Social Functioning in Individuals Affected by Childhood Maltreatment: Establishing a Research Agenda to Inform Interventions.

Childhood maltreatment (CM) is linked to impairments in various domains of social functioning. Here, we argue that it is critical to identify factors that underlie impaired social functioning as well as processes that mediate the beneficial health effects of positive relationships in individuals exposed to CM. Key research recommendations are presented, focusing on: (1) identifying attachment-related alterations in specific inter- and intrapersonal processes (e.g., regulation of closeness and distance) that underlie problems in broader domains of social functioning (e.g., lack of perceived social support) in individuals affected by CM; (2) identifying internal (e.g., current emotional state) and external situational factors (e.g., cultural factors, presence of close others) that modulate alterations in specific social processes; and (3) identifying mechanisms that explain the positive health effects of intact social functioning. Methodological recommendations include: (1) assessing social processes through interactive and (close to) real-life assessments inside and outside the laboratory; (2) adopting an interdisciplinary, lifespan perspective to assess social processes, using multi-method assessments; (3) establishing global research collaborations to account for cultural influences on social processes and enable replications across laboratories and countries. The proposed line of research will contribute to globally develop and refine interventions that prevent CM and further positive relationships, which - likely through buffering the effects of chronic stress and corresponding allostatic load - foster resilience and improve mental and physical health, thereby reducing personal suffering and the societal and economic costs of CM and its consequences. Interventions targeting euthymia and psychological well-being are promising therapeutic concepts in this context.

Glial cell-derived neurotrophic factor gene polymorpisms affect severity and functionality of bipolar disorder.

Glial cell-derived neurotrophic factor and other neurotrophins have important role in the development of mental disorders. Here, we aimed to assess the effects of Single nucleotide polymorphisms at potentially regulated regions of GDNF on severity and functionality of bipolar disorder and GDNF serum levels in bipolar disorder patients and healthy volunteers. Severity and functionality of bipolar disorder were evaluated using the Clinical Global Impression and Global Assessment of Functioning scales in sixty-six bipolar disorder patients. The GDNF serum levels obtained from bipolar disorder patients and healthy volunteers who had been already reported SNPs information by our group. GAF scales were lower and GDNF serum levels were higher in Bipolar disorder patients with T/A genotype at 5:37812784 and 5:37812782 compared to patients with T/T genotype. There were significant difference in severity and functionality scores, but not in GDNF serum levels, between patients with G/G and G/A genotype of rs62360370 G > A SNP.rs2075680 C > A and rs79669773 T > C SNPs had no effect on bipolar disorder severity and functionality scores and GDNF serum levels. The results suggest that some SNPs of GDNF have potential association with severity and functionality of bipolar disorder. In addition, except two SNPs, none of GDNF SNPs had association with GDNF serum levels.

Mutation/SNP analysis in EF-hand calcium binding domain of mitochondrial Ca[Formula: see text] uptake 1 gene in bipolar disorder patients.

Calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. Impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (BP). MCU is the most important calcium transporter in mitochondria inner membrane responsible for influx of Ca[Formula: see text]. MICU1 is linked with MCU and has two canonical EF hands that are vital for its activity and regulates MCU-mediated Ca[Formula: see text] influx. In the current study, we aimed to investigate the role of genetic alteration of EF hand calcium binding motifs of MICU1 on the development of BP. We examined patients with BP, first degree relatives of these patients and healthy volunteers for mutations and polymorphisms in EF hand calcium binding motifs of MICU1. The result showed no SNP/mutation in BP patients, in healthy subjects and in first degree relatives. Additionally, alignment of the EF hand calcium binding regions among species (Gallus-gallus, Canis-lupus-familiaris, Bos-taurus, Mus-musculus, Rattus-norvegicus, Pan-troglodytes, Homosapiens and Danio-rerio) showed exactly the same amino acids (DLNGDGEVDMEE and DCDGNGELSNKE) except in one of the calcium binding domain of Danio-rerio that there was only one difference; leucine instead of Methionine. Our results showed that the SNP on EF-hand Ca[Formula: see text] binding domains of MICU1 gene had no effect in phenotypic characters of BP patients.

