Young Mania Rating Scale Scores Research Articles

The effect of adding curcumin to sodium valproate in treatment of patients with bipolar disorder in the acute phase of mania: A randomized double-blind clinical trial.

Inflammatory processes play a role in the etiopathogenesis of bipolar disorder type 1. Full therapeutic responses are seldom seen and the ongoing inflammatory processes in the brain could lead to neuronal loss. Curcumin, a relatively safe herbal compound, has been shown to have anti-inflammatory effects. The present randomized double-blind clinical trial study aimed to investigate the effect of adding curcumin to the treatment regimen of BID. This randomized double-blind clinical trial was conducted on 78 patients diagnosed with BID according to the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria. The sample were divided into two groups. Patients in both groups received sodium valproate starting at a dose of 600 milligrams per day and administered up to 20 milligrams per kilogram per day or the highest dosage of the patient's tolerance. Patients in the intervention group also received curcumin as nanomicelle in soft gelatin capsules 40 milligrams per day. The control group received placebo tablets with the same characteristics as the curcumin tablets. They were assessed by a psychiatrist using the Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), and a medication side effect questionnaire at the beginning of the study, as well as in the first, second, and fourth weeks of the study. Among the 78 patients chosen to participate in the project, 54 people completed the trial. No specific side effect was observed in the two groups. Both groups showed an increase in their MMSE scores compared to the beginning of the study (value of p < 0.001). Although this increase was not statistically different between the two groups (value of p = 0.68). The YMRS score of both groups decreased significantly by the end of the study (value of p < 0.001); however, this decrease was not significantly different between the two groups (value of p = 0.64). In addition, the two groups experienced a significant increase in their CGI scores throughout the study (value of p < 0.001), this increase however was not statistically different between the two groups (value of p = 0.88). The present study suggested that curcumin may not be a useful adjuvant agent in the management of patients with BID receiving sodium valproate as treatment.Clinical trial registration: Iranian Registry of Clinical Trials (IRCT), identifier IRCT2016102530504N1.

Postpartum-onset obsessive-compulsive disorder: A harbinger of bipolar disorder.

Postpartum-onset obsessive-compulsive disorder: A harbinger of bipolar disorder.

Validation of the Longitudinal Interval Follow-Up Evaluation for the Long-Term Measurement of Mood Symptoms in Bipolar Disorder.

The long-term burden of symptoms is an important outcome in bipolar disorder (BD). A method which has minimal burden of assessment uses a retrospective interview, the Longitudinal Interval Follow-up Examination (LIFE), although this may be subject to problems with recall. This study examines the relationship between the retrospective LIFE scale and concurrently-rated mood rating scales in two clinical trials of 18 months of psychotherapy for patients with BD. The Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were administered every eight to nine weeks and the LIFE was carried out every 6 months. Correlations between scores on mood rating scales and at equivalent times on the LIFE were examined, as well as of potential clinical moderators. There were significant correlations between LIFE depression ratings and concurrent MADRS score (r = 0.57) and between LIFE mania ratings and YMRS score (r = 0.40). In determining "mild depression" on the MADRS, a receiver operating characteristics (ROC) analysis showed an AUC of 0.78 for LIFE scores. Correlations, particularly for depression scores, were high even when the LIFE rating was several months before the interview, suggesting that the LIFE has validity in examining the burden of mood symptoms over time, with relatively little burden of assessment. Future research should examine the relationship between symptom burden and quality of life measured in this way.

Neurobiological Markers for Predicting Treatment Response in Patients with Bipolar Disorder.

Predictive neurobiological markers for prognosis are essential but underemphasized for patients with bipolar disorder (BD), a neuroprogressive disorder. Hence, we developed models for predicting symptom and functioning changes. Sixty-one patients with BD were recruited and assessed using the Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Positive and Negative Syndrome Scale (PANSS), UKU Side Effect Rating Scale (UKU), Personal and Social Performance Scale (PSP), and Global Assessment of Functioning scale both at baseline and after 1-year follow-up. The models for predicting the changes in symptom and functioning scores were trained using data on the brain morphology, functional connectivity, and cytokines collected at baseline. The correlation between the predicted and actual changes in the YMRS, MADRS, PANSS, and UKU scores was higher than 0.86 (q &lt; 0.05). Connections from subcortical and cerebellar regions were considered for predicting the changes in the YMRS, MADRS, and UKU scores. Moreover, connections of the motor network were considered for predicting the changes in the YMRS and MADRS scores. The neurobiological markers for predicting treatment-response symptoms and functioning changes were consistent with the neuropathology of BD and with the differences found between treatment responders and nonresponders.

