Chronic Psychiatric Disorders Research Articles

Gender specificity of frontal activity based on fNIRS in distinguishing bipolar depression population from health control.

Bipolar depression (BD) is a chronic psychiatric disorder characterized by recurring bouts of bipolar mania or hypomania followed by depression. In this essay, we used the functional near-infrared spectroscopy to investigate the frontal function of BD in males and females, which included a total of 43 BD patients and 28 healthy subjects. The hemodynamic response associated with the task was estimated using the generalized linear model (GLM) approach. Wavelet transforms coherence and Granger causality (GC) methods were employed to calculate brain connectivity. GLM and GC results revealed that female patients were more distinguishable from healthy controls than males. Additionally, the correlation between BD scores and GLM results showed that the brain activation of male subjects was affected by their anxiety levels. This study suggests that traditional diagnostic methods for BD may not be as sensitive in men as in women.

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

ABSTRACT 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.

Dopamine in the Regulation of Glucose Homeostasis, Pathogenesis of Type 2 Diabetes, and Chronic Conditions of Impaired Dopamine Activity/Metabolism: Implication for Pathophysiological and Therapeutic Purposes.

Dopamine regulates several functions, such as voluntary movements, spatial memory, motivation, sleep, arousal, feeding, immune function, maternal behaviors, and lactation. Less clear is the role of dopamine in the pathophysiology of type 2 diabetes mellitus (T2D) and chronic complications and conditions frequently associated with it. This review summarizes recent evidence on the role of dopamine in regulating insular metabolism and activity, the pathophysiology of traditional chronic complications associated with T2D, the pathophysiological interconnection between T2D and chronic neurological and psychiatric disorders characterized by impaired dopamine activity/metabolism, and therapeutic implications. Reinforcing dopamine signaling is therapeutic in T2D, especially in patients with dopamine-related disorders, such as Parkinson's and Huntington's diseases, addictions, and attention-deficit/hyperactivity disorder. On the other hand, although specific trials are probably needed, certain medications approved for T2D (e.g., metformin, pioglitazone, incretin-based therapy, and gliflozins) may have a therapeutic role in such dopamine-related disorders due to anti-inflammatory and anti-oxidative effects, improvement in insulin signaling, neuroinflammation, mitochondrial dysfunction, autophagy, and apoptosis, restoration of striatal dopamine synthesis, and modulation of dopamine signaling associated with reward and hedonic eating. Last, targeting dopamine metabolism could have the potential for diagnostic and therapeutic purposes in chronic diabetes-related complications, such as diabetic retinopathy.

Sulfur-containing amino acids and risk of schizophrenia

BackgroundSchizophrenia is a chronic and complex severe psychiatric disorder. Male and female are different in their risks for schizophrenia for the biologic and sociocultural reasons. Homocysteine (Hcy), Cysteine (Cys), and methionine (Met) play important roles in metabolism, and the three amino acids may also be involved in pathogenesis of schizophrenia. ObjectiveThis study aimed to test the associations between sulfur-containing amino acid blood levels and risk of schizophrenia, evaluating the different risk in male and female. MethodsWe organized a case-control study on 876 individuals with schizophrenia and 913 age- and sex-matched healthy subjects as control group. The concentrations of Hcy, Cys and Met were measured by liquid chromatography-tandem mass spectrometry technology. Subsequently, restricted cubic spline was applied to explore full-range associations of these amino acids with schizophrenia. Interactions between levels of the three amino acids and sex on additive scale were also tested. ResultsHcy levels at ≤29 μmol/L were associated with sharply increased risk of schizophrenia, inversely, Met was associated with sharply decreased risk of schizophrenia at levels ≤22 μmol/L. Increased Cys levels were associated with decreased risk of schizophrenia. Almost inverse associations were observed between Cys/Hcy and Met/Hcy ratios and schizophrenia. Significant synergistic interactions between levels of all the three amino acids and sex were discovered on an additive scale. ConclusionsOur study suggests a close association between sulfur-containing amino acids and schizophrenia with different risk in male and female. Future studies are demanded to clarify the pathogenic role of Hcy, Cys and Met in schizophrenia.