Response inhibition and interference control in patients with bipolar I disorder and first-degree relatives.

OBJECTIVES: The current study aimed to assess both response inhibition (RI) and interference control (IC) in euthymic patients with bipolar disorder (BD-Ps) as well as asymptomatic first-degree relatives (BD-Rs) and healthy controls (HCs) in order to evaluate trait-as opposed to illness-associated features of these components. METHODS: BD-Ps (n = 35) who had been in the euthymic state for at least six months, BD-Rs (n = 30), and HCs (n = 33) completed a Stop-Signal Task (SST) and Stroop Task to assess RI and IC, respectively. Groups were compared on the stop-signal reaction time (SSRT), stop-signal delay (SSD), mean reaction time on go trials (go-RT), Stroop interference score (S-interference), and number of errors on the color-word-naming trial (S-error). Associations between the patient's clinical features and RI and IC, between the patient's treatment and RI and IC, and between RI and IC in each group were investigated. RESULTS: BD-Ps and BD-Rs had significantly shorter go-RT and SSD, and longer SSRT compared to HCs, with these scores being similar between the BD-Ps and BD-Rs. Also, both BD-Ps and BD-Rs made significantly more S-errors than HCs, whereas, the S-interference score was not significantly different between groups. There were no significant correlations between Stroop Task and SST scores within each group, nor between clinical features or treatment variables and RI and IC in BD-Ps. CONCLUSIONS: Overall, impairment in RI and IC (only on S-error score) was present in both patients and relatives. The persistence of these deficits in the absence of mood symptoms suggests that these features may represent candidate endophenotypes for bipolar disorder.

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.

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.

A comparative meta-analysis of peripheral 8-hydroxy-2'-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder.

OBJECTIVE: Oxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach. METHOD: A literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted. RESULTS: The current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distribution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels. CONCLUSION: Our findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.

Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression.

Background: Mood disorders are common disabling psychiatric disorders caused by both genetic and environmental factors. Mitochondrial DNA (mtDNA) modifications and epigenetics are promising areas of research in depression since mitochondrial dysfunction has been associated with depression. In this study we aimed to investigate the mtDNA changes in depressive disorder (MDD) and bipolar disorder (BD). Methods: Displacement loop methylation (D-loop-met), relative mtDNA copy number (mtDNA-cn) and mtDNA oxidation (mtDNA-oxi) were investigated in DNA samples of individuals with MDD (n = 34), BD (n = 23), and healthy controls (HC; n = 40) using the Real-Time Polymerase Chain Reaction (RT-PCR). Blood samples were obtained from a subset of individuals with MDD (n = 15) during a depressive episode (baseline) and after remission (8th week). Results: The study groups exhibited significant differences in D-loop-met (p = 0.020), while relative mtDNA-cn and mtDNA-oxi showed comparable results. During the remission phase (8th week), there were lower levels of relative mtDNA-cn (Z = -2.783, p = 0.005) and D-loop-met (Z = -3.180, p = 0.001) compared to the acute MDD baseline, with no significant change in mtDNA-oxi levels (Z = -1.193, p = 0.233). Conclusion: Our findings indicate significantly increased D-loop methylation in MDD compared to BD and HCs, suggesting distinct mtDNA modifications in these conditions. Moreover, the observed alterations in relative mtDNA-cn and D-loop-met during remission suggest a potential role of mtDNA alterations in the pathophysiology of MDD. Future studies may provide valuable insights into the dynamics of mtDNA modifications in both disorders and their response to treatment.

Clinical and developmental characteristics of cognitive subgroups in a transdiagnostic sample of schizophrenia spectrum disorders and bipolar disorder.

