ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2013
Using the high-risk family design to identify biomarkers for major depression.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Relationship Between Family History of Depression and Brain Structure and Function: A Systematic Review of Large Cohorts.Biological psychiatry · 2026Pooled it
- Efficacy and Safety of Morinda Officinalis Oligosaccharides Combined with Probiotics as a Therapeutic Strategy for Major Depressive Disorder with Gastrointestinal Symptoms: A Randomized, Double-Blind, Controlled Clinical Trial.Neuropsychiatric disease and treatment · 2025Trial
- Neurobiology and Cognition in Girls at High-Risk of Eating Disorders: Exploring Imaging-Derived Trait Markers.European eating disorders review : the journal of the Eating Disorders Association · 2025Article
- Associations Between Parental Mood and Anxiety Psychopathology and Offspring Brain Structure: A Scoping Review.Clinical child and family psychology review · 2022Article
- Dissociating default mode network resting state markers of suicide from familial risk factors for depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Orbitofrontal cortex grey matter volume is related to children's depressive symptoms.NeuroImage. Clinical · 2020Article
- A diffusion tensor imaging study of brain microstructural changes related to religion and spirituality in families at high risk for depression.Brain and behavior · 2019Article
- Family Risk for Depression and Prioritization of Religion or Spirituality: Early Neurophysiological Modulations of Motivated Attention.Frontiers in human neuroscience · 2019Article
- Children of Mentally III Parents at Risk Evaluation (COMPARE): Design and Methods of a Randomized Controlled Multicenter Study-Part I.Frontiers in psychiatry · 2019Article
- The Lausanne-Geneva cohort study of offspring of parents with mood disorders: methodology, findings, current sample characteristics, and perspectives.Social psychiatry and psychiatric epidemiology · 2017Article
- Associations between serotonin transporter and behavioral traits and diagnoses related to anxiety.Psychiatry research · 2017Article
- Motivated attention and family risk for depression: Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal blunted emotional responsivity.NeuroImage. Clinical · 2017Article
- Comparison of the effectiveness of duloxetine in depressed patients with and without a family history of affective disorders in first-degree relatives.Shanghai archives of psychiatry · 2015Article
- Biomarkers of intergenerational risk for depression: a review of mechanisms in longitudinal high-risk (LHR) studies.Journal of affective disorders · 2015Review
- The Effects of Tryptophan on Everyday Interpersonal Encounters and Social Cognitions in Individuals with a Family History of Depression.The international journal of neuropsychopharmacology · 2015Article
- Developmental change in amygdala reactivity during adolescence: effects of family history of depression and stressful life events.The American journal of psychiatry · 2015Article
- A two-factor model of relapse/recurrence vulnerability in unipolar depression.Journal of abnormal psychology · 2015Article
- Trajectories of individual depressive symptoms in adolescents: gender and family relationships as predictors.Developmental psychology · 2014Article
- Using multiple methods to characterize the phenotype of individuals with a family history of major depressive disorder.Journal of affective disorders · 2013Article
- Biomarkers in pediatric depression.Depression and anxiety · 2013Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The familial nature of major depressive disorder (MDD) is now well recognized. We followed children and grandchildren of probands with and without MDD to examine transmission of depression over generations, and to identify early vulnerability markers prior to the onset of disease. The study now includes three generations and five completed assessment waves spanning 25 years, with a sixth wave underway. Beginning with the fourth wave, we collected measures of brain structure (magnetic resonance imaging, MRI) and physiology (electroencephalography, EEG) and DNA in order to examine at a biological level why the offspring of depressed parents were at higher risk. In this paper, we provide an overview of the study design, the main findings, including new data, and the role of the high-risk design in translational research. We demonstrate that offspring of depressed parents ('high-risk'), when compared with those of non-depressed parents ('low-risk'), were at increased risk for depressive and anxiety disorders, with anxiety appearing earlier and being a predisposing factor for MDD. Offspring with two generations previously affected were at greatest risk. Thinning of the cortical mantle (MRI) and reduced resting-state activity (EEG) within the right parieto-temporal hemisphere differentiated high- from low-risk offspring, regardless of whether the offspring had MDD, suggesting that these measures might serve as familial trait markers for depression and related syndromes. The high- and low-risk offspring also differed by serotonin transporter promoter length polymorphism genotypes, even though the same genotypes were not associated with the presence of MDD. The high-risk epidemiological design appears to be a particularly valuable asset in translational research as it allows targeting of biological processes that emerge prior to the onset of disease, and identifies individuals at high risk for the disorder who may carry the trait or marker but not yet be affected.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.