Dysbindin (DTNBP1) – A role in psychotic depression?

Domschke, Katharina; Lawford, Bruce R.; Young, Ross McD.; Voisey, Joanne; Morris, C. Phillip; Roehrs, Tilmann; Hohoff, Christa; Birosova, Eva; Arolt, Volker; Baune, Bernhard T.

doi:10.1016/j.jpsychires.2010.09.014

Cited by 22 publications

(19 citation statements)

References 60 publications

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“…A recent meta-analysis of more than 6,500 patients demonstrated that the interaction between a high-risk genotype for the serotonin transporter and physical disease is associated with a significantly increased risk for depression [55]. The present findings of differences in the relative risk contribution of physical morbidity in PD and non-PD adds some support to the hypothesis that non-psychotic severe depression may more often occur secondary to physical disease (environmental risk factor) than PD, which, on the other hand, may be a more ‘primary’ disorder, characterized by stronger genetic penetrance [25,27,28]. …”

Section: Discussionsupporting

confidence: 70%

“…With these many differences between non-PD and PD in mind, it seems plausible that the two subtypes would also have a different etiology. Indeed, some authors have suggested that non-PD more often arises secondary to environmental stress, such as physical disease, than does PD, which is considered to be a more primary/heritable disorder [25,26,27,28]. The aim of the present study was to investigate the association between physical morbidity and the subsequent risk of developing the non-psychotic versus the psychotic subtype of severe depression.…”

Section: Introductionmentioning

confidence: 95%

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The Association between Physical Morbidity and Subtypes of Severe Depression

Østergaard

Petrides

Dinesen

et al. 2012

Psychother Psychosom

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Background: Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype of severe depression. Methods: This is a historical prospective cohort study. The study population consisted of all patients diagnosed with ICD-10 severe depression, either nonpsychotic or psychotic subtype, in Danish psychiatric hospitals between 1994 and 2008. The patients’ history of physical disease was assessed using the Danish National Patient Register. Using logistic regression it was investigated whether specific physical diseases were associated with relative increased risk for subsequent development of either the nonpsychotic or psychotic depressive subtype. Results: A total of 24,173 patients with severe depression were included in the study. Of those, 8,260 (34%) were of the psychotic subtype. A history of the following physical diseases, as opposed to their absence, increased the relative risk for subsequent development of the nonpsychotic compared to the psychotic depressive subtype [adjusted incidence odds ratio (AIOR) nonpsychotic vs. psychotic]: ischemic heart disease (AIOR = 1.3, p < 0.001), hypertension (AIOR = 1.2, p = 0.008), stroke (AIOR = 1.2, p = 0.042) and chronic lower pulmonary disease (AIOR = 1.2, p = 0.005). The total load of physical disease also increased the relative risk of nonpsychotic depression [AIOR = 1.05 (per disease), p = 0.001]. Conclusions: This study revealed that, in severe depression, a history of physical disease increased the relative risk of the nonpsychotic rather than the psychotic subtype.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 95%

The Association between Physical Morbidity and Subtypes of Severe Depression

Østergaard

Petrides

Dinesen

et al. 2012

Psychother Psychosom

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“…The only study, to the best of our knowledge, conducted with peripheral samples of BD patients that reported changes in DNA methylation in the glutamatergic system is the report on increased dystrobrevin binding protein 1 (DTNB1) promoter methylation in BD patients with psychotic depression compared to other BD patients (Abdolmaleky et al, 2015; Fries et al, 2016). The DTNB1, also known as dysbindin, has been suggested to be involved in glutamatergic neurotransmission by influencing exocytotic glutamate release (Domschke et al, 2011). Epigenetic studies of the glutamatergic system in patients with schizophrenia reported differential methylation of the glutamate receptor ionotrophic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid 2 and 3 and glutamate metabotropic receptors 2, 5, and 8 (Aberg et al, 2012; Kordi-Tamandani et al, 2013; Teroganova et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction

Jia

Choi

Ayers-Ringler

et al. 2017

Front. Cell. Neurosci.

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While downregulation of excitatory amino acid transporter 2 (EAAT2), the main transporter removing glutamate from the synapse, has been recognized in bipolar disorder (BD), the underlying mechanisms of downregulation have not been elucidated. BD is influenced by environmental factors, which may, via epigenetic modulation of gene expression, differentially affect illness presentation. This study thus focused on epigenetic DNA methylation regulation of SLC1A2, encoding for EAAT2, in BD with variable environmental influences of addiction. High resolution melting PCR (HRM-PCR) and thymine–adenine (TA) cloning with sequence analysis were conducted to examine methylation of the promoter region of the SLC1A2. DNA was isolated from blood samples drawn from BD patients (N = 150) with or without addiction to alcohol, nicotine, or food, defined as binge eating, and matched controls (N = 32). In comparison to controls, the SLC1A2 promoter region was hypermethylated in BD without addiction but was hypomethylated in BD with addiction. After adjusting for age and sex, the association of methylation levels with nicotine addiction (p = 0.0009) and binge eating (p = 0.0002) remained significant. Consistent with HRM-PCR, direct sequencing revealed increased methylation in CpG site 6 in BD, but decreased methylation in three CpG sites (6, 48, 156) in BD with alcohol and nicotine addictions. These results suggest that individual point methylation within the SLC1A2 promoter region may be modified by exogenous addiction and may have a potential for developing clinically valuable epigenetic biomarkers for BD diagnosis and monitoring.

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“…The dystrobrevin binding protein 1 (DTNBP1), also known as dysbindin, has been suggested to be involved in glutamatergic neurotransmission by influencing exocytotic glutamate release (Domschke et al, 2011). Due to the role of glutamate in BD and psychosis, several studies have been assessing the potential role of genetic variations in the DTNBP1 gene in these disorders (Corvin et al, 2008; Joo et al, 2007; Yun et al, 2008).…”

Section: Dna Methylation In Bdmentioning

confidence: 99%

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

Fries

McAlpin

et al. 2016

Neuroscience & Biobehavioral Reviews

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Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the ‘plastic’ characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients.

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Dysbindin (DTNBP1) – A role in psychotic depression?

Cited by 22 publications

References 60 publications

The Association between Physical Morbidity and Subtypes of Severe Depression

The Association between Physical Morbidity and Subtypes of Severe Depression

Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction

The role of DNA methylation in the pathophysiology and treatment of bipolar disorder

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