Publications by authors named "Martin Preisig"

195 Publications

Associations of job strain and family strain with risk of major depressive episode: A prospective cohort study in U.S. working men and women.

J Psychosom Res 2021 Aug 8;147:110541. Epub 2021 Jun 8.

Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, United States; School of Nursing, University of California, Los Angeles, United States. Electronic address:

Background: Studies assessing sex differences in the associations of psychosocial strain with depression have shown mixed and inconsistent results. Our objective was to examine prospective associations of job strain and family strain with risk of major depressive episode (MDE) among United States workers, as well as assess potential effect modification by sex.

Methods: Using data from the nationally representative and population-based Mid-life in the United States (MIDUS) study with a prospective cohort design and a 9-year follow-up period, the effects of job strain and family strain at baseline on risk of MDE within the 12 months prior to the follow-up assessment were examined in 1581 workers (805 men, 776 women) who were free from MDE within the 12 months prior to the baseline survey, by multivariate Poisson regression analysis.

Results: After adjustment for relevant covariates, there was evidence for effect modification by sex for the association between job strain and MDE but not for the association between family strain and MDE. Indeed, high job strain was prospectively associated with the risk of MDE (RR and 95% CI = 2.14 [1.14, 4.03]) in men but not in women. Moreover, high family strain was prospectively associated with a higher risk of MDE (RR and 95% CI = 1.57 [1.05, 2.37]) in the whole sample.

Conclusion: Family strain was associated with risk of MDE regardless of the sex of a person. In contrast, high job strain may involve an increased risk of developing MDE only in men but not in women.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110541DOI Listing
August 2021

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.

Biol Psychiatry 2021 Mar 23. Epub 2021 Mar 23.

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois; Department of Psychiatry and Behavioral Sciences, North Shore University Health System, Evanston, Illinois.

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.

Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.

Results: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10; rs73033497, p = 8.8 × 10; rs7914279, p = 6.4 × 10), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05).

Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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http://dx.doi.org/10.1016/j.biopsych.2021.02.972DOI Listing
March 2021

Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort.

Calcif Tissue Int 2021 May 18. Epub 2021 May 18.

Interdisciplinary Center for Bone Diseases, Service of Rhumatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = - 0.153, p < 0.001) and sc-8PM (r = - 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.
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http://dx.doi.org/10.1007/s00223-021-00863-yDOI Listing
May 2021

Brain tissue properties link cardio-vascular risk factors, mood and cognitive performance in the CoLaus|PsyCoLaus epidemiological cohort.

Neurobiol Aging 2021 Jun 16;102:50-63. Epub 2021 Feb 16.

Department of Clinical Neurosciences, Laboratory for Research in Neuroimaging LREN, Centre for Research in Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Electronic address:

Given the controversy about the impact of modifiable risk factors on mood and cognition in ageing, we sought to investigate the associations between cardio-vascular risk, mental health, cognitive performance and brain anatomy in mid- to old age. We analyzed a set of risk factors together with multi-parameter magnetic resonance imaging (MRI) in the CoLaus|PsyCoLaus cohort (n > 1200). Cardio-vascular risk was associated with differences in brain tissue properties - myelin, free tissue water, iron content - and regional brain volumes that we interpret in the context of micro-vascular hypoxic lesions and neurodegeneration. The interaction between clinical subtypes of major depressive disorder and cardio-vascular risk factors showed differential associations with brain structure depending on individuals' lifetime trajectory. There was a negative correlation between melancholic depression, anxiety and MRI markers of myelin and iron content in the hippocampus and anterior cingulate. Verbal memory and verbal fluency performance were positively correlated with left amygdala volumes. The concomitant analysis of brain morphometry and tissue properties allowed for a neuro-biological interpretation of the link between modifiable risk factors and brain health.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.02.002DOI Listing
June 2021

The association between genetically determined ABO blood types and major depressive disorder.

Psychiatry Res 2021 May 24;299:113837. Epub 2021 Feb 24.

Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.
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http://dx.doi.org/10.1016/j.psychres.2021.113837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071927PMC
May 2021

Dietary Patterns are Differentially Associated with Atypical and Melancholic Subtypes of Depression.