Evidence suggests that neurocognitive dysfunction is a transdiagnostic feature of individuals across the continuum between schizophrenia and bipolar disorder. However, there is significant heterogeneity of neuropsychological and social-cognitive abilities in schizophrenia, schizoaffective disorder, and bipolar disorder. The current study aimed to investigate the clinical and developmental characteristics of cognitive subgroups within the schizo-bipolar spectrum. 147 clinically stable patients with schizophrenia, schizoaffective or bipolar disorder were assessed using clinical rating scales for current psychotic and affective symptoms, and a comprehensive neuropsychological battery including measures of social cognition (Hinting and Reading the mind from the Eyes (RMET) task)). Developmental history and premorbid academic functioning were also evaluated. The study also included 36 healthy controls. Neurocognitive subgroups were investigated using latent class analysis (LCA). The optimal number of clusters was determined based on the Bayesian information criterion. A logistic regression analysis was conducted to investigate the predictors of membership to the globally impaired subgroup. LCA revealed two neurocognitive clusters including globally impaired (n = 89, 60.5%) and near-normal cognitive functioning (n = 58, 39.5%) subgroups. The near-normal cognitive functioning subgroup was not significantly different from healthy controls. The globally impaired subgroup had a higher score of developmental abnormalities (p<0.001), poorer premorbid academic functioning, mothers who were less educated and more severe disorganized speech (p = 0.001) and negative symptoms (p = 0.004) compared to the near-normal cognitive functioning group. History of developmental abnormalities and persistent disorganization rather than diagnosis are significant predictors of the subgroup of individuals with global cognitive impairment in the schizophrenia-bipolar disorder continuum.

Quality of Life of Individuals with Bipolar Disorder and Schizophrenia.

Introduction: Quality of life (QoL) is a concept defined as a subjective perception of one's position in life and is negatively affected in many psychiatric illnesses such as bipolar disorder (BD) and schizophrenia (SCZ). It is hypothesized that therapeutic approaches based on QoL can increase the patient's adherence to treatment and contribute to a satisfactory life. This study aimed to compare the QoL of individuals having BD and schizophrenia with that of healthy controls (HCs) and to investigate the impact of the state of remission on QoL. Method: The World Health Organization QoL Scale-Short Form (WHOQOL-Bref) was administered to individuals with BD (n=124) and SCZ (n=74) and to HCs (n=81) to evaluate QoL. The WHOQOL-Bref subscale and total scores were compared between the groups using multifactor analysis of covariance (MANCOVA) by considering age and education level as the covariates. Then, the patient groups were compared using MANCOVA based on the state of remission by taking age, level of education, and Global Assessment of Functioning scores as the covariates. The relationship between clinical features and QoL scores was evaluated using correlation analysis, and linear regression analysis was applied for the variables that were found to be significant. Results: It was found that individuals with SCZ or BD had lower WHOQOL-Bref psychological, social, and total scores than HCs. Those with SCZ additionally had lower physical and environmental subscale scores than HCs. Furthermore, those with SCZ had lower WHOQOL-Bref physical, psychological, social, and total scores than individuals with BD. There was no significant difference in WHOQOL-Bref scores between individuals with BD and SCZ in the remission period. WHOQOL-Bref physical, psychological, and total scores were found to be significantly lower in unremitted BD patients when compared with remitted BD patients. Unremitted BD patients were found to have significantly lower WHOQOL-Bref psychological, environmental, and total scale scores than unremitted SCZ patients. Conclusion: It can be concluded that the QoL of individuals with BD is between that of healthy individuals and those with SCZ. However, unremitted BD patients have lower QoL than unremitted SCZ patients. Both patient groups display similar features during remission. Identifying the similarities and differences in terms of QoL in both patient groups is of great importance to develop the best type of treatment for the patients.

The role of base excision repair in major depressive disorder and bipolar disorder.

