Bipolar Disorder Manic Episode Research Articles

Creatine Supplementation in Depression: A Review of Mechanisms, Efficacy, Clinical Outcomes, and Future Directions.

Depression, affecting millions of people worldwide, is a leading cause of disability globally. It affects not only daily functioning but also interpersonal relationships and overall health by increasing the risks of chronic physical and mental illnesses. Creatine, traditionally recognized for boosting physical performance through its role in producing adenosine triphosphate, has recently shown potential as an adjunctive therapy for treating depression. Creatine's ability to enhance brain energy metabolisms and provide neuroprotection suggests that it can alleviate mood disorders by improving mitochondrial function, increasing cellular resilience, and modulating neurotransmitter systems that regulate mood. This narrative review aims to critically evaluate the research on creatine supplementation for depression, focusing on its efficacy, mechanism of action, risks, and benefits as a treatment for mood disorders. It analyzes preclinical and clinical studies to understand creatine's potential as an adjunctive or alternative therapy for major depressive disorder and bipolar depression and underscores any gaps in current research. Both animal models and human trials indicate creatine's efficacy for the treatment of depression. Creatine supplementation reduces depressive symptoms, particularly when combined with selective serotonin reuptake inhibitors, and may improve brain energy metabolism and neuroplasticity. It is generally well tolerated, though caution is warranted due to potential side effects such as manic episodes in bipolar disorder and renal function impairment in patients with kidney dysfunction. Overall, creatine presents a promising addition to current depression treatments, though further research is needed to establish optimal dosing, long-term efficacy, and safety across diverse patient populations.

Recent Advances in representative small-molecule DRD2 inhibitors: Synthetic Routes and clinical applications

The dopamine D2 receptor (DRD2) represents a pivotal target for therapeutic intervention in the treatment of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and Parkinson's disease. The successful discovery of numerous effective DRD2 inhibitors has led to their clinical application and ongoing evaluation in various clinical trials. This review explores the synthetic approaches and clinical applications of prototypical small-molecule DRD2 inhibitors that have received approval or are currently undergoing clinical trials, highlighting their therapeutic potential and challenges. The synthesis of these inhibitors employs various chemical strategies, including modifications of phenothiazine and butyrophenone structures, which have yielded significant antipsychotic agents like chlorpromazine and haloperidol. Additionally, newer classes of inhibitors, such as aripiprazole, exhibit partial agonist activity at DRD2, offering a unique therapeutic profile. Clinically, DRD2 inhibitors demonstrate efficacy in managing positive symptoms of schizophrenia, manic episodes in bipolar disorder, and dopaminergic imbalance in Parkinson's disease. However, the emergence of adverse effects, including tardive dyskinesia, extrapyramidal symptoms and metabolic syndrome, presents substantial challenges. Advances in the development of second-generation antipsychotics aim to balance efficacy with a better side effect profile by targeting additional neurotransmitter receptors. This review aims to deliver an overview of the synthesis and clinical applications of representative small-molecule DRD2 inhibitors across various clinical phases, thereby offering strategic insights for the advancement of DRD2 inhibitor development.

A large-scale study on uric acid-related biomarkers in patients with bipolar disorder

Objective: Recent research has provided strong evidence supporting the use of uric acid-related ratios as potential biomarkers for disease diagnosis. Notable ratios among these include uric acid-to-albumin ratio (UAR), uric acid-to-creatinine ratio (UCR), uric acid-to-high-density lipoprotein ratio (UHR), and uric acid-to-lymphocyte ratio (ULR). The aim of the study is to analyze these biomarkers in bipolar disorder (BD) patients. Methods: 5465 BD patients were enrolled in this study and 6629 healthy subjects served as controls. We compared differences of the above ratio indicators among different BD diagnostic groups and analyzed factors leading to the onset of BD. Results: BD-M (manic episodes of BD) group had higher ULR, UHR, UCR, UAR than HC (Heathy Controls) and BD-D (depressive episodes of BD) groups, while BD-D group showed lower ULR and UCR than HC group. P-BD-M (BD-M with psychotic symptoms) group displayed higher ULR, UHR, UCR, UAR than HC group, while even higher ULR, UHR, UAR than NP-BD-M (BD-M without psychotic symptoms) group. High UAR was risk factor in BD-M. Conclusions: Our study suggests BD-M has more intense inflammatory response than BD-D. Furthermore, there is heterogeneity in the pathogenesis of psychotic symptoms between BD-M and BD-D. Additionally, High UAR was risk factor in BD-M.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Towards a natural treatment for mania: red onion husk extract modulates neuronal resilience, redox signalling, and glial activation