COMT rs4680 and DRD2 rs6275 variants and their association with YMRS scores in children with early-onset bipolar disorder

Background and objectivesBipolar disorder (BD) is a clinical status with at least one manic, hypomanic or mixed attacks. Genetic factors take part significantly in early-onset BD (EOBD). Dopamine receptors (DRD) act in neurological mechanisms like motivation, learning, memory, and, control of neuroendocrine signaling. DRD2 receptor has been reported to influence the stability of DRD2 transcript. Catechol-O-Methyl transferase (COMT) inactivates catecholamines and Val158Met variation on COMT has effects on COMT activity. This study aims to explore DRD2 and COMT variants in the clinical development of EOBD. MethodsIn this case-control study, 102 EOBD patients and 168 healthy control subjects were used. DRD2 rs6275 and COMT Val158Met variations were detected by real-time polymerase chain reaction (RT-PCR). Young Mania Rating Scale (YMRS) was utilized to determine the EOBD severity. ResultsFor DRD2 rs6275 and COMT Val158Met polymorphisms, no significant relationship was observed in the genotype and allele frequencies between patient and control groups. Nevertheless, TT genotype carriers of DRD2 rs6275 polymorphism demonstrated significantly increased YMRS scores when compared with CC and CT genotype carriers (p = 0.039). Nevertheless, no significant difference was observed between COMT Val158Met genotypes and YMRS scores. ConclusionsWe suggest that the DRD2 rs6275 TT variant can be associated with symptom severity in children with EOBD and can have a clinical significance in EOBD pathogenesis. However, these results need to be confirmed with larger samples of patient and control groups.

Psychopathological profile and sagittal alignment in low-back pain

IntroductionLow-back pain requires comprehensive care using a biopsychosocial model. The psychologic dimension plays an important role, but the link between sagittal alignment and a given psychopathological profile is little studied. The aim of this study was to analyze the psychopathological profiles and sagittal parameters of a population with low-back pain and to assess the link. Material and methods205 patients, with a mean age of 49.6 years (range, 18–70 years), presenting chronic common low-back pain without radicular involvement, were included prospectively. Mood scores comprised: the self-administered “Hospital Anxiety and Depression Scale” (HAD), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D) and Young Mania Rating Scale (YMRS). Radiological parameters, measured on lateral full-spine radiographs, included: L1-S1 lordosis, T1-T12 kyphosis, pelvic incidence, pelvic tilt, sacral slope, sagittal vertical axis (SVA), T1 slope, and Roussouly type. ResultsMean HAM-A score was 16.1; 54% of patients had scores ≥14, indicating anxiety disorder. Mean HAM-D score was 10.8; 55% of patients had scores ≥10, indicating depressive disorder. Mean YMRS score was 2.6; only 1 patient had a score ≥20, indicating manic disorder. The 112 patients with HAM-A score >14 showed mean 51.6° L1-S1 lordosis (p=0.356), 48.3° T1-T12 kyphosis (p=0.590), –4.3mm C7 SVA (p=0.900), and 29.3° T1 slope (p=0.451). In case of HAM-A <14, there were no significant differences. The 113 patients with HAM-D score >10 showed significant differences in T1-T12 kyphosis (mean 49.0°; p<0.05) and T1 slope (30.2°; p<0.05); mean L1-S1 lordosis was 50.5° (p=0.861) and C7 SVA 1.6mm (p=0.462). In case of HAM-D <10, T1-T12 kyphosis was 45.5° (p<0.05) and T1 slope 26.2° (p<0.05); mean lordosis was 50.9° (p=0.861) and mean C7 SVA –7.1mm (p=0.259). Multivariate analysis found no significant link between Roussouly type and psychiatric scores: HAD (p=0.715), HAM-A (p=0.652), and HAM-D (p=0.902). ConclusionMore than 50% of patients with common low-back pain presented a mood disorder. Depressive disorder was associated with greater T1-T12 kyphosis and T1 slope. There was no relationship between psychiatric scores and overall sagittal alignment. Level of evidenceII.

