This 3-generation study of families at high and low risk for Major Depressive Disorder (MDD) has documented the strong familial transmission of mood disorders across generations. We have conducted 5 waves of assessments in this cohort over 25 years. In the 5th wave, we added Magnetic Resonance Imaging (MRI) measures and found a remarkably robust association of familial risk for MDD with asymmetries in cortical thickness, with a nearly 30% reduction in thickness observed in the lateral parietal, temporal, and frontal cortices of the right hemisphere of the high risk group. These MRI findings are consistent with EEG findings from the 4th wave of assessments that demonstrated reduced activity over the posterior cortices of the right cerebral hemisphere. Both the MRI and EEG findings were present in high-risk individuals who never had MDD in their lifetimes, suggesting that these abnormalities were not simply a consequence of previously having been depressed or having been treated for depression. Thinning of the cortical mantle and reduced electrophysiological activity in the right hemisphere therefore may constitute related endophenotypes for familial vulnerability to developing MDD. We are proposing a 6th wave of study to gain a deeper understanding of the right hemisphere abnormalities in familial MDD in the 216 individuals imaged thus far. This represents the largest MRI study published for MDD to date, and it is the only sample studying 3 generations of individuals at high or low risk for MDD. We are proposing to collect additional MRI and EEG measures, as well as clinical and cognitive neuroscience data, that will inform us about the neural bases of the right hemisphere thinning and their consequences for brain function and emotional processing. We will also determine whether additional cortical thinning in the left cerebral hemisphere predicts new or recurrent MDD in those people who were imaged in Wave 5. Our cohort has exceptional attributes that will aid our search for detecting MDD endophenotypes, including (1) an elevated clinical risk for developing MDD in the high risk group that has been amply demonstrated;(2) multiple prospective assessments, conducted blind to risk status, provide great confidence in the accuracy of the clinical diagnoses;and (3) the sample contains individuals who have not yet become ill but who are nevertheless at elevated risk of becoming ill, thereby allowing us to disentangle the neurobiological determinants of vulnerability from the compensatory responses that would be present in already-affected individuals. MDD is an early-onset, highly prevalent disorder with significant morbidity, and it afflicts people in their most productive years. Identifying the biological vulnerability for depression before the onset of illness has important implications for prevention and public health.

Public Health Relevance

MDD is an early-onset, highly prevalent disorder with significant morbidity, and it afflicts people in their most productive years. Identifying the biological vulnerability for depression before the onset of illness, as we have described in the study, has important implications for prevention and public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH036197-28
Application #
8605917
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Garriock, Holly A
Project Start
1987-07-01
Project End
2015-01-31
Budget Start
2014-03-01
Budget End
2015-01-31
Support Year
28
Fiscal Year
2014
Total Cost
$950,202
Indirect Cost
$211,237
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Desai, Jay; Huo, Yuankai; Wang, Zhishun et al. (2017) Reduced perfusion in Broca's area in developmental stuttering. Hum Brain Mapp 38:1865-1874
Tenke, Craig E; Kayser, Jürgen; Svob, Connie et al. (2017) Association of posterior EEG alpha with prioritization of religion or spirituality: A replication and extension at 20-year follow-up. Biol Psychol 124:79-86
Svob, Connie; Liu, Jie; Wickramaratne, Priya et al. (2017) Neuroanatomical correlates of familial risk-for-depression and religiosity/spirituality. Spiritual Clin Pract (Wash D C ) 4:32-42
Talati, Ardesheer; Wickramaratne, Priya J; Wesselhoeft, Rikke et al. (2017) Prenatal tobacco exposure, birthweight, and offspring psychopathology. Psychiatry Res 252:346-352
Talati, Ardesheer; Odgerel, Zagaa; Wickramaratne, Priya J et al. (2017) Associations between serotonin transporter and behavioral traits and diagnoses related to anxiety. Psychiatry Res 253:211-219
Hao, Xuejun; Talati, Ardesheer; Shankman, Stewart A et al. (2017) Stability of Cortical Thinning in Persons at Increased Familial Risk for Major Depressive Disorder Across 8 Years. Biol Psychiatry Cogn Neurosci Neuroimaging 2:619-625
Anderson, Micheline R; Miller, Lisa; Wickramaratne, Priya et al. (2017) Genetic Correlates of Spirituality/Religion and Depression: A Study in Offspring and Grandchildren at High and Low Familial Risk for Depression. Spiritual Clin Pract (Wash D C ) 4:43-63
Cha, Jiook; Guffanti, Guia; Gingrich, Jay et al. (2017) Effects of Serotonin Transporter Gene Variation on Impulsivity Mediated by Default Mode Network: A Family Study of Depression. Cereb Cortex :1-11
Kayser, Jürgen; Tenke, Craig E; Abraham, Karen S et al. (2017) Motivated attention and family risk for depression: Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal blunted emotional responsivity. Neuroimage Clin 14:692-707
Weissman, Myrna M; Berry, Obianuju O; Warner, Virginia et al. (2016) A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression. JAMA Psychiatry 73:970-7

Showing the most recent 10 out of 173 publications