The long-term objective of this application is to develop a career as an independent researcher focusing on the genetic and environmental etiology of depression, anxiety disorders, and posttraumatic stress disorder (PTSO). A better understanding of the genesis of these disorders would help develop more targeted prevention and treatment strategies. This objective is consistent with the National Institute of Mental Health's mission to reduce the burden of mental disorders. The career development award will build on the investigator's strong background in psychiatric epidemiology and applied statistics to develop expertise in genetic epidemiology and applied statistical genetics.
The specific aims of the proposed research study are to conduct a genetic linkage study of depression and anxiety disorders to identify genes that influence their development in an Arab Bedouin kindred in a village in Northern Israel. This kindred has high rates of suicide, depression, and anxiety disorders (12 percent, 30 percent, and 36 percent, respectively). This kindred is also highly homogeneous originating from one founder and has high rates of endogamy, which make it unique and promising for identifying genes influencing these phenotypes. We will also conduct linkage analysis of neuroticism, a personality trait referring to emotional reactivity, as a quantitative endophenotype that may represent an intermediate form of expression between genes and phenotypes. As an exploratory aim, we will conduct linkage analyses of PTSD and examine the interaction between genes and stressful life events in their influence on depression and PTSD. Relevance: Almost 50 percent of the population in the United States suffer from at least one mental health disorder. Depression and anxiety disorders are the most common and thus constitute a major public health problem. The proposed study will allow us to identify genes associated with depression and anxiety disorders and would greatly advance our ability to identify subjects at high risk and develop treatment for these disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Vogel, Michael W
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University of Pittsburgh
Schools of Medicine
United States
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Melhem, Nadine M; Hamdan, Sami; Klei, Lambertus et al. (2017) Runs of homozygosity, copy number variation, and risk for depression and suicidal behavior in an Arab Bedouin kindred. Psychiatr Genet 27:169-177
Bodea, Corneliu A; Middleton, Frank A; Melhem, Nadine M et al. (2017) Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31. Mol Neuropsychiatry 2:173-184
Melhem, Nadine M; Keilp, John G; Porta, Giovanna et al. (2016) Blunted HPA Axis Activity in Suicide Attempters Compared to those at High Risk for Suicidal Behavior. Neuropsychopharmacology 41:1447-56
Melhem, Nadine M; Brent, David (2016) Commentary: The course of depression after childhood parental death - a reflection on Berg et al. (2016). J Child Psychol Psychiatry 57:1467-1469
Brent, David A; Melhem, Nadine M; Oquendo, Maria et al. (2015) Familial pathways to early-onset suicide attempt: a 5.6-year prospective study. JAMA Psychiatry 72:160-8
Melhem, Nadine M; Lu, Cong; Dresbold, Cara et al. (2014) Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate. Am J Med Genet B Neuropsychiatr Genet 165B:521-30
Hamdan, Sami; Melhem, Nadine M; Porta, Giovanna et al. (2013) Alcohol and substance abuse in parentally bereaved youth. J Clin Psychiatry 74:828-33
Melhem, Nadine M; Porta, Giovanna; Walker Payne, Monica et al. (2013) Identifying prolonged grief reactions in children: dimensional and diagnostic approaches. J Am Acad Child Adolesc Psychiatry 52:599-607.e7
Hamdan, Sami; Mazariegos, David; Melhem, Nadine M et al. (2012) Effect of parental bereavement on health risk behaviors in youth: a 3-year follow-up. Arch Pediatr Adolesc Med 166:216-23
Hamdan, Sami; Melhem, Nadine M; Porta, Giovanna et al. (2012) The phenomenology and course of depression in parentally bereaved and non-bereaved youth. J Am Acad Child Adolesc Psychiatry 51:528-36

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