Matthew K. Nock - US grants

DESCRIPTION (Adapted from the Applicant?s Abstract): Dropping out of mental health services is a significant problem for children and their families, as 40-60% of those who begin mental health treatment terminate prematurely. Attrition from psychotherapy is an issue that raises broad concerns for both research and clinical practice, and often leads to adverse methodological, clinical, and financial outcomes. Previous work on attrition from treatment has focused primarily on identifying pre-treatment predictors of dropout, and has generally failed to address the question of why families terminate treatment prematurely or to develop effective programs for reducing the rate of attrition. The main goal of this research project is to test a theoretically informed attrition prevention program in a sample of 115 aggressive and antisocial children and their families seeking treatment at a university-based outpatient clinic. The present study will use a randomized, controlled design and will assess factors related to treatment attrition and participation, as well as therapeutic progress, throughout the study period. The specific aims of this project are to (1) examine if the prevention program decreases the rate of attrition from treatment and increases treatment participation, (2) examine whether the program leads to better therapeutic progress, and (3) examine whether changes in parents? perceptions of "barriers-to-treatment" (e.g., stressors, obstacles) will predict attrition. This project will extend the current research on attrition in several ways, and will provide important data about the mechanisms involved in attrition, as well as information about techniques that may be useful in reducing attrition from child therapy.

DESCRIPTION (provided by applicant): Suicide is among the leading causes of death worldwide and the World Health Organization and U.S. Department of Health and Human Services have highlighted the need for improved methods of identifying individuals at risk for suicide. Current methods for evaluating suicide risk rely almost exclusively on self report of suicidal thoughts and intent, which can provide biased or limited information as many suicidal individuals may deny self-injurious thoughts in order to avoid hospitalization or to facilitate discharge from hospital care. The long-term objective of the proposed line of research is the development of more objective and accurate methods of identifying those at risk for suicide. The primary goal of the research proposed in this application is to use methods from the social and cognitive sciences to develop and evaluate a clinical tool for assessing suicide risk. More specifically, the proposed research evaluates the usefulness of the Implicit Association Test (IAT), a computerized reaction-time task that evaluates individuals' automatic associations about different concepts, for examining implicit associations about suicide among individuals presenting to an emergency department at a major metropolitan hospital. The specific aims of this research are to (1) evaluate the validity of the suicide IAT by using it to assess implicit associations about suicide in a psychiatric emergency department setting among (a) individuals who have made a recent suicide attempt (N = 30), (b) individuals who report suicidal thoughts who have not made a suicide attempt (N = 30), and (c) individuals presenting to the emergency department who deny a recent suicide attempt or current suicidal thoughts (N = 30); (2) evaluate changes in implicit associations about suicide over the course of hospitalization; and (3) evaluate the ability of the implicit association measured in the hospital to predict suicidal thoughts and attempts over a six-month follow-up period. The results of this research have significant implications for research and clinical efforts related to suicide assessment.

DESCRIPTION (provided by applicant): Suicide is among the leading causes of death worldwide. The World Health Organization (WHO), the U.S. Surgeon General, and the U.S. Department of Health and Human Services have all strongly stated that more comprehensive data are needed on the prevalence of suicidal thoughts and attempts, as well as on the risk and protective factors associated with such outcomes. In response to these recommendations and to NIMH PA-06-438 (Research on the Reduction and Prevention of Suicidality) and PA-06-439 (Risk Factors for Psychopathology Using Existing Data Sets), this application seeks support for a program of research that examines the prevalence of and risk and protective factors for suicidal thoughts and behaviors. This project uses data from the 26 coordinated national population surveys (n =193,096) participating in the WHO World Mental Health (WMH) Survey Initiative. The unprecedented size, representativeness, and richness of the WMH database provides a unique opportunity to conduct comprehensive analyses of a range of suicide- related outcomes, including: suicidal ideation, suicide plans, suicide gestures, and suicide attempts. Analyses will address the three specific aims of this project: (1) estimate the cross-national prevalence, onset, and transitions between suicide-related outcomes;(2) examine risk and protective factors for lifetime occurrence of suicide-related outcomes;and (3) examine risk and protective factors for 12-month occurrence of suicide attempts. The results of these analyses will advance understanding of suicide-related outcomes and are expected to generate significant progress in scientific, clinical, and policy efforts aimed at the prediction and prevention these dangerous outcomes.