A Positron Emission Tomography Study of Dopamine Transporter Density in Patients With Bipolar Disorder With Current Mania and Those With Recently Remitted Mania

Although dopamine is implicated in the pathophysiology of bipolar disorder (BD), the precise alterations in the dopaminergic system remain unknown. To assess dopamine transporter (DAT) density in the striatum in patients with BD with current and recently remitted mania in comparison to healthy control individuals and its correlation with severity of manic symptoms. This cross-sectional study conducted in a tertiary care referral center for mood disorders in Vancouver, British Columbia, Canada, recruited 26 patients with BD (9 with current mania; 17 with recently remitted mania) and 21 matched healthy control individuals. DAT density was measured using positron emission tomography with [11C]d-threo-methylphenidate (MP). The differences between the groups in nondisplaceable binding potential (BPND) for DAT was assessed using statistical parametric mapping. The study was conducted from November 2001 to February 2007 and the data were analyzed from November 2020 to December 2021. DAT density as indexed by BPND for MP across groups; manic symptom severity as measured with the Young Mania Rating Scale (YMRS) and correlated with BPND values in patients with BD. Of 47 total participants (mean [SD] age, 37.8 [14.4] years), 27 (57.4%) were female; 26 individuals had BD (9 with current mania and 17 with recently remitted mania) and there were 21 healthy control individuals. MP BPND was significantly lower in patients with BD in the right putamen and nucleus accumbens (mean reduction [MR] = 22%; cluster level familywise error [FWE]-corrected P < .001) as well as left putamen and caudate (MR = 24%; cluster level FWE-corrected P < .001). The reduction in BPND was more extensive and pronounced in patients with current mania, while patients with recently remitted mania had lower BPND in the left striatum but not the right. There was a significant negative correlation between YMRS scores and MP BPND in the right striatum in patients with current mania (ρ = -0.93; 95% CI, -0.99 to -0.69; P < .001) and those with recently remitted mania (ρ = 0.64; 95% CI, -0.86 to -0.23; P = .005) but not in the left striatum in either group. These findings indicate that mania was associated with reduced DAT density and remitted mania was associated with DAT levels that approximated those present in individuals without BD. These results have potential implications for drug development for mania.

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder

The antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N-methyl-D-aspartate (NMDA)-receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD. To test whether low doses of the NMDA-receptor partial-agonist, D-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD. This was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level). Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plus D-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4. The primary outcome was change in depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores. A total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plus D-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plus D-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, -6.15; 95% CI, -2.43 to -9.88; Hedges g = 0.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plus D-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred. Findings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation. ClinicalTrials.gov Identifier: NCT03937596.

Low α-N-acetylgalactosaminidase plasma concentration correlates with the presence and severity of the bipolar affective disorder

Objectives Believing that a neurodevelopmental pathology may cause bipolar affective disorder (BAD), we aimed to measure the concentrations of α-N-acetylgalactosaminidase (α-NAGAL), a lysosomal enzyme. Methods The study included 32 patients with BAD and 32 healthy controls. The Young Mania Rating Scale was used to measure the severity of the disease. Serum α-N-acetylgalactosaminidase concentrations were measured in all blood samples using the human α-N-acetylgalactosaminidase ELISA Kit. Results A statistically significant difference was found in the α-NAGAL values between the groups. The mean α-NAGAL values of BAD patients are lower than the mean α-NAGAL values of the control group. A strong negative and statistically significant relationship was found between the α-NAGAL values of patients with BAD and their Young Mania Rating Scale scores. And a positive strong correlation was found between the age of onset of the disease and α-NAGAL levels. Conclusions Low α-N-acetylgalactosaminidase concentrations may cause the accumulation of some glycoproteins in the lysosomes in the brain during the gestational period, producing the clinical symptoms of BAD. α-N-acetylgalactosaminidase deficiency may not be the only cause of BAD, but it may be an important factor in the aetiology of this disease.

Bipolar Affective Disorder in a Patient of Achalasia Cardia: A Case Report of Young Man

We present a case of 22-year-old known Achalasia cardia, previously treated for depression, presented with irritable behaviour, aggression, over-talkativeness, ideas of self-importance, running away from home and decreased sleep. He was treated for imperforate anus with anoplasty on the first day of birth and for Achalaisa Cardia with heller myotomy at 17 years of age. His Young Mania Rating Scale score was 22, and his Brief Psychiatric Rating Scale score was 50. He was diagnosed as a case of bipolar affective disorder. Marked improvement in the symptoms occurred after two weeks of the treatment with sodium valproate, olanzapine and clonazepam.

