Publications by authors named "Stephanie Le Hellard"

Article Synopsis
  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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Article Synopsis
  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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What distinguishes vulnerability and resilience to posttraumatic stress disorder (PTSD) remains unclear. Levering traumatic experiences reporting, genetic data, and electronic health records (EHR), we investigated and predicted the clinical comorbidities (co-phenome) of PTSD vulnerability and resilience in the UK Biobank (UKB) and All of Us Research Program (AoU), respectively. In 60,354 trauma-exposed UKB participants, we defined PTSD vulnerability and resilience considering PTSD symptoms, trauma burden, and polygenic risk scores.

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  • Obsessive-compulsive disorder (OCD) affects about 1% of people and has a strong genetic component, but previous studies have not fully explained its genetic causes or biological mechanisms.
  • A large genome-wide association study (GWAS) analyzed data from over 53,000 OCD cases and over 2 million control participants, identifying 30 significant genetic markers related to OCD and suggesting a 6.7% heritability from SNPs.
  • The research also found 249 candidate risk genes linked to OCD, particularly in specific brain regions, and showed genetic correlations with various psychiatric disorders, laying the groundwork for further studies and potential treatments.
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Sex differences in the epidemiology and clinical characteristics of schizophrenia are well-known; however, the molecular mechanisms underlying these differences remain unclear. Further, the potential advantages of sex-stratified meta-analyses of epigenome-wide association studies (EWAS) of schizophrenia have not been investigated. Here, we performed sex-stratified EWAS meta-analyses to investigate whether sex stratification improves discovery, and to identify differentially methylated regions (DMRs) in schizophrenia.

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Article Synopsis
  • Four GWAS studies on obsessive-compulsive disorder (OCD) have been conducted, showing a SNP-heritability of 28% but revealing only one significant SNP so far.
  • A new meta-analysis significantly increased the sample size to analyze 37,015 OCD cases against 948,616 controls, identifying 15 independent genome-wide significant loci, 14 of which were novel.
  • The research highlighted genetic correlations between OCD and various psychiatric disorders, while also mapping the genetic basis and biological pathways associated with OCD susceptibility.
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  • The study investigates how environmental factors, specifically perinatal asphyxia, impact DNA methylation and contribute to the development of schizophrenia and bipolar disorder, suggesting shared molecular mechanisms for these disorders.
  • Researchers analyzed data from 643 individuals with schizophrenia or bipolar disorder and 676 healthy controls to explore the relationship between perinatal asphyxia and DNA methylation patterns in blood cells, uncovering significant differences in methylation associated with this condition.
  • Findings indicated that individuals with a history of perinatal asphyxia showed different epigenetic responses compared to healthy controls, highlighting specific regions of DNA linked to brain development and function that may influence psychiatric risk factors.
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Background: Noninvasive neurostimulation treatments are increasingly being used to treat major depression, which is a common cause of disability worldwide. While electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are both effective in treating depressive episodes, their mechanisms of action are, however, not completely understood. ECT is given under general anesthesia, where an electrical pulse is administered through electrodes placed on the patient's head to trigger a seizure.

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  • Carriers of specific genetic variants (1q21.1 distal and 15q11.2 BP1-BP2) show both regional and global brain structure differences compared to noncarriers, but analyzing these differences can be complicated.
  • The study used MRI data from various groups (carriers and noncarriers) to assess how regional brain characteristics diverge from overall brain structure differences.
  • Findings revealed that certain brain regions in carriers exhibited distinct patterns of cortical surface area and thickness that deviated from the global average, suggesting more complex effects of these genetic variants on brain development.
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Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396).

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Background: Early stages of the COVID-19 pandemic have been associated with increasing obsessive-compulsive symptoms (OCS), but less is known regarding these symptoms' long-term trajectories. The aim of this study was to examine changes in contamination-related OCS in the Norwegian public during early and late stages of the pandemic, as well as characteristics that might be associated with these changes.

Methods: In a longitudinal online survey, 12 580 participants completed self-report questionnaires in April 2020, including a retrospective assessment of contamination-related OCS severity (DOCS-SF) prior to COVID-19.

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Background: Several risk factors for anxious-depressive symptomatology during the COVID-19 pandemic have been established. However, few studies have examined the relationship between personality traits, hardiness, and such symptomatology during the pandemic. These constructs might serve as risk- and/or protective factors for such mental distress through the pandemic.

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Patients with a severe mental disorder report significantly higher levels of childhood trauma (CT) than healthy individuals. Studies have suggested that CT may affect brain plasticity through epigenetic mechanisms and contribute to developing various psychiatric disorders. We performed a blood-based epigenome-wide association study using the Childhood Trauma Questionnaire-short form in 602 patients with a current severe mental illness, investigating DNA methylation association separately for five trauma subtypes and the total trauma score.

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Article Synopsis
  • The human brain evolves over time, with changes in structure affecting mental health and diseases throughout life.
  • This study identifies genetic variants that influence brain growth and shrinkage, using data from 15,640 individuals and focusing on 15 brain structures.
  • Key genes linked to metabolism were found, highlighting connections to conditions like depression and schizophrenia, and suggesting that understanding these genetic factors could lead to insights about healthy and problematic brain development and aging.
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Background: The COVID-19 pandemic has led to major social and economic changes that could impact public mental health. The main aim of the current study was to investigate mental health in Norway during the COVID-19 outbreak (since the first confirmed case on 26 February 2020).

Methods: The results are from the first wave of the data collection (1 April-2 June 2020), which took place during the outbreak along with its initial restrictions.

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  • This study explores the role of genetics in the age of onset of anorexia nervosa (AN) by analyzing data from a large genome-wide association study involving 9,335 cases and 31,981 control participants.
  • Researchers found significant genetic variations linked to typical-onset AN and identified different genetic correlations for early-onset (before age 13) and typical-onset AN, indicating distinct biological influences.
  • Results suggest a genetic relationship between the age at menarche and early-onset AN, implying that earlier menarche may increase the risk of developing AN at a younger age.
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Major mental disorders are highly prevalent and make a substantial contribution to the global disease burden. It is known that mental disorders share clinical characteristics, and genome-wide association studies (GWASs) have recently provided evidence for shared genetic factors as well. Genetic overlaps are usually identified at the single-marker level.

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Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets.

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Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively.

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Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold.

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The complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered use was associated with changes in circulating immune and neuroendocrine markers in schizophrenia (SCZ) and bipolar disorder (BD) patients.

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Article Synopsis
  • Scientists studied the brain's outer layer, called the cerebral cortex, to learn how genes can affect its structure.
  • They looked at brain scans from over 51,000 people and found 199 important genetic markers that relate to how the cortex is shaped.
  • The study showed that these genetic markers are linked to different brain functions and conditions like thinking skills, sleep problems, and ADHD.
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  • Researchers analyzed data from genome-wide association studies (GWAS) to explore genetic correlations across four eating disorder types and eight substance-use-related traits, involving large sample sizes ranging from ~2400 to ~537,000 participants.
  • Findings indicated positive genetic associations between anorexia nervosa and alcohol use disorder, as well as cannabis initiation, while some negative correlations were found between anorexia without binge eating and smoking behaviors, suggesting a complex relationship between these disorders influenced by genetic and possibly depressive factors.
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