DESCRIPTION (provided by applicant): Especially among girls, the adolescent transition is associated with dramatic increases in the prevalence of suicidal ideation, and several forms of self-injury, including non-suicidal self-injury (NSSI;i.e., self-mutilation), suicidal gestures, threats, and attempts. This study proposes, and will test a theoretical model suggesting that biological and cognitive responses to social stressors explain the association between psychopathology (i.e., depression) and self-injury (i.e., mediation) and that specific interactions between stress responses (i.e., moderation) will help identify which girls with psychopathology are most likely to engage in self-injury longitudinally. Specific combinations of cognitive and biological stress responses are proposed to uniquely identify risks for different types of self-injury/suicidality (i.e., NSSI vs. suicidal ideation). Moreover, this study will examine trajectories of, and associations among self-injury constructs, addressing several limitations of past work. The aims of this research thus address several of the goals outlined in PA # 07-079, Research on the Reduction and Prevention of Suicidality as well as many of the goals articulated the NIMH Strategic Plan (NIMH, 2008) and the NAMHC Workgroup report on Transformative Neurodevelopmental Research (NAMHC, 2008). This study will use an innovative, lab-based methodological paradigm to examine cognitive (i.e., attributions, social problem solving) and biological (i.e., neuroendocrine, cardiovascular) responses to an in vivo social stressor. Participants will include 250 female adolescents from both outpatient and inpatient clinically-referred samples. Data will be collected from multiple informants (adolescents, parents) and multiple sources (observational methods, structured interviews, questionnaires, biological assays). It is expected that observed stress responses in the lab will interact with the experience of actual social stress measured during follow-up to predict self-injury trajectories over an 18 month interval. In other words, this study will address long-standing, but under-explored questions regarding why and how psychological symptoms, and/or the experience of stress, are associated with self-injurious behaviors. PUBLIC HEALTH RELEVANCE: Although much research has indicated that adolescents with a history of psychopathology are at increased risk for self-injury (e.g., self-mutilation;suicide attempts), little is known about why or how psychological symptoms lead to self-injury. Thus, there are few directions for evidence-based prevention/intervention. This research will examine specific psychological and biological responses to social stress that may increase the risk for girls'self- injury, and help to elucidate the development of self-injurious behaviors by exploring the course of these behaviors across a sensitive and critical developmental period.

DESCRIPTION (provided by applicant): Especially among girls, the adolescent transition is associated with dramatic increases in the prevalence of suicidal ideation, and several forms of self-injury, including non-suicidal self-injury (NSSI; i.e., self-mutilation), suicidal gestures, threats, and attempts. This study proposes, and will test a theoretical model suggesting that biological and cognitive responses to social stressors explain the association between psychopathology (i.e., depression) and self-injury (i.e., mediation) and that specific interactions between stress responses (i.e., moderation) will help identify which girls with psychopathology are most likely to engage in self-injury longitudinally. Specific combinations of cognitive and biological stress responses are proposed to uniquely identify risks for different types of self-injury/suicidality (i.e., NSSI vs. suicidal ideation). Moreover, this study will examine trajectories of, and associations among self-injury constructs, addressing several limitations of past work. The aims of this research thus address several of the goals outlined in PA # 07-079, Research on the Reduction and Prevention of Suicidality as well as many of the goals articulated the NIMH Strategic Plan (NIMH, 2008) and the NAMHC Workgroup report on Transformative Neurodevelopmental Research (NAMHC, 2008). This study will use an innovative, lab-based methodological paradigm to examine cognitive (i.e., attributions, social problem solving) and biological (i.e., neuroendocrine, cardiovascular) responses to an in vivo social stressor. Participants will include 250 female adolescents from both outpatient and inpatient clinically-referred samples. Data will be collected from multiple informants (adolescents, parents) and multiple sources (observational methods, structured interviews, questionnaires, biological assays). It is expected that observed stress responses in the lab will interact with the experience of actual social stress measured during follow-up to predict self-injury trajectories over an 18 month interval. In other words, this study will address long-standing, but under-explored questions regarding why and how psychological symptoms, and/or the experience of stress, are associated with self-injurious behaviors.

