- Email: [email protected]
31.2 INCREASED DEFAULT MODE NETWORK CONNECTIVITY IN INDIVIDUALS AT HIGH FAMILIAL RISK FOR DEPRESSION
SYMPOSIA 31.0 – 31.3
SYMPOSIUM 31 TRANSMISSION OF MAJOR DEPRESSION ACROSS THREE GENERATIONS: SEARCH FOR BIOMARKERS Myrna M. Weissman, PhD, Chief, Division of Epidemiology, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032; Jonathan Posner, MD, Division of Child and Adolescent Psychiatry, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 78, New York, NY 10032; Daniel N. Klein, PhD Objectives: The increased risk of major depression in the offspring of depressed parents is well known. Whether this risk is transmitted beyond two generations is less known. This information is important for detecting individuals at highest risk for early intervention and possibly for biological marker studies. Data are presented on an up-to-30-year follow-up of a three generation cohort of grandchildren and their biological parents who were at high or low risk for major depression by virtue of their grandparents’ status of depression. Methods: Longitudinal cohort study of 251 grandchildren of 127 biological parents from 62 families followed an average 4.6 times up to 30 years. The grandchildren and their parents were assessed blind to the grandparents’ diagnostic status using structured diagnostic assessments for adults and separate ones for children administered by clinically trained assessors. Bestestimates diagnoses were also made by psychiatrists or PhD psychologists blind to the original proband group’s clinical status. Results: The biological offspring of depressed parents compared with depressed parents have more than a twofold increased risk of depression, disruptive disorders, substance abuse, suicidal ideation, and poor functioning. However, embedded within the group are the grandchildren of both a depressed parent and grandparent who were at the highest risk for mood disorders and major depression. More than 70 percent of these grandchildren had at least one psychiatric diagnosis. The findings on subjects, with three generations affected with MDD, were not confounded by other risks, such as parental comorbid diagnosis, divorce, and abuse. Conclusions: The biological offspring with two previous generations affected with major depression are at highest risk of major depression. This finding suggests the potential value of determining family history of depression in children and adolescents beyond one generation. A simple clinical family history assessment can be useful in identifying risk and initiating surveillance or early treatment. The strength and specificity of transmission of major depression across three generations may make this group a homogenous sample one for biological marker studies.
DDD FAM IMAGS http://dx.doi.org/10.1016/j.jaac.2016.07.295
31.1 THREE GENERATIONS AT HIGH-RISK AND LOW-RISK FOR DEPRESSION Myrna M. Weissman, PhD, Chief Division of Epidemiology, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032 Objectives: The increased risk of major depression in the offspring of depressed parents is well known. Whether this risk is transmitted beyond two generations is less known. This information is important for detecting individuals at highest risk for early intervention and possibly for biological marker studies. Data are presented on up to a 30-year follow-up study of a three-generation cohort of grandchildren and their biological parents who were at high or low risk for major depression by virtue of their grandparents’ depression status. Methods: Longitudinal cohort study of 251 grandchildren of 127 biological parents from 62 families followed an average of 4.6 times up to 30 years. The grandchildren and their parents were assessed blind to grandparent’s diagnostic status by use of structured diagnostic assessments, administered by clinically trained assessors, for adults and separate ones for children. Bestestimates diagnoses were also made by psychiatrists or psychologists with doctorate degrees blind to the original proband group’s clinical status.
S306
www.jaacap.org
Results: The biological offspring of depressed parents compared with nondepressed parents have over a twofold increased risk of depression, disruptive disorders, substance abuse, suicidal ideation, and poor functioning. However, embedded within the group are the grandchildren of both a depressed parent and grandparent who were at the highest risk for mood disorders and major depression. More than 70 percent of these grandchildren had at least one psychiatric diagnosis. The findings on subjects with three generations affected with MDD were not confounded by other risks that might explain them such as parental comorbid diagnosis, divorce, and abuse. Conclusions: The biological offspring, with two previous generations affected with major depression, are at highest risk for major depression. This finding suggests the potential value of determining family history of depression in children and adolescents beyond one generation. A simple clinical family history assessment can be useful in identifying risk and initiating surveillance or early treatment. The strength and specificity of transmission of major depression across three generations may make this group a homogenous sample group for biological marker studies.
