Mood Disorders

Treatment of Adolescent Suicide-Attempters

Principal Investigator:  John T. Walkup, M.D.

This multisite research study, sponsored by the National Institute of Mental Health, is a controlled clinical trial of three treatment interventions - medication management plus supportive clinical care, cognitive-behavior therapy, or the combination of the two - over a six-month research trial and a one-year follow-up period for adolescents who are depressed and who have a recent history of a suicide attempt or an interrupted attempt. The primary purpose of the study is to assess the effectiveness of the treatments decreasing the risk of recurrence of suicidal behavior.

A study targeting depressed suicide-attempters is important both because of this clinical population's high risk for suicide and repeated suicidal behavior, and because seriously suicidal subjects are routinely excluded from most clinical trials. Multimodal treatment is proposed because combined treatment may be more efficacious than single-modality treatment.

A total of 124 adolescents, ages 12-18, were enrolled and 25 of these were at Johns Hopkins. This study is no longer recruiting but Dr. Walkup and the other investigators are currently analyzing the results. The study team is expected to publish results by early 2008.

Treatment of Early-Age Mania

Principal Investigator: John T. Walkup, M.D.

This study, sponsored by the National Institute of Mental Health, evaluates the effectiveness of medication treatments for mania in children and adolescents ages, 6-15. The effectiveness of lithium, valproate, and risperidone for the treatment of mania is being evaluated to further our knowledge of pharmacotherapy for youth. A total of 540 children who meet criteria for Bipolar I disorder (manic or mixed phase) will participate across six sites, with 90 participants at Johns Hopkins over a five-year period. The design of the study is such that participants are assigned to a treatment condition based on their current use of an antimanic drug as well as on their response to that drug. After eight weeks of treatment, partial responders and non-responders are assigned to receive an antimanic drug they have not yet been prescribed. Given the severity and low recovery rates of childhood mania, this is the first large scale pharmacology study to provide data on the effectiveness of lithium, valproate, and risperidone as single treatments and as additional medication for childhood mania.

STATUS: Data analysis phase. This study is no longer recruiting new participants.

Offspring of Suicide Decedents Study

Principal Investigator: Holly C. Wilcox, Ph.D.

The primary aims of this study are to estimate the influence of parental death by suicide, as compared to other types of parental death, on mental disorders (including drug and alcohol dependence), violent criminal convictions, and suicidal behaviors among offspring; and to estimate the extent to which suicide by a parent, independent of the parent’s mental disorders and criminal convictions, increases the risk of serious mental disorders, violent criminal convictions, and suicidal behavior among offspring. Secondary aims of the study are: (1) to estimate whether parental suicide has a greater impact on psychiatric and criminal outcomes if it occurs during the subject's childhood or adolescence, as compared to adulthood and; (2) to estimate whether there is differential impact of maternal versus paternal suicide on offspring mental health and criminal outcomes, by sex of the offspring. Data is from over 30 years of Swedish population-based registries. Because we are studying two rare outcomes, suicide attempt and completed suicide, and the national registers are large and population-based, we are in a unique position to clarify a number of critical issues involving the familial-genetic transmission of suicidal behavior.

STATUS: This study has been completed.

Publications

Wilcox, H.C., Kuramoto, S.J, Lichtenstein, P., Långström, P., Brent, D.A., Runeson, B. Long-term Psychiatric and Violent Criminal Outcomes of Children Exposed to Parental Death: A Population-Based Registry Study in Sweden.  In preparation.

Kuramoto, S.J., Stuart, E.A., Runeson, B., Lichtenstein, P., Långström, N., Wilcox, H.C. Long-term Risk of Psychiatric Disorders and Suicidal Behavior among Child and Adolescent Survivors of Maternal and Paternal Suicide. Kuramoto, S.J., Stuart, E.A., Runeson, B., Lichtenstein, P., Långström, N., Wilcox, H.C. In preparation.

Parental Suicidal Behavior and Offspring Environmental Risk:
A Population-Based Adoption Study

Principal Investigator:  Holly C. Wilcox, Ph.D.

This study was designed to compare the relative impact of genetic vulnerability versus aspects of rearing environment (e.g., adoptive parent psychiatric disorder, suicidal behaviors, and criminal convictions) using an adoption design by studying biological offspring of suicide decedents and suicide attempters who were adopted at birth and raised by nonrelatives. The proposed study is focused on identifying: 1) which aspects of the family environment enhance or reduce risk to offspring of birth parents who took their lives to suicide or attempted suicide and 2) whether this risk is conferred by genetic or environmental factors or an interaction between the two. The proposed study will allow us to begin to disentangle the effects of genetic risk from the impact of the environment on vulnerability and resilience among offspring at high genetic risk for suicidal behaviors. This study has a high likelihood to provide unique information to the field of suicide research as well as lay the foundation for more advanced research in this area.

STATUS: This study is in the data analysis stage.

Childhood Trauma and Suicidal Behaviors: the Role of the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Mediating Risk

Principal Investigator: Holly C. Wilcox, Ph.D.

The goal of this project is to study the role of HPA axis dysfunction in mediating risk for suicidal behaviors among those exposed to childhood trauma. The potential pathway from childhood trauma to suicidal behaviors will be studied by assessing whether: 1) childhood trauma increases risk for HPA axis dysfunction and 2) whether HPA axis dysfunction increases risk for suicidal behaviors via increasing impulsive aggression. The aforementioned associations will be analyzed among offspring of adults enrolled in the Baltimore site of GenRED and GenRED II (Genetics of Recurrent Early-Onset Major Depressive Disorder). Elements of the proposed pathway to suicidal behavior will be elucidated for potential preventive and therapeutic targets.

STATUS: This study is in the recruitment stage.

Learn more about treatment of children and adolescents with mood disorders at Johns Hopkins