Clinical Global Impression Scale Research Articles

Are S100B and VILIP-1 Involved in a Common Mechanism of Neuroinflammation in Major Depressive Disorder?

This study aimed to evaluate the role of neuroinflammation in neuronal and glial cells in the pathophysiology of Major Depressive Disorder (MDD) through different biomarkers.S100-B and VILIP-1 levels of patients diagnosed with MDD were evaluated before and after antidepressant treatment. A total of 65 patients diagnosed with MDD and 69 healthy controls were included. Serum levels of S100B and VILIP-1 were measured at the time of diagnosis and after eight weeks antidepressant treatment and compared with healthy controls. Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression Scale (CGI) were applied to assess the severity of depression. In our study, although serum S100B levels were higher in patients before treatment compared to healthy controls, this difference was not statistically significant. Regarding VILIP-1 levels, there was no statistically significant difference between patients and healthy controls. A positive and statistically significant correlation was found between S100B and VILIP-1 levels in MDD group before the treatment. At the eighth week of treatment, a statistically significant positive correlation was also found between S100B and VILIP-1 levels. Our research is the first study to evaluate MDD through two separate biomarkers specific to glial and neuronal cells.The fact that S100B and VILIP-1 levels showed significant correlations in patients diagnosed with MDD both before and after treatment suggests that they may play a shared role in the pathophysiology of the disorder. The correlation between S100B and VILIP-1 may serve as a guide in understanding the pathophysiology of the disorder and in identifying new drug development targets.

Amyloid deposition and its association with depressive symptoms and cognitive functions in late-life depression: a longitudinal study using amyloid-β PET images and neuropsychological measurements

BackgroundAlthough depression is linked to an increased risk of dementia, the association between late-onset depression (LOD) and amyloid burden remains unclear. This study aimed to determine amyloid deposition in patients with LOD compared to healthy controls (HC) using amyloid-beta (Aβ) positron emission tomography (PET) images and neuropsychological assessments.MethodsForty patients first diagnosed with major depressive disorder after the age of 60 (LOD) and twenty-one healthy volunteers (HC) were enrolled. Depression and anxiety were evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale. Cognitive function was assessed using the Korean versions of the Mini-Mental Status Examination, Montreal Cognitive Assessment, and Seoul Neuropsychological Screening Battery at baseline and 3-month follow-up. 18F-florbetapir PET images were co-registered with T1-weighted magnetic resonance images.ResultsThere was no significant difference in Aβ deposition between LOD and HC groups. No significant correlation between Aβ burden and depressive symptom severity was found in LOD patients. Higher somatic anxiety was correlated with lower Aβ burden in multiple brain regions, including the left inferior frontal lobe (p = 0.009), right anterior cingulate (p = 0.003), and right superior frontal lobe (p = 0.009). Despite cognitive recovery in areas such as attention (Digit Span Forward, p = 0.026), memory (Auditory Verbal Learning Test Recall Total, p = 0.010; Rey Complex Figure Test Delayed Recall, p = 0.039), and frontal executive function (Contrasting Program, p = 0.033) after three months of antidepressant treatment, cognitive improvement showed no association with amyloid deposition.ConclusionsThese findings suggest distinct mechanisms may underlie amyloid deposition in neurodegenerative changes associated with depression. While amyloid burden in specific brain regions negatively correlated with somatic anxiety, it showed no significant correlation with the severity of depression or overall cognitive function.

Sleep Awareness of Japanese Outpatients: A Survey at a Psychiatry Department of a University Hospital.

Background: Insomnia is common in patients with psychiatric disorders. However, patients' awareness of sleep has seldom been examined in detail. In this study, we investigated sleep awareness in outpatients at the psychiatry department of a university hospital. Methods: The participants (n = 241) were recruited at the psychiatry department of Ehime University Hospital between 11 October and 5 November 2021. The following questionnaires were used: Clinical Global Impression Scale of Severity (CGI-S), Global Assessment of Functioning (GAF), General Health Questionnaire (GHQ-30), Athens Insomnia Scale (AIS), and Epworth Sleepiness Scale (ESS). Psychiatric disorders were diagnosed by certified psychiatrists using the International Statistical Classification of Diseases and Related Health Problems 10. Participants with an AIS score of ≥6 were allocated to the insomnia group for statistical analysis. A logistic regression analysis was conducted to identify which items of sleep hygiene the patients with insomnia practiced using the Sleep Guidelines for Health Promotion. Results: Of 241 participants, 133 (55.2%) were allocated to the insomnia group. The mean scores for the CGI were significantly higher and the GAF scores were significantly lower in the insomnia group than in the healthy sleep group (p < 0.01). Of the 12 sleep guidelines proposed by the Japanese Government, "Do not go to bed until you are sleepful, do not delay getting up", was the item that maximally influenced insomnia. Conclusions: The insomnia group had worse scores on various medical assessment scales compared to the healthy sleep group. Based on a survey of outpatients at the psychiatry department of the university hospital, appropriate stimulus control techniques may help clinicians to treat outpatients with insomnia.

