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Epigenetic Epidemiology of Psychiatric Disorders

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Epigenetic Epidemiology

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Abstract

Exciting developments in the field of epigenetics have generated great interest within psychiatric epidemiology to focus on direct and indirect evidence for epigenetic involvement in behavior, mental health, and complex psychiatric disorders. Epidemiologic evidence on epigenetics in psychiatry, however, is currently very sparsely available. With the aim to address the current status of the literature on evidence indicative of involvement of epigenetic mechanisms in psychiatric disorders, we describe a clear role for epigenetic mechanisms in development and aging of the brain, with experiences and environmental exposures particularly during early life having considerable impact on the development of functional abilities of the brain. Besides the psychiatric consequences of classical syndromes of genetic imprinting in humans, findings of twin discordance, parent-of-origin effects, paternal age effects, and sex differences in psychiatric disorders suggest epigenetic involvement in the etiology of psychiatric disorders. The evidence is further strengthened by observations of endurable effects of various environmental exposures during life on risk of psychiatric disorders, and preliminary epigenetic studies showing differential epigenetic profiles in patients with several psychiatric disorders. Findings of these first (and preliminary) epigenetic studies should be interpreted with caution because of small samples sizes, lack of replication, limitations in the etiologic validity of psychiatric diagnoses, and in accessibility of the regions and cell types of the brain at “appropriate” periods during life. Despite the sparse availability, the current evidence for epigenetic involvement in (particularly early) brain development, mental health, and psychiatric disorders appears very promising, and may be used in bringing together inherited and acquired risk factors into a neurodevelopmental etiological model of psychiatric disorders with epigenetics as a plausible key mediating mechanism. Given the dynamic nature of epigenetic regulation of gene expression and the potential reversibility of epigenetic modifications, future well-designed multidisciplinary and translational studies will be of key importance in order to identify new targets for prevention and therapeutic strategies.

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Abbreviations

5-mC:

5-methyl cytidine

AD:

Alzheimer’s disease

ADHD:

Attention deficit hyperactivity disorder

AKT1:

v-akt murine thymoma viral oncogene homolog 1

APOE:

Apolipoprotein E

APP:

Amyloid precursor protein

BDNF:

Brain derived neurotrophic factor

CB1:

Cannabis-1

CDH1:

Cadherin 1

Cdk5:

Cyclin-dependent kinase 5

COMT:

Catechol-O-methyltransferase

DC-MZ:

Dichorionic monozygotic

DNMT:

DNA methyl transferase

DRD2:

Dopamine D2 receptor

DSM-IV:

Diagnostic and Statistical Manual of Mental Disorders 4th edition

DZ:

Dizygotic

GABA:

Gamma-aminobutyric acid

GAD:

Glutamic-acid decarboxylase

H4K12:

Histone H4 lysine 12

H4K16:

Histone H4 lysine 16

HIST1H2AG:

Histone cluster 1, H2ag

HIST1H2AH:

Histone cluster 1, H2ah

HIST1H2BJ:

Histone cluster 1, H2bj

HIST1H2BK:

Histone cluster 1, H2bk

HIST1H4I:

Histone cluster 1, H4i

HTERT:

Telomerase reverse transcriptase

MAPT:

Microtubule-associated protein tau

MC-MZ:

Monochorionic monozygotic

MeCP2:

Methyl CpG binding protein 2

MS:

Multiple sclerosis

MTHFR:

Methylenetetrahydrofolate reductase

MZ:

Monozygotic

NPAS3:

Neuronal PAS domain protein 3

NR3C1:

Glucocorticoid receptor

OCM:

One-carbon metabolism

PBCs:

Pregnancy and birth complications

PCR:

Polymerase chain reaction

PPIEL:

Peptidylprolyl isomerae E-like

PSEN1:

Presenilin 1

PTSD:

Post-traumatic stress disorder

RELN:

Reelin

SIRT3:

Sirtuin 3

SMARCA5:

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5

SMS:

Spermine synthase

SNP:

Single nucleotide polymorphism

THC:

Δ9-tetrahydrocannabinol

TRKB:

Neurotrophic tyrosine kinase, receptor, type 2

UBE3A:

Ubiquitin protein ligase E3A

WHO:

World Health Organization

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Authors and Affiliations

  1. Department of Psychiatry and Psychology, School for Mental Health and Neuroscience, European Graduate School of Neuroscience (EURON), South Limburg Mental Health Research and Teaching Network (SEARCH), Maastricht University Medical Centre, 616 (VIJV), 6200, Maastricht, MD, The Netherlands

    Bart P. F. Rutten & Jim van Os

  2. Department of Psychosis Studies, Institute of Psychiatry, King’s College London, King’s Health Partners, London, UK

    Jim van Os

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  1. Bart P. F. Rutten
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  2. Jim van Os
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Correspondence to Bart P. F. Rutten .

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  1. , Obstetrics and Gynecology Epidemiology D, Brigham and Women’s Hospital, Longwood Avenue 221, Boston, 02115, Massachusetts, USA

    Karin B. Michels

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Rutten, B.P.F., van Os, J. (2012). Epigenetic Epidemiology of Psychiatric Disorders. In: Michels, K. (eds) Epigenetic Epidemiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2495-2_18

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