57 Olfaction in Veterans with a History of Deployment-Related Mild Traumatic Brain Injury

Objective:Olfaction is a critical sensory function and changes in the ability to detect smells could affect quality of life by diminishing appreciation of food, drink, and other aroma-based experiences, increase danger of hazardous exposures, and cause a loss of employment. Additionally, decrements in olfaction have been related to onset of some neurodegenerative conditions. Olfactory impairments in military populations are highly prevalent and often attributed to the long-term effects of mild traumatic brain injury (mTBI) and chronic psychiatric disorders. The main goal of this investigation was to examine olfactory function in a cohort of combat veterans using a quantitative smell test.Participants and Methods:Participants underwent a neurological examination using a revised version of the Neurological Outcome Scale for Traumatic Brain Injury. Olfactory function was examined using a set of essential oil vials with common odors. Based on the number of correctly identified odors, the following grading system was employed: no deficit; mild; moderate; severe deficit; and absence of smell detection. All study assessments were performed prior to March of 2020 (onset of COVID-19 pandemic). In addition, participants completed performance validity testing (PVT) and screening for ongoing substance misuse using the Alcohol Use Disorders Identification Test and Drug Abuse Screening Test-10. Lifetime history of brain injury, combat-related extracranial injuries, and deployment characteristics were assessed using structured interview. All available medical records were reviewed.Results:Participants were 38 veterans with a deployment-related mTBI who passed the PVT and did not have ongoing substance misuse issues. Olfactory examination revealed normosmia in 20 participants and various degrees of deficit in 18 (11= mild; 4=moderate; and 3=severe). The groups did not differ in demographics, post-injury interval, or current clinical (non-psychiatric) conditions. Participants with hyposmia frequently reported being exposed to a higher number of blasts and being positioned closer to the nearest primary blast, and more often endorsed a period of loss of consciousness after the most serious mTBI. In addition, they more often reported tympanic membrane perforation, extracranial injuries, and histories of both blast and blunt force mTBI. Comorbid diagnoses of posttraumatic stress disorder (PTSD), depression, chronic headaches, and pain were more common among these participants as well.Conclusions:Several blast exposure and specific injury-related characteristics increase the likelihood of long-term olfactory impairments, comorbid psychiatric conditions, and chronic pain among veterans with a history of deployment-related mTBI. Notably, none of the participants with hyposmia had a clinical diagnosis of olfactory dysfunction or were receiving service-connected disability for a loss of sense of smell at the time of their assessment. Multidisciplinary rehabilitation care provided to combat veterans with history of mTBI and/or PTSD should include olfactory examination using both quantitative and qualitative smell tests, education regarding the adversities related to loss of smell, management of current psychiatric symptoms, and follow-up assessments. The lack of a comparison group without a history of mTBI and the small sample size were the main limitations of this investigation.

Detection of auditory hallucinations from electroencephalographic brain–computer interface signals

Schizophrenia is a chronic psychiatric disorder that is highly debilitating. One of the most frequent symptoms is the presence of auditory hallucinations (AH), which could be related to alterations in brain electrical activity measurable with electroencephalography (EEG). Although many previous works have recorded EEG signals of schizophrenia patients with medical EEG devices, the study of AH has never been developed by means of portable EEG measuring instruments. Therefore, the aim of this study is to detect AH in schizophrenia patients with a wireless EEG device. For that purpose, the spectral power from EEG recordings of periods with and without AH has been evaluated in a group of nine schizophrenia patients. Results reported that the main activation during hallucinations was found in right frontal locations, whereas the left hemisphere presented a stronger activation in hallucination-free periods. Furthermore, a generalized decrease of spectral power in hallucination with respect to hallucination-free episodes has been observed. Hence, this work demonstrates the possibility of detecting AH episodes with a wearable EEG device. In addition, the results obtained were compatible with the default model network, reporting a greater activation during no hallucination periods compared to hallucination moments.