FAM Supported by NIMH Grant R01 MH-036197, the Sackler Institute for Developmental Biology and the Silvio O. Conte Center Grant IP50MH090966 http://dx.doi.org/10.1016/j.jaac.2016.07.296
31.2 INCREASED DEFAULT MODE NETWORK CONNECTIVITY IN INDIVIDUALS AT HIGH FAMILIAL RISK FOR DEPRESSION Jonathan Posner, MD, Division of Child and Adolescent Psychiatry, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 78, New York, NY 10032 Objectives: Current approaches are effective in treating MDD, yet more than half of the patients either fail to remit or drop out of treatment prematurely. An alternative strategy is to identify those at high risk for developing MDD, with the goal of advancing prevention and early intervention. However, critical to advancing this preventive approach is the identification of biomarkers that are predictive of the development of MDD. Methods: By use of resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 112 individuals (ages 11–60 years) at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Results: Based on rs-fcMRI, individuals at high versus low familial risk for depression showed increased DMN connectivity, as well as decreased DMNCEN negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMNCEN negative connectivity. Path analyses indicated that decreased DMN-CEN negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Conclusions: Our findings suggest that DMN and DMN-CEN connectivity differ in those at high versus low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.
PRE Supported by NIMH Grants R01-MH036197, K23-MH091249, and Shire Pharmaceuticals. http://dx.doi.org/10.1016/j.jaac.2016.07.297
31.3 HYPERACTIVE DEFENSE-SURVIVAL CIRCUITRY AND BRAIN VOLUMES: A THREEGENERATION STUDY Virginia Warner, DrPH, Epidemiology, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032-1098 Objectives: Hyperactive defense-survival circuit response to threatening childhood family environments have been shown to be associated with risk for depression and could be an innate familial trait that is transmitted across generations. We tested the hypothesis in our 30-year multigenerational study
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
SYMPOSIUM 31 TRANSMISSION OF MAJOR DEPRESSION ACROSS THREE GENERATIONS: SEARCH FOR BIOMARKERS Myrna M. Weissman, PhD, Chief, Division of Epidemiology, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032; Jonathan Posner, MD, Division of Child and Adolescent Psychiatry, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 78, New York, NY 10032; Daniel N. Klein, PhD Objectives: The increased risk of major depression in the offspring of depressed parents is well known. Whether this risk is transmitted beyond two generations is less known. This information is important for detecting individuals at highest risk for early intervention and possibly for biological marker studies. Data are presented on an up-to-30-year follow-up of a three generation cohort of grandchildren and their biological parents who were at high or low risk for major depression by virtue of their grandparents’ status of depression. Methods: Longitudinal cohort study of 251 grandchildren of 127 biological parents from 62 families followed an average 4.6 times up to 30 years. The grandchildren and their parents were assessed blind to the grandparents’ diagnostic status using structured diagnostic assessments for adults and separate ones for children administered by clinically trained assessors. Bestestimates diagnoses were also made by psychiatrists or PhD psychologists blind to the original proband group’s clinical status. Results: The biological offspring of depressed parents compared with depressed parents have more than a twofold increased risk of depression, disruptive disorders, substance abuse, suicidal ideation, and poor functioning. However, embedded within the group are the grandchildren of both a depressed parent and grandparent who were at the highest risk for mood disorders and major depression. More than 70 percent of these grandchildren had at least one psychiatric diagnosis. The findings on subjects, with three generations affected with MDD, were not confounded by other risks, such as parental comorbid diagnosis, divorce, and abuse. Conclusions: The biological offspring with two previous generations affected with major depression are at highest risk of major depression. This finding suggests the potential value of determining family history of depression in children and adolescents beyond one generation. A simple clinical family history assessment can be useful in identifying risk and initiating surveillance or early treatment. The strength and specificity of transmission of major depression across three generations may make this group a homogenous sample one for biological marker studies.