Nutrients 2021 Feb 26;13(3). Epub 2021 Feb 26.

Department of Psychiatry, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.

Diet has been associated with the risk of depression, whereas different subtypes of depression have been linked with different cardiovascular risk factors (CVRFs). In this study, our aims were to 1) identify dietary patterns with exploratory factor analysis, 2) assess cross-sectional associations between dietary patterns and depression subtypes, and 3) examine the potentially mediating effect of dietary patterns in the associations between CVRFs and depression subtypes. In the first follow-up of the population-based CoLaus|PsyCoLaus study (2009-2013, 3554 participants, 45.6% men, mean age 57.5 years), a food frequency questionnaire assessed dietary intake and a semi-structured interview allowed to characterize major depressive disorder into current or remitted atypical, melancholic, and unspecified subtypes. Three dietary patterns were identified: Western, Mediterranean, and Sweet-Dairy. Western diet was positively associated with current atypical depression, but negatively associated with current and remitted melancholic depression. Sweet-Dairy was positively associated with current melancholic depression. However, these dietary patterns did not mediate the associations between CVRFs and depression subtypes. Hence, although we could show that people with different subtypes of depression make different choices regarding their diet, it is unlikely that these differential dietary choices account for the well-established associations between depression subtypes and CVRFs.
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http://dx.doi.org/10.3390/nu13030768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996872PMC
February 2021

Does Cognitive Functioning Predict Chronic Pain in Older Adult? Results From the CoLaus|PsyCoLaus Longitudinal Study.

J Pain 2021 Feb 25. Epub 2021 Feb 25.

Department of Psychiatry, Service of Old Age Psychiatry (SUPAA), Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Chronic pain (CP) and cognitive impairment are common in older adults. CP was found to be associated with cognitive impairment in many cross-sectional studies. However, their cross-sectional design precluded inference on temporality. Accordingly, we aimed to prospectively assess the association between cognitive functioning and the occurrence of CP in older community dwellers. Analyses were based on data of the first (FU1) and the second follow-up (FU2) of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland) including the participants aged 65 and over. Neuropsychological functioning including memory, language, attention and executive function was measured at FU1. CP was assessed at FU1 and FU2 by self-rating questionnaire. The association between cognitive scores and subsequent CP was determined using multiple logistic regressions. Among the 337 participants without CP at FU1, 107 (31.8%) developed CP at FU2. A significant association was observed between higher Stroop color-time and interference index at FU1 and a higher risk of CP at FU2 (OR = 1.02; P = .03 and OR = 1.49; P = .03, respectively). Our results suggest that patients with inhibitory deficit may be at higher risk of developing CP in the presence of painful events. A cognitive assessment could be recommended to identify frail patients in these situations. Perspective: This study suggests that presence of inhibitory deficits is associated with a higher risk of developing subsequent CP in older adults. In the presence of painful events, a cognitive assessment should be recommended to identify frail patients and to manage them carefully.
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http://dx.doi.org/10.1016/j.jpain.2021.01.007DOI Listing
February 2021

Retrospectively assessed trajectories of PTSD symptoms and their subsequent comorbidities.

J Psychiatr Res 2021 04 2;136:71-79. Epub 2021 Feb 2.

Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.

Background: Dynamic trajectories of psychopathology, such as post-traumatic stress disorder (PTSD) provide a key to understanding human adjustment processes after trauma exposure. Recent studies have suggested more heterogeneous mental health outcomes than the initially identified four adjustment trajectories. To explore this heterogeneity, we investigated the after-trauma adjustment patterns of psychopathology based on retrospective lifetime data. This was first carried out on the PTSD symptoms (PTSS, including no symptoms, few symptoms, partial and full PTSD), and secondly together with their post-trauma comorbidities.

Methods: Data of trauma and the post-trauma mental disorders were collected for a large and randomly selected community sample, resulting in a N = 960 trauma-exposed subsample. Pattern recognition as carried out by latent class analysis (LCA) was implemented on this subsample. LCA was first exploited to identify the potential trajectory patterns of PTSS and next to explore the patterns of mental adjustments when additional post-trauma comorbid disorders, such as anxiety, mood and substance use disorders, were assessed.