Disability in Patients With Bipolar Disorder in Full or Partial Remission: A Cross-Sectional Study.

Objective: To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD). Methods: This cross-sectional study was conducted in a tertiary care general hospital psychiatric unit with 100 patients with BD in partial or full remission (DSM-IV-TR criteria) from January 2017 to March 2018. Patients were assessed using a semistructured proforma, the Mini-International Neuropsychiatric Interview 5.0–Hindi version, the Hamilton Depression Rating Scale (HDRS) or the Young Mania Rating Scale (YMRS), and the Indian Disability Evaluation and Assessment Scale (IDEAS). Results: All patients with BD had at least mild disability. The mean ± SD IDEAS global score was 5.1 ± 2.59. Of the sample, 66% and 34% had mild or moderate, disability, respectively. The global score of disability was associated with the number of episodes, number of manic episodes, frequency of episodes in the past year, YMRS and HDRS scores, partial remission, and hospitalization. Categories of disability were associated with the type of last episode, type of remission, and treatment setting. Conclusions: Patients with BD had at least a mild level of disability even during remission. Disability worsened with the increasing number, frequency, and severity of episodes; number of manic episodes; partial remission; and hospitalization.

The Mediation Effect of Peripheral Biomarkers of Calcium Metabolism and Chronotypes in Bipolar Disorder Psychopathology.

Calcium (Ca++) metabolism may be impaired in several psychiatric diseases. We hypothesize that calcium imbalance might also correlate with a specific chronotype and could be recognized as a marker of illness severity in bipolar disorder (BD). We aimed to (1) identify the association between calcium imbalance and a specific chronotype in a cohort of BD patients, and (2) test the mediation role of high parathyroid hormone (PTH) levels towards a specific chronotype and illness severity in BD patients. Patients’ socio-demographic and clinical characteristics were collected with an ad-hoc schedule. We administered the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Young Mania Rating Scale (YMRS), and the Morningness Eveningness Questionnaire (MEQ). 100 patients affected by BD were recruited. The Kruskal-Wallis test showed a significant difference between the three MEQ groups in PTH levels (p < 0.001) and vitamin D levels (p = 0.048) but not in Ca++ levels (p = 0.426). Dwass-Steel-Critchlow-Fligner Pairwise analyses performed concerning three MEQ groups revealed significantly higher scores on PTH levels in MEQ-E subjects compared to MEQ-M and MEQ-I (in both cases, p < 0.001). No differences emerged between calcium levels among the three chronotypes. The mediation analysis has shown that elevated PTH levels are directly influenced by more severe HAM-A, HAM-D, and YMRS scores. MEQ-E could be a marker related to BD and predispose to various factors influencing mood symptoms. The combination of vitamin D therapy in MEQ-E may help to improve prognosis in this subtype of patients affected by BD.

Linkage of Young Mania Rating Scale to Clinical Global Impression Scale to Enhance Utility in Clinical Practice and Research Trials.

The Young Mania Rating Scale (YMRS) is the gold standard to assess manic symptoms of bipolar disorder, yet the clinical meaning of scores is unknown. To clinically understand and interpret YMRS scores, we examined linkages between the total and change scores of YMRS with the Clinical Global Impression (CGI) ratings. Individual participant data (N=2,988) from eight randomized, double-blind, placebo-controlled trials were included. Data were collected at baseline and subsequent visits. Spearman's correlation coefficients ρ were computed, and equipercentile linking was implemented. A YMRS score of 6 points corresponded approximately to 'borderline mentally ill,' 12 points to 'mildly ill,' 20 points to 'moderately ill,' 30 points to 'markedly ill,' 40 points to 'severely ill,' and 52 points to 'among the most extremely ill' patients on the CGI-S. A reduction of CGI-S by one point as well as 'minimally improved' on the CGI-I corresponded approximately to an absolute decrease of 4 to 8 YMRS points or a 21% to 29% reduction of YMRS baseline score whereas a reduction of CGI-S by two points and 'much improved' on the CGI-I corresponded to an absolute decrease of 10 to 15 points or a 42% to 53% reduction of YMRS baseline score. The current study findings offer clinicians meaningful cutoff values to interpret YMRS scores. Moreover, these values contribute to the definition of treatment targets, response, remission, and entry criteria in mania trials.

