CBP or usual care (UC) and followed for 32 months post intake to determine the impact of CBP vs. UC on onset of depressive disorders and symptoms, level of functioning, and medical and mental health care utilization. We hypothesize that participants in the CBP intervention will have a significantly lower prospective incidence of first and repeated episodes of depressive disorders and symptoms compared to adolescents in the usual care group. In addition, we will explore whether participants in CBP have a reduced prospective incidence of non-affective symptoms and disorders, and will show improved global functioning relative to the comparison group. Analyses also will focus on the incremental cost-effectiveness of providing the CBP over usual care from the health care perspective. This study builds on previous work by the Portland site (Clarke et al., 2001) showing a nearly six-fold reduction in the incidence of depression in CBP vs. UC, and extends this work in two ways - first, by testing whether the program can be replicated at several different sites, thereby greatly increasing the generalizability of the original findings; and second, by changing the timing and spacing of the intervention to provide continuation sessions to prolong the duration of the effect of CBP. This program of research is significant for several reasons: (1) depression is a chronic, prevalent, and impairing condition in adolescence that is often undetected, and which is more difficult to treat as chronicity increases; (2) there have been no large-scale studies of the prevention of depression in adolescence; and (3) by basing this study in managed care organizations, it will be possible to ascertain the costs and benefits of incorporating this intervention into "best practice" in real world settings. This application is based in Nashville (Judy Garber, PI), and interlocks with applications from Boston (William Beardslee, PI), Pittsburgh (David Brent, PI), and Portland (Greg Clarke, PI).

[unreadable] DESCRIPTION (provided by applicant): This two-year, six-site, competitive renewal compares four strategies for the treatment of SSRI-resistant adolescent depression. We propose to complete our recruitment of 400 adolescents, aged 12-18, who continue to be depressed despite an adequate trial of one of the SSRI antidepressants currently used in community practice (i.e., fluoxetine, citalopram, escitalopram, sertraline). During this project period, we will empanel 100 adolescents with SSRI-resistant depression to complete our target recruitment. The rates of clinically acceptable response (defined as a CGI-I < 2, CGIS < 3, and > 50% decrease in the CDRS-R), slope of decrease of depressive symptoms on the CDRS-R, and direct cost of treatment per unit of improvement will be compared across the 4 cells in a 2x2 factorial design: (1) switch within SSRI class (those on citalopram switch to fluoxetine; those on fluoxetine switch to citalopram; those on sertraline switch randomly to either fluoxetine or citalopram); (2) switch to a different class of agent (venlafaxine); (3) switch within SSRI class plus receive cognitive behavior therapy (CBT); and (4) switch to a different class of agent (venlafaxine) plus CBT. "Adequate treatment" with an SSRI is defined as > 8 weeks of total treatment, at least 4 weeks of which were at the equivalent of 20 mg of fluoxetine, and at least 4 weeks of which were at the equivalent > 40 mg of fluoxetine. In order to enter the study, subjects are assessed at two points in time 2 weeks apart, and must demonstrate sufficient severity (CDRS-R > 40, CGI-S > 4) and stability (decline in CDRS over two weeks < 30%). Subjects meeting these criteria will be cross-tapered gradually from their current regimen. The acute phase of treatment is 12 weeks, during which subjects can receive up to 40 mg of fluoxetine or citalopram, or 225 mg of venlafaxine. Subjects who show a clinically acceptable response will receive continuation treatment for an additional 12 weeks. All subjects, regardless of treatment compliance, will be assessed at intake, midpoint, and the end of acute treatment, and every 6 months thereafter for 1 year after the end of continuation treatment. We hypothesize that, with regard to adequate clinical response and rate of decline of depressive symptoms, venlafaxine will be superior to SSRI switch, CBT + medication will be superior to medication alone, and that CBT + venlafaxine will be superior to the other three cells. Significance. Because 40% of depressed adolescents do not respond to initial treatment with an SSRI, this is a common and serious public health problem. Subjects empaneled thus far are a high-risk group, with prevalent chronic depression and suicidality at intake. This is the only extant study to address the treatment of SSRI-resistant adolescent depression, and will be uniquely informative about treatment guidelines, the relative safety and efficacy of different antidepressants, and the value of adding CBT to medication treatment for this condition. This site is based in Pittsburgh, which also serves as the Data Coordinating Center for the study [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This is a 5-year A1 competitive renewal to study the impact of sudden parental death on children. During the initial project period, we recruited a cohort of 245 children who have lost a parent to suicide, accident, or sudden natural death, and a demographically similar, non-bereaved control group of 185 children and assessed them at 1 and 2 years after parental death. We find evidence of a persistent impact two years after the death: parental bereavement quadruples the risk for child depression, even adjusting for pre-death risk factors. We propose to reassess this cohort at 3 and 6 years after the parental death for a total of 4 follow-up assessment points in order to examine the relationship between parental loss and child outcomes in the domains of psychopathology (e.g., incident disorder, symptom trajectory), attainment of developmental competence (educational, vocational, relational), and health-related outcomes (e.g., BMI, impact on the hypothalamic pituitary adrenal [HPA] axis). We evaluate the construct and discriminant validity of complicated grief to determine if it has a stable factor structure and explains a unique proportion of the variance in outcome. We test an explanatory model by examining specific pathways that may mediate (e.g., child coping, family cohesion) or moderate (e.g., pre-death psychopathology, gender) the relationship between parental death and child mental health, developmental, and physical health outcomes. As an exploratory aim, we examine if polymorphisms in genes may moderate the relationship between parent death and cortisol response to a social stressor (e.g., glucocorticoid receptor) or depression (e.g., serotonin transporter promoter). This project will lead to new knowledge, because it: (1) is the only controlled, prospective study of parentally bereaved children with a follow-up period of longer than 2 years;(2) assesses outcomes complementary to psychiatric outcome, namely developmental competency, health, and the HPA axis;(3) tests models of mediation and moderation;(4) is large enough to assess if parental bereavement by suicide is uniquely deleterious;and (5) will address whether complicated grief in youth has construct and discriminant validity and has a direct impact on functional outcome. These results will help to identify bereaved youth and families at risk for sub-optimal mental and physical health and developmental outcomes, thus framing targets for future prevention and intervention studies.Project Narrative: The loss of a parent is widely recognized to be among the most stressful events that a child can experience, and numerous retrospective studies indicate that parent loss has serious and enduring mental health effects. However, there have been no long-term, controlled, prospective studies of the effects of parental bereavement on children.

DESCRIPTION (provided by applicant): In this second revision of our application, we addressed the reviewers'questions about our comparison condition and several other design issues, and propose a 5-year study of the efficacy of Contextual Emotion Regulation Therapy (CERT), a novel intervention for childhood depression. CERT is an empirically based, developmentally sensitive treatment that targets emotion regulation response skills in depressed children, and deploys parents as co-therapists;parents are taught to effectively coach their children in various tasks, including developmentally appropriate use of emotion regulatory strategies in response to experiencing distress/dysphoria. Altogether 100 children, aged 7-12, with a DSM-IV depressive disorder, will be randomly assigned to CERT or Child-Centered Therapy (CCT), a psychotherapy based on Rogerian principles. Both treatments entail 22 sessions, conducted jointly with the parent and child: weekly sessions across the first 4 months are followed by biweekly sessions (across a two month period) to consolidate treatment gains. Both groups will be followed for 1 year after the end of treatment to evaluate the longer-term effects of the interventions. A multi-perspective assessment battery (clinical interviews and ratings, and parent- and child-self rated inventories) will provide the data to test our hypotheses. We hypothesize that CERT will result in more rapid, complete, and sustained recovery from depression than CCT;that symptomatic improvement will be mediated by improvement in children's and parents'self-regulation of dysphoric affect and by improved parent-child relationship;and that treatment outcome will be moderated by baseline clinical characteristics of the child and parental depressive symptoms. An open treatment trial of CERT with 20 children with dysthymic and/or major depressive disorder showed that a high proportion achieved remission, which was sustained across an additional 12 months of follow-up. Our proposed project has great public health significance because childhood depression is a gateway to adult depression, one of the leading causes of disability worldwide, and there are currently no published, empirically validated treatments for clinical depression for referred children aged 12 years and younger. Public Health Relevance: We plan to test the efficacy of Contextual Emotion Regulation Therapy (CERT), a novel psychosocial treatment for childhood depression, among 7 to 12-year olds. This project has great public health significance because childhood depression is a gateway into adult depression, one of the leading causes of disability worldwide, and there are currently no empirically validated treatments for clinical depression in this age group. CERT translates years of observational and experimental evidence in developmental psychopathology and identifies emotion regulation as the key deficit in depression. As a psychosocial treatment, CERT is 1) flexible, insofar as it can be tailored to the emotion regulatory needs and abilities of the child and family, 2) ecologically valid, as it actively involves the parent as a co-therapist, and 3) likely to result in more complete and enduring treatment response.