BackgroundRed onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the safety and therapeutic potential of red onion husk extract in managing manic-like symptoms and associated neurochemical dysfunctions.MethodsAcute and repeated oral dose studies were conducted in mice and rats to evaluate the safety profile of the extract. FT-IR analysis identified functional groups in the extract, while GC-MS analysis identified specific bioactive compounds in the flavonoid-rich fraction. A ketamine-induced manic behaviour model in Wistar rats was employed to assess the extract’s efficacy in attenuating manic-like symptoms. Behavioural and neurochemical analyses were performed to further investigate the extract’s effects.ResultsThe extract demonstrated a favourable safety profile in both acute and repeated dose studies. FT-IR analysis revealed a complex mixture of organic compounds, including hydroxyl groups, alkynes/nitriles, aromatic and non-aromatic C = C bonds, amines, and polysaccharides. GC-MS analysis identified 17 bioactive compounds, including five-methyl-2-phenylindolizine, methadone N-oxide, and 3-phenylthiane, S-oxide. Ketamine administration significantly increased oxidative stress markers, TBARS, and suppressed antioxidant enzyme activities (SOD, GPx, CAT) in both the cerebral cortex and hippocampus, alongside elevated acetylcholinesterase (AchE) activity, indicating enhanced neuronal excitability. Pre-treatment with FRF (25 mg/kg) effectively mitigated ketamine-induced oxidative stress, as evidenced by reduced TBARS levels and partially restored SOD and GPx activities. Interestingly, FRF significantly increased CAT activity (p < 0.001), potentially suggesting an additional compensatory mechanism. Notably, FRF pre-treatment also counteracted ketamine-upregulated AchE activity, offering neuroprotection against heightened neuronal excitability.ConclusionRed onion husk extract exhibits a favourable safety profile and exerts potent antioxidant and neuroprotective effects, possibly through modulating Nrf2 signalling pathways. Its ability to counteract ketamine-induced oxidative stress and neuronal hyperactivity highlights its potential as a complementary therapeutic strategy for managing manic episodes in bipolar disorder. Further research is warranted to elucidate the precise molecular mechanisms underlying FRF’s action and explore its clinical efficacy in human studies.

Metabolic Differentiation in Manic Episode of Bipolar Disorder Compared to Substance-Induced Psychosis and Substance Use Disorder Based on Serum Valproate Level

Aim: Valproic acid (VPA) is primarily used in the treatment of epilepsy but also has uses in the treatment of manic episodes in bipolar disorder and substance use disorders. Manic episodes and psychosis may also affect hepatic clearance and drug distribution volume. The aim of this study was to assess the effect of mania and psychosis compared to substance use on VPA pharmacokinetics, specifically changes in total and unbound clearance. Material and Methods: Fifty patients with a manic episode of bipolar disorder, and 51 patients with substance use disorder, 38 of whom were considered as substance-induced psychosis, were included in this retrospective study. All patients received a constant dose of 1000 mg VPA daily for at least five days, and serum VPA concentrations were measured. Results: The mean serum levels of VPA were 59.2±17.4 μg/ml in the substance use disorder group, 60.9±13.5 μg/ml in the substance-induced psychosis group, and 61.8±13.7 μg/ml in the manic episode of bipolar disorder group. No significant difference was found between the groups (p=0.840). When considering substance use disorder and substance-induced psychosis as one group, the mean VPA level of 60.5±14.4 μg/ml in this group showed no significant difference compared to 61.8±13.7 μg/ml in the manic episode of bipolar disorder (p=0.630). Conclusion: After reaching steady-state plasma levels, no significant difference in serum VPA levels was observed between the three groups. This suggests that manic episodes do not lead to a significant increase in VPA metabolism compared to substance use disorder or substance-induced psychosis.

Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII.