Mind–body and art therapies impact on emotional regulation in patients with chronic diseases: a pragmatic mixed-methods randomized controlled trial

BackgroundEffective emotional regulation is recognized as essential to a good mental health of people with chronic diseases, and Mind–body and Art Therapies (MBATs) could have a positive effect on emotional regulation skills in this population. Thus, we aimed to evaluate the effect of MBATs on emotional regulation as measured by the Difficulties in Emotion Regulation Scale (DERS) questionnaire.MethodsA convergent mixed approach nested in a pragmatic superiority two arms parallel randomized controlled trial was conducted. French speaking adults with one or more chronic somatic illnesses and not suffering from a chronic psychiatric disorder unrelated to one of their chronic somatic illness were included. At inclusion, non-directive interviews were conducted, followed by an initial DERS assessment. The same combination of evaluation was implemented after 6 months of activity (T1). After inclusion, each participant was randomized within either the intervention group (G1) or the control group (G2) following a controlled wait-list design by use of a pregenerated randomization list. Staff and patient were blinded to this list until the initial evaluation was completed, after which the trial was conducted in an open-label fashion. Participants chose 2 mediations: one creativity-focused (art-therapy, writing workshop, theatre of life, vocal workshop) and one mind–body-focused (mindfulness meditation, Pilates, shiatsu, ayurvedic massages). G1 started their mediations immediately after inclusion, while G2 started 6 months later. Primary outcome was the change in means at 6 months in the overall DERS score compared between each group. Non-directive interviews were carried out at the inclusion and after 6 months of MBATs. A continuous inductive analysis was carried out on gathered material in G1 to explore the participants' experiences regarding their disease and their perceived changes associated to the intervention.ResultsA total of 150 patients was randomized (75 per groups) at the end of the study. At T1, 133 patients filled out the final questionnaire (67 in G1 vs 66 in G2) and 112 interviews were analysed (54 in G1 vs 58 in G2). All 150 patients were analysed (intention to treat) using a multiple imputation approach. The mean DERS score at T0 was equal to 82.8 ± 21.1 and 85.0 ± 20.2 in G1 and G2 respectively. On average, at T1, the score decreased in the G1 (Δ = -4.8, SD = 21.3) and in G2 (Δ = -0.11, SD = 17.8). The difference in decrease, however, was not statistically significant (p = 0.13). Qualitative analysis underlined some MBATs benefits on emotional regulation, especially on regulation strategies. No harms related to the intervention has been observed.ConclusionsThis study only partially supports benefits on MBAT on emotional regulation skills enhancement in patients with chronic disease receiving MBATs, as measured by the DERS scale.Trial registrationThe protocol was registered on Clinical Trials (NCT02911207).

Does Decreased Vitamin D Level Trigger Bipolar Manic Attacks?

Bipolar disorder is a chronic psychiatric disorder with depression and manic episodes. It is one of the leading causes of disease-related disability worldwide. Despite the presence of various alternative drug options for bipolar disorder, some patients do not adequately benefit from the treatment. Therefore, possible underlying mechanisms need to be clarified. Recently, studies on the relationship between bipolar disorder and vitamin D (Vit D) have attracted attention. Although many studies have found an association between depression and Vit D deficiency, little is known about the relationship between manic episodes and Vit D. The aim of this study was to compare Vit D and related metabolites of bipolar manic episodes prior to treatment, bipolar remission after treatment, and healthy control groups. This case-control study consisted of 34 bipolar manic episode patients and 34 healthy controls. Disease activity was evaluated with the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Firstly, serum 25-hydroxy vitamin D (25-OHD), calcium (Ca) and phosphorus (P) levels of patients in the bipolar manic episode were measured and compared with healthy control. Secondly, serum 25-OHD, Ca and P levels in the euthymic periods of the same patients were measured and compared with healthy control. Bipolar manic episode Vit D levels were lower when compared to healthy controls; while there was no difference in terms of Ca and P levels. There was no significant difference between the bipolar euthymic period patients and the healthy control group in terms of 25-OHD, Ca and P levels. Our results demonstrated low serum Vit D concentrations in the acute manic episode of bipolar disorder. Decreased Vit D level may play a role in the onset of the manic episode, or malnutrition and insufficient sunlight during the manic episode may have caused Vit D deficiency. Future studies are needed to exclude potential confounding factors and to compare all mood episodes.