DESCRIPTION (provided by applicant): This 5-year, two-site A2 competitive renewal of "Familial Pathways to Early-Onset Suicide Attempts" seeks to identify familial and individual precursors of early-onset suicidal behavior and mechanisms by which suicidal risk is transmitted from parent to child. The cohort consists of 308 offspring of 135 probands with major depressive disorder (MDD) and a history of suicide attempt and a comparison group of 232 offspring of 120 non-attempters probands with MDD, all of whom have been followed for an average of 3.8 years. The aims of the study are to: (1) continue annual follow-up of offspring of attempters and non-attempters in order to document incident and recurrent suicide attempts;(2) characterize all subjects, probands and offspring, on four putative intermediate phenotypes (IP) (impulsive aggressive traits, early-onset depression, neuropsychological function, cortisol response to stress) as well as other risk (e.g., child abuse and neglect) and protective factors (e.g., family cohesion) for suicidal behavior;and (3) examine the role of IPs in mediating the familial transmission of suicidal behavior and predicting new-onset suicide attempts both alone and in interaction with early childhood abuse and neglect. In a projected 4,693 person years of follow-up, a total of 67 new-onset suicide attempts are expected, which will allow for adequate statistical power to test our hypotheses that IPs are familially transmitted, and mediate the familial transmission of suicidal behavior. The identification of IPs will facilitate future genetic studies of suicidal behavior. This study sample is unique because it permits identification of risk factors for familial transmission of suicidal behavior, and the identification of precursors of early-onset suicidal behavior. Because there are now no empirically validated interventions for suicidal youth, the findings from this unique cohort should help to frame treatment targets in high-risk families and individuals designed to alter prodromal at-risk behavior and psychopathology and prevent future suicidal behavior. This study is of public health importance because suicidal behavior is the single biggest risk factor for completed suicide, which is the third leading cause of death among adolescents and young adults in the United States. The aims of this study are consistent with several priorities of the NIMH and the Division of Pediatric Translational Research (DPTR): (1) reduction of the public health burden of suicide and suicidal behavior;(2) inclusion of family-genetic approaches to elucidate the interplay of biological and environmental factors to childhood psychopathology and to identify behavioral and biological markers of vulnerability and resilience;and (3) research that is likely to lead to novel psychosocial and pharmacological preventive and therapeutic interventions. This application is from the Pittsburgh site (Principal Investigator: David Brent, MH56612). PUBLIC HEALTH RELEVANCE: This study, "Familial Pathways to Early-Onset Suicidal Behavior," seeks to identify the familial and individual precursors of early-onset suicidal behavior and the mechanisms by which suicidal risk is transmitted from parent to child. We anticipate that certain traits, namely impulsive aggressive traits, early-onset depression, memory and decision making ability, and a greater physiological reaction to stress (measured by cortisol secretion) are familial and will: (1) explain how suicidal behavior runs in families;(2) predict suicidal behavior in the children of parents who have attempted suicide;and (3) yield intermediate phenotypes that can advance genetic studies of suicidal behavior. This study is important because suicide and suicidal behavior are leading causes of mortality and morbidity among adolescents, there are currently no empirically validated interventions to prevent or treat adolescent suicidal behavior, and the results of this study could frame targets for prevention and treatment.

DESCRIPTION (provided by applicant): This A1competitive renewal is one of four collaborative, linked R01s that proposes to examine the long-term effects of a Cognitive Behavioral Program (CBP) for preventing depression provided when adolescents were 13-17 years old. The sample is at high risk by virtue of familial (parental depression) and individual factors (past history of depression and/or current subsyndromal depressive symptoms). In the original study, we successfully enrolled 99% (N=316) of our proposed target recruitment of 320 adolescents, with equal recruitment across the 4 sites. Participants were randomized into either CBP or treatment as usual (TAU), with equally high retention (92%) in both conditions. Results through the 8-month follow-up indicated a significant prevention effect of CBP with regard to depressive episodes (HR=.60, 95% CI, .38-.96;effect size, d=.25), thus replicating and extending the earlier, single site study by Clarke et al., (2001). The aims of the current proposal are to (a) study the longer term impact of CBP on preventing depression during the critical developmental transition to early adulthood, a period of multiple new life challenges and stressors;(b) assess potential biological (e.g., genetic) and psychosocial (e.g., childhood abuse, stressful life events) moderators of response to the intervention;(c) examine the broader impact of the CBP program on sequelae of depression including other mental and medical health problems, health risk behaviors, and impairment in the attainment of developmental competencies;and (d) assess the long-term cost-efficacy of CBP, identify markers of the impact of CBP on key economic outcomes (e.g., workplace productivity), and examine the longer-term economic benefits of preventing or delaying the onset of mood disorders in adolescents with CBP. We will explore the potential role of adolescent depression in mediating these outcomes in young adulthood. These aims are consistent with the areas of highest priority for the NIMH Division of Services and Intervention Research (DSIR) insofar as this project will evaluate the durability and broader effects as well as cost-efficacy of an innovative prevention strategy, will potentially reduce the burden of suicidality by increasing depression-free days, and will both aid in the personalization of the intervention and the identification of new prevention targets through our study of biological and psychosocial moderators of treatment effects. Knowledge gained from this study will be used to identify individuals who are most and least likely to benefit from this prevention program, and will provide an empirical foundation for novel and innovative strategies for the prevention of depression. In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths'schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit. Public Health Relevance: In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths'schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit.