In this study, the relationship between treatment response, clinical features of episodes such as psychosis, suicidal behavior, and agitation, duration of hospitalization, and systemic inflammation markers Systemic Inflammatory Index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in bipolar affective disorder manic episode (BAD-M), bipolar affective disorder-depressive episode (BAD-D), and major depressive disorder (MDD) were investigated. TheNLR, MLR, PLR, and log SII were measured using parameters from a complete blood count. Admission and discharge Young Mania Rating Scale and Hamilton Depression Rating Scale scores were evaluated. This is a retrospective study conducted with a total of 451 inpatients, 122 (27.10%) of whom were diagnosed with BAD-M, 60 (13.20%) with BAD-D, and 269 (56.60%) with MDD. The patients with manic episodes have higher levels of NLR (P = .019), MLR (P = .002), and log SII (P = .007). In the bipolar depression and mania groups, the patients with and without treatment responses did not differ in terms of inflammation markers; the log PLR value was found to be higher in the unipolar depression group in the patients who did not reach remission (P = .048). This study reveals associations between inflammation markers and different types of mood episodes. Higher NLR, MLR, and log SII levels in bipolar mania and lower NLR levels in agitated unipolar depression provide clues about changes in inflammation across different episodes. Studies with larger samples are needed to evaluate the relationship between inflammatory markers, the severity of mania and depression, and the response to treatment.

Olink proteomics analysis uncovers inflammatory proteins in patients with different states of bipolar disorder

Study Design: A prospective study. BackgroundThis study aims to investigate the relationship between different states of bipolar disorder (BD) and plasma inflammatory proteins, which may be used as their biomarkers. Materials and methodsWe totally collected admission plasma from 16 healthy subjects and 32 BD patients, including 16 patients with BD manic episodes (BD-M) and 16 patients with BD depressive episodes (BD-D). Ten samples in each group were analyzed by proximity extension assays of 92 inflammation-related proteins, and all samples were verified by ELISA. Receiver-operating characteristic (ROC) curve analysis was performed to identify the diagnostic ability and cut-off values of potential biomarkers. ResultsOur findings showed that BD patients had significantly higher levels of IL6, MCP-1, TGF-α, IL8, and IL10-RB in comparison with healthy subjects, and their cut-off values were 0.531 pg/ml, 0.531 pg/ml, 0.469 pg/ml, 0.406 pg/ml, and 0.406 pg/ml, respectively. The levels of IL6, MCP-1, TGF-α, and IL8 in BD-M patients were significantly greater than in healthy individuals, and their cut-off values were 0.813 pg/ml, 0.688 pg/ml, 0.438 pg/ml, and 0.625 pg/ml, respectively. Moreover, we found cut-off values of 0.500 pg/mL and 0.688 ng/mL for TGF-α and β-NGF, respectively, even though the levels in the BD-D group were much higher than in the control group. Furthermore, BD-M patients had significantly higher levels of IL6, FGF-19, IFN-γ, and IL-17C in comparison with BD-D patients. Likewise, 0.687 pg/ml, 0.500 pg/ml, 0.438 pg/ml, and 0.375 pg/ml were their cut-off values, respectively. Our findings also showed that the combination of these proteins had the highest diagnostic accuracy. ConclusionsOur findings showed that plasma inflammatory proteins were related to BD and its subtypes, which may be utilized as potential biomarkers of different stages of BD. Furthermore, we also found their cut-off values and their combinations to have the highest diagnostic accuracy, providing clinicians with a new method to rapidly differentiate BD and its subtypes and manage early targeted interventions.

Co-occurrence of bipolar disorder and personality disorders in the United States: Prevalence, suicidality, and the impact of substance abuse

BackgroundThis study investigates prevalence rates of specific personality disorders (PDs) in individuals with bipolar disorder (BD) and their impact on substance abuse and suicidality, addressing existing gaps in the literature. MethodsUsing Nationwide Inpatient Sample data (2016–2020), adult hospitalizations for BD with coexisting PDs were analyzed. Study variables were defined using ICD-10-CM codes. Prevalence of PD were reported as cases per 100,000 BD admissions. Regression models assessed the association between substance abuse and suicidality. ResultsAbout 993,000 admissions for BD were analyzed. The cohort was predominantly Caucasian (70.5 %) with higher female representation (54.5 %). The mean age was 41 years. 89.4 % of individuals had a Charlson Comorbidity Index score ≤ 1. The most common diagnostic subtype was manic episode of BD with or without psychotic features (32.3 %). Coexisting PDs were observed in 12.2 % of the population, with borderline PD (8.2 %) and antisocial PD (2.6 %) being most prevalent. Substance abuse was common (44.8 %), with cannabis (23.8 %), alcohol (19.4 %), cocaine (10.5 %), and opioids (9.6 %) being most reported. Substance abuse was higher in individuals with BD and PD (50 %) compared to BD alone (44.1 %). 596 suicide attempts were recorded (60 per 100,000 BD admissions). Substance abuse and coexisting PD in bipolar individuals elevated the likelihood of attempts (P < 0.001). LimitationsUse of administrative data (retrospective, inpatient); treatment not studied. ConclusionThe study reveals a notable prevalence of PDs in individuals with BD, with increased likelihood of substance abuse and suicide attempts in those with coexisting BD and PD compared to BD alone.

