Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

AbstractAnxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset.We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N=4,178, 65.5% female; mean age=41.5 years; N=1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age=45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets.In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD.These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Download Full-text

Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

PLoS ONE ◽

10.1371/journal.pone.0248254 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0248254

Author(s):

Joanna Martin ◽

Kimiya Asjadi ◽

Leon Hubbard ◽

Kimberley Kendall ◽

Antonio F. Pardiñas ◽

...

Keyword(s):

Mental Health ◽

Sex Differences ◽

Family History ◽

Psychiatric Disorders ◽

Genetic Risk ◽

Age At Onset ◽

Anxiety And Depression ◽

Rare Cnvs ◽

Genetic Liability ◽

History Of

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Download Full-text

Parental family history of dementia in relation to subclinical brain disease and dementia risk

Neurology ◽

10.1212/wnl.0000000000003871 ◽

2017 ◽

Vol 88 (17) ◽

pp. 1642-1649 ◽

Cited By ~ 19

Author(s):

Frank J. Wolters ◽

Sven J. van der Lee ◽

Peter J. Koudstaal ◽

Cornelia M. van Duijn ◽

Albert Hofman ◽

...

Keyword(s):

Risk Factors ◽

Family History ◽

Genetic Risk ◽

Brain Mri ◽

Age At Onset ◽

Age At Diagnosis ◽

Parental History ◽

Dementia Risk ◽

History Of ◽

Parental Family

Objective:To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort.Methods:From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI.Results:Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12–2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61–4.15; ≥80 years: HR 1.01, 95% CI 0.58–1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history.Conclusions:Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.

Download Full-text

Delineating genetic and familial risk for psychopathology in the ABCD study

10.1101/2020.09.08.20186908 ◽

2020 ◽

Author(s):

Clare E Palmer ◽

Robert John Loughnan ◽

Carolina Makowski ◽

Wesley Thompson ◽

Deanna Barch ◽

...

Keyword(s):

Family History ◽

Psychiatric Disorders ◽

Genetic Risk ◽

Familial Risk ◽

Risk Scores ◽

Typically Developing ◽

Polygenic Risk ◽

Hyperactivity Disorder ◽

History Of ◽

Risk Predictors

Psychiatric disorders place a huge burden on those affected and their families, as well as society. Nearly all psychiatric disorders have a heritable component and lifetime prevalence rates of several disorders are higher among first degree biological relatives of individuals with a diagnosis. Given that many psychiatric disorders have their onset in adolescence, estimating genetic risk during childhood may identify at-risk individuals for early intervention that can reduce this burden. Here we measured genetic risk for psychopathology using both polygenic risk scores (PRS) and family history in a large typically developing sample of 9-10 year old children from the Adolescent Brain and Cognitive Development (ABCD) StudySM and determined associations with a large battery of behavioural phenotypes. By including all genetic risk predictors in the same model, we were able to delineate unique behavioral associations across these measures. Polygenic risk for Attention Deficit Hyperactivity Disorder (ADHD) and depression (DEP) was associated with unique patterns of both externalizing and internalizing behaviors. Family history of conduct problems, depression and anxiety/stress additionally predicted unique behavioral variance across similar measures. These findings provide important insight into the potential predictive utility of PRS and family history in early adolescence and suggest that they may be signaling differential, additive information that could be useful for quantifying risk during development.

Download Full-text

Sex differences in brain aging among adults with family history of Alzheimer’s disease and APOE4 genetic risk

NeuroImage Clinical ◽

10.1016/j.nicl.2021.102620 ◽

2021 ◽

Vol 30 ◽

pp. 102620

Author(s):

Sivaniya Subramaniapillai ◽

Sricharana Rajagopal ◽

Jamie Snytte ◽

A. Ross Otto ◽

Gillian Einstein ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Family History ◽

Genetic Risk ◽

Brain Aging ◽

History Of

Download Full-text

Family History of Mental Health Disorders and Parental Help-Seeking for Behavioral Health Concerns in Pediatric Primary Care Offices

Journal of Pediatric Health Care ◽

10.1016/j.pedhc.2021.04.004 ◽

2021 ◽

Author(s):

Alyssa Linkenheil ◽

Lisa Honigfeld ◽

Anne Pidano

Keyword(s):