DESCRIPTION (provided by applicant): This application describes an interlocking, two-site collaborative R01 to test the effects of a brief cognitive behavioral therapy (BCBT) protocol for youths (age 8-15) presenting with anxiety and/or depression in primary care. Over a five year period, 210 youths (105 per site) will be randomly assigned to (a) BCBT delivered in primary care or (b) enhanced referral to specialty mental health care (SMHC). This application builds on a preliminary study (N=60), in which a pilot version of BCBT was well-accepted by families and clinicians and was more efficacious than referral to SMHC. We now propose to test BCBT against an enhanced SMHC referral model in a larger, more diverse sample to establish its utility as a community-based intervention. Outcomes will be assessed by independent evaluators blind to participant status at 16 and 32 weeks post- randomization (Aim 1). It is hypothesized that BCBT will be superior to enhanced SMHC referral in terms of overall clinical improvement (CGI-I <2) and change in anxiety (PARS) and depression (CDRS-R) symptoms. Response also will be evaluated on brief self-report measures (SCARED, MFQ), as future community care may need to rely more heavily on these types of assessments. In addition, individual trajectories of participants will be examined to understand predictors of treatment response (Aim 2). It is hypothesized that severity of depression symptoms (youth and/or parent) will predict poorer response across treatments but that the BCBT program will still outperform the enhanced SHMC referral model. The effects of ethnicity also will be explored and use of two sites will allow greater enrollment of Hispanic (San Diego) and African-American (Pittsburgh) families than could be achieved by either in isolation. Targeting depression and anxiety as a unified problem area is innovative and in line with calls for new approaches to conceptualizing comorbidity and treating near neighbor disorders. Availability of an effective BCBT program for internalizing youths is needed as service settings struggle with limited sessions and resources available to train clinicians in multiple protocols. The application is noteworthy in adopting a deployment-focused model and testing this intervention early in its development within a real world context (primary care) and against a plausible public health comparision condition (enhanced SMHC referral) relevant for future treatment dissemination. Primary care has become a de facto site of mental health care delivery, with the possibilities of easier access, earlier identification and treatment, and prevention of chronicity. In line with this focus, data will be collected on the cost-effectiveness of the program (Aim 3) in order to lay the groundwork for future investigations focused on issues of dissemination, implementation, and real world sustainability. Site-unique contributions include expertise in practice-based research (San Diego) and data coordination (Pittsburgh). San Diego will serve as the overall coordinating site for the project. PUBLIC HEALTH RELEVANCE: This study will test whether a brief (12 week) psychological treatment program, based in primary care, can help youths struggling with depression and anxiety. Impact of the program on symptoms and cost-effectiveness will be measured. This will be the first study to assess if anxiety and depression can be treated with one, simple program, and results may help move effective treatments for these serious problems into community practice.