Efficacy and safety of palmitoylethanolamide as an adjunctive treatment for acute mania: A randomized, double-blind, placebo-controlled trial.

Palmitoylethanolamide is an endogenous fatty acid amide with neuroprotective and anti-inflammatory actions. We performed a randomized, double-blind, placebo-controlled clinical trial to investigate the efficacy and safety of palmitoylethanolamide combination therapy in acute mania. Patients in the acute phase of mania were assigned into two parallel groups given either lithium (blood level of 0.8-1.1 mEq/L) and risperidone 3 mg plus palmitoylethanolamide 600 mg or placebo twice per day for 6 weeks. All participants were assessed with the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, and 6. A total of 63 patients (32 in palmitoylethanolamide and 31 in placebo groups) completed the trial. We found a significant effect for time×treatment interaction on the YMRS score (F=5.22, d.f.=2.34, P= 0.004) from baseline to study end point. Results from independent t test showed a significantly greater decrease in YMRS scores in the palmitoylethanolamide group, compared with the placebo group, from baseline to weeks 4 and 6 (P= 0.018 and P= 0.002, respectively). There was no significant difference between palmitoylethanolamide and placebo groups based on ESRS scores or ESRS changes in scores (P>0.05). Our findings provide preliminary evidence that palmitoylethanolamide is an effective adjunctive medication that improves manic symptoms and overall clinical status in acute episodes of mania. However, larger sample sizes and more extended follow-up therapy are needed in future studies to confirm our findings.

Clinical Features of Bipolar Disorder Patients with Metabolic Syndrome: A Cross Sectional Clinic Based Study

IntroductionMetabolic Syndrome (MS) is highly prevalent in patients with bipolar disorder(BD), and may affect the functionality of this population.The increased rate of MS in BD might be due to poorer access to physical health care, unhealthy lifestyle related with psychiatric symptoms and adverse effects of pharmacological treatments.ObjectivesWe sought to compare differences in clinical features of patients with Bipolar Disorder Type 1 (BPD-1)with and without MS in euthymic period.MethodsThis study included 67 euthymic BPD-1 patients without MS and 33 age- and sex-matched BPD-1 patients with MS. All participants completed a sociodemographic form; took the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Young Mania Rating Scale score. MS was diagnosed according to the International Diabetes Federation (IDF) criteria.ResultsAge at onset of disease was significantly lower in BPD-1 group with MS than without MS (p &lt; 0.05). Number of suicide attempts, psychiatric hospitalisation, was significantly higher in BPD-1 group with MS than without MS (p &lt; 0.05). Catatonic and melancholic depression were significantly more prevalent in the BPD-1 with MS than without MS (p &lt; 0.05). Having history of comorbid psychiatric diseases, mixed episodes, are significantly more prevalent in the BPD-1 with MS than without MS (p &lt; 0.05). There was not significant difference between groups in terms of the medication between groups (p&gt;0.05)ConclusionsOur findings suggest that MS might have an effect on the course of BD patients. The development and testing of interventions for preventing and treating the MS and its components in patients with BD might be important .DisclosureNo significant relationships.

Quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478CA/del polymorphism and clinical parameters.

We aimed to investigate the quantitative detection of methylated suppressor of cytokine signaling-1 (SOCS-1) in schizophrenia (SCZ) and bipolar disorder (BD), considering SOCS-1 -1478CA/del polymorphism and clinical parameters. Our research is a case-control study in which 114 patients with SCZ, 86 patients with BD, and 80 volunteers as a healthy group participated. Bisulfite-converted DNA samples were analyzed using the real-time quantitative methylation-specific PCR (qMS-PCR) method to measure the methylation level of the SOCS-1 gene. In addition, SOCS-1 -1478CA/del gene polymorphism was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). When the SOCS-1 promoter methylation levels of SCZ and BD patients were compared with the control group, the methylation levels of SCZ and BD were significantly lower than the control group. An earlier age of illness onset was significantly related to the SOCS-1 promoter hypermethylation in DNA samples of SCZ patients. Again, SOCS-1 promoter hypermethylation was significantly associated with the higher Young Mania Rating Scale (YMRS) score in BD patients. While the SOCS-1 CA/CA genotype frequency was significantly higher in the control group than in the BD group, the del/del genotype was significantly related to a higher frequency of rapid cycling and a lower frequency of family history in the BD patient group. In summary, the methylated SOCS-1 quantity in DNA samples of SCZ and BD patients were significantly lower than in control samples. Whereas the SOCS-1 -1478CA/del polymorphism was not related to SCZ, it may be associated with the BD.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania

BackgroundPediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.MethodsWe conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5–17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children’s Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.ResultsThis study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.ConclusionsThese pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.Trial RegistrationClinicalTrials.gov Identifier: NCT02357290. First Registration 06/02/2015.

