Epigenome Defines Aberrant Brain Laterality in Major Mental Illnesses.

Brain-hemisphere asymmetry/laterality is a well-conserved biological feature of normal brain development. Several lines of evidence, confirmed by the meta-analysis of different studies, support the disruption of brain laterality in mental illnesses such as schizophrenia (SCZ), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), and autism. Furthermore, as abnormal brain lateralization in the planum temporale (a critical structure in auditory language processing) has been reported in patients with SCZ, it has been considered a major cause for the onset of auditory verbal hallucinations. Interestingly, the peripheral counterparts of abnormal brain laterality in mental illness, particularly in SCZ, have also been shown in several structures of the human body. For instance, the fingerprints of patients with SCZ exhibit aberrant asymmetry, and while their hair whorl rotation is random, 95% of the general population exhibit a clockwise rotation. In this work, we present a comprehensive literature review of brain laterality disturbances in mental illnesses such as SCZ, BD, ADHD, and OCD, followed by a systematic review of the epigenetic factors that may be involved in the disruption of brain lateralization in mental health disorders. We will conclude with a discussion on whether existing non-pharmacological therapies such as rTMS and ECT may be used to influence the altered functional asymmetry of the right and left hemispheres of the brain, along with their epigenetic and corresponding gene-expression patterns.

Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.

Multiple lines of evidence have shown that lactate-mediated pH alterations in the brains of patients with neuropsychiatric diseases such as schizophrenia (SCZ), Alzheimer's disease (AD) and autism may be attributed to mitochondrial dysfunction and changes in energy metabolism. While neuronal activity is associated with reduction in brain pH, astrocytes are responsible for rebalancing the pH to maintain the equilibrium. As lactate level is the main determinant of brain pH, neuronal activities are impacted by pH changes due to the binding of protons (H+) to various types of proteins, altering their structure and function in the neuronal and non-neuronal cells of the brain. Lactate and pH could affect diverse types of epigenetic modifications, including histone lactylation, which is linked to histone acetylation and DNA methylation. In this review, we discuss the importance of pH homeostasis in normal brain function, the role of lactate as an essential epigenetic regulatory molecule and its contributions to brain pH abnormalities in neuropsychiatric diseases, and shed light on lactate-based and pH-modulating therapies in neuropsychiatric diseases by targeting epigenetic modifications. In conclusion, we attempt to highlight the potentials and challenges of translating lactate-pH-modulating therapies to clinics for the treatment of neuropsychiatric diseases.

Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.

The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common age-related brain diseases. The incidence of AD is almost 20% in individuals over the age of 80 years, and the incidence of PD is 1­4% in individuals over the age of 60 years. Research scientists are studying various links among key factors involved in AD and PD pathogenesis, including diet, gut microbiota (communal bacteria living in our gut), neuroinflammation, epigenetic modifications (regulation of gene expression that is affected by environmental factors) and genetic changes to obtain greater insights into the mechanisms of disease development to design better therapeutics for these disabling diseases. The discovery of these relationships will provide opportunities to maintain favorable health via diet­microbiota­epigenetic modifications, since diet and surrounding environments play crucial roles in gut microbial alterations. Here, we discuss the interactions between destructive protein misfolding/aggregation in AD and PD, with neuroinflammation and epigenetic alterations that all are affected by nutrition, microbiota dysbiosis (imbalance), leaky gut (gut­blood barrier disruption) and internal or environmental toxins. We also present thought-provoking discussions and ideas about recent preventive/therapeutic approaches like special diets, probiotics, fecal microbiota transplantation and even specific antibiotics for preventing or improving neuropsychiatric symptoms in AD and PD.

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies.

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.

Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations.