DESCRIPTION (provided by applicant): We propose a 2-site R34 to develop a brief, flexible, manualized intervention with supporting phone app to reduce the risk of suicidal behavior in adolescents with high suicidal ideation or a recent suicide attempt, during the transition from inpatient to outpatient care. This transition period is the highest risk period for attempted and completed suicide. Suicide is the 3rd leading cause of adolescent mortality, and there are currently no established interventions for suicidal teens. By developing a treatment that can be delivered on an inpatient unit prior to the transition to outpatient treatment, we anticipate being able to lower suicidal risk and increase the likelihood that participants will attend subsequent outpatient treatment. In keeping with the priorities of NIMH, this intervention aimed at reducing the risk of suicide and suicidal behavior will be trans-diagnostic. We term the intervention ASAP, with anticipated components: (1) Adherence- promoting engagement and adherence to treatment through motivational interviewing; (2) Safety planning; and (3) Affect Protection- selecting from a menu of techniques for maintaining positive affect (e.g. savoring and switching strategies, mobilizing social support, maintaining sobriety, and improving sleep). Each of these components will be delivered within a Motivational Interviewing framework for enhancing intrinsic motivation for change. Treatment is brief (6-8 hours), and flexibly delivered on inpatien units or in home visits prior to initiation of outpatient treatment. ASAP augments protective factors against recurrent suicidal behavior and includes the family in the treatment. A safety plan phone app to extend the impact of treatment will also be developed. Innovative features include: (1) delivery of an intervention at a time and place when suicidal risk is highest; (2) augmentation of protective factors against recurrent suicidal behavior, specifically by promoting development of positive affect, healthy sleep and social support; (3) a Safety plan phone app to extend the impact of treatment; and (4) liaison with the outpatient therapist to ensure continuity of care. Th specific aims are 5 treatment development phases: (1) Open semi-structured interviews with 5 suicidal teens and parents and 5 clinicians at each site on the proposed content and context of the proposed treatment; (2) Develop the ASAP modules, adherence/competence measures, and phone app, and repeat open interviews; (3) Open trial of ASAP in 10 adolescents (5 at each site); (4) Debrief patients and families, inpatient and outpatient providers, examine the impact of treatment on proximal indicators of suicidal risk, and revise accordingly; (5) Conduct an RCT of ASAP followed by Aftercare (AC) vs. AC alone in 80 suicidal teens (across both sites) to determine ASAP's feasibility, acceptability, impact on proximal targets (e.g., adherence to outpatient care, sleep, positive affect, substance use), suicidal ideation and behavior. ASAP, developed with and intended for community clinicians, has the potential to be a sustainable intervention to reduce the burden of adolescent suicidality.

DESCRIPTION (provided by applicant): Suicide is the 2nd leading cause of death among youth ages 12 to 17 in the United States. However, most youth at high risk for suicide go unrecognized and untreated, and for half of adolescent suicides, the first suicide attempt is fatal To improve identification of youth at risk for suicide, in response to RFA-MH-14-070, Pediatric Suicide Prevention in Emergency Departments, we propose a multi-site collaborative project with the Pediatric Emergency Care Applied Research Network (PECARN) and the Whiteriver PHS Indian Hospital. These EDs serve geographically and socio-demographically diverse groups of youth, including American Indian youth who are at particularly high risk for suicide. In Study 1, we will implement a universal suicide risk assessment using a broad range of risk factors with 6743 youth, ages 12 to 17 years, who present to one of 14 emergency departments (EDs) during randomly chosen screening shifts. We will follow-up a subsample of 30% of these youth, enriched for suicide risk factors, at 3 and 6 months. Our specific aims are to: (1) develop a computerized adaptive screen (CAS) for predicting suicide attempts; (2) compare the psychometric properties (e.g., sensitivity, specificity) of the CAS to those of a standard screen, the Ask Suicide-Screening Questions (ASQ); (3) test the ability of the Implicit Association Test (IAT), a behavioral test of implicit suicidal cognitions, to add incrementally to the prediction of suicide attempts above and beyond screening scores; and (4) develop and validate a parsimonious CAS-based algorithm for risk stratification to facilitate the triage of youths. In Study 2, we will recruit a new sample of 2340 youth (stratified by suicide risk factors), administe the CAS and ASQ, and follow-up youth at 3-months with interviews and medical chart reviews. Our Study 2 aim is to validate the specificity and sensitivity of the CAS and ASQ for predicting suicide attempts. The optimal screen developed in this collaborative project will have the potential to be disseminated nationwide to enhance the capacity of emergency departments to identify and effectively triage youth at acute risk for suicide attempts. This project is significat because the screening and triage of at-risk youth in healthcare settings are key strategies of the National Strategy for Suicide Prevention to reduce adolescent suicide. It is highly innovative because it will develop and test a computerized adaptive screen (CAS), which results in individualized sequences of screening questions conditional on previous responses; and it will test a wide range of acute suicide risk indicators for possible inclusion in the CAS. In addition, this project will test the incremental value of the IAT, which is important as many at-risk youth may deny suicidal thoughts. This project is feasible given PECARN's strong infrastructure and record of successful recruitment, and the investigative team's collective experience in multi-site studies, computerized adaptive testing, and youth suicide research in ED settings.

