Epigenetic Mechanisms in Psychiatric Diseases and Epigenetic Therapy

Karslı-Çeppioğlu, Seher

doi:10.1002/ddr.21340

Cited by 26 publications

(15 citation statements)

References 81 publications

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“…Furthermore, early life deprivation has been shown to negatively affect cortical GABA function in adult life, including impaired prefrontal expression of enzymes required for GABA synthesis ( Labouesse et al, 2015 ), which likely has an adverse effect on WM. Epigenetic effects are associated with WM as summarized above, and play a major role in the development and maintenance of psychiatric disorder ( Karsli-Ceppioglu, 2016 ; Luoni and Riva, 2016 ).…”

Section: Theories Of Working Memory and Cognitive Control In The Healmentioning

confidence: 99%

The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder

et al. 2017

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Prefrontal cortex executive functions, such as working memory (WM) interact with limbic processes to foster impulse control. Such an interaction is referred to in a growing body of publications by terms such as cognitive control, cognitive inhibition, affect regulation, self-regulation, top-down control, and cognitive–emotion interaction. The rising trend of research into cognitive control of impulsivity, using various related terms reflects the importance of research into impulse control, as failure to employ cognitions optimally may eventually result in mental disorder. Against this background, we take a novel approach using an impulse control spectrum model – where anorexia nervosa (AN) and substance use disorder (SUD) are at opposite extremes – to examine the role of WM for cognitive control. With this aim, we first summarize WM processes in the healthy brain in order to frame a systematic review of the neuropsychological, neural and genetic findings of AN and SUD. In our systematic review of WM/cognitive control, we found n = 15 studies of AN with a total of n = 582 AN and n = 365 HC participants; and n = 93 studies of SUD with n = 9106 SUD and n = 3028 HC participants. In particular, we consider how WM load/capacity may support the neural process of excessive epistemic foraging (cognitive sampling of the environment to test predictions about the world) in AN that reduces distraction from salient stimuli. We also consider the link between WM and cognitive control in people with SUD who are prone to ‘jumping to conclusions’ and reduced epistemic foraging. Finally, in light of our review, we consider WM training as a novel research tool and an adjunct to enhance treatment that improves cognitive control of impulsivity.

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Section: Theories Of Working Memory and Cognitive Control In The Healmentioning

confidence: 99%

The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder

et al. 2017

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“…These genes may also be future targets for pharmacological and behavioral interventions. Some psychiatric medications have been found to affect epigenetics and expression of the genes that regulate epigenetic imprints ( 37 – 39 ); better understanding of such genes could one day allow appropriate treatment to attenuate the effects of maternal depression and anxiety during pregnancy, improving long-term health of these infants and potentially interrupting transgenerational transmission of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to maternal depression and anxiety on imprinted gene expression in placenta and infant neurodevelopment and growth

et al. 2018

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BackgroundDepression and/or anxiety during pregnancy have been associated with impaired fetal growth and neurodevelopmental. Because placental imprinted genes play a central role in fetal development and respond to environmental stressors, we hypothesized that imprinted gene expression would be affected by prenatal depression and anxiety.MethodsPlacental gene expression was compared between mothers with prenatal depression and/or anxiety/obsessive compulsive disorder/panic and control mothers without psychiatric history (n=458) in the Rhode Island Child Health Study.ResultsTwenty-nine genes were identified as being significantly differentially expressed between placentae from infants of mothers with both depression and anxiety (n=54), with depression (n=89), or who took perinatal psychiatric medications (n=29) and control mother/infant pairs, with most genes having decreased expression in the stressed group. Among placentae from infants of mothers with depression, we found no differences in expression by medication use, indicating that our results are related to the stressor rather than the treatments. We did not find any relationship between the stress-associated gene expression and neonatal neurodevelopment as measured using the Neonatal Intensive Care Unit Network Neurobehavioral Scale.ConclusionsThis variation in expression may be part of an adaptive mechanism by which the placenta buffers the infant from the effects of maternal stress.

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“…The plastic nature of epigenetic marks offers the possibility to modulate and possibly correct epigenetic alterations through classical pharmacology. 79 Epigenetic machinery comprises a variety of DNA/histone modifiers and epigenetic medicine commonly falls into two main categories: DNA methyltransferase (DNMT) inhibitors acting on DNA methylation (such as 5-aza (2'deoxy)cytidine or decitabine); and histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA) or trichostatin A, targeting histone PTM. Even though the efficacy of DNMT inhibitors has been recognized in the context of cancer, their therapeutic potential in treatment of psychiatric disorders is still at the preclinical stage.…”

Section: Epigenetic Pharmacotherapymentioning

confidence: 99%

Epigenetics applied to psychiatry: Clinical opportunities and future challenges

Kular

2018

Psychiatry Clin Neurosci

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Psychiatric disorders are clinically heterogeneous and debilitating chronic diseases resulting from a complex interplay between gene variants and environmental factors. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, instruct the cell/tissue to correctly interpret external signals and adjust its functions accordingly. Given that epigenetic modifications are sensitive to environment, stable, and reversible, epigenetic studies in psychiatry could represent a promising approach to better understanding and treating disease. In the present review, we aim to discuss the clinical opportunities and challenges arising from the epigenetic research in psychiatry. Using selected examples, we first recapitulate key findings supporting the role of adverse life events, alone or in combination with genetic risk, in epigenetic programming of neuropsychiatric systems. Epigenetic studies further report encouraging findings about the use of methylation changes as diagnostic markers of disease phenotype and predictive tools of progression and response to treatment. Then we discuss the potential of using targeted epigenetic pharmacotherapy, combined with psychosocial interventions, for future personalized medicine for patients. Finally, we review the methodological limitations that could hinder interpretation of epigenetic data in psychiatry. They mainly arise from heterogeneity at the individual and tissue level and require future strategies in order to reinforce the biological relevance of epigenetic data and its translational use in psychiatry. Overall, we suggest that epigenetics could provide new insights into a more comprehensive interpretation of mental illness and might eventually improve the nosology, treatment, and prevention of psychiatric disorders.

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Epigenetic Mechanisms in Psychiatric Diseases and Epigenetic Therapy

Cited by 26 publications

References 81 publications

The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder

The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder

Prenatal exposure to maternal depression and anxiety on imprinted gene expression in placenta and infant neurodevelopment and growth

Epigenetics applied to psychiatry: Clinical opportunities and future challenges

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