Nutrition and metabolism modify epigenetic signatures like histone acetylation and DNA methylation. Histone acetylation and DNA methylation in the central nervous system (CNS) can be altered by bioactive nutrients and gut microbiome via the gut-brain axis, which in turn modulate neuronal activity and behavior. Notably, the gut microbiome, with more than 1000 bacterial species, collectively contains almost three million functional genes whose products interact with millions of human epigenetic marks and 30,000 genes in a dynamic manner. However, genetic makeup shapes gut microbiome composition, food/nutrient metabolism, and epigenetic landscape, as well. Here, we first discuss the effect of changes in the microbial structure and composition in shaping specific epigenetic alterations in the brain and their role in the onset and progression of major mental disorders. Afterward, potential interactions among maternal diet/environmental factors, nutrition, and gastrointestinal microbiome, and their roles in accelerating or delaying the onset of severe mental illnesses via epigenetic changes will be discussed. We also provide an overview of the association between the gut microbiome, oxidative stress, and inflammation through epigenetic mechanisms. Finally, we present some underlying mechanisms involved in mediating the influence of the gut microbiome and probiotics on mental health via epigenetic modifications.

Alternation in functional connectivity within default mode network after psychodynamic psychotherapy in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by impairments in emotion regulation, impulse control, and interpersonal and social functioning along with a deficit in emotional awareness and empathy. In this study, we investigated whether functional connectivity (FC) within the default mode network (DMN) is affected by 1-year psychodynamic psychotherapy in patients with BPD. METHODS: Nine BPD patients filled out the demography, Interpersonal Reactive Index (IRI), Toronto Alexithymia Scale 20 (TAS 20), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the Borderline Evaluation Severity over Time (BEST) questionnaire. The BPD group (9F) and the control group (9F) had a mean ± SD age of 28.2 ± 5.3 years and 30.4 ± 6.1 years, respectively. BPD subjects underwent longitudinal resting-state fMRI before psychodynamic psychotherapy and then every 4 months for a year after initiating psychotherapy. FC in DMN was characterized by calculating the nodal degree, a measure of centrality in the graph theory. RESULTS: The results indicated that patients with BPD present with aberrant DMN connectivity compared to healthy controls. Over a year of psychotherapy, the patients with BPD showed both FC changes (decreasing nodal degree in the dorsal anterior cingulate cortex and increasing in other cingulate cortex regions) and behavioral improvement in their symptoms and substance use. There was also a significant positive association between the decreased nodal degree in regions of the dorsal cingulate cortex and a decrease in the score of the TAS-20 indicating difficulty in identifying feelings after psychotherapy. CONCLUSION: In BPD, there is altered FC within the DMN and disruption in self-processing and emotion regulation. Psychotherapy may modify the DMN connectivity and that modification is associated with positive changes in BPD emotional symptoms.

Grief experience among ICU staff with loss of family members during COVID-19 outbreak in IRAN: A qualitative study.

Introduction: The COVID-19 crisis created a lot of problems in people's lives. Different lifestyles, mental health, communication, rituals and traditions, particularly those involved in mourning, have changed drastically. Medical staff faced numerous critically ill patients every day. This greatly distressed the staff, especially the ICU staff. The end result was considerable amounts of mental distress for the medical staff who lost family members to COVID-19 making the distress even more complex. Methods: We carried out this qualitative research to study the grief experiences of 12 Iranian ICU staff members at the Rasoul Akram Hospital who had experienced the loss of a family member to the COVID-19 pandemic. We studied the effects of how their own grief experience and how constant exposure to critically ill patients influenced their work with patients. All semi-structured interviews were held in the presence of a faculty member of the psychiatry department of Iran University of Medical Sciences. The interview on the grief experience among ICU staff during the COVID-19 pandemic, consists of 4 issues: Familiarity, Experience during the COVID-19 pandemic, Grieving the loss of a family member and Effects of parallel grief. Results: We found five common themes in the result of the experiences of the participants based on content analysis. These consisted of: complex grieving process, new experiences for coping with loss, more empathy for patients, change the meaning of death, and the need for support in work places. Likewise, there were 22 sub themes. Conclusion: Paying attention to the details of staff members' life, gender differences, and cultural aspects can give us a better understanding and perception of their grief experiences. This understanding brings out valuable points which can help policy makers pass better laws for the wellbeing of society and people in order to promote leadership in turbulent times.

Chronic fatigue syndrome and cognitive deficit are associated with acute-phase neuropsychiatric manifestations of COVID-19: A 9-month follow-up study.