Efficacy of Cariprazine in the Psychosis Spectrum: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials in Schizophrenia and Bipolar Disorder.

Psychosis represents one of the most challenging clinical presentations in psychiatry. Schizophrenia and bipolar disorder may both present psychotic features, and cariprazine may offer improvement in the treatment and care of these conditions. Therefore, the objective of the current work was to synthesise results of efficacy for cariprazine in these disorders. In total, five electronic databases were searched for randomized controlled trials enrolling patients across the psychosis spectrum, using the search term 'Cariprazine' (PubMed, Embase, clinicaltrials.gov, EUDRACT, Cochrane-last search January 2024). No filter or limits were employed. Effect sizes were extracted, by the mean difference in psychometric variables before and after the intervention (Clinical Global Impression Scale, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, Hamilton Anxiety Rating Scale). In total, 12 studies enrolling either patients with schizophrenia or bipolar disorder were included (total n = 6477; n = 4814 patients treated with cariprazine, n = 1663 controls treated with placebo). Cariprazine was effective in reducing global clinical severity, and higher improvements were observed at increasing dosages (- 0.25 at ≤ 1.5 mg/day, - 0.45 at ≥ 3 mg/day). Cariprazine also effectively reduced psychotic total scores: - 6.74, [95% confidence interval (CI) - 8.31; - 5.17], depression: - 1.78, [95% CI - 2.54; - 1.02], mania: - 5.72, [95% CI - 6.95; - 4.49], and anxiety symptoms: - 1.24, [95% CI - 1.92; - 0.56]. Cariprazine was observed as efficacious across retrieved studies, offering a potential for tailored treatments across the psychosis spectrum. https://osf.io/pmyhq .

Exploring correlations between Conners' Continuous Performance Test and subjective measures of attention deficit hyperactivity disorder symptoms in a paediatric clinical sample.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterised by inattention and/or hyperactivity-impulsivity. The ADHD symptoms are often evaluated and quantified using various assessment tools, such as the Conners' Continuous Performance Test II (CCPT-II), ADHD Rating Scale (ADHD-RS), Child Behaviour Checklist (CBCL), Clinical Global Assessment Scale (CGAS) and Clinical Global Impression Scale (CGIS). This study sought to compare CCPT-II with parent- and clinician-rated rating scales (ADHD-RS, CBCL, CGAS and CGIS) in measuring the core ADHD symptoms within the paediatric ADHD population. The data, gathered from a large-scale randomised controlled trial involving 172 children aged 6-12 years with ADHD, was pooled, and a Pearson correlation analysis was conducted. No significant correlations were observed between CCPT-II and ADHD-RS, as well as the various subscales of CBCL, CGAS and CGIS. While CCPT-II may offer insights into ADHD symptomatology, its relationship with parent- and clinician-rated rating scales such as ADHD-RS, CBCL, CGAS and CGIS appears limited. Further research is warranted to elucidate the nuances of these assessment tools and their roles in evaluating ADHD.

The minimal important difference in obsessive-compulsive disorder: An analysis of double-blind SSRI trials in adults.

The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

Investigation of optical coherence tomography angiography findings in patients with bipolar disorder

ObjectivesBipolar Disorder (BD) is an important psychiatric disease that progresses with attacks, can be chronic and causes serious mental problems. In this study, we aimed to identify the retinal vascular pathologies in BD patients by optical coherence tomography angiography (OCTA) imaging. MethodsRetinal vascular analysis from 35 BD patients and 30 healthy controls (HCs) were scanned using the OCTA machine. In addition, psychometric tests such as the Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale (CGI-S) were applied to BD patients to assess the severity of the disease and determine the patient's level of functionality. ResultsAs a result of OCTA scans, there were significant differences between the groups as following; Deep retinal vessel density (VD) in the total, parafoveal and perifoveal area, Macular thickness in the inner parafoveal area, VD of retinal capillary plexuses in the inside disk and the Choroidal thickness (p < 0.05). Furthermore, according to the results of Pearson correlation analysis between OCTA scans and YMRS and CGI-S scores, it was determined that there was no significant relationship in any measurement (p > 0.05). ConclusionIn our study, it was determined that there were general differences in deep retinal vascular density and inner macular thickness in BD patients. These findings demonstrate that the deep and inner zone of the retina is affected in BD patients.

