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Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.

ABSTRACT: Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome-wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently developed BD or MDD [ill later (IL)] and those who remained well [well later (WL)].DNA methylation profiles were obtained from whole-blood samples from 22 IL and 23 WL individuals using the Infinium HumanMethylation450 BeadChip. Differential methylation was assessed on a single-locus and regional basis. Pathway analysis was performed to assess enrichment for particular biological processes amongst nominally significantly differentially methylated loci.Although no locus withstood correction for multiple testing, uncorrected P-values provided suggestive evidence for altered methylation at sites within genes previously implicated in neuropsychiatric conditions, such as Transcription Factor 4 (TCF4) and Interleukin 1 Receptor Accessory Protein-Like 1 ([IL1RAPL1]; P?3.11×10(-5) ). Pathway analysis revealed significant enrichment for several neurologically relevant pathways and functions, including Nervous System Development and Function and Behavior; these findings withstood multiple testing correction (q?0.05). Analysis of differentially methylated regions identified several within the major histocompatibility complex (P?.000 479), a region previously implicated in schizophrenia and BD.Our data provide provisional evidence for the involvement of altered whole-blood DNA methylation in neurologically relevant genes in the aetiology of mood disorders. These findings are convergent with the findings of genome-wide association studies.

SUBMITTER: Walker RM

PROVIDER: S-EPMC5006843 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.

Walker Rosie May RM Sussmann Jessika Elizabeth JE Whalley Heather Clare HC Ryan Niamh Margaret NM Porteous David John DJ McIntosh Andrew Mark AM Evans Kathryn Louise KL

Bipolar disorders 20160721 5

<h4>Objectives</h4>Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome-wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently develo ...[more]

PMID: 27440233

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Project description:IntroductionResearch has shown that eating disorder (ED) patients who abuse substances demonstrate worse ED symptomatology and poorer outcomes than those with EDs alone, including increased general medical complications and psychopathology, longer recovery times, poorer functional outcomes and higher relapse rates. This article provides a broad overview of the prevalence, aetiology, assessment and management of co-morbid EDs and substance use disorders (SUDs).ReviewThe co-occurrence of EDs and SUDs is high. The functional relationship between EDs and SUDs vary within and across ED subtypes, depends on the class of substance, and needs to be carefully assessed for each patient. Substances such as caffeine, tobacco, insulin, thyroid medications, stimulants or over the counter medications (laxatives, diuretics) may be used to aid weight loss and/or provide energy, and alcohol or psychoactive substances could be used for emotional regulation or as part of a pattern of impulsive behaviour. A key message conveyed in the current literature is the importance of screening and assessment for co-morbid SUDs and EDs in patients presenting with either disorder. There is a paucity of treatment studies on the management of co-occurring EDs and SUDs. Overall, the literature indicates that the ED and SUD should be addressed simultaneously using a multi-disciplinary approach. The need for medical stabilization, hospitalization or inpatient treatment needs to be assessed based on general medical and psychiatric considerations. Common features across therapeutic interventions include psycho-education about the aetiological commonalities, risks and sequelae of concurrent ED behaviours and substance abuse, dietary education and planning, cognitive challenging of eating disordered attitudes and beliefs, building of skills and coping mechanisms, addressing obstacles to improvement and the prevention of relapse. Emphasis should be placed on building a collaborative therapeutic relationship and avoiding power struggles. Cognitive behavioural therapy has been frequently used in the treatment of co-morbid EDs and SUDs, however there are no randomized controlled trials. More recently evidence has been found for the efficacy of dialectical behavioural therapy in reducing both ED and substance use behaviours.ConclusionFuture research would benefit from a meta-analysis of the current research in order to better understand the relationships between these two commonly co-occurring disorders.

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Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.

Publications

Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.

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