The preva lence of long-COVID symptoms is rising but it is not still possible to predict which patients will present them, and which types of symptoms they will present. We followed up 95 patients with confirmed COVID-19 for 9 months to identify and characterize long-COVID symptoms. Easy fatigability was the most common symptom (51.04%), followed by anxiety (38.54%), dyspnea (38.54%), and new-onset headache (38.54%). There was no association between COVID-19 severity in the acute phase and the number of long-COVID symptoms (F(1,93) = 0.75, p = 0.45), and cognitive function (MoCA) scores (F(1,90) = 0.073, p = 0.787) at follow-up. Being female (F(1,92) = - 2.27, p = 0.02), having a higher number of symptoms (F(1,93) = 2.76, p = 0.0068), and experiencing constitutional neuropsychiatric symptoms (F(1,93) = 2.529, p = 0.01) in the acute phase were associated with having chronic fatigue syndrome at follow-up. Moreover, constitutional neuropsychiatric symptoms in the acute phase were associated with a lower MoCA score (F(1,93) = 10.84, p = 0.001) at follow-up. Specific clinical presentations such as constitutional neuropsychiatric symptoms in the acute phase might be predictors of debilitating long-COVID symptoms such as chronic fatigue syndrome and cognitive deficits.

Neurological Manifestations and their Correlated Factors in COVID-19 Patients; a Cross-Sectional Study.

INTRODUCTION: COVID-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. This study aimed to evaluate the neurologic manifestations and their correlated factors in COVID-19 patients. METHODS: This retrospective observational study was conducted from March 17, 2020 to June 20, 2020 in a tertiary hospital in Iran. The study population consisted of adult patients with a positive result for COVID-19 real-time reverse transcriptase polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. Both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. RESULTS: 727 COVID-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). At least one neurological symptom was observed in 403 (55.4%) cases. Headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. Patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (BMI) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to COVID-19 patients without neurological symptoms. O2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). In addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (NLR) (p = 0.02) and c-reactive protein (CRP) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. CONCLUSION: The prevalence of neurological manifestations in the studied cases was high (55.4%). This prevalence was significantly higher in older age, grated BMI, longer lasting disease, and opium usage.

Clinical and Epidemiological Characteristics of Postdischarge Patients With COVID-19 in Tehran, Iran: Protocol for a Prospective Cohort Study (Tele-COVID-19 Study).

BACKGROUND: COVID-19 was declared a pandemic on March 11, 2020. Given that the severe shortage of hospital beds has led to early discharge and insufficient patient education on home care routines and isolation protocols, the close follow-up of patients and their immediate relatives is an integral part of transitioning from hospital care to home care for patients with COVID-19. OBJECTIVE: We designed the Tele-COVID-19 prospective cohort to follow-up with COVID-19 patients in Tehran, Iran, and improve health care delivery and the recording of postdischarge patients' clinical profiles. METHODS: All adult patients who were admitted to the COVID-19 wards of teaching hospitals in Tehran, Iran were eligible to participate in this cohort study. At baseline, patients were recruited from 4 major hospitals from March 9, 2020 to May 20, 2020. Telephone follow-ups, which were led by volunteer medical students, were conducted on postdischarge days 1-3, 5, 7, 10, and 14. We collected data on a range of sociodemographic, epidemiological, and clinical characteristics by using a standard questionnaire. RESULTS: Of the 950 patients with confirmed COVID-19 who were approached, 823 (response rate: 86.6%) consented and were enrolled into the cohort. Of the 823 participants, 449 (54.5%) were male. The mean age of participants was 50.1 years (SD 12.6 years). During the initial data collection phase, more than 5000 phone calls were made and over 577 reports of critical patients who were in need of urgent medical attention were recorded. CONCLUSIONS: The Tele-COVID-19 cohort will provide patients with sufficient education on home care and isolation, and medical advice on care and the proper use of drugs. In addition, by preventing unnecessary hospital returns and providing information on household SARS-CoV-2 transmission as early as possible, this cohort will help with effective disease management in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23316.

Non-Compliance and Related Factors in Patients With Bipolar I Disorder: A Six Month Follow-Up Study.

