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1. A prospective cohort study of prodromal Alzheimer’s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA)

Author

Michelle K. Lupton, Gail A. Robinson, Robert J. Adam, Stephen Rose, Gerard J. Byrne, Olivier Salvado, Nancy A. Pachana, Osvaldo P. Almeida, Kerrie McAloney, Scott D Gordon, Parnesh Raniga, Amir Fazlollahi, Ying Xia, Amelia Ceslis, Saurabh Sonkusare, Qing Zhang, Mahnoosh Kholghi, Mohan Karunanithi, Philip E Mosley, Jinglei Lv, Léonie Borne, Jessica Adsett, Natalie Garden, Jurgen Fripp, Nicholas G. Martin, Christine C Guo, and Michael Breakspear

Subjects
Alzheimer’s disease, Neuroimaging, Neuropsychology, Genetic risk prediction, Protocol, At risk cohort, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

This prospective cohort study, “Prospective Imaging Study of Ageing: Genes, Brain and Behaviour” (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.

Published
2021
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2. Novel genetic loci affecting facial shape variation in humans

Author

Ziyi Xiong, Gabriela Dankova, Laurence J Howe, Myoung Keun Lee, Pirro G Hysi, Markus A de Jong, Gu Zhu, Kaustubh Adhikari, Dan Li, Yi Li, Bo Pan, Eleanor Feingold, Mary L Marazita, John R Shaffer, Kerrie McAloney, Shu-Hua Xu, Li Jin, Sijia Wang, Femke MS de Vrij, Bas Lendemeijer, Stephen Richmond, Alexei Zhurov, Sarah Lewis, Gemma C Sharp, Lavinia Paternoster, Holly Thompson, Rolando Gonzalez-Jose, Maria Catira Bortolini, Samuel Canizales-Quinteros, Carla Gallo, Giovanni Poletti, Gabriel Bedoya, Francisco Rothhammer, André G Uitterlinden, M Arfan Ikram, Eppo Wolvius, Steven A Kushner, Tamar EC Nijsten, Robert-Jan TS Palstra, Stefan Boehringer, Sarah E Medland, Kun Tang, Andres Ruiz-Linares, Nicholas G Martin, Timothy D Spector, Evie Stergiakouli, Seth M Weinberg, Fan Liu, Manfred Kayser, and On behalf of the International Visible Trait Genetics (VisiGen) Consortium

Subjects
genome-wide association study, face, European, gene regulation, images, GWAS, Medicine, Science, Biology (General), QH301-705.5
Abstract

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10−8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10−3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

Published
2019
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3. A prospective cohort study of prodromal Alzheimer’s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA)

Author

Natalie Garden, Philip E. Mosley, Scott D. Gordon, Stephen E. Rose, Gerard J. Byrne, Mahnoosh Kholghi, Ying Xia, Michael Breakspear, Parnesh Raniga, Jurgen Fripp, Saurabh Sonkusare, Nicholas G. Martin, Qing Zhang, Jessica Adsett, Christine C. Guo, Nancy A. Pachana, Osvaldo P. Almeida, Gail Robinson, Mohan Karunanithi, Amir Fazlollahi, Léonie Borne, Kerrie McAloney, Olivier Salvado, Robert Adam, Michelle K. Lupton, Jinglei Lv, and Amelia Ceslis

Subjects
Gerontology, Adult, Aging, Cognitive Neuroscience, Neuroimaging, Disease, Neuropathology, lcsh:Computer applications to medicine. Medical informatics, 050105 experimental psychology, lcsh:RC346-429, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Neuropsychology, medicine, Protocol, Dementia, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cognitive Dysfunction, Prospective Studies, Prospective cohort study, lcsh:Neurology. Diseases of the nervous system, business.industry, 05 social sciences, Australia, Brain, Regular Article, medicine.disease, At risk cohort, Cognitive test, Neurology, Cohort, Disease Progression, lcsh:R858-859.7, Genetic risk prediction, Neurology (clinical), business, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract

Highlights • Detailed protocol of the Prospective Imaging Study of Ageing (PISA) Study. • Genetic risk prediction to identify those at differing risk of Alzheimer’s disease. • Longitudinal cohort for the study of precursors and lifestyle risk factors. • Use of online surveys and cognitive testing for large scale phenotyping. • Functional, structural and molecular neuroimaging with neurocognitive testing., This prospective cohort study, “Prospective Imaging Study of Ageing: Genes, Brain and Behaviour” (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.