Results: Four PTSS trajectory patterns were found, namely resilient, chronic, recovered, and delayed onset, consistent with findings from longitudinal PTSD studies. When post-trauma comorbidities were evaluated, other than the trajectory pattern of delayed onset which retained a low comorbidity profile, the other three split respectively and paired up with either low, moderate or high comorbidity profile.

Conclusions: Mental health outcomes after trauma exposure were considerably more complex than the four previously established adjustment trajectories. Here, we uncovered additional and more heterogeneous adjustment patterns comprised of PTSS trajectories and post-trauma comorbidity profiles.
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http://dx.doi.org/10.1016/j.jpsychires.2021.01.049DOI Listing
April 2021

Factors associated with subjective cognitive decline in dementia-free older adults-A population-based study.

Int J Geriatr Psychiatry 2021 Aug 16;36(8):1188-1196. Epub 2021 Mar 16.

Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.

Background: Subjective cognitive decline (SCD) is common in older adults, affects quality of life (QoL), and may represent the earliest clinical manifestation of cognitive decline evolving to dementia. Still little is known about factors associated with SCD.

Objectives: (1) Assess the associations between SCD and demographic, social, clinical, and personality characteristics as well as QoL, with and without adjustment for objective cognitive performance, and (2) investigate the relations between neuroticism, QoL, and SCD.

Methods: Cross-sectional analysis of a cohort of 1567 dementia-free community-dwellers from the urban area of Lausanne, Switzerland, aged 64 years and older (mean age 70.9 ± 4.7 years), from CoLaus/PsyCoLaus. SCD was assessed using a validated 10-item questionnaire. Personality traits, QoL, and perceived social support were evaluated using self-report measures. Information on depression and anxiety status and socioeconomic characteristics including professional activity were elicited using a semi-structured interview. Cognitive functioning was assessed through a comprehensive neuropsychological test battery. Statistical analysis was based on logistic regression.

Results: SCD was present in 18.5% of the sample and it was associated with lower performance in memory and verbal fluency tasks. After controlling for possible confounders, professional activity, neuroticism, and current depression were associated with SCD. Exploratory analysis revealed associations of SCD with QoL, neuroticism, and their interaction.

Conclusion: Besides objective cognitive performance, SCD is related to several psychosocial factors in dementia-free community-dwelling older people. These findings are relevant for the development of healthcare interventions to reduce cognitive complaints, improve QoL, and prevent cognitive decline in general population.
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http://dx.doi.org/10.1002/gps.5509DOI Listing
August 2021

Obesity and atypical depression symptoms: findings from Mendelian randomization in two European cohorts.

Transl Psychiatry 2021 02 4;11(1):96. Epub 2021 Feb 4.

Institute of Primary Care and Public Health (Unisante), University of Lausanne, Lausanne, Switzerland.

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.
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http://dx.doi.org/10.1038/s41398-021-01236-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862438PMC
February 2021

Bi-directional association between depression and HF: An electronic health records-based cohort study.

J Comorb 2020 Jan-Dec;10:2235042X20984059. Epub 2020 Dec 24.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Objective: To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs).

Methods: This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions.

Results: 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4-6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89-2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17-1.54) after adjusting for all 16 comorbid chronic conditions.

Conclusion: These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.
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http://dx.doi.org/10.1177/2235042X20984059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768856PMC
December 2020

Mapping grip force to motor networks.

Neuroimage 2021 04 14;229:117735. Epub 2021 Jan 14.

LREN, Department of clinical neurosciences - CHUV, University Lausanne, Switzerland; Max-Planck Institute for Human Brain and Cognitive Sciences, Leipzig, German. Electronic address:

Aim: There is ongoing debate about the role of cortical and subcortical brain areas in force modulation. In a whole-brain approach, we sought to investigate the anatomical basis of grip force whilst acknowledging interindividual differences in connectivity patterns. We tested if brain lesion mapping in patients with unilateral motor deficits can inform whole-brain structural connectivity analysis in healthy controls to uncover the networks underlying grip force.