BACKGROUND: Medication treatment compliance among bipolar patients is quite widespread. OBJECTIVES: Treatment compliance depends on multiple factors. The aim of this study was to evaluate the predicting factors of noncompliance in patients with bipolar I disorder admitted to an Iranian hospital during a six-month follow up period. MATERIALS AND METHODS: This cross-sectional study included 47 bipolar I disorder subjects who were admitted to the Iran psychiatric hospital and that were chosen using a non-randomized convenient sampling model. The patients were assessed at baseline, and at two and six months after admission. For evaluating the patients, we used the medication possession ratio (MPR), the drug attitude inventory (DIA-10), the young mania rating scale (Y-MRS) and the scale for the assessment of positive symptoms (SAPS). The data were analyzed using a general linear model by SPSS 16 software. RESULTS: The repeated measures analysis revealed that medication compliance increased successively (P = 0.045), and age, gender and symptom severity did not alter the pattern. CONCLUSIONS: There is an increasing pattern in treatment compliance in bipolar I disorder patients, regardless of the known predicting factors for nonadherence.

Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.

Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively. We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P = 0.032), DRD4 (P = 0.05), MB-COMT (P = 0.009), and AKT1 (P = 0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P = 0.022, P = 0.034, P = 0.035, P = 0.038, respectively), and to a lesser degree in some of the candidate genes in non-psychotic patients versus the control subjects. In general, methamphetamine dependency is associated with reduced DNA methylation and corresponding increase in expression of several key genes involved in the pathogenesis of psychotic disorders. While these epigenetic changes can be useful diagnostic biomarkers for psychosis in methamphetamine abusers, it is also consistent with the use of methyl rich diet for prevention or suppression of psychosis in these patients. However, this needs to be confirmed in future studies. © 2016 Wiley Periodicals, Inc.

Psychological aspects in brain tumor patients: A prospective study.

OBJECTIVE: Very few studies have utilized specific criteria to assess mental disorders in brain tumor patients, and from them, they are mainly descriptive. The purpose of this study is to examine mental disorders in relation to tumor characteristics and patients' psychosocial factors using DSM-IV (depression, sleep and mood) criteria, among brain tumor patients. MATERIALS AND METHODS: From March 2009 to July 2011, 98 patients who surgically treated with intracranial neoplasm were included in this prospective study. The mean age of the patient group was 42.2 years with a range of 18-60 years with a male to female ratio of 1.2. The most common tumor type was glioblastoma multiform (30.3%), followed by meningioma (16.8%) and anaplastic glioma (12.3%). RESULTS: In our study, the prevalence of mild depression was about 30% for males and 38% for females before surgery; however at 3 months after surgery, this amount decreased to the amount of 25.6% and 26% for male and female patients respectively. Before tumor operation, the prevalence of major depression was 10.4% for males and 19.7% for females. At 3 months after operation the prevalence of major depression was 12.8% for males, and 6.7% for females. Aggression or suicide attempts were not seen related to depression. Before operative intervention, severe anxiousness as well as severe Obsessive Compulsive Disorder (OCD) symptoms was present in 14.7% of males while at 3 months after operation, prevalence of severe anxiousness and severe OCD symptoms decreased to 4% and 9.3% respectively. In females, 28.7% of the subjects had reported to have severe anxiousness and 25.6% severe OCD symptoms. Three months after surgery, these amounts were 17.6% and 38.7% respectively. CONCLUSION: Depressive symptoms as well as anxious and OCD psychopathology were shown to be prevalent signs among patients with brain tumor. Diagnosis of the previous mentioned symptoms were totally based on DSM-IV criteria and these disorders and the percentiles don't seem to be related to each other. Due to high variability of tumor stages, statistical analysis of whether the mentioned psychiatric symptoms get worsen at the later stages of the tumor genesis was not feasible. Although not measured directly, mentioned psychiatric symptoms seem to get worsen at the later stages of the brain tumor. The associated factors are tumor location, patient's premorbid psychiatric status, cognitive symptoms and adaptive or maladaptive response to stress.

DNA hypermethylation of serotonin transporter gene promoter in drug naïve patients with schizophrenia.