DESCRIPTION (provided by applicant): This application is a competitive renewal of 5T32 MH18951-23, a postdoctoral clinical research clinical and translational research training program in child mental health. Support is requested annually for 2 post- residency child psychiatrists, 4 post-doctoral child psychologists or other doctorally-prepared professionals, and four medical students for summer research electives. The postdoctoral training program, 2-3 years in duration, aims to develop scientists who can formulate original and significant research on the pathogenesis, course, treatment and prevention, and dissemination of effective treatments for child mental disorders. A multi- disciplinary faculty group with a long and successful history of research and research training provides mentorship to trainees. Most importantly, the T32 program pairs the trainee with an academically successful mentor and co-mentor committed to research training. The mentors and trainee develop a career development plan with targeted goals for acquisition of skills, presentations, publications, gathering pilot daa, and preparation of proposals for external funding, usually a career award; this plan is reviewed every 6 months with the mentors, trainee, Program Director and selected Training Faculty in order to ensure forward progress. An individually tailored course of didactic study will be developed for each trainee to insure the acquisition of core knowledge in research design, statistics, and content areas relevant to research. Trainees also participate in ongoing seminars on Research Survival Skills, dealing with formulation of scientific questions, grant writing, and project management, as well required didactic and interactive training on the responsible conduct of research. There is high institutional commitment to this T32, with salary and benefit supplementation by the Department, a formal K-award review process to aid trainees in grant preparation, and resources from the CTSI to support every aspect of project development and management. Of the 28 trainees who left the program since 2003, 93% completed the program, 82% have faculty appointments, including 19% at Associate Professor or higher, and 75% had external funding (including 15 K awards), and 15% were from under- represented minorities. The program is highly competitive, with 66 inquiries and 48 applications for 17 positions during this program period. In the summer research program, medical students work with a research mentor from the training faculty on a project leading to a publishable product in order to stimulate interest in child psychiatry research. Since 2003, 44% of the students who have graduated entered psychiatry, and 57% published at least one peer-reviewed paper.

? DESCRIPTION (provided by applicant): The suicide rate in the USA is the same as 60 years ago. Better prevention needs more data on risk and resilience biomarkers. We seek to determine both resilience and vulnerability potential endophenotypes for suicide attempts in major depressive disorder (MDD). Both endophenotypes may aid estimation of risk and provide new targets for prevention intervention. The study design compares healthy volunteers (Group 1) with medication-free adult offspring of a parent with MDD and suicidal behavior who are through the age of risk and can thus be divided into a resilient group (Group 4), a group with a diathesis for MDD (Group 2) and one with diatheses for MDD and suicide attempts (Group 3). Comparison of Groups 2 and 3 indicates the diathesis for suicidal behavior. Comparison of Group 1 and 4 indicates the resilience phenotype. Comparison of Group 1 and Group 2 indicates the diathesis for MDD. This study is a new direction based on our almost complete longitudinal two-site follow-up study (PI, J. John Mann, MD, MH056390, Columbia University, NYC and PI, David Brent, MD, MH056612, UPMC, Pittsburgh) of 701 offspring of 334 probands with mood disorder entitled: Familial Pathways to Early-Onset Suicide Attempts that has sought to identify mechanisms by which suicidal behavior risk is transmitted from parent to offspring. Our findings on risk traits in the domains of cognition, mood regulation and stress responses, together with a new domain of brain PET imaging of the 5-HT1A autoreceptor that regulates serotonin release, will focus the search for resilience and vulnerability phenotypes. This study will involve the same two performance sites as the current funded application that ends January 2015. The teams have worked together for >15 years and both teams have conducted PET studies of depressed and suicidal patients. We will recruit eligible offspring from the old study and recruit new offspring as needed for the four groups. Both sites will perform clinical and cognitive assessments, stress tests and PET/MRI scans using identical protocols. The New York site will be the data management site including image analyses and statistics, and assay cortisols.