Evaluating the association of vitamin D3, parathyroid hormone, and C-reactive protein serum levels in patients with an acute psychotic episode: a cross-sectional study in tertiary centre in Iran

BackgroundThe high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population.MethodsThis descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups.ResultsAmong our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients.ConclusionThis study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.

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.

Antidepressant-induced mania in panic disorder: a single-case study of clinical and functional connectivity characteristics.

Mental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20-40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited. In this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001. The patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = -6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = -7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = -5.02 and -5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group. Here, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue.

Neutrophil-Lymphocyte Ratio, Monocyte-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Manic Episode Patients with Bipolar Disorder

Objective: Inflammation is one of several etiopathological mechanisms contributing to bipolar disorder. Neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are relatively cheap hematological parameters recommended to measure the level of inflammation. In this study, the NLR, MLR, and PLR values of the same patients during manic and euthymic periods were compared to a healthy control group. Methods: This retrospective study was conducted on inpatients with bipolar disorder manic episodes at the University Faculty of Medicine psychiatry clinic. Ninety-nine patients with manic episodes of bipolar disorder and age and gender-matched 101 volunteers without prior psychiatric illness were included in the study. Neutrophil, lymphocyte, monocyte, and platelet counts during the disease period were recorded, and NLR, MLR, and PLR values were calculated from these values. Similar hematological parameters of the same patients in the euthymic period after discharge were compared. Results: Patients with manic episodes were shown to have significantly higher neutrophil, platelet, NLR, MLR, and PLR levels than the control group (p&lt;0.001). Monocyte count was significantly lower in manic episode patients compared to controls (p&lt;0.001). Neutrophil and monocyte counts were significantly lower during the euthymic period compared to the control group, while NLR, MLR, and PLR levels were higher (p&lt;0.001). Conclusions: The fact that NLR, MLR, and PLR are higher in BD patients compared to the healthy control group in both manic and euthymic periods indicates that they can be used as trait biomarkers.

Sociodemographic, psychiatric and criminal characteristics of elderly offenders under evaluation for criminal responsibility in Turkey

ObjectiveThe aim of this study was to examine a sample (n = 150) of elderly offenders to analyse the psychiatric, medical, demographic, criminal and if available neuropsychological test characteristics and criminal responsibility. MethodData were gathered through a retrospective chart review of applicants aged 65 and over who were referred for determination of criminal responsibility from 2014 to 2019 at the Observation Department of Council of Forensic Medicine (Adli Tip Kurumu Baskanligi, Gözlem İhtisas Dairesi) who were evaluated under inpatient status by law. ResultsThere were 150 forensic cases aged 65 and over. The majority of the crimes were homicide (25.3%), homicide attempt (10%), and sexual offence (26%). The majority of sexual offence victims were children (34 of 39 cases). The percentages of decisions on criminal liability were as follows: 76% (n = 114) had full criminal liability, 21.3% of them (n = 32) had no criminal liability, 2.7% of them (n = 4) had reduced criminal liability. For the reduced/no criminal liability group, diagnoses were as follows: 37.1% dementia syndromes, 31.4% schizophrenia, 11.5% delusional disorder and 2.8% bipolar disorder manic episode. ConclusionWhen the findings in our study and current literature data are examined, it is seen that certain crime groups such as murder and attempted murder, and sexual crimes against children are high in elderly forensic psychiatric evaluations.

A novel murine model of mania.