Is There a Link Between Sleep Quality and a Tendency for Eating Disorders?

Aim: Poor sleep quality has been associated with an increased risk of developing eating disorders, and unhealthy eating behaviours. The aim of the study was to explore the potential link between sleep quality and eating disorders. Subjects and Method: This descriptive, observational, and cross-sectional study was conducted with 357 (84 male; 273 female) university students between the ages of 18-25 years. Exclusion criteria included being diagnosed with chronic disease and psychiatric disorders, being pregnant and lactating, using drugs that affect sleep patterns, being shift workers, and participants who did not complete the questionnaire. The questionnaire consisted of six parts including Pittsburgh Sleep Quality Index (PSQI), Three-Factor Eating Questionnaire (TFEQ-21), SCOFF (REZZY) Eating Disorders Scale, anthropometric measurements, demographic properties, and nutritional habits. Results: The prevalence of poor sleep quality was found to be 63% and there was no significant difference between gender in terms of sleep quality (p=0.769). There was significant relationship between total TFEQ 21 (p=0.02), SCORF (REZZY) (p&lt;0.001) scores and sleep quality. Uncontrolled eating behaviours was found higher in students with poor sleep quality (p&lt;0.05). Age, body mass index (kg/m2), and smoking were not significant predictors of sleep quality. However, participants with a tendency towards eating disorders behaviour were found to have a significantly higher risk of poor sleep quality (odds ratio [OR]: 2.338, 95% confidence interval [CI]: 1.444-3.785, p=0.001), as were those with a tendency towards emotional eating behaviour (OR: 1.575, 95% CI: 1.022-2.427, p=0.040). Conclusion: Students with poor sleep quality had higher levels of uncontrolled eating behaviour and a tendency towards unhealthy eating attitudes than those with good sleep quality.

Satisfaction of Patients and Their Relatives Who Are Reminded of Their Appointments and Treatments with "Treatment Collaboration Portal".

Community Mental Health Centers have been established in Turkey for patients with chronic psychiatric disorders actively engaged in treatment. The Treatment Collaboration Portal is a web-based voice response platform offered to Community Mental Health Centres to support the treatment compliance processes of patients. The Treatment Collaboration Portal automatically reminds patients or their families of injection treatments and psychiatry appointments at regular intervals. The purpose of this study is to determine the satisfaction of patients or their relatives enrolled in the Treatment Collaboration Portal and the reasons why. A semi-structured 1-item 6-point satisfaction questionnaire, which we prepared for the Treatment Collaboration Portal reminder calls, was administered to the volunteer participants who registered to the Treatment Collaboration Portal and Community Mental Health Centre. Satisfaction levels were determined first with the questionnaire, and then the reasons for satisfaction were investigated for each patient and their relatives. The questionnaire was given to 132 participants. About 121 participants were satisfied and 11 of them were dissatisfied. When the reasons for those who were satisfied with the application reminders were examined, it was seen that the most frequent one was "prevention of forgetfulness" (53.7%). A significant difference was found between the Treatment Collaboration Portal registration reasons and satisfaction status. Also, there was a difference between the people who patients live with and the "satisfied" and "unsatisfied" groups (P = .023). All the reasons given by the group satisfied with Treatment Collaboration Portal use contribute to patients remaining in remission. Therefore, in clinical practice, it is very important to recognize these reasons.