? DESCRIPTION (provided by applicant): In response to public calls from the US President, Congress, Surgeon General, and a recent NIMH-co- sponsored Suicide Research Prioritization Agenda, the proposed research will examine how suicidal ideation and attempts develop within one of the most vulnerable populations at risk for suicide (i.e., adolescent girls). This work will examine how girls' atypical acute stress responses to interpersonal stress at physiological, genomic, and behavioral units of analysis moderate the association between actual experiences of interpersonal stress and suicidal ideation among girls with distal suicide risk factors (i.e., elevated depressive symptoms/lifetime interpersonal adversity). Moreover, this research will examine how these distal risk factors transact with pubertal processes to produce risk for atypical acute stress responses. Last, inhibitory control will be examined as a moderator of the association between suicide ideation and suicide attempts. This research will identify numerous biomarkers of suicide risk, significantly advancing progress towards identification and prevention of an enormous public health issue that has been woefully understudied and for which no evidence- based approaches exist. Using a combination of a RDoC conceptual framework, experimental lab-based stressor paradigm, biological assays, performance-based assessments of executive function, longitudinal methods, and innovative bioinformatics approaches for measuring gene expression, this work offers a substantial advance within a field that almost exclusively has relied on cross-sectional, single-informant, retrospective reports of suicidality. Participants will include 200 girls (age 9-14 years) at pre-, peri-, and post-pubertal stages of development. Recruitment will oversample girls with elevated depressive symptoms/lifetime interpersonal adversity to participate in a lab-based study involving the assessment of physiological, genomic, and behavioral responses following an experimentally-induced social stressor. A multi-wave assessment occurring over a one-year longitudinal interval will be conducted to obtain extensive data on suicidal ideation and attempts over time. Biological data will be collected to measure the autonomic nervous system, hypothalamic-pituitary-adrenal axis system, gene expression (using microarray-based genome-wide transcriptional profiling), and pubertal development. Ongoing research conducted by this investigative team utilizing many of the same recruitment, data collection, and analytic procedures strongly supports the feasibility of the proposed research.