Methods: Using magnetic resonance imaging (MRI) and whole-brain voxel-based morphometry in chronic stroke patients (n=55) and healthy controls (n=67), we identified the brain regions in both grey and white matter significantly associated with grip force strength. The resulting statistical parametric maps (SPMs) provided seed areas for whole-brain structural covariance analysis in a large-scale community dwelling cohort (n=977) that included beyond volume estimates, parameter maps sensitive to myelin, iron and tissue water content.

Results: The SPMs showed symmetrical bilateral clusters of correlation between upper limb motor performance, basal ganglia, posterior insula and cortico-spinal tract. The covariance analysis with the seed areas derived from the SPMs demonstrated a widespread anatomical pattern of brain volume and tissue properties, including both cortical, subcortical nodes of motor networks and sensorimotor areas projections.

Conclusion: We interpret our covariance findings as a biological signature of brain networks implicated in grip force. The data-driven definition of seed areas obtained from chronic stroke patients showed overlapping structural covariance patterns within cortico-subcortical motor networks across different tissue property estimates. This cumulative evidence lends face validity of our findings and their biological plausibility.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117735DOI Listing
April 2021

[Psychiatry].

Rev Med Suisse 2021 Jan;17(720-1):85-89

Faculté de biologie et de médecine, Université de Lausanne, 1005 Lausanne.

The Covid-19 pandemic has a major impact on psychiatry by its social consequences and possible direct effect of certain forms of Covid-19 on mental health. During this crisis, the accessibility of technology meets a state of necessity, which has propelled telepsychiatry from the shadows into the light. The contribution of several technologies (i.e. virtual reality, actigraphy, computational psychiatry) combining clinical data and neuroscience underlines the great neurobehavioural variability even within the same diagnostic category, calling for greater precision in therapeutic offers as suggested e.g. by developments in neurofeedback. The place of intranasal esketamin in the panoply of antidepressent drug treatments for resistant depression has not yet been defined.
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January 2021

Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study.

Brain Behav Immun 2020 11 10;90:303-310. Epub 2020 Sep 10.

UMR1027, Université de Toulouse, UPS, Inserm, Toulouse, France. Electronic address:

Background: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1β and tumor necrosis factor α- in 6 European cohort studies.

Methods: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation.

Results: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1β and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated with higher inflammation even after adjusting for health behaviours and body mass index. No association was found with interleukin 1β and tumor necrosis factor α.

Conclusions: Our study suggests different educational patterning of inflammatory biomarkers. Further large-scale research is needed to explore social differences in the inflammatory cascade in greater detail and the extent to which these differences contribute to social inequalities in health.
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http://dx.doi.org/10.1016/j.bbi.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140486PMC
November 2020

Psychopathological precursors of the onset of mood disorders in offspring of parents with and without mood disorders: results of a 13-year prospective cohort high-risk study.

J Child Psychol Psychiatry 2021 Apr 25;62(4):404-413. Epub 2020 Aug 25.

Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: There is still limited evidence from prospective high-risk research on the evolution of specific disorders that may emerge early in the development of mood disorders. Moreover, few studies have examined the specificity of mood disorder subtypes among offspring of parents with both major subtypes of mood disorders and controls based on prospective tracking across the transition from childhood to adulthood. Our specific objectives were to (a) identify differences in patterns of psychopathological precursors among youth with (hypo)mania compared to MDD and (b) examine whether these patterns differ by subtypes of parental mood disorders.

Methods: Our data stem from a prospective cohort study of 449 directly interviewed offspring (51% female, mean age 10.1 years at study intake) of 88 patients with BPD, 71 with MDD, 30 with substance use disorders and 60 medical controls. The mean duration of follow-up was 13.2 years with evaluations conducted every three years.