Causal link between thyroid function and schizophrenia: a two-sample Mendelian randomization study

Schizophrenia is a chronic psychiatric disorder with inconsistent behavioral and cognitive abnormalities with profound effects on the individual and the society. Individuals with schizophrenia have altered thyroid function, but results from observational studies are conflicting. To date, it remains unclear whether and in which direction there is a causal relationship between thyroid function and schizophrenia. To investigate causal paths, a bidirectional two-sample Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies including up to 330,132 Europeans. Thyroid function was described by the normal-range thyroid-stimulating hormone (TSH) and free thyroxine levels as well as an increased and decreased TSH status. The iterative radial inverse-variance weighted approach with modified second order weights was used as the main method. Based on a discovery and replication sample for schizophrenia, pooled effect estimates were derived using a fixed-effect meta-analysis. Robustness of results was assessed using both a range of pleiotropy robust methods and a network analysis that clustered genetic instruments potentially responsible for horizontal pleiotropy. Genetic liability for hypothyroidism was inversely associated with schizophrenia (beta =-0.06; 95% CI: (-0.10; -0.02); P=0.004). No notable associations were observed between other thyroid parameters and schizophrenia. Furthermore, no associations could be detected in the reverse direction. Our results suggest that an elevated level of TSH reduce the risk for schizophrenia. The role of thyroid function and the hypothalamic-pituitary-thyroid axis in the development of schizophrenia should be subject of further research.

Biological rhythms are correlated with Na+, K+-ATPase and oxidative stress biomarkers: A translational study on bipolar disorder

BackgroundBipolar disorder (BD) is a chronic, severe, and multifactorial psychiatric disorder. Although biological rhythms alterations, sodium potassium pump (Na+, K+-ATPase) changes, and oxidative stress appear to play a critical role in the etiology and pathophysiology of BD, the inter-connection between them has not been described. Therefore this study evaluated the association between biological rhythms, Na+, K+-ATPase, and oxidative stress parameters in BD patients and the preclinical paradoxical sleep deprivation model (PSD). MethodsA translational study was conducted, including a case-control protocol with 36 BD and 46 healthy controls (HC). Subjects completed the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). In addition, Erythrocyte Na+, K+-ATPase activity, and oxidative and nitrosative stress markers were assessed (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], thiobarbituric acid reactive substances [TBARS], carbonyl, 3-nitrotyrosine [3-nitro]). In the preclinical protocol, the same biomarkers were evaluated in the frontal cortex, hippocampus, and striatum from mice submitted to the PSD. ResultsBD patients had a significantly higher total score of BRIAN versus HCs. Additionally, individuals with BD showed decreased Na+, K+-ATPase activity and increased oxidative stress parameters compared to HC without psychiatric disorders. This difference was driven by actively depressed BD subjects. The mice submitted to the PSD also demonstrated decreased Na+, K+-ATPase activity and increased oxidative stress parameters. LimitationsBRIAN biological underpinning is less well characterized; We did not control for medication status; Sample size is limited; PSD it is not a true model of BD. ConclusionsThe present study found a significant correlation between Na+, K+-ATPase and oxidative stress with changes in biological rhythms, reinforcing the importance of these parameters to BD.

Psychological distress in healthcare workers during COVID-19 pandemic: A systematic review

Objectives: Healthcare workers serving during the COVID-19 pandemic may have been exposed to high work overload, which may have had an impact on their physical, mental, and social health. The aim of this study was to assess the risk factors associated with psychological distress among healthcare workers serving during the COVID-19 pandemic from January 2020 to December 2022. Methods: A systematic review was conducted based on the 2020 PRISMA statement. Articles were searched in the Pubmed, Scopus, Web of Science, CINAHL, and PsycINFO databases. Results: A total of 59 articles were included in this systematic review. It was observed that the prevalence of psychological distress during the COVID-19 pandemic was high. Female sex, being a nurse, being young, living alone/being single, and having a chronic disease or psychiatric disorder history are the main risk factors at the personal level. Other occupational and pandemic-related factors such as having many years of work experience, the presence of COVID-19 symptoms and contact history, not enough sleep, having lower family support and limited social relationships, fear of infecting friends and family, having a reduced perception of protection by personal protective equipment, working on the frontline, and having longer service duration were found to be factors influencing the development of psychological distress during the COVID-19 pandemic. Conclusions: There are personal, interpersonal, and organizational risk factors that can lead to the occurrence of psychological distress among healthcare staff working during the COVID-19 pandemic.