Published
2021

4. A prospective cohort study of prodromal Alzheimer′s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA)

Author

Michelle K Lupton, Gail A Robinson, Robert J Adam, Stephen Rose, Gerard J Byrne, Olivier Salvado, Nancy A Pachana, Osvaldo P Almeida, Kerrie McAloney, Scott D Gordon, Parnesh Raniga, Amir Fazlollahi, Ying Xia, Amelia Ceslis, Saurabh Sonkusare, Qing Zhang, Mahnoosh Kholghi, Mohan Karunanithi, Philip E Mosley, Jinglei Lv, Jessica Adsett, Natalie Garden, Jurgen Fripp, Nicholas G Martin, Christine C Guo, and Michael Breakspear

Subjects
Gerontology, 0303 health sciences, business.industry, Disease, Neuropathology, medicine.disease, Cognitive test, Natural history, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Cohort, medicine, Dementia, Prospective cohort study, business, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

This prospective cohort study, “Prospective Imaging Study of Ageing: Genes, Brain and Behaviour” (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). In particular, we are recruiting mid-life Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling nearly 3,000 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for lifestyle monitoring, detailed neurocognitive testing, blood sample donation, plus functional, structural and molecular neuroimaging. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.Author ApprovalAll authors have seen and approved this manuscript.

Published
2020
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5. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author

