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A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression.

ABSTRACT: The increased risk of major depression in the offspring of depressed parents is well known. Whether the risk is transmitted beyond 2 generations is less well known. To our knowledge, no published study with direct interviews of family members and the generations in the age of risk for depression has evaluated beyond 2 generations. This information is important for detecting individuals at highest risk who may benefit from early intervention.To examine the familial aggregation of psychiatric disorder and functioning in grandchildren by their biological parents' and grandparents' depression status.Longitudinal retrospective cohort family study of 251 grandchildren (generation 3 [mean age, 18 years]) interviewed a mean of 2.0 times and their biological parents (generation 2) interviewed a mean of 4.6 times and grandparents (generation 1) interviewed up to 30 years. The study dates were January 1982 (wave 1) to June 2015 (wave 6).Cumulative rates of psychiatric disorders and functioning collected for all generations by clinically trained interviewers and best-estimate diagnosis made blind to diagnoses in members of previous generations.There were 91 families (G1) in the original sample, of whom 77 were eligible for inclusion (had a grandchild older than 5 years), and 80.5% (62 of 77) participated in the study. When first examining only 2 generations, the biological children (generation 3) of depressed compared with nondepressed parents (generation 2) had 2-fold increased risk for major depressive disorder (MDD) (hazard ratio [HR], 2.02; 95% CI, 1.08-3.79; P?=?.03), any disruptive disorder (HR, 1.70; 95% CI, 1.05-2.75; P?=?.03), substance dependence (HR, 2.96; 95% CI, 1.24-7.08; P?=?.01), any suicidal ideation or gesture (HR, 2.44; 95% CI, 1.28-4.66; P?=?.007), and poor functioning (F?=?38.25, P?

SUBMITTER: Weissman MM

PROVIDER: S-EPMC5512549 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression.

Weissman Myrna M MM Berry Obianuju O OO Warner Virginia V Gameroff Marc J MJ Skipper Jamie J Talati Ardesheer A Pilowsky Daniel J DJ Wickramaratne Priya P

JAMA psychiatry 20160901 9

<h4>Importance</h4>The increased risk of major depression in the offspring of depressed parents is well known. Whether the risk is transmitted beyond 2 generations is less well known. To our knowledge, no published study with direct interviews of family members and the generations in the age of risk for depression has evaluated beyond 2 generations. This information is important for detecting individuals at highest risk who may benefit from early intervention.<h4>Objective</h4>To examine the fam ...[more]

PMID: 27532344

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Project description:RATIONALE:Possible genetic correlates of spirituality and depression have been identified in community samples. We investigate some of the previously identified candidates in a sample of families at both high and low-risk for depression. METHOD:Offspring and grandchildren of individuals at high and low-risk for depression, participating in a multi-wave thirty-year longitudinal study, were assessed for seven SNPS drawn from four single gene candidates associated with systems implicated in both depression and spirituality: Serotonin (5-HT1B and 5-HT2A), Dopamine (DRD2), Oxytocin (OT) and Monoamine Vesicular Transporter (VMAT1). RESULTS:Dopamine (DRD2) Serotonin (5-HT1B), their Transporter (VMAT1) and Oxytocin (OXTR) were positively associated with a high level of importance of spirituality or religion (S/R) in the group at low familial risk for depression. DRD2 minor allele was associated with both lifetime major depressive disorder (MDD) and spirituality in the low-risk group for depression. No SNPs were related to S/R in the group at high familial risk for depression. OXTR was associated with lifetime MDD in the full sample. CONCLUSION:Genes for dopamine, serotonin, their vesicular transporter, and oxytocin may be associated with S/R in people at low familial risk for depression. Genes for dopamine may be associated both with S/R and increased risk for depression in people at low-risk for depression, suggesting a common pathway or physiology to mild to moderate depression. MDD is associated with oxytocin across risk groups. In the high-risk group, phenotypic expression of S/R may be suppressed. IMPLICATIONS:The shared association of DRD2 by S/R and depression, generally found to be inversely related, calls for further research on their common physiological pathways, and the phenotypic expression of these pathways based upon use and environment. Prevention for offspring at high familial risk for depression might include support for the development of child spirituality.

Project description:We previously reported a 90% decreased risk in major depression, assessed prospectively, in adult offspring of depressed probands who reported that religion or spirituality was highly important to them. Frequency of church attendance was not significantly related to depression risk. Our previous brain imaging findings in adult offspring in these high-risk families also revealed large expanses of cortical thinning across the lateral surface of the right cerebral hemisphere.To determine whether high-risk adults who reported high importance of religion or spirituality had thicker cortices than those who reported moderate or low importance of religion or spirituality and whether this effect varied by family risk status.Longitudinal, retrospective cohort, familial study of 103 adults (aged 18-54 years) who were the second- or third-generation offspring of depressed (high familial risk) or nondepressed (low familiar risk) probands (first generation). Religious or spiritual importance and church attendance were assessed at 2 time points during 5 years, and cortical thickness was measured on anatomical images of the brain acquired with magnetic resonance imaging at the second time point.Cortical thickness in the parietal regions by risk status.Importance of religion or spirituality, but not frequency of attendance, was associated with thicker cortices in the left and right parietal and occipital regions, the mesial frontal lobe of the right hemisphere, and the cuneus and precuneus in the left hemisphere, independent of familial risk. In addition, the effects of importance on cortical thickness were significantly stronger in the high-risk than in the low-risk group, particularly along the mesial wall of the left hemisphere, in the same region where we previously reported a significant thinner cortex associated with a familial risk of developing depressive illness. We note that these findings are correlational and therefore do not prove a causal association between importance and cortical thickness.A thicker cortex associated with a high importance of religion or spirituality may confer resilience to the development of depressive illness in individuals at high familial risk for major depression, possibly by expanding a cortical reserve that counters to some extent the vulnerability that cortical thinning poses for developing familial depressive illness.

Project description:Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95%CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95%CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95%CI = 9.5-130). Mortality associated with birth length below -4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95%CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio = 3.9, 95%CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95%CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95%CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95%CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.

Dataset Information

A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression.

Publications

A 30-Year Study of 3 Generations at High Risk and Low Risk for Depression.

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