Neuropathological mechanisms of manic syndrome or manic episodes in bipolar disorder remain poorly characterised, as the research progress is severely limited by the paucity of appropriate animal models. Here we developed a novel mania mice model by combining a series of chronic unpredictable rhythm disturbances (CURD), which include disruption of circadian rhythm, sleep deprivation, exposure to cone light, with subsequent interference of followed spotlight, stroboscopic illumination, high-temperature stress, noise disturbance and foot shock. Multiple behavioural and cell biology tests comparing the CURD-model with healthy controls and depressed mice were deployed to validate the model. The manic mice were also tested for the pharmacological effects of various medicinal agents used for treating mania. Finally, we compared plasma indicators of the CURD-model mice and the patients with the manic syndrome. The CURD protocol produced a phenotype replicating manic syndrome. Mice exposed to CURD presented manic behaviours similar to that observed in the amphetamine manic model. These behaviours were distinct from depressive-like behaviours recorded in mice treated with a depression-inducing protocol of chronic unpredictable mild restraint (CUMR). Functional and molecular indicators in the CURD mania model showed multiple similarities with patients with manic syndrome. Treatment with LiCl and valproic acid resulted in behavioural improvements and recovery of molecular indicators. A novel manic mice model induced by environmental stressors and free from genetic or pharmacological interventions is a valuable tool for research into pathological mechanisms of mania.

Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration

AimNeurofilament light chain protein (NEFL), is defined as a structural protein which exists particularly in axones of neurons and is released to the cerum in consequence of neuroaxonal damage. The aim of this study is to investigate the peripheral cerumNEFLlevels of children and adolescents with early onset schizophrenia and bipolar disorder. MethodIn this study, we evaluated serum levels of NEFL in children and adolescents (13–17 years) with schizophrenia, bipolar disorder and healthy control group. The study is conducted with 35 schizophrenia, 38 bipolar disorder manic episode patients and 40 healthy controls. ResultsThe median age of the patient and control groups was 16 (IQR- Interquartile Range: 2). There was no statistical difference in median age (p = 0.52) and gender distribution(p = 0.53) between groups. NEFL levels of the patients with schizophrenia were significantly higher than the controls. NEFL levels of the patients with bipolar disorder were significantly higher than the controls. Serum levels of NEFL of the schizophrenia were higher than the bipolar disorder; however, the difference was not statistically significant. ConclusionIn conclusion, serum NEFL level, as a confidential marker of neural damage, is increased in the children and adolescents with bipolar disorder and schizophrenia. This result may indicatea degenerative period in neurons of children and adolescents with schizophrenia or bipolar disorder and may play a role in the pathophisiology of these disorders. This result shows that there is neuronal damage in both diseases, but neuronal damage may be more in schizophrenia.

Role of DSM5 anxious distress specifier interview in acute manic episode: sociodemographic characteristics, clinical presentation and quality of life

BackgroundDSM 5 anxious distress specifier is one of the newly added specifiers for bipolar and related disorders. It may have impacts on the symptoms severity, insight, impulsivity, and different domains of quality of life of acute manic episodes of bipolar disorders. The current study aimed to study the effects of DSM 5 anxious distress specifier in acute manic episodes and its relation to sociodemographic data, clinical characteristics, and quality of life. 380 patients with the diagnosis of acute manic episode were recruited in the study, sociodemographic data, clinical features, DSM 5 anxious distress specifier interview, attitude and insight of the disorder, impulsivity and different aspects of quality of life were also evaluated in those patients.ResultsThe studied patients were divided into 2 subgroups according to the presence of high DSM5 anxious distress specifier interview score. The duration of a manic episode (P < 0.001), the severity of the manic episode (P < 0.001), and the presence of psychotic features (P = 0.002) were more common in the subgroup with high DSM 5 anxious distress. DSM 5 anxious distress specifier was severe (P < 0.001) and more frequent (P < 0.001) in the 1st subgroup than the 2nd one. There was a statistically significant difference regarding the attentional facet of the Barratt impulsiveness scale between the studied groups (P = 0.002). In addition, there was a statistically significant difference regarding the mean score (P < 0.001) and severe impairment (P < 0.001) domains of work and social adjustment scale between the 2 subgroups.ConclusionsDSM 5 anxious distress specifier interview is a very crucial parameter of evaluation the patients with acute manic episodes which may have implications on the clinical presentations, symptoms severity, impulsivity, and variable aspects of quality of life in those patients. All these implications might change the course, prognosis, and outcomes of an acute manic episode of bipolar disorder.