The effect of scapular stabilisation exercises on posture and pain in patients with fibromyalgia: a randomised controlled trial

Background/Aims Fibromyalgia is a complex syndrome characterised by chronic widespread pain, postural problems, sleep disorders, fatigue and psychiatric disorders. This study investigated the effect of scapular stabilisation exercises on cervical posture and pain in patients with fibromyalgia. Methods The study included 59 patients between the ages of 18–60 years. Individuals were divided into two groups: the study group (n=29) and control group (n=30). Both groups underwent hot pack application, transcutaneous electrical nerve stimulation and ultrasonography before the exercises. This application continued for a total of 6 weeks in both groups, 5 days a week. After this treatment, the control group was asked to perform conventional shoulder exercises and the scapular stabilisation group was asked to perform scapular stabilisation exercises. The patients were evaluated in terms of pain and cervical posture. Results Pain levels significantly decreased in both groups after the treatment (P=0.019). A decrease in tragus-to-wall distance occurred in the conventional exercise group (P=0.005). Scapular stabilisation exercises were found to be more effective than conventional exercises In terms of pain (P&lt;0.001) and cervical posture, (P=0.024). Conclusions Both exercise programmes reduced pain levels in patients with fibromyalgia. However, scapular stabilisation exercises were more effective at both reducing pain and improving posture. Physiotherapists can use scapular stabilisation exercises to patients with fibromyalgia to reduce pain, improve posture and reduce the load on the joints.

Global environmental risk factors of schizophrenia: a study protocol for systematic review and meta-analysis of cohort studies

IntroductionSchizophrenia is a chronic, complex and severe psychiatric disorder affecting millions of people every year and inflicting different costs to the individual, family and community. A growing body of evidence...

Update on Oxytocin, Phosphodiesterase, Neurokinin, Glycine as a Therapeutic Approach in the Treatment of Schizophrenia.

Schizophrenia is a chronic psychiatric disorder characterized by disrupted thoughts, perception, mood, and behavior. It has a heterogeneous genetic and neurobiological background and affects about 0.5-1% of the adult population worldwide. Herein, we review the current approaches and advances in schizophrenia. The potential therapeutic compounds for the treatment of schizophrenia act on the oxytocin receptor, phosphodiesterase system, neurokinin receptor, and glycine transport 1 receptor. Therefore, this article provides an update on the pharmacology of different receptors in addition to the dopaminergic system. These findings would guide the readers on novel targets for schizophrenia with the potential to be therapeutic agents in the future. To provide the researchers an update on the emerging role of oxytocin, phosphodiesterase, neurokinin, and glycine which can be explored as potential pharmacotherapeutic targets in the treatment of schizophrenia. An extensive literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: schizophrenia, novel receptors, oxytocin, phosphodiesterase, neurokinin, and glycine. Furthermore, to provide insights into newer drug treatments for Schizophrenia, Furthermore, Clinicaltrials.gov website was searched for newer receptor-based drugs. Current literature supported by preclinical and clinical provides substantial evidence that oxytocin, phosphodiesterase, neurokinin, and glycine play a crucial role in Schizophrenia. Our findings indicate that though multiple antipsychotic drugs are prescribed to treat schizophrenia, novel approaches and/or mechanisms are plausible. Moreover, sensitive and specific diagnostic tools and safe and effective interventions, including novel therapeutic agents, are required to yield substantially improved future outcomes.

Lipid-correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia.

Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA-seq data and a correlation analysis between levels of gene expression and lipids. RNA-Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3-kinase (PI3K)-Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. This study provided results of the integrated analysis of the schizophrenia-associated transcriptome and lipidome within the PFC and revealed that lipid-correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.