DDD FAM IMAGS http://dx.doi.org/10.1016/j.jaac.2016.07.295
31.1 THREE GENERATIONS AT HIGH-RISK AND LOW-RISK FOR DEPRESSION Myrna M. Weissman, PhD, Chief Division of Epidemiology, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032 Objectives: The increased risk of major depression in the offspring of depressed parents is well known. Whether this risk is transmitted beyond two generations is less known. This information is important for detecting individuals at highest risk for early intervention and possibly for biological marker studies. Data are presented on up to a 30-year follow-up study of a three-generation cohort of grandchildren and their biological parents who were at high or low risk for major depression by virtue of their grandparents’ depression status. Methods: Longitudinal cohort study of 251 grandchildren of 127 biological parents from 62 families followed an average of 4.6 times up to 30 years. The grandchildren and their parents were assessed blind to grandparent’s diagnostic status by use of structured diagnostic assessments, administered by clinically trained assessors, for adults and separate ones for children. Bestestimates diagnoses were also made by psychiatrists or psychologists with doctorate degrees blind to the original proband group’s clinical status.
S306
www.jaacap.org
Results: The biological offspring of depressed parents compared with nondepressed parents have over a twofold increased risk of depression, disruptive disorders, substance abuse, suicidal ideation, and poor functioning. However, embedded within the group are the grandchildren of both a depressed parent and grandparent who were at the highest risk for mood disorders and major depression. More than 70 percent of these grandchildren had at least one psychiatric diagnosis. The findings on subjects with three generations affected with MDD were not confounded by other risks that might explain them such as parental comorbid diagnosis, divorce, and abuse. Conclusions: The biological offspring, with two previous generations affected with major depression, are at highest risk for major depression. This finding suggests the potential value of determining family history of depression in children and adolescents beyond one generation. A simple clinical family history assessment can be useful in identifying risk and initiating surveillance or early treatment. The strength and specificity of transmission of major depression across three generations may make this group a homogenous sample group for biological marker studies.
FAM Supported by NIMH Grant R01 MH-036197, the Sackler Institute for Developmental Biology and the Silvio O. Conte Center Grant IP50MH090966 http://dx.doi.org/10.1016/j.jaac.2016.07.296
31.2 INCREASED DEFAULT MODE NETWORK CONNECTIVITY IN INDIVIDUALS AT HIGH FAMILIAL RISK FOR DEPRESSION Jonathan Posner, MD, Division of Child and Adolescent Psychiatry, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Unit 78, New York, NY 10032 Objectives: Current approaches are effective in treating MDD, yet more than half of the patients either fail to remit or drop out of treatment prematurely. An alternative strategy is to identify those at high risk for developing MDD, with the goal of advancing prevention and early intervention. However, critical to advancing this preventive approach is the identification of biomarkers that are predictive of the development of MDD. Methods: By use of resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 112 individuals (ages 11–60 years) at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Results: Based on rs-fcMRI, individuals at high versus low familial risk for depression showed increased DMN connectivity, as well as decreased DMNCEN negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMNCEN negative connectivity. Path analyses indicated that decreased DMN-CEN negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Conclusions: Our findings suggest that DMN and DMN-CEN connectivity differ in those at high versus low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.
PRE Supported by NIMH Grants R01-MH036197, K23-MH091249, and Shire Pharmaceuticals. http://dx.doi.org/10.1016/j.jaac.2016.07.297
31.3 HYPERACTIVE DEFENSE-SURVIVAL CIRCUITRY AND BRAIN VOLUMES: A THREEGENERATION STUDY Virginia Warner, DrPH, Epidemiology, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032-1098 Objectives: Hyperactive defense-survival circuit response to threatening childhood family environments have been shown to be associated with risk for depression and could be an innate familial trait that is transmitted across generations. We tested the hypothesis in our 30-year multigenerational study
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016