Long-Term Treatment for Unspecified Anxiety Disorders with Cannabidiol: A Retrospective Case Series from Real-World Evidence in Colombia

Introduction: Preclinical and clinical evidence has elucidated that cannabis-based medical formulations (CBMFs) may display anxiolytic, antidepressive, and neuroprotective properties. CBMFs are often considered as novel therapeutic anxiolytic agents that can be prescribed as pharmacotherapy for symptomatic domains in anxiety disorders (ADs). Our aim was to explore effectiveness and tolerability of enriched cannabidiol (CBD) oil extract formulations in adults with anxiety symptoms in an outpatient mental health program in Colombia during the COVID-19 pandemic. Methods: We conducted an observational, retrospective, real-world evidence case series from electronic health records at Zerenia Clinic in Bogotá, Colombia between June 2021 and December 2022. Our convenience sample consisted of people searching for CBMFs for the treatment of anxiety symptoms. A cohort of 24 adults was prescribed with enriched CBD in the form of non-sterile oral liquids suspended in sesame seed oil extracts for DSM-5 unspecified anxiety disorder and followed throughout the first year of treatment. CBMFs were prepared by dissolving full-spectrum cannabis extracts in sesame seed oil to a standardized concentration of active ingredients which is CBD-enriched. The oil extract contained 100 mg/mL of CBD and less than 1.9 mg/mL of THC. Primary outcome measures established were the anxiety subscale in the Hospital Anxiety and Depression Scale (HADS-A), and the clinical global impression scale with regard to severity (CGI-S) and improvement (CGI-I) at baseline, 6 months, and 12 months during follow-up. Secondary outcome measures established were HADS depression subscale (HADS-D) and the Epworth Sleepiness Scale (ESS), respectively. Participants also completed the patient-reported outcome measures (PROMs) during each visit throughout the 12-month follow-up. PROMs documented both participantʼs subjective improvement experience and progressive adverse effects. Results: After 6 months of treatment with sublingually administered enriched CBD oil extracts in a median dosage of 100 mg, more than half (54.17%) of the sample continued to report significant anxiety symptoms. After 12 months, only 37.50% persisted with significant anxiety symptoms with a median dose of 120 mg of enriched CBD oil extracts. Similar subjective improvements were reported with regard to sleep disturbances (SDs) as a secondary outcome. At baseline, less than half (46.83%) of the sample reported significant daytime sleepiness. After 6 months of enriched CBD oil extract treatment, less than one third (29.17%) continued to report SDs. At end point, a high proportion of the sample (87.50%) were considered to have normal daytime sleepiness. The cohort showed no clinically relevant depressive symptoms at baseline based on HADS-D scores; therefore, no improvement could be reported throughout the 12-month follow-up. Minimal gender differences with regard to HADS-D scores may be attributed to modifying effects of menopause-related symptoms. No significant adverse drug reactions or deaths were reported during the 12-month follow-up. Conclusions: Further research should determine the long-term efficacy, safety, and appropriate dosages of enriched CBD oil extracts in treating specific ADs rather than broad and unspecified anxiety symptoms. The state of the art of CBMFs for ADs should be warranted by future randomized controlled trials. The next stage for cannabis research should be focused in performing head-to-head trials comparing enriched CBD extracts or capsules versus first-line treatments proven to be effective in ADs.

Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels

BackgroundThis randomized placebo-controlled study examined the effect of ashwagandha root and leaf extract 60 mg (AE60) and 120 mg (AE120) (35 % withanolide glycosides, Shoden) in physically healthy subjects with higher stress and anxiety. It is hypothesized that a low dose extract with higher withanolide glycosides would decrease cortisol and increase testosterone thereby reducing stress and anxiety. MethodsThis parallel arm study recruited 60 subjects with an allocation ratio of 1:1:1 (AE60:AE120: placebo) for 60 days. Subjects who fulfilled the DSM –IV Criteria for generalized anxiety disorder (GAD) with a Hamilton Anxiety Rating Scale, HAMA score >20, and morning serum cortisol >25 mcg/dl were included in the study. The participants did not have depression symptoms and were screened using Montgomery-Asberg Depression Rating Scale. The primary outcome measure was HAMA and the secondary measures were morning serum cortisol, testosterone, perceived stress scale (PSS), clinical global impressions scale (CGI), and patient's global impression of change scale (PGIC). ResultsAfter 60 days, significant differences were observed between the treatment groups and placebo. HAMA scores decreased by 59 % in both AE60 and AE120 groups compared to a negligible increase of 0.83 % in the placebo group (p < 0.0001). Morning serum cortisol levels decreased by 66 % in AE60 and 67 % in AE120, compared to a 2.22 % change in the placebo group (p < 0.0001). Testosterone levels increased by 22 % in AE60 and 33 % in AE120, compared to a 4 % increase in males in the placebo group (p < 0.0001). PSS scores decreased by 53 % in AE60 and 62 % in AE120, CGI-severity scores decreased by 72 % in AE60 and 68 % in AE120, and PGIC scores improved by 60 % in both AE60 and AE120 groups, all showing significant differences compared to the placebo group. ConclusionAshwagandha extract with 35 % withanolide glycosides (Shoden) at 60 mg and 120 mg was significantly effective in reduced morning serum cortisol and increasing total testosterone. Therefore, it can be recommended for reducing high stress and anxiety. Clinical trial registrationThe study was prospectively registered in Clinical Trial Registry, India with registration number CTRI/2022/04/042133 [Registered on: April 25, 2022].

Efficacy of tryushnadya churna in metabolic syndrome with obesity – A randomized double blind controlled clinical trial

Metabolic syndrome (MetS) with obesity has significant mortality and morbidity. Integrative Ayurveda management is explored for it's possible effect. To evaluate the effect of Tryushnadi churna in the management of Metabolic syndrome with obesity. Study is a Randomized, Controlled, double blind, parallel group comparative clinical trial. 48 participants meeting the National Cholesterol Education Programme Adult Treatment panel 3 diagnostic criteria were recruited in the study. They were divided in two 2 groups. Placebo group were administered with Placebo 1gm twice a day, Ayurveda diet and yoga. Tryushnadi Group were intervened with Tryushnadi churna 1gm twice a day, Ayurveda diet and yoga. Interventions were for 90 days. Assessments criteria included Weight, BMI,Waist circumference (WC), Waist hip ratio, Skin fold thickness (SFT), Body fat, blood pressure, WHO-QOL BREF scale, Clinical Global Impression Scale (CGI)- Severity, Global improvement and Efficacy index, Fasting blood sugar (FBS) were assessed on every 30th day. Other blood parameters like Glycated haemoglobin (HbA1c), Triglycerides, High density lipoproteins (HDL), Low density lipoproteins (LDL), Total cholesterol (TC) were evaluated at pre and post study. Between groups comparison showed, Tryushnadi group had significant improvements in BMI, Weight, WHOQOL-Bref and had large effect size. Both the groups showed improvement in WC, body fat, SFT, CGI severity, CGI efficacy index and improvement in quality of life in within group assessment. Study showed that Tryushnadi churna was effective in management of MetS with Obesity. Integrated management of Ayurveda medicine, Ayurveda diet and yoga had beneficial effect.

Using Precision Medicine to Disentangle Genotype-Phenotype Relationships in Twins with Rett Syndrome: A Case Report.