Neuropsychological and Neurophysiological Assessment in Different Phases of Bipolar Disorder.

Recent studies have shown that cognitive deficits are significant and pervasive even among remitted bipolar disorder patients. The aim of the current controlled study was to investigate the relationships between cognitive performances, symptom severity, and event-related potentials with regard to different episodes in bipolar patients. This study was conducted on a total of 60 patients diagnosed with bipolar disorder (20 depressive, 20 manic, and 20 in remission). The Frontal Assessment Battery and Stroop test were used for neuropsychological assessment. Event-related potentials were measured using frontal, central, and parietal EEG recordings, while Nihon-Kohden EMG-EP system was used. Delayed P300 latencies were observed in all phases of bipolar disorder when compared to the controls. There was a positive relationship between frontal, central P300 latencies, and Young Mania Rating Scale scores. A strong positive relationship was also observed between Young Mania Rating Scale scores and Stroop interference scores. A negative relationship was observed between Frontal Assessment Battery scores and frontal, central, and parietal N100 latencies and amplitudes in depressed patients. Consistent with these findings, there was a relationship between Hamilton Depression Rating Scale scores and N100 latencies. There was also a positive relationship between Stroop interference scores and central N200 latency, as well as frontal N200 and parietal N200 amplitudes, while a negative relationship was observed between Stroop total time scores and central N200 latency as well as parietal N200 amplitude in depressed patients. Study findings imply that depression episodes could be associated with decision-making autonomy and memory issues, while there is also a relationship between episodes of mania, impaired inhibitory control, and issues with selective attention. Moreover, these cognitive impairments might be included in the initial phases of processing observed in N100 responses in depression, while processing impairment could be pervasive in mania that results in P300 delays.

A DSM-5-based tool to monitor concurrent mood and premenstrual symptoms: the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS)

BackgroundDespite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood symptoms. In this study, we developed a new DSM-5-based questionnaire to prospectively monitor concurrent premenstrual and mood symptoms.MethodsFifty-two females with bipolar or major depressive disorder, ages 16–45, were enrolled in the study. Participants completed two months of prospective symptom charting including the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS) and the Daily Record of Severity of Problems (DRSP). At the end of the prospective charting, participants also completed the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The MAC-PMSS was correlated with the DRSP, MADRS, HDRS and YMRS.ResultsAll individual items of the MAC-PMSS correlated strongly with the individual DRSP scores (all p < 0.001). The mood section of the MAC-PMSS also significantly correlated with MADRS (r = 0.572; p < 0.01), HDRS (r = 0.555; p < 0.01) and YMRS scores (r = 0.456; p < 0.01).ConclusionsThe MAC-PMSS is a reliable to tool to measure concurrent mood and premenstrual symptoms in women with mood disorders.

Mitochondrial modulators in the treatment of bipolar depression: a systematic review and meta-analysis

Mitochondrial dysfunction has been implicated in the risk, pathophysiology, and progression of mood disorders, especially bipolar disorder (BD). Thus, the objective of this meta-analysis was to determine the overall antidepressant effect of mitochondrial modulators in the treatment of bipolar depression. Outcomes included improvement in depression scale scores, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) score. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of diverse mitochondrial modulators were pooled to determine standard mean differences (SMDs) compared with placebo.13 RCTs were identified for qualitative review. The overall effect size of mitochondrial modulators on depressive symptoms was −0.48 (95% CI: −0.83 to −0.14, p = 0.007, I2 = 75%), indicative of a statistically significant moderate antidepressant effect. In the subgroup analysis, NAC improved depressive symptoms compared with placebo (−0.88, 95% CI: −1.48 to −0.27, I2 = 81%). In addition, there was no statistical difference between mitochondrial modulators and placebo in YMRS. Although mitochondrial modulators were superior to placebo in CGI-S score (−0.44, 95% CI: −0.83 to −0.06, I2 = 71%), only EPA was superior to placebo in subgroup analysis. Overall, a moderate antidepressant effect was observed for mitochondrial modulators compared with placebo in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.