BACKGROUND: In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Imbalance between DNA damage and repair is an emerging research area examining pathophysiological mechanisms of these major mood disorders. This systematic review sought to review DNA repair enzymes, with emphasis on the base excision repair (BER), in mood disorders. METHODS: We conducted a comprehensive literature search of Ovid MEDLINE® Epub Ahead of Print, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, EMBASE (1947), and PsycINFO for studies investigating the alterations in base excision repair in patients with MDD or BD. RESULTS: A total of 1364 records were identified. 1352 records remained after duplicates were removed. 24 records were selected for full-text screening and a remaining 12 articles were included in the qualitative synthesis. SNPs (single nucleotide polymorphisms) of several BER genes have been shown to be associated with MDD and BD. However, it was difficult to draw conclusions from BER gene expression studies due to conflicting findings and the small number of studies. LIMITATIONS: All studies were correlational so it was not possible to draw conclusions regarding causality. CONCLUSION: Future studies comparing DNA repair during the manic or depressive episode to remission will give us a better insight regarding the role of DNA repair in mood disorders. These alterations might be utilized as diagnostic and prognostic biomarkers as well as measuring treatment response.

EFFECTS OF ISOLATED POSTERIOR VAGINAL WALL PROLAPSE ON LOWER URINARY TRACT SYMPTOMS.

AIM: To investigate the effects of isolated posterior vaginal compartment prolapse to lower urinary tract symptoms (LUTS). MATERIALS-METHODS: Patients who were admitted with any kind of LUTS and diagnosed with posterior compartment defects were retrospectively analyzed at urogynecology units of 2 different tertiary referral centers. Patients were included in the analysis if they had isolated posterior vaginal compartment defects with no clinically significant anterior and apical compartment defects. The control group consisted of patients with no pelvic organ prolapse (POP). All pelvic examinations were performed by the same 2 specialists. The responses to a detailed LUTS questionnaire in the unit were assessed. RESULTS: Of the 340 women with posterior POP, 280 were excluded from the analysis due to combined anterior and/or apical POP with posterior POP and stage 4 POP. When we compared the symptoms between the control group and the remaining 60 patients with isolated posterior POP, there was a statistically significant difference in urge, frequency, nocturia, abnormal emptying, vaginal winding, difficult stool passage (p = 0.031, p < 0.001, p < 0.001, p = 0.022, p = 0.041, and p = 0.039, respectively). CONCLUSION: Women with posterior POP should be carefully examined not only for anorectal or bulging symptoms but also for LUTS.

Neurocognitive Functions in Bipolar Disorder in Relation to Comorbid ADHD.

INTRODUCTION: Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) often co-occur in adult population. Both conditions present various neurocognitive and behavioral problems. We aimed to examine neurocognitive functions in adult patients with comorbid BD and ADHD (BD+ADHD) in comparison to patients with only BD, only ADHD and healthy controls (HCs). METHOD: An extensive cognitive battery which evaluates verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency, was used to assess neurocognitive functions respectively in adult (age 18-65 years) patients with BD (n=37), ADHD (n=43), BD+ADHD (n=20) in comparison to HCs (n=51). The Multivariate Analysis of Covariance models, where age, level of education and total BIS-11 scores were included as covariates, were used for comparing neurocognitive scores among groups. RESULTS: Both BD and BD+ADHD groups showed significantly poorer performance than HCs in processing speed, attention, executive functions, and verbal fluency domains. The BD group had additional significant deficits in executive functions, verbal learning and memory domains. There were no significant differences between BD and BD+ADHD groups with regards to verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency domains. Patients with only ADHD showed significantly poorer performance than HCs in verbal fluency domain. CONCLUSIONS: Our results show similarities in the neurocognitive functions of adults with BD and BD+ADHD across a wide range of cognitive domains. The findings point to the need for further exploration of diverging and converging neurodevelopmental trajectories of BD and ADHD.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Circulating exosomal microRNAs in bipolar disorder.