Rett syndrome (RTT) is a paediatric neurodevelopmental disorder spanning four developmental stages. This multi-system disorder offers a unique window to explore genotype-phenotype relationships in a disease model. However, genetic prognosticators of RTT have limited clinical value due to the disorder's heterogeneity on multiple levels. This case report used a precision medicine approach to better understand the clinical phenotype of RTT twins with an identical pathogenic MECP2 mutation and discordant neurodevelopmental profiles. Targeted genotyping, objective physiological monitoring of heart rate variability (HRV) parameters, and clinical severity were assessed in a RTT twin pair (5 years 7 months old) with an identical pathogenic MECP2 mutation. Longitudinal assessment of autonomic HRV parameters was conducted using the Empatica E4 wristband device, and clinical severity was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI) and the Multi-System Profile of Symptoms Scale (MPSS). Genotype data revealed impaired BDNF function for twin A when compared to twin B. Twin A also had poorer autonomic health than twin B, as indicated by lower autonomic metrics (autonomic inflexibility). Hospitalisation, RTT-CGI-S, and MPSS subscale scores were used as measures of clinical severity, and these were worse in twin A. Treatment using buspirone shifted twin A from an inflexible to a flexible autonomic profile. This was mirrored in the MPSS scores, which showed a reduction in autonomic and cardiac symptoms following buspirone treatment. Our findings showed that a combination of a co-occurring rs6265 BDNF polymorphism, and worse autonomic and clinical profiles led to a poorer prognosis for twin A compared to twin B. Buspirone was able to shift a rigid autonomic profile to a more flexible one for twin A and thereby prevent cardiac and autonomic symptoms from worsening. The clinical profile for twin A represents a departure from the disorder trajectory typically observed in RTT and underscores the importance of wider genotype profiling and longitudinal objective physiological monitoring alongside measures of clinical symptoms and severity when assessing genotype-phenotype relationships in RTT patients with identical pathogenic mutations. A precision medicine approach that assesses genetic and physiological risk factors can be extended to other neurodevelopmental disorders to monitor risk when genotype-phenotype relationships are not so obvious.

Multicenter, Open-Label, Prospective Study Shows Safety and Therapeutic Benefits of a Defined Ginkgo Biloba Extract for Adults with Major Neurocognitive Disorder.

The safety and therapeutic effects of Gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking. This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with major neurocognitive disorder due to Alzheimer's disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12-24. Patients took 120 mg EGb 761® twice daily for 18 weeks. Therapeutic effects were assessed by CERAD constructional praxis and recall of constructional praxis (CERAD CP, CERAD recall of CP), Trail-Making Test (TMT), Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Clinical Global Impressions (CGI) scale, and 11-point box scales for tinnitus and vertigo. Safety assessment was based on the occurrence of adverse events as well as changes in clinical, laboratory, and functional parameters. After 18 weeks, significant improvements compared to baseline were found in constructional praxis (CERAD CP, p &lt; 0.0001), memory (CERAD recall of CP, p &lt; 0.0001), speed and executive functioning (TMT A, p &lt; 0.0001; TMT B, p &lt; 0.0001), and behavioral symptoms (BEHAVE-AD, p &lt; 0.0001). Forty-five adverse events were reported in 33 (22.0%) patients in total, including ten presumed adverse drug reactions in 9 (6.0%) patients. Headache and diarrhea of mild-to-moderate severity were the most frequent events. Two serious adverse events, both considered unrelated to the study drug, occurred in 2 (1.3%) patients. This study confirmed the favorable safety profile and suggested therapeutic benefits of EGb 761® in Indian patients with major neurocognitive disorder.

The Role of Selected Speech Signal Characteristics in Discriminating Unipolar and Bipolar Disorders.

The objective of this study is to explore and enhance the diagnostic process of unipolar and bipolar disorders. The primary focus is on leveraging automated processes to improve the accuracy and accessibility of diagnosis. The study aims to introduce an audio corpus collected from patients diagnosed with these disorders, annotated using the Clinical Global Impressions Scale (CGI) by psychiatrists. Traditional diagnostic methods rely on the clinician's expertise and consideration of co-existing mental disorders. However, this study proposes the implementation of automated processes in the diagnosis, providing quantitative measures and enabling prolonged observation of patients. The paper introduces a speech signal pipeline for CGI state classification, with a specific focus on selecting the most discriminative features. Acoustic features such as prosodies, MFCC, and LPC coefficients are examined in the study. The classification process utilizes common machine learning methods. The results of the study indicate promising outcomes for the automated diagnosis of bipolar and unipolar disorders using the proposed speech signal pipeline. The audio corpus annotated with CGI by psychiatrists achieved a classification accuracy of 95% for the two-class classification. For the four- and seven-class classifications, the results were 77.3% and 73%, respectively, demonstrating the potential of the developed method in distinguishing different states of the disorders.

Randomized Trial of the Effectiveness of Videoconferencing-Based Versus Message-Based Psychotherapy on Depression.