Eduardo Nagore, Caroline Hayward, Christopher I. Amos, Douglas F. Easton, Zaida García-Casado, Julie Lang, Anjali K. Henders, Veronica Höiom, Lisa Bowdler, Kathryn P. Burdon, Laura Del Regno, Nick Orr, Per Arne Andresen, Tongwu Zhang, Rose Yang, Myriam Brossard, Eric K. Moses, Dirk Schadendorf, Laura Cattaneo, Casey Rowe, Essen-Heidelberg Investigators, Hans-Joachim Schulze, Jamie E Craig, D. Timothy Bishop, Anne E. Cust, Johan Hansson, David E. Elder, Nelleke A. Gruis, Donato Calista, Wei V. Chen, Abrar A. Qureshi, Amy Hutchinson, Pilar Galan, Leanne Wallace, Jennifer H. Barrett, Nilesh J. Samani, Maria Teresa Landi, Per Helsing, Andreas Hadjisavvas, Fengju Song, Celia Requena, Elizabeth M. Gillanders, Arantxa Rodriguez, Joan Anton Puig-Butille, Blair H. Smith, Mark Smithers, Michael Malasky, Marianna Sanna, Miriam Potrony, Maria A. Loizidou, Evangelos Evangelou, Richard A. Scolyer, Karen A. Pooley, Rachel E. Neale, Mario Falchi, Adèle C. Green, Monica Rodolfo, Ketty Peris, Licia Rivoltini, Mark M. Iles, Catherine M. Olsen, Alexander J. Stratigos, Tadeusz Dębniak, Weiyin Zhou, H. Peter Soyer, Xin Li, Margaret A. Tucker, Rajesh Kumar, Håkan Olsson, Anders Molven, Nicholas G. Martin, Anthony J. Swerdlow, Aurelie Vogt, Lars A. Akslen, Stuart MacGregor, Sarah V. Ward, Hamida Mohamdi, Bruna Dalmasso, Grant W. Montgomery, Rona M. MacKie, Esther Azizi, Gonçalo R. Abecasis, Chiara Menin, Alison M. Dunning, Ibd investigators, Kevin M. Brown, Jiali Han, Veryan Codd, Graham J. Mann, Nicholas K. Hayward, Marko Hočevar, Eitan Friedman, Richard A. Sturm, Paola Queirolo, Qtwin Investigators, Lawrie Wheeler, Lars G. Fritsche, Shenying Fang, Kiarash Khosrotehrani, Nicole A Kukutsch, Pol Gimenez-Xavier, Belynda Hicks, Matthew Zawistowski, Alessia Visconti, Jessica Harris, Chad M. Brummett, Paola Ghiorzo, andMe, David G. Hunter, Veronique Bataille, Julia Newton-Bishop, Srdjan Novaković, Amfs Investigators, Siranoush Manoukian, Jianxin Shi, Mitchell J. Machiela, G. Mark Lathrop, Josep Malvehy, Katerina P. Kypreou, Susana Puig, Dale R. Nyholt, I. Stefanaki, Maria Concetta Fargnoli, Lisa A. Simms, Kerrie McAloney, M. Malt, Adam J. Trower, Matthew Law, Lei Song, Paul D.P. Pharoah, Christian Ingvar, Jiyeon Choi, Alisa M. Goldstein, Jeffrey E. Lee, Mark Harland, Cristina Pellegrini, Daniela Massi, Sarah Simi, Scott D. Gordon, Jacobo Martinez, Florence Demenais, Kristine Jones, Graham L. Radford-Smith, David C. Whiteman, Lorenza Pastorino, Lisa Elefanti, Arcangela De Nicolo, Mario Mandalà, Juliette Randerson-Moor, Q-Mega, Jan Lubinski, Stephen J. Chanock, Marie-Françoise Avril, David L. Duffy, Helen Gogas, Nienke van der Stoep, Peter A. Kanetsky, Georgina V. Long, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University of Leeds, QIMR Berghofer Medical Research Institute, National and Kapodistrian University of Athens (NKUA), Ospedale Policlinico San Martino [Genoa], Universita degli studi di Genova, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maurizio Bufalini Hospital, University of L'Aquila [Italy] (UNIVAQ), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Cyprus Institute of Neurology and Genetics, University of Athens Medical School [Athens], The University of Sydney, Universitat de Barcelona (UB), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Michigan [Ann Arbor], University of Michigan System, Instituto Valenciano de Oncologia, Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], IRCCS Istituto Nazionale dei Tumori [Milano], Ninewells Hospital and Medical School [Dundee], Cyprus Institute (CyI), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Queensland [Brisbane], Haukeland University Hospital, University of Bergen (UiB), Geisel School of Medicine at Dartmouth, Oslo University Hospital [Oslo], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], King‘s College London, Menzies School of Health Research [Australia], Charles Darwin University, The University of Texas M.D. Anderson Cancer Center [Houston], University of Leicester, Flinders University [Adelaide, Australia], West Pomeranian University of Technology Szczecin, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Human Genome Research Institute (NHGRI), Leiden University Medical Center (LUMC), Karolinska Institutet [Stockholm], Queensland University of Technology [Brisbane] (QUT), Institute of Oncology Ljubljana, Harvard T.H. Chan School of Public Health, Lund University [Lund], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Glasgow, Statistical Genetics, and Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH) United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAU19CA148112SEARCH team (Cancer Research UK) C490/A16561AOCS (US Army Medical Research and Material Command) DAMD17-01-1-0729Canadian Institutes of Health Research (CIHR)Cancer Council Victoria Queensland Cancer Fund Cancer Council New South Wales Cancer Council South Australia Cancer Council Western Australia Cancer Council Tasmania National Health and Medical Research Council of AustraliaID400413ID400281National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS Ministry of Health, Italy Associazione Italiana per la Ricerca sul Cancro (AIRC)IG 15460Spanish Fondo de Investigaciones Sanitarias grant - FEDER 'Una manera de hacer Europa' PI15/00716PI15/00956CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain - European Development Regional Fund 'A way to achieve Europe' ERDF AGAUR of the Catalan Government, Spain 2014_SGR_603European CommissionEuropean Commission Joint Research CentreLSHC-CT-2006-018702European Union (EU) 'Fundacio La Marato de TV3', Catalonia, Spain 201331-30'Fundacion Cientifica de la Asociacion Espanola Contra el Cancer', Spain GCB15152978SOENCERCA Programme/Generalitat de Catalunya Italian Ministry of the University and Scientific Research (PRIN-2012 grant) 2012JJX494Melanoma Research Alliance United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)CA88363CA83115CA122838CA87969CA055075CA100264CA133996CA49449National Health and Medical Research Council of Australia200071241944339462380385389927389875389891389892389938443036442915442981496610496675496739552485552498APP1049894Cancer Council Queensland Cancer Institute New South Wales Australian GovernmentDepartment of Industry, Innovation and ScienceCooperative Research Centres (CRC) Programme Australian Cancer Research Foundation Wellcome TrustWT084766/Z/08/ZNational Health and Medical Research Council of Australia Australian Research Council Department of Health and Human Services (DHHS)

Subjects
Sequence Variants, Male, medicine.medical_specialty, Skin Neoplasms, Genotype, Medizin, Identifies 3, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Malignant-melanoma, 0302 clinical medicine, Genetics, medicine, Genetic predisposition, Nevus, Humans, Hla Class-i, Genetic Predisposition to Disease, Polymorphism, Melanoma, 030304 developmental biology, Telomere Length, Cancer, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Loci, Pigmentation, E-cadherin, Single Nucleotide, medicine.disease, Genetic architecture, Attributable Fraction, 3. Good health, Phenotype, Female, Genetic Loci, Genome-Wide Association Study, Cutaneous melanoma, Medical genetics, Settore MED/35 - MALATTIE CUTANEE E VENEREE, 030217 neurology & neurosurgery, Familial Melanoma
Abstract

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.