INTRODUCTION: Dysfunctional serotonin signaling has been linked to the pathogenesis of autism, obsessive compulsive disorder, mood disorders and schizophrenia. While the hypo-activity of serotonin signaling is involved in the pathogenesis of depression, anxiety and obsessive compulsive disorder; LSD, an agonist of serotonin type 2 receptor (5-HTR2A) induces psychosis. Therefore, anxiety and depressive disorders are treated by SSRIs which inhibit serotonin transporter (5-HTT) while psychotic disorders are controlled by drugs that block serotonin and/or dopamine receptors. Since genetic polymorphisms and epigenetic dysregulation of 5-HTT are involved in the pathogenesis of mental diseases, we analyzed DNA methylation of 5-HTT promoter in post-mortem brains and saliva samples of patients with schizophrenia (SCZ) and bipolar disorder (BD) to evaluate its potential application as a diagnostic and/or therapeutic biomarker in SCZ and BD. METHODS: Whole genome DNA methylation profiling was performed for a total of 24 samples (including two saliva samples) using the Illumina 27K (for 12 samples) and 450K DNA methylation array platform (for another 12 samples), followed by bisulfite sequencing to identify candidate CpGs for further analysis. Quantitative methylation specific PCR (qMSP) was used to assess the degree of CpG methylation of 5-HTT promoter in 105 post-mortem brains (35 controls, 35 SCZ and 35 BD) and 100 saliva samples (30 controls, 30 SCZ, 20 BD and 20 first degree relatives of SCZ or BD). The U133 2.0 Plus Human Transcriptome array for a total of 30 post-mortem brain samples (each group 10) followed by quantitative real-time PCR was used to study 5-HTT expression in 105 post-mortem brain samples. RESULTS: The qMSP analysis for 5-HTT promoter region showed DNA hypermethylation in post-mortem brain samples of SCZ patients (~30%), particularly in drug free patients (~60%, p=0.04). Similarly, there was a trend for DNA hypermethylation in antipsychotic free BD patients (~50%, p=0.066). qMSP analysis of DNA extracted from the saliva samples also exhibited hypermethylation of 5-HTT promoter in patients with SCZ (~30%, p=0.039), which was more significant in drug naïve SCZ patients (>50%, p=0.0025). However, the difference was not significant between the controls and unaffected first degree relatives of patients with SCZ (p=0.37) and versus patients using antipsychotic drugs (p=0.2). The whole genome transcriptome analysis of post-mortem brain samples showed reduced expression of 5-HTT in SCZ compared to the control subjects (~50%, p=0.008), confirmed by quantitative real-time PCR analysis (~40%, p=0.035) which was more significant in drug free SCZ patients (~70%, p=0.022). CONCLUSION: A correlation between reduction in 5-HTT expression and DNA hypermethylation of the 5-HTT promoter in drug naïve SCZ patients suggests that an epigenetically defined hypo-activity of 5-HTT may be linked to SCZ pathogenesis. Furthermore, this epigenetic mark in DNA extracted from saliva can be considered as one of the key determinants in a panel of diagnostic and/or therapeutic biomarkers for SCZ.

Quality of life in patients with bipolar I disorder: is it related to disorder outcome?

Bipolar I disorder (BID) and its treatments have shown to be associated with deep impacts on patients' subjective feelings and quality of life (QOL). There are also some comments about impact of these feelings on course and outcome of patients with BID. This study was aimed to evaluate quality of life in patients with BID and to assess its relationship with course of disorder. Fifty patients with BID were recruited based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) from May 2008 and followed for 12 months. Quality of life and mood disorder recurrence were assessed through World Health Organization Quality of Life and SCID-I tools respectively at baseline and after 6 and 12 months. Repeated measures analysis and logistic regression were used to analyze the independent effect of QOL and demographic factors on BID recurrence. Fifty patients (66% male; 48% never married; 48% in primary school level) with mean ± SE age and age of BID onset 33.8±1.5 and 26.6±1.1 years were studied. They had 3.4±0.6 episodes already. Twenty eight percent suffered from recurrences during the follow-up. The QOL scores at baseline, after 6 and 12 months were 70±1.8, 69.6±1.1 and 73±1.3 respectively. There were no significant change in QOL and its sub-domains during the follow-up (P=0.37). QOL showed no independent relationship with BID recurrences (P>0.1). No change in the QOL during the follow-up could denote lack of effectiveness of routine interventions on this factor. Also, short-term follow-up might be concerned as the possible reason. Of prime importance is to consider quality of life independently in treating patients with bipolar disorder.

Suicide Risk Factors in Iranian Patients With Bipolar Disorder: A 21- Month Follow-Up From BDPF Study.