INTRODUCTION: Emerging evidence suggests central roles of miRNAs in the pathogenesis of bipolar disorder (BD). Exosomes are membrane-bound vesicles acting as "biological cargo carriers" of various types of molecules including microRNAs. In this study, we aimed to investigate circulating exosomal microRNAs as potential diagnostic biomarkers for BD. METHODS: The exosomes were precipitated from plasma samples of patients with BD (n = 69; 15 depressed, 27 manic, 27 euthymic) and healthy controls (n = 41). Total RNA was extracted from the exosomes and the levels of miRNAs were assayed by qPCR. Dysregulated miRNAs were subjected to Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis by DIANA-miRPath v3.0 to identify the predicted targets and the related pathways. RESULTS: Thirteen miRNAs showed significant differences between patients with BD and healthy individuals; among these, MiR-484, -652-3p, -142-3p remained significantly downregulated and miR-185-5p remained significantly upregulated after accounting for multiple comparisons and adjustments for potential confounders. There were no significant alterations among different states of BD. The KEEG analysis of four dysregulated miRNAs highlighted several target pathways including PI3K/Akt signaling, fatty acid biosynthesis/metabolism, extracellular matrix and adhesion pathways. CONCLUSION: Our findings suggest that dysregulation of miRNAs might be involved in the underlying pathophysiology of BD through several biological pathways; and highlight the importance of the exosomal miRNAs for biomarker research in BD. Further longitudinal studies may clarify the roles of exosomal miRNAs and their targets in the neurobiology of BD.

Neurocognitive functioning during symptomatic states and remission in bipolar disorder and schizophrenia: A comparative study.

Aims Patients with bipolar disorder present milder cognitive impairment in comparison to patients with schizophrenia. Psychotic symptoms are associated with poorer cognitive functioning in both disorders. We aim to compare cognitive dysfunction between bipolar disorder and schizophrenia across symptomatic and remitted states. Methods An extensive cognitive battery was used to assess bipolar disorder patients (32 in manic episodes with psychotic features, 44 in euthymia), patients with schizophrenia (41 symptomatic, 39 remitted), and 55 healthy controls. A global cognitive factor and six neurocognitive domain factors were identified using principal component analyses. Results Global cognition components differed according to both illness and remission status; working memory differed according to remission status regardless of diagnosis; verbal fluency differed according to diagnosis regardless of remission status. An omnibus F test revealed that the remission state had a significant impact on processing speed in schizophrenia. Conclusion Our data suggest that both disorders are associated with state dependent (i.e., global cognition and working memory) and diagnosis dependent (i.e., global cognition and verbal fluency) neurocognitive dysfunctions. Processing speed was exclusively influenced by symptomatic states of schizophrenia.

Alterations in levels of 8-Oxo-2'-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression.

INTRODUCTION: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. METHODS: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. RESULTS: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. CONCLUSION: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

Differential Dorsolateral Prefrontal Cortex Proteomic Profiles of Suicide Victims with Mood Disorders.

Suicide is a major public health concern; nevertheless, its neurobiology remains unknown. An area of interest in suicide research is the dorsolateral prefrontal cortex (DLPFC). We aimed to identify altered proteins and potential biological pathways in the DLPFC of individuals who died by suicide employing mass spectrometry-based untargeted proteomics. Postmortem DLPFC from age-matched male suicide mood disorder cases (n = 5) and non-suicide mood disorder cases (n = 5) were compared. The proteins that differed between groups at false discovery rate (FDR) adjusted p-values (Benjamini-Hochberg-Yekutieli) <0.3 and Log2 fold change (FC) >|0.4| were considered statistically significant and were subjected to pathway analysis by Qiagen Ingenuity software. Thirty-three of the 5162 detected proteins showed significantly altered expression levels in the suicide cases and two of them after adjustment for body mass index. The top differentially expressed protein was potassium voltage-gated channel subfamily Q member 3 (KCNQ3) (Log2FC = -0.481, p = 2.10 × 10-09, FDR = 5.93 × 10-06), which also showed a trend to downregulation in Western blot (p = 0.045, Bonferroni adjusted p = 0.090). The most notably enriched pathway was the GABA receptor signaling pathway (p < 0.001). Here, we report a reduction trend of KCNQ3 levels in the DLPFC of male suicide victims with mood disorders. Further studies with a larger sample size and equal sex representation are needed.