Results: Within the whole cohort of offspring, MDE (Hazard Ratio = 4.44; 95%CI: 2.19-9.02), CD (HR = 3.31;1.55-7.07) and DUD (HR = 2.54; 1.15-5.59) predicted the onset of (hypo)manic episodes, whereas MDD in offspring was predicted by SAD (HR = 1.53; 1.09-2.15), generalized anxiety (HR = 2.56; 1.05-6.24), and panic disorder (HR = 3.13; 1.06-9.23). The early predictors of (hypo)mania in the whole cohort were also significantly associated with the onset of (hypo)mania among the offspring of parents with BPD.

Conclusions: The onset of mood disorders is frequently preceded by identifiable depressive episodes and nonmood disorders. These precursors differed by mood subtype in offspring. High-risk offspring with these precursors should be closely monitored to prevent the further development of MDD or conversion to BPD.
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http://dx.doi.org/10.1111/jcpp.13307DOI Listing
April 2021

Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression.

Am J Med Genet B Neuropsychiatr Genet 2020 09 18;183(6):309-330. Epub 2020 Jul 18.

Max Planck Institute of Psychiatry, Munich, Germany.

It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.
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http://dx.doi.org/10.1002/ajmg.b.32807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991693PMC
September 2020

Salivary cortisol and five-year change in cognitive performance in non-demented elderly subjects: a population-based study.

Neurobiol Aging 2020 10 13;94:34-37. Epub 2020 May 13.

Service of Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, Psychiatry University Hospital Zürich, Zürich, Switzerland.

Elevated cortisol levels have been associated with poorer cognitive performance in cross-sectional studies; this may be both a factor contributing to neurodegeneration and cognitive decline and a result of developing brain pathologies. However, it is still unclear (1) whether cortisol measures predict later cognitive decline and (2) whether cortisol changes over the years might be associated with cognitive changes. We analyzed data from CoLaus/PsyCoLaus, a prospective population-based study. Salivary cortisol (4 different measures on 1 day) and neuropsychological assessments were performed at a first visit and a follow-up visit 5 years later in 625 dementia-free participants aged ≥65 years. Salivary cortisol levels at waking and 30 minutes after waking, as well as longitudinal changes in cortisol 30 minutes after waking, cortisol awakening response, and cortisol AM-PM difference were associated with decline in global cognition. After controlling for potential confounders, only longitudinal changes in cortisol 30 minutes after waking remained associated with cognitive decline. These mostly negative findings indicate absent or subtle association between salivary cortisol and cognitive decline.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.05.006DOI Listing
October 2020

Generalized Anxiety Disorder is Prospectively Associated With Decreased Levels of Interleukin-6 and Adiponectin Among Individuals from the Community.

J Affect Disord 2020 06 3;270:114-117. Epub 2020 Apr 3.

Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, and University of Zurich, Zurich, Switzerland.

Background: Anxiety disorders have been related to cardiovascular diseases via low-grade inflammation, but longitudinal studies on the association between generalized anxiety disorder (GAD) and inflammatory biomarkers are sparse. Furthermore, no studies have examined the association between GAD and the "cardio-protective" adipocytokine adiponectin in this context so far.

Methods: In a Swiss population-based sample of 2,415 adults participating in baseline and follow-up exams (mean follow-up duration=5.5 years), we diagnosed a total of 55 persons (2.3%) with GAD using a validated semi-structured psychiatric interview. We prospectively examined the relation between GAD and circulating levels of inflammatory biomarkers (i.e., C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and adiponectin), in linear regression models, statistically controlled for the baseline inflammatory marker, socioeconomic status, cardiovascular risk factors, health behaviors, and psychiatric disorders.

Results: Compared to those without GAD, individuals with GAD had lower IL-6 (β=-0.249, 95%-CI -0.493-(-0.004), p=0.046), and adiponectin (β=-0.264, 95%-CI -0.482-(-0.045), p=0.018) levels at follow-up after adjustment for all covariates. Moreover, GAD was unrelated to several other inflammatory measures.

