Oxidatively-induced DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder DNA damage and repair in bipolar disorder.

Previous evidence suggests elevated levels of oxidatively-induced DNA damage, particularly 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in bipolar disorder (BD). However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidatively-induced DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POLß). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POLß expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidatively-induced DNA damage and BER, suggesting a link between abnormalities in DNA damage/BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidatively-induced DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.

Integrating mitoepigenetics into research in mood disorders: a state-of-the-art review.

Mood disorders, including major depressive disorder and bipolar disorder, are highly prevalent and stand among the leading causes of disability. Despite the largely elusive nature of the molecular mechanisms underpinning these disorders, two pivotal contributors-mitochondrial dysfunctions and epigenetic alterations-have emerged as significant players in their pathogenesis. This state-of-the-art review aims to present existing data on epigenetic alterations in the mitochondrial genome in mood disorders, laying the groundwork for future research into their pathogenesis. Associations between abnormalities in mitochondrial function and mood disorders have been observed, with evidence pointing to notable changes in mitochondrial DNA (mtDNA). These changes encompass variations in copy number and oxidative damage. However, information on additional epigenetic alterations in the mitochondrial genome remains limited. Recent studies have delved into alterations in mtDNA and regulations in the mitochondrial genome, giving rise to the burgeoning field of mitochondrial epigenetics. Mitochondrial epigenetics encompasses three main categories of modifications: mtDNA methylation/hydroxymethylation, modifications of mitochondrial nucleoids, and mitochondrial RNA alterations. The epigenetic modulation of mitochondrial nucleoids, lacking histones, may impact mtDNA function. Additionally, mitochondrial RNAs, including non-coding RNAs, present a complex landscape influencing interactions between the mitochondria and the nucleus. The exploration of mitochondrial epigenetics offers valuable perspectives on how these alterations impact neurodegenerative diseases, presenting an intriguing avenue for research on mood disorders. Investigations into post-translational modifications and the role of mitochondrial non-coding RNAs hold promise to unravel the dynamics of mitoepigenetics in mood disorders, providing crucial insights for future therapeutic interventions.

Lymphocyte-related ratios, systemic immune-inflammatory and systemic inflammatory response index in alcohol use disorder.

Addictive disorders are associated with systemic and central nervous system inflammation, which may be important for the onset and development of these diseases. Although lymphocyte-related parameters have recently been studied in alcohol use disorder (AUD), systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) haven't. Lymphocyte-related ratios, SII and SIRI levels were evaluated between AUD and healthy controls (HC) in this study. It was a retrospective and cross-sectional study. This study included 72 patients with AUD and 184 individuals in the HC group. Lymphocyte related ratios such as neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR), SII and SIRI values were compared. Compared to HC group, NLR (p < 0.001), MLR (p < 0.001), and SIRI (p < 0.001) levels were significantly higher in AUD group. There was also a significant relationship between NLR and AST/ALT ratio in the AUD group (p = 0.022). The results of this study support that AUD is a chronic inflammatory psychiatric disorder. In addition, it may be useful to evaluate these markers in relation to liver enzymes in patients with AUD, as alcohol consumption causes liver damage. These markers may also be used in future studies to assess treatment response and disease severity.

Double-Edged Sword: A Case with Withdrawal-Emergent Dyskinesia. / Iki Ucu Keskin Biçak: Nöroleptik Kesilmesiyle Gelisen Diskinezi Olgusu.

Tardive dyskinesia is defined as involuntary athetoid or choreiform movements that develop due to the use of neuroleptic drugs for at least a few months. Tongue, lower face, jaw, upper and lower extremities are the most affected parts of the body in tardive dyskinesia. Quality of life is negatively affected because of the low remission rates. Besides tardive dyskinesia, involuntary movements may appear after discontinuation, change or a reduction in the dose of antipsychotic medications, which is called withdrawal-emergent dyskinesia (WED). Unlike tardive dyskinesia, the involuntary movements involve mainly the neck, trunk, and limbs and regress in shorter period of time in WED. A consensus has not yet been reached for the treatment of WED. Restarting the previous antipsychotic agent with slow titration or switching to an atypical antipsychotic with low affinity for dopamine D2 receptors are among the primary options for treatment. As WED is one of the predictors of tardive dyskinesia development, early detection and treatment is believed to have positive effect on the quality of life. In this report, the case of a patient followed up for bipolar disorder type I (BD-I) and started on clozapine for WED after discontinuation of haloperidol on account of adverse effects is discussed. It is necessary for clinicians to consider these types of complications when discontinuing or changing treatment. Further research is needed in order to reach a common approach for the treatment of WED.