Published
2020
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6. The Anorexia Nervosa Genetics Initiative: Study description and sample characteristics of the Australian and New Zealand arm

Author

Gu Zhu, Cynthia M. Bulik, Laura M. Thornton, Nicholas G. Martin, Warren Ward, Janice Russell, Martin A. Kennedy, Sarah Maguire, Elizabeth K. Hughes, A. Kate Fairweather-Schmidt, Anthea Fursland, Jeremy Freeman, Tracey D. Wade, Sloane Madden, Katherine M. Kirk, Fiona Wagg, Julie McCormack, Susan M Sawyer, Amy Mao, Felicity C Martin, Richard Parker, Christine Morgan, Kerrie McAloney, Jennifer Jordan, and Phillipa Hay

Subjects
Adult, Male, medicine.medical_specialty, Anorexia Nervosa, Adolescent, International Cooperation, Sample (statistics), Computer-assisted web interviewing, Body Mass Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, mental disorders, medicine, Humans, Psychiatry, Genetics, Clinical interview, Patient Selection, High mortality, Australia, General Medicine, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Eating disorders, Anorexia nervosa (differential diagnoses), Etiology, Female, Psychology, Body mass index, 030217 neurology & neurosurgery, Clinical psychology, Genome-Wide Association Study, New Zealand
Abstract

Objectives:Anorexia nervosa is a severe psychiatric disorder with high mortality rates. While its aetiology is poorly understood, there is evidence of a significant genetic component. The Anorexia Nervosa Genetics Initiative is an international collaboration which aims to understand the genetic basis of the disorder. This paper describes the recruitment and characteristics of the Australasian Anorexia Nervosa Genetics Initiative sample, the largest sample of individuals with anorexia nervosa ever assembled across Australia and New Zealand.Methods:Participants completed an online questionnaire based on the Structured Clinical Interview Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) eating disorders section. Participants who met specified case criteria for lifetime anorexia nervosa were requested to provide a DNA sample for genetic analysis.Results:Overall, the study recruited 3414 Australians and 543 New Zealanders meeting the lifetime anorexia nervosa case criteria by using a variety of conventional and social media recruitment methods. At the time of questionnaire completion, 28% had a body mass index ⩽ 18.5 kg/m2. Fasting and exercise were the most commonly employed methods of weight control, and were associated with the youngest reported ages of onset. At the time of the study, 32% of participants meeting lifetime anorexia nervosa case criteria were under the care of a medical practitioner; those with current body mass index < 18.5 kg/m2were more likely to be currently receiving medical care (56%) than those with current body mass index ⩾ 18.5 kg/m2(23%). Professional treatment for eating disorders was most likely to have been received from general practitioners (45% of study participants), dietitians (42%) and outpatient programmes (42%).Conclusions:This study was effective in assembling the largest community sample of people with lifetime anorexia nervosa in Australia and New Zealand to date. The proportion of people with anorexia nervosa currently receiving medical care, and the most common sources of treatment accessed, indicates the importance of training for general practitioners and dietitians in treating anorexia nervosa.

Published
2017
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7. Hair Cortisol and Its Association With Psychological Risk Factors for Psychiatric Disorders: A Pilot Study in Adolescent Twins

Author

Narelle K. Hansell, Fabian Streit, Marcella Rietschel, Stephanie H. Witt, Margaret J. Wright, John J. McGrath, Liz Rietschel, Kerrie McAloney, Nicholas G. Martin, Clemens Kirschbaum, Josef Frank, and Gu Zhu

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Hydrocortisone, Perceived Stress Scale, Pilot Projects, 610 Medicine & health, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Twins, Dizygotic, Humans, Chronic stress, Psychiatry, Genetics (clinical), Extraversion and introversion, Depression, Mental Disorders, Stressor, Obstetrics and Gynecology, Twins, Monozygotic, Mental health, Twin study, Neuroticism, Eysenck Personality Questionnaire, 030227 psychiatry, Pediatrics, Perinatology and Child Health, Female, Psychology, 030217 neurology & neurosurgery, Stress, Psychological, Hair
Abstract

Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables.

Published
2016
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