Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice

被引:153
作者
Doherty, Joanne L.
Owen, Michael J. [1 ]
机构
[1] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales
基金
英国惠康基金; 英国医学研究理事会;
关键词
DEFICIT HYPERACTIVITY DISORDER; COPY-NUMBER VARIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; DE-NOVO MUTATIONS; BIPOLAR-DISORDER; DELETION SYNDROME; WIDE ASSOCIATION; PATERNAL AGE; INTELLECTUAL DISABILITY;
D O I
10.1186/gm546
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder and autism spectrum disorder are common and result in significantmorbidity andmortality. Although currently classified into distinct disorder categories, they show clinical overlap and familial co-aggregation, and share genetic risk factors. Recent advances in psychiatric genomics have provided insight into the potential mechanisms underlying the overlap between these disorders, implicating genes involved in neurodevelopment, synaptic plasticity, learning andmemory. Furthermore, evidence from copy number variant, exome sequencing and genome-wide association studies supports a gradient of neurodevelopmental psychopathology indexed by mutational load ormutational severity, and cognitive impairment. These findings have important implications for psychiatric research, highlighting the need for new approaches to stratifying patients for research. They also point the way for work aiming to advance our understanding of the pathways from genotype to clinical phenotype, which will be required in order to inform new classification systems and to develop novel therapeutic strategies.
引用
收藏
页数:13
相关论文
共 151 条
[1]  
[Anonymous], 65 NAT CTR HLTH STAT
[2]  
[Anonymous], 2013, DIAGN STAT MAN MENT
[3]   Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion) [J].
Antshel, Kevin M. ;
Aneja, Alka ;
Strunge, Leslie ;
Peebles, Jena ;
Fremont, Wanda P. ;
Stallone, Kimberly ;
AbdulSabur, Nuria ;
Higgins, Anne Marie ;
Shprintzen, Robert J. ;
Kates, Wendy R. .
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, 2007, 37 (09) :1776-1786
[4]   ADHD, major depressive disorder, and simple phobias are prevalent psychiatric conditions in youth with velocardiofacial syndrome [J].
Antshel, KM ;
Fremont, W ;
Roizen, NJ ;
Shprintzen, R ;
Higgins, AM ;
Dhamoon, A ;
Kates, WR .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 2006, 45 (05) :596-603
[5]   Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP) [J].
Baird, Gillian ;
Simonoff, Emily ;
Pickles, Andrew ;
Chandler, Susie ;
Loucas, Tom ;
Meldrum, David ;
Charman, Tony .
LANCET, 2006, 368 (9531) :210-215
[6]   Mortality, ADHD, and Psychosocial Adversity in Adults With Childhood ADHD: A Prospective Study [J].
Barbaresi, William J. ;
Colligan, Robert C. ;
Weaver, Amy L. ;
Voigt, Robert G. ;
Killian, Jill M. ;
Katusic, Slavica K. .
PEDIATRICS, 2013, 131 (04) :637-644
[7]   Prevalence of autism-spectrum conditions: UK school-based population study [J].
Baron-Cohen, Simon ;
Scott, Fiona J. ;
Allison, Carrie ;
Williams, Joanna ;
Bolton, Patrick ;
Matthews, Fiona E. ;
Brayne, Carol .
BRITISH JOURNAL OF PSYCHIATRY, 2009, 194 (06) :500-509
[8]   Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders [J].
Ben-Shachar, S. ;
Lanpher, B. ;
German, J. R. ;
Qasaymeh, M. ;
Potocki, L. ;
Nagamani, S. C. Sreenath ;
Franco, L. M. ;
Malphrus, A. ;
Bottenfield, G. W. ;
Spence, J. E. ;
Amato, S. ;
Rousseau, J. A. ;
Moghaddam, B. ;
Skinner, C. ;
Skinner, S. A. ;
Bernes, S. ;
Armstrong, N. ;
Shinawi, M. ;
Stankiewicz, P. ;
Patel, A. ;
Cheung, S-W ;
Lupski, J. R. ;
Beaudet, A. L. ;
Sahoo, T. .
JOURNAL OF MEDICAL GENETICS, 2009, 46 (06) :382-388
[9]   Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature [J].
Bena, Frederique ;
Bruno, Damien L. ;
Eriksson, Mats ;
van Ravenswaaij-Arts, Conny ;
Stark, Zornitza ;
Dijkhuizen, Trijnie ;
Gerkes, Erica ;
Gimelli, Stefania ;
Ganesamoorthy, Devika ;
Thuresson, Ann Charlotte ;
Labalme, Audrey ;
Till, Marianne ;
Bilan, Frederic ;
Pasquier, Laurent ;
Kitzis, Alain ;
Dubourgm, Christele ;
Rossi, Massimiliano ;
Bottani, Armand ;
Gagnebin, Maryline ;
Sanlaville, Damien ;
Gilbert-Dussardier, Brigitte ;
Guipponi, Michel ;
van Haeringen, Arie ;
Kriek, Marjolein ;
Ruivenkamp, Claudia ;
Antonarakis, Stylianos E. ;
Anderlid, Britt Marie ;
Slater, Howard R. ;
Schoumans, Jacqueline .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2013, 162B (04) :388-403
[10]   Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities [J].
Brunetti-Pierri, Nicola ;
Berg, Jonathan S. ;
Scaglia, Fernando ;
Belmont, John ;
Bacino, Carlos A. ;
Sahoo, Trilochan ;
Lalani, Seema R. ;
Graham, Brett ;
Lee, Brendan ;
Shinawi, Marwan ;
Shen, Joseph ;
Kang, Sung-Hae L. ;
Pursley, Amber ;
Lotze, Timothy ;
Kennedy, Gail ;
Lansky-Shafer, Susan ;
Weaver, Christine ;
Roeder, Elizabeth R. ;
Grebe, Theresa A. ;
Arnold, Georgianne L. ;
Hutchison, Terry ;
Reimschisel, Tyler ;
Amato, Stephen ;
Geragthy, Michael T. ;
Innis, Jeffrey W. ;
Obersztyn, Ewa ;
Nowakowska, Beata ;
Rosengren, Sally S. ;
Bader, Patricia I. ;
Grange, Dorothy K. ;
Naqvi, Sayed ;
Garnica, Adolfo D. ;
Bernes, Saunder M. ;
Fong, Chin-To ;
Summers, Anne ;
Walters, W. David ;
Lupski, James R. ;
Stankiewicz, Pawel ;
Cheung, Sau Wai ;
Patel, Ankita .
NATURE GENETICS, 2008, 40 (12) :1466-1471