ABSTRACT: The assessment of suicidal risk is critical for treatment planning and monitoring of therapeutic progress for suicidal individuals. Current standard-of-care relies on patient self-report and clinician impression, which are not strongly predictive of imminent suicidal risk. This project advances a highly innovative approach to the assessment of suicidal risk, by using machine-learning detection of brain activation patterns that are neural signatures of individual concepts that have been altered in suicidal individuals. The overarching goal is to establish reliable neurocognitive markers of suicidal ideation (SI) and attempt (SA) in individual participants, and to assess these measures? ability to predict future ideation and attempts. In previous work, this approach was applied to the fMRI-based neurosemantic signature (NSS?s) during the thinking about each of 30 words related to either to suicide, negative concepts, or positive concepts in 17 SI young adults and 17 healthy controls (HCs). A machine learning classifier was able to discriminate between the SI and HCs with 91% accuracy, based on differential brain activation patterns in the L superior medial frontal cortex and anterior cingulate, areas known to be involved in self-referential thinking. Within the ideators, NSS?s also discriminated between those with a history of a SA from those without such a history with 94% accuracy. Moreover, using the classification algorithm derived from this sample, we were able to accurately classify a second sample of suicidal individuals with 87% accuracy. It was also possible to assess the emotions differentially manifested during the thinking about these words, and thus to differentiate SI from HC with 85% accuracy, and SI with and without SA with 88% accuracy. On the basis of these promising pilot findings, we propose to study 300 young adult SI (about half of whom will have made a SA), 100 never-suicidal psychiatric controls, and 100 HCs, use fMRI to assess NSS at intake and 3 months, and assess for suicidal ideation and behavior at intake, 3, 6, and 9 months thereafter. The goals are to determine if: (1) NSS?s are sensitive to changes in level of suicidal ideation when repeated at 3 months; and (2) whether NSS can predict trajectories of suicidal ideation and behavior upon prospective follow-up. We will also examine the relationship between NSS activation of circuits related to self-referential thinking and the death/suicide Implicit Association Test (IAT) that examines the extent to which a person associates suicide-related concepts with self. Finally, as a translational goal, we aim to develop and test a neurally based IAT that examines associations of suicidal concepts with self and with emotions as informed by NSS findings. This study, by shedding light on alterations in suicidal individuals? neural representation of suicide-relevant concepts could be extremely useful for: (1) identification of those with suicidal ideation who may not self-report their level of risk; (2) monitoring fluctuations in suicidal risk over time; (3) identification of emotional states associated with suicidal ideation; (4) guiding therapy to mitigate these alterations; and (5) the prediction of future suicidal ideation and behavior.

Abstract: The emergency assessment of acute suicidal risk in adolescents is a daunting clinical challenge because our current ability to predict suicide attempts is weak, and because the risk for suicide attempts in suicidal adolescents is high. Nevertheless, there have been no studies that have examined the best approaches to the prediction of suicidal behavior in suicidal youth presenting to a psychiatric emergency department (PED). To address this research gap, we propose a study of 1800 youth presented to a regional PED, 1350 of whom present for evaluation of suicidal risk, in which youth are assessed in the PED, and followed up at 1, 3, and 6 months to determine which youth have made a suicide attempt. We propose 3 complementary approaches to assessment of suicidal risk. First, in this competitive renewal, we build on our success in developing computerized adaptive tests for 6 diagnostic groups, plus suicidal risk, during our previous project period. These self- and parent-reports can be completed in a total of 10-15 minutes. Second, because theory-driven assessments of suicide risk have strong predictive power in adults, but have never been tested prospectively in adolescents, we propose to test the predictive power of measures of Shneidman?s psychache (mental pain) and Joiner?s Interpersonal Theory of Suicide, which posits interactive roles of perceived burdensomeness, thwarted belonging, and acquired capacity for suicide in driving suicidal risk. Third, we aim to use machine learning (ML) and natural language processing (NLP) of electronic health records (EHRs) to identify youth at risk for suicide attempts. We hypothesize that each of these approaches: (1) CATs for suicide risk and for depression, anxiety, bipolar, ADHD, oppositional defiant, and conduct disorders); (2) theory-derived measures of suicidal risk; and (3) ML and NLP of EHRs, will each be superior to clinical assessment alone in the prediction of attempts, and that the combination of the 3 approaches will be more powerful than any one of these approaches alone. This study is innovative because it is one of the first to use CATs for the prediction of suicidal risk, in a consistently high risk population, the first prospective test of two leading theories of suicide in adolescents, the first to use machine learning and natural language processing to identify EHR predictors of suicide attempts in adolescents, and the first to test a combination of approaches to the identification of imminent suicidal risk in adolescents in a sufficiently large, high risk sample. The study is of potentially high impact because it could identify brief, easily disseminated assessment strategies to identify youth at high risk for suicidal behavior and add to clinicians? ability to match intensity and type of resources to those at greatest clinical need. The approaches to be tested in this study could yield assessments that reflect the two imperatives of emergency mental health care: brevity and accuracy. With better ability to identify who is at risk for suicidal behavior, we will be in a much stronger position to identify who needs intervention and reverse the disturbing, decade-long trend of increases in adolescent suicide and suicidal behavior.