The authors compared the engagement, clinical outcomes, and adverse events of text or voice message-based psychotherapy (MBP) versus videoconferencing-based psychotherapy (VCP) among adults with depression. The study used a sequential multiple-assignment randomized trial design with data drawn from phase 1 of a two-phase small business innovation research study. In total, 215 adults (ages ≥18 years) with depression received care from Talkspace, a digital mental health care company. Participants were initially randomly assigned to receive either asynchronous MBP or weekly VCP. All therapists provided evidence-based treatments such as cognitive-behavioral therapy. After 6 weeks of treatment, participants whose condition did not show a response on the Patient Health Questionnaire-9 or was rated as having not improved on the Clinical Global Impressions scale were randomly reassigned to receive either weekly VCP plus MBP or monthly VCP plus MBP. Longitudinal mixed-effects models with piecewise linear time trends applied to multiple imputed data sets were used to address missingness of data. Participants who were initially assigned to the MBP condition engaged with their therapists over more weeks than did participants in the VCP condition (7.8 weeks for MBP vs. 4.9 weeks for VCP; p<0.001). No meaningful differences were observed between the two groups in rates of change by 6 or 12 weeks for depression, anxiety, disability, or global ratings of improvement. Neither treatment resulted in any adverse events. MBP appears to be a viable alternative to VCP for treating adults with depression.

Differentiating Stages of Bipolar and Unipolar Depression-The Possible Role of sICAM-1 and sVCAM-1.

Increased immune-inflammatory activation has been repeatedly linked to etiopathogenesis and the progression of both major depressive disorder (MDD) and bipolar depression (BD). We explore the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in diagnostic differentiation and disorder progression in patients with MDD and BD. Serum levels of sICAM-1 and sVCAM-1 were measured in 137 patients (MDD = 93 and BD = 44) and compared with 73 healthy controls. The severity of psychopathology was assessed using the Hamilton Depression Rating Scale and Clinical Global Impression Scale. After adjustment for multiple confounders, we noticed significant downregulation of sVCAM-1 and upregulation of sICAM-1 levels in both patient groups. Decreased sVCAM-1 levels were detected in patients with acute episodes of BD when compared to MDD. Immune mediators were related to indicators of progression in both mood disorders. They also followed different post-treatment normalization patterns in MDD and BD and in relation to the stage of each disorder. Adhesion molecules could potentially be useful in discriminating between patients with MDD and BD and determining the possible progression of the disorders. Future nosological methods should include time-dependent pathoplasticity and biological correlates, at least for affective disorders.

Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials

BackgroundRett syndrome (RTT) is a rare, life-threatening, genetic neurodevelopmental disorder. Treatment in RTT encounters many challenges. Trofinetide, a modified amino-terminal tripeptide of insulin-like growth factor 1, has demonstrated clinically promising results in RTT. In this study, trofinetide efficacy and safety in RTT are systematically reviewed and meta-analyzed.MethodsA systematic search of five electronic databases was conducted until January 2024. Review Manager 5.4 software was used for the analysis. The analysis was based on a weighted mean difference and standard error with a confidence interval (CI) of 95%, and a statistically significant P-value was considered if it was < 0.05. The study was registered on PROSPERO with registration number CRD42024499849. Quality of evidence was assessed using GRADE.ResultsThree randomized controlled trials (RCTs) with 276 patients were included in the analysis. Trofinetide improved both caregiver outcomes and clinical scales by improving the Rett Syndrome Behavior Questionnaire (RSBQ) (mean difference (MD): − 3.46 points, 95% CI: − 5.63 to − 1.27, P = 0.0002) and Clinical Global Impression Scale–Improvement (CGI-I) (MD: − 0.35, 95% CI: − 0.51 to − 0.18, P < 0.0001), respectively. However, trofinetide neither improved the Caregiver Top 3 Concerns Visual Analog Scale nor the Rett Motor Behavioral Assessment. Regarding safety, trofinetide was significantly associated with vomiting compared to placebo (odds ratio (OR): 3.17, 95% CI: 1.57 to 6.43, P = 0.001). After solving heterogeneity, results showed a statistically significant incidence of diarrhea in the trofinetide (200 mg) group compared to placebo (OR: 18.51, 95% CI: 9.30 to 36.84, P ≤ 0.00001).ConclusionsTrofinetide demonstrated statistically significant improvements in CGI-I and RSBQ in pediatrics and adult patients with Rett. Side effects are limited to vomiting and diarrhea. Although diarrhea yielded an insignificant result in our analysis, it emerged as a cause for treatment discontinuation in the participating trials, and a statistically significant risk for diarrhea emerged when excluding the study using a lower dose of the drug, hence causing heterogeneity, in the meta-analysis. Given the diverse genetic landscape of RTT, future RCTs investigating correlations between RTT genotype and phenotypic improvements by trofinetide will be beneficial. RCTs encompassing male patients with larger and longer cohorts are recommended.Graphical

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series.

Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.

Co-Occurring Methylenetetrahydrofolate Reductase (MTHFR) rs1801133 and rs1801131 Genotypes as Associative Genetic Modifiers of Clinical Severity in Rett Syndrome.

Remethylation disorders such as 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency reduce the remethylation of homocysteine to methionine. The resulting hyperhomocysteinemia can lead to serious neurological consequences and multisystem toxicity. The role of MTHFR genotypes has not been investigated in patients with Rett Syndrome (RTT). In this study, we sought to assess the impact of co-occurring MTHFR genotypes on symptom profiles in RTT. Using pharmacogenomic (PGx) testing, the MTHFR genetic polymorphisms rs1801133 (c.665C>T mutation) and rs1801131 (c.1286A>C mutation) were determined in 65 patients (18.7 years ± 12.1 [mean ± standard deviation]) with RTT as part of routine clinical care within the Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, a National and Specialist Child and Adolescent Mental Health Service (CAMHS) in the UK. The clinical severity of patients was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI). The clinical severity symptom distribution varied between the homozygous and heterozygous MTHFR rs1801133 and rs1801131 genotypes. Those with the homozygous genotype had a narrower spread of severity scores across several domains (language and communication, ambulation, hand-use and eye contact clinical domains). Patients with the homozygous genotype had statistically significantly greater CGI-Severity scores than individuals with a non-homozygous MTHFR genotype (Z = -2.44, p = 0.015). When comparing the ratings of moderately impaired (4), markedly impaired (5), severely impaired (6) and extremely impaired (7), individuals with the homozygous MTHFR genotype were more impaired than those with the non-homozygous MTHFR genotype (Z = -2.06, p = 0.039). There was no statistically significant difference in the number of prescribed anti-epileptic drugs between the genotypes. Our findings show that in those with a pathogenic RTT genetic variant, co-occurring homozygotic MTHFR rs1801133 and rs1801131 polymorphisms may act as associative genetic modifiers of clinical severity in a subset of patients. Profiling of rs1801133 and rs1801131 in RTT may therefore be useful, especially for high-risk patients who may be at the most risk from symptom deterioration.

The Impact of Umbilical Cord Mesenchymal Stem Cells on Motor Function in Children with Cerebral Palsy: Results of a Real-world, Compassionate use Study.

The aim of this study was to analyze the impact of human umbilical cord-derived MSCs (hUC-MSCs) on motor function in children with cerebral palsy (CP). The study enrolled 152 children with CP who received up to two courses of five hUC-MSCs injections. Children's motor functions were assessed with the Gross Motor Function Measure (GMFM), 6-Minute Walk Test (6-MWT), Timed Up and Go test (Up&Go test), and Lovett's test, and mental abilities were assessed with the Clinical Global Impression (CGI) scale. Data collected at visit 1 (baseline) and visit 5 (after four injections) were analyzed retrospectively. After four hUC-MSCs administrations, all evaluated parameters improved. The change in GMFM score, by a median of 1.9 points (IQR: 0.0-8.0), correlated with age. This change was observed in all GFMCS groups and was noticed in all assessed GMFM areas. A median increase of 75m (IQR: 20.0-115.0) was noted on the 6-MWT, and this correlated with GMFM score change. Time on the Up&Go test was reduced by a median of 2s (IQR: -3 to - 1) and the change correlated with age, GMFM score at baseline, and the difference observed on the 6-MWT. Results of Lovett's test indicated slight changes in muscle strength. According to the CGI, 75.5% (96/151) of children were seriously (level VI) or significantly ill (level V) at the 1st visit, with any improvement observed in 63.6% (96/151) of patients at the 5th visit, 23.8% (36/151) with improvement (level II) or great improvement (level I). In conclusion, the application of hUC-MSCs generally enhanced functional performance, but individual responses varied. The therapy also benefited children with high level of disability but not to the same extent as the initially less disabled children. Although younger patients responded better to the treatment, older children can also benefit. Trial Registration152/2018/KB/VII and 119/2021/KB/VIII. Retrospective registration in ClinicalTrials: ongoing.