Conclusion: Individuals with GAD do not seem to exhibit chronic low-grade inflammation, suggesting different underlying biobehavioral mechanisms to those from other anxiety disorders. Low adiponectin levels may be linked to symptoms of GAD through brain areas directly involved in the processing of fear and anxiety.
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http://dx.doi.org/10.1016/j.jad.2020.03.123DOI Listing
June 2020

Evaluation of Cardiometabolic Risk in a Large Psychiatric Cohort and Comparison With a Population-Based Sample in Switzerland.

J Clin Psychiatry 2020 03 31;81(3). Epub 2020 Mar 31.

Hôpital de Cery, 1008 Prilly-Lausanne, Switzerland.

Background: Psychiatric patients are known to be at high risk of developing cardiovascular diseases (CVDs), leading to an increased mortality rate.

Objective: To assess the CVD risk (presence of metabolic syndrome [MetS] and calculated 10-year CVD risk) in a Swiss psychiatric cohort taking weight gain-inducing psychotropic drugs, compare the findings to a Swiss population-based cohort, and evaluate the prevalence of participants treated for metabolic disruptions in both cohorts.

Methods: Data for 1,216 psychiatric patients (of whom 634 were aged 35-75 years) were obtained between 2007 and 2017 from a study with metabolic parameters monitored during psychotropic treatment and between 2003 and 2006 for 6,733 participants from the population-based CoLaus|PsyCoLaus study.

Results: MetS as defined by the International Diabetes Federation (IDF) was identified in 33% of the psychiatric participants and 24.7% of the population-based subjects. Specifically, prevalence per the IDF definition was more than 3 times higher in the psychiatric cohort among women aged 35 to 49 years (25.6% vs 8.0%; P < 10-4). The psychiatric and population-based cohorts, respectively, had comparable predicted CVD risk (10-year risk of CVD event > 20%: 0% vs 0.1% in women and 0.3% vs 1.8% [P = .01] in men; 10-year risk of CVD death > 5%: 8.5% vs 8.4% [P = .58] in women and 13.4% vs 16.6% [P = .42] in men). No difference was observed among the proportion of participants with MetS treated for metabolic disturbances in the two cohorts, with the exception of women aged 35-49 years, for whom those in the psychiatric cohort were half as likely to receive treatment compared to participants in CoLaus|PsyCoLaus (17.8% vs 38.8% per the IDF definition; P = .0004).

Conclusions: These findings emphasize the concern that psychiatric patients present an altered metabolic profile and that they do not receive adequate treatment for metabolic disruptions. Presence of metabolic disturbances should be routinely assessed, and adequate follow-up is needed to intervene early after illness onset.
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http://dx.doi.org/10.4088/JCP.19m12796DOI Listing
March 2020

Minimal phenotyping yields genome-wide association signals of low specificity for major depression.

Nat Genet 2020 04 30;52(4):437-447. Epub 2020 Mar 30.

Department of Psychiatry, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, USA.

Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.
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http://dx.doi.org/10.1038/s41588-020-0594-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906795PMC
April 2020

Mean Oxygen Saturation during Sleep Is Related to Specific Brain Atrophy Pattern.

Ann Neurol 2020 06 20;87(6):921-930. Epub 2020 Apr 20.

Laboratory for Research in Neuroimaging, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Objective: There is much controversy about the neurobiological mechanisms underlying the effects of sleep-disordered breathing on the brain. The aim of this study was to investigate the association between markers of sleep-related hypoxemia and brain anatomy.

Methods: We used data from a large-scale cohort from the general population (n = 775, 50.6% males, age range = 45-86 years, mean age = 60.3 ± 9.9) that underwent full polysomnography and brain magnetic resonance imaging to correlate respiratory variables with regional brain volume estimates.

Results: After adjusting for age, gender, and cardiovascular risk factors, only mean oxygen saturation during sleep was associated with bilateral volume of hippocampus (right: p = 0.001; left: p < 0.001), thalamus (right: p < 0.001; left: p < 0.001), putamen (right: p = 0.001; left: p = 0.001), and angular gyrus (right: p = 0.011; left: p = 0.001). We observed the same relationship in left hemispheric amygdala (p = 0.010), caudate (p = 0.008), inferior frontal gyrus (p = 0.004), and supramarginal gyrus (p = 0.003). The other respiratory variables-lowest oxygen saturation, percentage of sleep time with oxygen saturation < 90%, apnea-hypopnea index, and oxygen desaturation index-did not show any significant association with brain volumes.