Overview Abstract Suicide is the 2nd leading cause of death among adolescents and has increased by 20% in the past decade. The majority of suicide decedents have their last clinical contact in primary care. This ALACRITY Center proposes 3 studies designed to help PCPs capitalize on universal screening for teen depression by enhancing pediatric primary care?s capacity to identify, triage, and manage depressed and suicidal adolescents. To promote a consistent, best practice approach to adolescents who screen positive for depression or suicidality, Study 1 develops a decision support system (DSS) to guide PCPs? treatment recommendations to reflect patient acuity, barriers, attitudes, and treatment preferences. To increase the low rate of treatment attendance among patients who screen positive for depression, Study 2 develops and tests a personalized texting intervention that targets patient and parent motivation, readiness, and barriers. To guide PCPs upon identification of suicidal adolescents through routine screening, Study 3 develops and tests an app to guide the PCP to develop a safety plan and stabilize the suicidal patient, thereby avoiding unnecessary referrals to the ED and hospital. These studies are innovative through their use of technology to personalize interventions on the basis of personal preferences, motivations, barriers, and clinical presentation. These interventions are likely to be of high impact, by potentially doubling the rate of treatment adherence in depressed adolescents and halving the rate of suicide attempts in those at high risk. We will solicit pilot projects through innovation contests for teams of investigators and stakeholders on novel methods to identify and reduce suicidal risk in adolescents, such use of data mining of health records to identify suicidal youth, and assessment of suicide risk via analysis of speech and facial expression. These studies will be conducted in our CTSI-supported pediatric research practice network, PittNet, which has successfully supported many mental health research studies. PittNet facilitated meetings with pediatricians and other stakeholders to collaboratively develop these priorities and associated studies, so that the ensuing products would be meaningful, practical, useful to clinicians and patients, and highly likely to be disseminated. This Center provides shared infrastructure for the engagement and collaboration with stakeholders, as well as for recruitment, assessment, technology development, data management and analysis, access to EHRs and costs analyses. Our multidisciplinary team of primary care and mental health professionals, data scientists, and health services researchers has collectively led 9 NIH funded trials of mental health interventions in primary care, 10 NIMH-funded intervention development or clinical trials for mood disordered and suicidal adolescents, and 7 NIH grants that develop and test technologies to support clinicians and patients. This team has extensive experience collaborating with stakeholders, managing research centers, and training early career scientists and forges a collaborative network dedicated to the reduction of youth suicide risk in pediatric primary care.

The specific aims of the Administrative Core (AC) are to develop and support research infrastructure to enhance the capacity of pediatric primary care to assess, triage, and manage depressed and suicidal youth. The AC will convene a Steering Committee (SC), made up of the primary investigators in the Center that sets scientific priorities, provides oversight of projects and resources, oversees human subjects? protection, and supports an annual evaluation. Scientific priorities are developed in collaboration with stakeholders, namely providers of pediatric and mental health care, policy leaders (e.g., health plan administrators, public health officials), parents of patients, and adolescent patients. The SC will appoint a Scientific Advisory Committee that will conduct an annual review of the scientific processes, priorities, and achievements of the Center goals. Human subjects? protection is a high priority because many participants are at moderate to high risk for suicide. Center investigators have extensive experience in recruiting, managing, and developing human subjects? protection procedures for suicidal patients in the context of clinical trials and other research studies. An external DSMB will be appointed that will review Center studies twice a year. Subcommittees of the SC support: (1) stakeholder engagement; (2) training of early career scientists; (3) dissemination of Center findings and products; and (4) innovative new pilots studies. The Stakeholder engagement subcommittee will meet with policy leaders, providers, and patients and parent stakeholders to review progress and problems with extant studies, share results and discuss implications, and to vet and solicit new research ideas. The Training subcommittee will recruit early career scientists to work in the area of adolescent mental health and suicide prevention in the context of pediatric primary care, including applicants from T32s that subcommittee members direct. The Center will support the development of early career scientists by providing scientific consultation, provision of access to data, and sponsoring pilot innovation contests. The Training subcommittee will also develop monthly seminars, sponsor a biannual conference on the delivery of mental health care in pediatric primary care settings, and co-sponsor an annual conference on the use of technology for promoting behavioral health. The Dissemination subcommittee will collaborate with stakeholders on dissemination strategies with regard to Center products such as interventions or decision support devices to determine next steps for implementation or dissemination. The Pilot subcommittee solicits pilot studies through a novel crowdsourcing platform that invites teams of stakeholders and investigators to compete in innovation contests judged by scientists, stakeholders, and business innovators. The Center will set up a website, and support communication of Center findings and products via website, presentations, publications, and social media. In summary, the AC ensures that the Center achieves its goals and serves as a national resource for pediatric primary care-based intervention research designed to reduce the burden of adolescent suicide.