OBJECTIVE: Bipolar disorder is strongly associated with suicidal ideations, attempts and commissions. Although several studies have been conducted on suicide risk factors in patients with bipolar disorder worldwide, a comprehensive study has not been reported from Iran. METHODS: Patients with bipolar disorder type I, hospitalized in Iran Hospital of Psychiatry since May 2008 to August 2011 were sequentially enrolled. Patients were evaluated using Demographic and Clinical Variables Questionnaire, the Structured Clinical Interview for DSM-IV axis I disorders (SCID-I), Young-Mania Rating Scale (Y-MRS), and Hamilton Depressive Rating Scale-7 (HDRS-7). One hundred patients were followed for 2 to 42 months (mean: 20.6 ± 12.5 months). RESULTS: Only one patient attempted suicide during the follow-up period. 33% of the patients had history of previous suicide attempts. Female gender, divorce, and early age at onset of the disease were independently correlated with suicide attempt. CONCLUSION: Suicide attempts rarely occur during systematic follow-up of patients with bipolar disorder type I. Larger samples and longer follow-ups are needed to confirm this finding. DECLARATION OF INTEREST: None.

Shared psychotic manic syndrome in monozygotic twins: a case report.

OBJECTIVE: A rare phenomenon of Shared Psychosis Disorder occurring in the context of Bipolar I Disorder, in identical twins is reported. CASE PRESENTATION: Two identical twins with shared Psychotic Manic Syndrome were admitted and received antipsychotic and lithium as their treatment. Psychotic symptoms of primary case did not improve and her diagnosis changed into Schizophrenia. They had hypothyroidism at the same time. CONCLUSION: Completely shared manic syndrome along with the psychotic features shows a need for the criteria of shared syndromes to develop, including both psychotic and mood symptoms.

DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder.

The failure in the discovery of etiology of psychiatric diseases, despite extensive genetic studies, has directed the attention of neuroscientists to the contribution of epigenetic modulations, which play important roles in fine-tuning of gene expression in response to environmental factors. Previously, we analyzed 115 human post-mortem brain samples from the frontal lobe and reported DNA hypo methylation of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene promoter, associated with an increased gene expression, as a risk factor for schizophrenia (SCZ) and bipolar disorder (BD). Since most epigenetic modifications are tissue specific and the availability of brain tissue to identify epigenetic aberrations in living subjects is limited, detection of epigenetic abnormalities in other tissues that represent the brain epigenetic marks is one of the critical steps to develop diagnostic and therapeutic biomarkers for mental diseases. Here, hypothesizing that; those factors that lead to the brain MB-COMT promoter DNA hypo-methylation may also cause concurrent epigenetic aberrations in peripheral tissues, we analyzed MB-COMT promoter methylation in DNA derived from the saliva in SCZ, BD and their first-degree relatives (20 cases each) as well as 25 control subjects. Using bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP), we found that similar to the brain, MB-COMT promoter was hypo-methylated (∼50%) in DNA derived from the saliva in SCZ and BD compared to the control subjects (p = 0.02 and 0.037, respectively). These studies suggest that DNA methylation analysis of MB-COMT promoter in saliva can potentially be used as an available epigenetic biomarker for disease state in SCZ and BD.

Hypomethylation of the serotonin receptor type-2A Gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder.

Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were ∼70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypo-methylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications.

Bipolar Disorder Patients Follow-up (BDPF): methods and materials.

BACKGROUND: The Bipolar Disorder Patients Follow-up (BDPF) project is a longitudinal, prospective and naturalistic study. The purpose of the present report is to introduce the project, elaborate its methods, and present the reliability data of the utilized symptoms rating scales. METHODS: The sampling started in May 2008 and is still in progress. The probands are assessed at the beginning of the sampling and then 2 and 6 months later and then every 6 months using several instruments to identify psychiatric comorbidities, symptoms severity, quality of life, attempted suicide rate, treatment compliance, and some other factors. RESULTS: The results could lead to increase the clinicians' awareness about the clinical picture of this disorder in Iranian patients. CONCLUSIONS: The present project could decrease to some extent the current shortcomings in Iran's psychiatric data at least about one of the major psychiatric disorders known as the eighth result which cause medical disability over the world.