Interpretation: Lower mean oxygen saturation during sleep was associated with atrophy of cortical and subcortical brain areas known for high sensitivity to oxygen supply. Their vulnerability to hypoxemia may contribute to behavioral phenotype and cognitive decline in patients with sleep-disordered breathing. ANN NEUROL 2020;87:921-930.
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http://dx.doi.org/10.1002/ana.25728DOI Listing
June 2020

Converging patterns of aging-associated brain volume loss and tissue microstructure differences.

Neurobiol Aging 2020 04 15;88:108-118. Epub 2020 Jan 15.

Laboratory for Research in Neuroimaging LREN, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. Electronic address:

Given the worldwide increasing socioeconomic burden of aging-associated brain diseases, there is pressing need to gain in-depth knowledge about the neurobiology of brain anatomy changes across the life span. Advances in quantitative magnetic resonance imaging sensitive to brain's myelin, iron, and free water content allow for a detailed in vivo investigation of aging-related changes while reducing spurious morphometry differences. Main aim of our study is to link previous morphometry findings in aging to microstructural tissue properties in a large-scale cohort (n = 966, age range 46-86 y). Addressing previous controversies in the field, we present results obtained with different approaches to adjust local findings for global effects. Beyond the confirmation of age-related atrophy, myelin, and free water decreases, we report proportionally steeper volume, iron, and myelin decline in sensorimotor and subcortical areas paralleled by free water increase. We demonstrate aging-related white matter volume, myelin, and iron loss in frontostriatal projections. Our findings provide robust evidence for spatial overlap between volume and tissue property differences in aging that affect predominantly motor and executive networks.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.01.006DOI Listing
April 2020

PsyCoLaus: une étude prospective des liens entre la santé mentale et les maladies cardiovasculaires.

Praxis (Bern 1994) 2020 Jan;109(1):9-12

Département de Psychiatrie, Centre d'Epidémiologie Psychiatrique et de Psychopathologie, Centre hospitalier universitaire vaudois (CHUV) et Université de Lausanne, Lausanne.

PsyCoLaus: A Prospective Study of the Links between Mental Health and Cardiovascular Diseases PsyCoLaus, which includes an investigation of mental disorders and cognitive functioning, aims to determine the prevalence and the course of mental disorders in the general population and to study the mechanisms underlying the association between these disorders and cardiovascular diseases. This investigation revealed a very high lifetime prevalence rate of 43.6 % for major depressive disorder in Lausanne. We have also observed that the association between major depression and cardio-metabolic risk factors is essentially attributable to the atypical subtype, characterized by an increased appetite, heaviness in limbs, hypersomnia and conserved affective reactivity. Patients who suffer from this type of depression have an increased risk to develop overweight, diabetes and the metabolic syndrome and deserve particular clinical attention on the metabolic level.
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http://dx.doi.org/10.1024/1661-8157/a003373DOI Listing
January 2020

Subtypes of alcohol use disorder in the general population: A latent class analysis.

Psychiatry Res 2020 03 27;285:112712. Epub 2019 Nov 27.

Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Alcohol use disorders (AUD) are often comorbid with other disorders with high levels of impairment, which is of relevance for the development and the progression of the disease. Evidence shows that AUD varies greatly with regard to its aetiology, which might lead to distinct clinical representations with important implications for treatment. The current study aimed to apply latent class analysis (LCA) techniques to investigate how comorbidity patterns in AUD vary with regard to specific explanatory factors. A Swiss community sample of N=439 individuals with AUD was subjected to LCA in order to find empirical AUD subtypes of comorbid psychiatric conditions. The subtypes were further validated based on a range of external criteria, including clinical and psycho-social factors as well as treatment variables. A three-class solution of empirical subtypes of AUD comorbidity (low, depressive-anxious, and drug-dependent antisocial) provided the best fit to the data. The three AUD subtypes showed homogeneous comorbidity patterns but varied along dimensions of psycho-social risk factors, consumption patterns and consequences as well as treatment history. Our findings provide strong evidence that AUD in non-treated samples can be described as a multidimensional disorder in terms of its comorbidity structure with distinct etiological factors and important consequences for treatment.
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http://dx.doi.org/10.1016/j.psychres.2019.112712DOI Listing
March 2020

Associations of Personality Traits With Chronic Low-Grade Inflammation in a Swiss Community Sample.