Accelerated aging in bipolar disorders: An exploratory study of six epigenetic clocks

Bipolar disorder (BD) is a chronic and severe psychiatric disorder associated with significant medical morbidity and reduced life expectancy. In this study, we assessed accelerated epigenetic aging in individuals with BD using various DNA methylation (DNAm)-based markers. For this purpose, we used five epigenetic clocks (Horvath, Hannum, EN, PhenoAge, and GrimAge) and a DNAm-based telomere length clock (DNAmTL). DNAm profiles were obtained using Infinium MethylationEPIC Arrays from whole-blood samples of 184 individuals with BD. We also estimated blood cell counts based on DNAm levels for adjustment. Significant correlations between chronological age and each epigenetic age estimated using the six different clocks were observed. Following adjustment for blood cell counts, we found that the six epigenetic AgeAccels (age accelerations) were significantly associated with the body mass index. GrimAge AgeAccel was significantly associated with male sex, smoking status and childhood maltreatment. DNAmTL AgeAccel was significantly associated with smoking status. Overall, this study showed that distinct epigenetic clocks are sensitive to different aspects of aging process in BD. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings of potential determinants of an accelerated epigenetic aging in BD.

Utilization of Antiseizure Medications in Women of Childbearing Age With Epilepsy and Nonepilepsy Indications: A Retrospective Cohort Study.

Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across different indications for therapy and for the newer-generation ASMs in this population. Thus, we assessed the pattern of ASM use in women of childbearing age with epilepsy and nonepilepsy indications (pain and psychiatric disorders). We conducted a retrospective analysis of deidentified administrative data submitted to the Optum Clinformatics database. Eligible participants included women aged 12-50 years who filled ASMs between year 2011 and 2017. Participants were followed from date of index prescription filled to study end or insurance disenrollment, whichever came first. For the overall cohort and potential therapy indications, we assessed the type and frequency of ASMs filled; proportion of participants on monotherapy, polytherapy, or treatment switching; and duration of continuous use. Trends were characterized using annual percent change from study start to study end. Our analysis included 465,131 participants who filled 603,916 distinct ASM prescriptions. At baseline, most of the participants had chronic pain (51.0%) and psychiatric disorders (32.7%), with epilepsy the least common (0.9%). The most frequently dispensed were diazepam (24.3%), lorazepam (20.1%), gabapentin (17.4%), clonazepam (12.7%), topiramate (11.3%), and lamotrigine (4.6%). Significant linear increase in trends were observed with gabapentin (annual percent change [95% CI]: 8.4 [7.3-9.4]; p < 0.001) and levetiracetam (3.4 [0.7-6.2]; p = 0.022) and decreasing trends for diazepam (-3.5 [-2.4 to 4.5]; p < 0.001) and clonazepam (-3.4 [-2.3 to 4.5]; p = 0.001). No significant change in trend was observed with valproate (-0.4 [-2.7 to 1.9]; p = 0.651), while nonlinear changes in trends were observed with lorazepam, topiramate, lamotrigine, and pregabalin. Decreasing trends were observed with older ASMs in the overall cohort and across the potential indications for therapy. Conversely, increasing trends were seen with the newer ASMs. Considering the risk of teratogenicity associated with the newer medications largely unknown, counseling and education in addition to a careful consideration of the benefits vs potential risks should remain pivotal when prescribing ASMs for women of childbearing age.

Life events in obsessive-compulsive disorder: A cross-sectional study

Background: Obsessive compulsive disorder (OCD) is a chronic psychiatric disorder having significant deterioration in patients’ socio-occupational functioning. Stressful life events (SLE) were noted before onset of this disorder. The previous study with Indian population found positive correlation between stressful and traumatic life events and OCD, but was with small sample size and thus result couldn’t be generalized. Aims and Objectives: The aim of the study was to examine the role of life events in patients with OCD and to find out correlation between them, if any. Materials and Methods: Consecutive 30 OPD patients fulfilling ICD-10 DCR criteria for OCD were rated with Yale Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Presumptive Stressful Life Events Scale (PSLES). A group of 30 healthy controls from unrelated patient party were also rated on PSLES. Finally, both groups were statistically compared in terms of life events. Results: Two groups were identical in distribution of age and sex. The frequency of life events, 1-year (P=0.000) and lifetime (P=0.000), were significantly higher in OCD group in comparison to healthy controls. There was significant positive correlation between PSLES scores and YBOCS scores. Step-wise linear regression analysis found positively predictability of PSLES score to OCD severity. Conclusion: OCD patients have statistically significant SLE before the onset of their disorder and total number of life events has positive correlation with severity of OCD.