PROJECT SUMMARY/ABSTRACT    Many leading causes of death have declined significantly over the past 100 years (e.g., tuberculosis,  pneumonia/influenza, gastritis);? however, the suicide rate is virtually identical to what it was 100 years  ago.  Lack  of  progress  in  the  prevention  of  suicide  is  due  in  large  part  to  the  limited  understanding  of  this problem. Suicidal thoughts and behaviors (STBs), like other behavior problems (e.g., alcohol use,  substance use, eating disorders), rarely occur in the research lab where they can be carefully probed  and  cannot  be  ethically  induced  in  the  lab.  As  a  result,  experts  lack  a  firm  understanding  of  the  fundamental  properties  of  STBs,  and  of  how,  why,  and  when  they  unfold  in  nature.  The  purpose  of  this  study  is  to  address  this  enormous  gap  by  using  newly  developed  smartphone  and  wearable  biosensor technologies to conduct an intensive longitudinal study that will advance the understanding  and prediction of STBs and related behaviors. This study will monitor 600 people (300 adults and 300  adolescents)  at  elevated  risk  of  STBs  (i.e.,  those  presenting  to  a  psychiatric  hospital  with  suicide  ideation and/or a recent suicide attempt) during a high risk time period (i.e., post-­hospitalization). The  first  aim  of  this  study  is  to  identify  digital  phenotypes  of  STBs  using  data  collected  both  actively/subjectively  using  repeated  smartphone  surveys  and  passively/objectively  using  continuous  data  from  smartphones  (e.g.,  GPS,  accelerometer,  communications  data)  and  wearable  biosensors  (e.g.,  electrodermal  activity,  accelerometer).  The  second  aim  is  to  map  the  dynamic  trajectories  of  STBs  over  time.  The  third  aim  is  to  identify  short-­term  predictors  of  STBs  during  the  6  months  post-­ hospital discharge. Ongoing research by the proposed team demonstrates the feasibility of: recruiting  and retaining the proposed samples, intensively monitoring them over time using digital devices, and  using  analyses  of  these  rich  data  streams  to  make  discoveries  about  how  STBs  and  related  behaviors unfold in nature. The data collected in this study will provide a rich data source that will be  used  by  our  research  team  and  collaborative  researchers  to  advance  the  understanding,  prediction,  and ultimate prevention of STBs and related outcomes.        

Project Summary/Abstract Suicide is the second leading cause of death (behind accidents) among those ages 10-34 years in the US and is the cause of mortality most strongly linked to mental illness. Starting at approximately age 12 years, the rate of suicidal thoughts and behaviors (STBs) increases dramatically, especially among girls, who experience STBs at twice the rate for boys. These pronounced increases for adolescents and for girls have been well-documented for decades and are seen in virtually every country/culture around the world, yet, there is no firm understanding of why they exist. Moreover, very little is known about when risk is highest. The proposed research extends our team?s prior work, funded by two prior R01 awards, examining adolescent girls? stress responses as prospective predictors of STB trajectories, and a K99/R00 award revealing that changes in reproductive hormones across the menstrual cycle produce specific periods of high STB risk (particularly during the peri-menstrual phase) among adult women. Specifically, we hypothesize that girls will report higher occurrence and severity of STBs on days in the peri-menstrual phase than on days in other cycle phases (mid-follicular, ovulatory, mid-luteal), that these increases will be mediated by daily changes in negative affect and stress-reactivity during the peri- menstrual phase, and that girls with greater cyclical hormone sensitivity are at greater long-term risk of STBs, particularly during times when interpersonal stress is elevated. We propose to test these hypotheses in a sample of 200 clinically-referred girls ages 12-17 years who are at least one year post-menarche. The design begins with 70 days (two cycles) of daily surveys to assess negative affect and STBs. In addition, girls will complete two counterbalanced laboratory visits (at high risk peri-menstrual and low risk mid-follicular phases) during which we will evaluate their affective and physiological (autonomic, cortisol, genomic) responses to a standardized laboratory stressor. Next, girls will complete weekly surveys measuring cycle phase, interpersonal stress, negative affect, and STBs through one year of follow up. The intensive two-month baseline phase allows us to examine how the menstrual cycle shapes daily affective and physiological risk for STBs and lets us diagnose each girl?s degree of hormone sensitivity. These baseline individual differences in hormone sensitivity then can be examined as a predictor of STBs across the follow-up year of assessments, particularly during periods of elevated social stress. This powerful design will clarify whether cyclical changes in daily STBs (Aim 1) are mediated by affective and physiological STB risk factors, such as negative affect (Aim 2a; measured via daily surveys) and social stress reactivity (Aim 2b; measured via lab-based behavioral, physiological, and molecular biomarker assays), while also acknowledging critical moderation by both individual differences in hormone sensitivity (i.e., not all girls will have severe cyclical mood changes) and time-varying interpersonal stress (Aim 3). This innovative study will address several long-standing questions in the literature, including why girls are at increased risk, when girls may be most at risk, and which girls are at highest risk for future STBs.