Front Psychiatry 2019 12;10:819. Epub 2019 Nov 12.

Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, Zurich, Switzerland.

Among the major dimensions of personality, high Neuroticism and low Conscientiousness have frequently been linked to worse health-related behaviors and poor health outcomes. However, studies on the association between personality traits and biomarkers of chronic low-grade inflammation reflecting increased morbidity and mortality risk are sparse; therefore, the aim of this study was to explore this association. A population-based Swiss sample of 2,182 persons (40-82 years, 42% men) completed a comprehensive personality questionnaire (NEO Five-Factor Inventory-Revised). Circulating levels of inflammatory markers, including C-reactive protein, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and levels of the "cardioprotective" adipo(cyto)kine adiponectin were also determined. Analyses controlled for sociodemographic factors, traditional cardiovascular risk factors and lifetime psychiatric disorders using a validated semi-structured psychiatric interview. The role of gender as a moderator of the personality-inflammation link was additionally explored. Controlling for all covariates, higher Extraversion (β = 0.092, 95%CI 0.004-0.180) was positively associated with higher IL-6 levels, and higher Conscientiousness (β = -0.095, 95%CI -0.180-[-0.009]) were significantly associated with lower IL-6 levels (all p-values < 0.05). Neuroticism and Agreeableness showed no significant association with any inflammatory biomarker. The associations between personality traits and inflammatory markers were not moderated by gender. Conscientiousness seems to be inversely related to chronic low-grade inflammation as measured by IL-6 levels, compatible with protection from the cardiovascular risk. The opposite may apply to Extraversion. Further research is needed to better understand the underlying mechanisms and their impact for health outcomes in the community.
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http://dx.doi.org/10.3389/fpsyt.2019.00819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863063PMC
November 2019

[The CoLaus/PsyCoLaus study : 16 years of follow-up with some key messages end images].

Rev Med Suisse 2019 Nov;15(672):2159-2163

Service de médecine interne, CHUV, 1011 Lausanne.

The main aims of the CoLaus/PsyCoLaus cohort study are to better understand: 1) the personal, biologic, genetic end environmental determinants of cardiovascular risk factors and diseases, and 2) the existing association of mental disorders with cardiovascular diseases. The study was initiated in 2003 and over 6700 participants from the city of Lausanne were include and very rich phenotypic data were collected making the study unique worldwide. Numerous scientific articles were published in various fields such as epidemiology, public health, genetic, social and environmental determinants of cardiovascular diseases and their association with mental health. We briefly present here some key results obtained over the last 16 years.
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November 2019

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity.

Cephalalgia 2020 04 24;40(4):347-356. Epub 2019 Oct 24.

Department of Neuroscience, University of Uppsala, Uppsala, Sweden.

Objective: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine.

Methods: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression.

Results: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype.

Conclusion: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.
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http://dx.doi.org/10.1177/0333102419884935DOI Listing
April 2020

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants.

Drug Dev Res 2020 02 16;81(1):102-113. Epub 2019 Oct 16.

Department of Neuroscience, Uppsala University, Uppsala, Sweden.

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p = .02) and ln CES-D score (p = .001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p = .02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p = .03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs.
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http://dx.doi.org/10.1002/ddr.21609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028038PMC
February 2020

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

Biol Psychiatry 2020 03 5;87(5):419-430. Epub 2019 Aug 5.

Max Planck Institute of Psychiatry, Munich, Germany.

Background: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.

Methods: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10) and a candidate threshold (1.6 × 10).

Results: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99).

Conclusions: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
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http://dx.doi.org/10.1016/j.biopsych.2019.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001040PMC
March 2020