Mental Health ◽

Primary Care ◽

Family History ◽

Behavioral Health ◽

Help Seeking ◽

Mental Health Disorders ◽

Pediatric Primary Care ◽

Health Concerns ◽

History Of ◽

Health Disorders

Download Full-text

Levels of anxiety, depression and denial in patients with myocardial infarction

European Psychiatry ◽

10.1016/s0924-9338(97)80204-0 ◽

1997 ◽

Vol 12 (3) ◽

pp. 149-151 ◽

Cited By ~ 4

Author(s):

D Sarantidis ◽

A Thomas ◽

K Iphantis ◽

N Katsaros ◽

J Tripodianakis ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Intensive Care Unit ◽

Family History ◽

Positive Family History ◽

Anxiety And Depression ◽

Previous Myocardial Infarction ◽

History Of ◽

Seeking Help ◽

Anxiety Depression

SummaryIn this study we investigated 1) the changes in anxiety, depression and denial from admission to discharge in patients admitted to the intensive care unit following an acute myocardial infarction and 2) the effect of smoking habits, time lapsed from the appearance of symptoms to seeking help behavior, presence of a person that motivated the patient to seek help, previous myocardial infarction (MI) and family history of MI, on these changes. The results indicated that 1) the levels of both anxiety and depression increased from admission to discharge, while denial decreased; 2) positive family history of MI was associated with lower difference of denial between admission and discharge.

Download Full-text

Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323646 ◽

2020 ◽

Vol 91 (10) ◽

pp. 1046-1054 ◽

Cited By ~ 2

Author(s):

Benjamin Meir Jacobs ◽

Daniel Belete ◽

Jonathan Bestwick ◽

Cornelis Blauwendraat ◽

Sara Bandres-Ciga ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Genetic Risk ◽

Positive Family History ◽

Risk Scores ◽

Uk Biobank ◽

Gene Environment ◽

History Of

ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores.MethodsWe identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene–environment interactions and compare predictive models for PD.ResultsStrong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes.InterpretationHere, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene–environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.

Download Full-text

Anxiety and depression in children and adolescents with obesity: a nationwide study in Sweden

BMC Medicine ◽

10.1186/s12916-020-1498-z ◽

2020 ◽

Vol 18 (1) ◽

Cited By ~ 9

Author(s):

Louise Lindberg ◽

Emilia Hagman ◽

Pernilla Danielsson ◽

Claude Marcus ◽

Martina Persson

Keyword(s):

Risk Factors ◽

Family History ◽

General Population ◽

Children And Adolescents ◽

Neuropsychiatric Disorders ◽

Obesity Treatment ◽

Sensitivity Analyses ◽

Anxiety And Depression ◽

History Of ◽

Anxiety Depression

Abstract Background Anxiety and depression are more common in children with obesity than in children of normal weight, but it is unclear whether this association is independent of other known risk factors. Interpretation of results from previous studies is hampered by methodological limitations, including self-reported assessment of anxiety, depression, and anthropometry. The aim of this study was to investigate whether obesity increases the risk of anxiety or depression independently of other risk factors in a large cohort of children and adolescents, using robust measures with regard to exposure and outcome. Methods Children aged 6–17 years in the Swedish Childhood Obesity Treatment Register (BORIS, 2005–2015) were included (n = 12,507) and compared with a matched group (sex, year of birth, and area of residence) from the general population (n = 60,063). The main outcome was a diagnosis of anxiety or depression identified through ICD codes or dispensed prescribed medication within 3 years after the end of obesity treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox proportional models were adjusted for several known confounders. Results Obesity remained a significant risk factor for anxiety and depression in children and adolescents after adjusting for Nordic background, neuropsychiatric disorders, family history of anxiety/depression, and socioeconomic status. Girls in the obesity cohort had a 43% higher risk of anxiety and depression compared to girls in the general population (adjusted HR 1.43, 95% CI 1.31–1.57; p < 0.0001). The risk in boys with obesity was similar (adjusted HR 1.33, 95% CI 1.20–1.48; p < 0.0001). In sensitivity analyses, excluding subjects with neuropsychiatric disorders and a family history of anxiety/depression, the estimated risks in individuals with obesity were even higher compared with results from the main analyses (adjusted HR [95% CI]: girls = 1.56 [1.31–1.87], boys = 2.04 [1.64–2.54]). Conclusions Results from this study support the hypothesis that obesity per se is associated with risk of both anxiety and depression in children and adolescents.

Download Full-text