Assessment of serum high mobility group box 1 protein (HMGB1) levels and its change with treatment in patients with manic episode of bipolar disorder

IntroductionThere has been an increasing evidence in recent years that inflammation plays a role in the pathophysiology of bipolar disorder (BD). In addition to central inflammation, systemic immune response is thought to be associated with disease stages and course. HMGB1 protein is a member of damage-associated molecular pattern which plays a role in the regulation of cytokine release and is important for innate immunity. It has been revealed that HMGB1 levels change in many autoimmun and inflammatory diseasesObjectivesOur study was designed to compare serum HMGB1 levels of inpatients with mania and healthy controls as well as analyzing its relationship with other inflammatory markers and disease severity. Another aim of our study is to determine the changes in serum HMGB1 levels before and after treatment in manic patients.MethodsOur study included 35 patients who were hospitalized in our hospital between November 2020 and April 2021, diagnosed with bipolar disorder, manic episode according to DSM-5 criteria, and 35 healthy controls who matched to the patient group in terms of age and gender. The sociodemographic and clinical characteristics data forms of the participants were filled in, and the patients were evaluated with the Young-Mania Rating Scale (YMRS) and the Hamilton Depression Scale (HAM-D). Serum HMGB1, CRP levels and complete blood count values were measured in healthy controls and patients before and after the treatment.ResultsThe main finding of our study is that HMGB1 levels did not show a statistically significant difference in the patient and healthy control groups (p&gt;0.05). In addition, there was no significant change in serum HMGB1 levels of the patients after treatment compared to the level before treatment (p&gt;0.05). Our study has also revealed that manic patients had a higher level of CRP than the ones in control group at a statistically significant level. The platelet/lymphocyte and neutrophil/lymphocyte rates of the patients increased after the treatment compared to the pre-treatment period (respectively p=0,026, p=0,003).ConclusionsThe higher CRP levels in manic patients support the hypothesis of low-grade chronic inflammation, which is thought to be involved in the etiology of BD. The most important finding of this study is that there is no statistically significant difference of serum HMGB1 levels between the two groups. This can be explained by the fact that HMBG1 is one of the late mediators of inflammation and does not rise immediately during the acute period. However, since the inflammation process includes complex mechanisms involving many systems, it makes it difficult to comment on this issue.Disclosure of InterestNone Declared

Sleep changes during a spontaneous manic episode: PSG assessment in a clinical context

Sleep plays a key role in the pathogenesis and clinical presentation of mood disorders. However, only a few studies have investigated sleep architecture during the manic episodes of Bipolar Disorder (BD) and changes in sleep parameters that follow clinical variations.Twenty-one patients (8 males, 13 females) affected by BD, manic phase, underwent polysomnographic recordings (PSG) at the beginning of the admission in our ward (T0) and after three weeks of hospital treatment (T1). All participants were clinically evaluated using Young Mania Rating Scale (YMRS), Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire (MEQ).During the admission, we observed an increase in both quantity (Total Sleep Time - TST) and quality (Sleep Efficiency - SE) of sleep. In addition, clinical improvement, evaluated with YMRS and PSQI scales, was accompanied by a significant increase in the percentage of REM sleep.According to our findings, the improvement of manic symptoms is accompanied by an increase in "REM pressure" (increase in REM% and REM density, reduction of REM latency).Overall, changes in sleep architecture appear to be markers sensitive to clinical variations during manic phases of Bipolar Disorder.

Family environment of youth with first episode Mania.

The purpose is to compare youth- and caregiver-reported characteristics of family environment, within and between families with a child experiencing a first manic episode of bipolar disorder (BPD), and families without a child with BPD or familial history of psychiatric disorders (HF). Family environment of 61 families with a child with BPD and 44 HF were assessed with Family Environment Scale (FES). We compared FES subscale scores between families with BPD and HF, and caregiver- and youth-rated scores. Families with BPD differed significantly from HF on 8/10 FES subscales scores. Youth differed significantly from their caregivers on 7/10 subscales. An interaction effect was observed such that youth with BPD reported lower cohesion and organization, and higher conflict than their caregivers; however, HF did not differ significantly on these domains. Our results suggest that families with BPD have higher conflict and lower cohesion and organization compared to HF. Results also indicate differences between youth and caregiver perspectives in both groups, which may contribute to family discord. Interventions targeting areas of cohesion, organization, and conflict may be beneficial for youth with BPD and their families, specifically those that identify and bridge perceptual divides.