Social support among individuals with bipolar disorder during euthymic phase: A systematic review.

INTRODUCTION: In spite of the recent increase in scientific publications showing an expressive interest in studies about social support, there are still scarce publications regarding this thematic and bipolar disorder, mostly when evaluating the individuals in the state of euthymia. Euthymia referred a state that a bipolar patient does not have signs/symptoms of (hipo)mania or depression, thus assessing individuals in this state may reduce response bias. OBJECTIVE: The objective of this study is to identify the impact of social support on bipolar disorder in patients in the euthymic phase. METHODS: A systematic search of observational studies on PubMed/Medline, PsycINFO, EMBASE, Scopus and Web of Science databases was performed from February 2021 to August 2022. RESULTS: In total, seven studies fulfilled the eligibility criteria. According to three studies, bipolar disorder patients had lower social support than healthy controls. Contrastingly, one study showed bipolar patients did not have different social support compared to healthy controls. CONCLUSIONS: Even though few papers with low or middle risk of bias were included in this review, we found that not only does social support could act as a protective factor for bipolar patients but also that clinical manifestations of the disorder seem to affect social support. This systematic review suggests the narrowed evidence field with different measures and type of evaluation from studies on social support and bipolar disorder, which highlights the need for further investigations on this theme.

Esketamine for Unipolar Major Depression With Psychotic Features: A Retrospective Chart Review and Comparison With Nonpsychotic Depression.

PURPOSES/BACKGROUND: The aims of the study were to assess subanesthetic esketamine as an antidepressant for major depressive disorder with psychotic features (PMDD) and to compare posttreatment symptoms among those with PMDD to a sample of nonpsychotic depression (major depressive disorder [MDD]). METHODS/PROCEDURES: This study is a retrospective chart review of patients with major depression and current psychotic symptoms, treated with a single parenteral 0.5-mg/kg dose of esketamine. Depression symptoms were assessed at baseline and 24-hour posttreatment with the Montgomery-Åsberg Depression Rating Scale. Individuals with PMDD were matched in a 1:2 ratio to nonpsychotic MDD patients from a randomized, noninferiority clinical trial of esketamine. FINDINGS/RESULTS: A total of 15 individuals with PMDD were included, which had higher baseline depression scores (PMDD = 40.9, MDD = 33.6, P = 0.004). A statistically significant change in depressive symptoms was found for the PMDD sample (ß = -16.20 [95% confidence interval, -23.30 to -9.10], P < 0.001), and no difference between PMDD and MDD groups was observed in the matched-sample analysis (ß = -2.2 [95% confidence interval, -9.32 to 4.58], P = 0.537). Treatment-induced dissociative symptoms were present for both groups, self-contained to within 2 hours after treatment, and no exacerbation of psychotic symptoms was found in clinical assessments. IMPLICATIONS/CONCLUSIONS: Results suggest a single 0.5-mg/kg dose of esketamine may benefit individuals with PMDD, and the symptom reduction may be comparable with esketamine's effects for MDD. Furthermore, esketamine may induce an antidepressant response in those with PMDD without complication of psychotic symptoms. Future research with controlled designs is warranted.

Clinical predictors of depressive symptom remission and response after racemic ketamine and esketamine infusion in treatment-resistant depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide and most people do not achieve symptom remission. Treatment-resistant depression (TRD) is characterized by the failure of at least one adequate trial of a major class of antidepressant, with adequate time and dosage. We aimed to identify clinical predictors of depressive symptom remission and response 24 h and 7 days after racemic ketamine and esketamine infusions. METHODS: A randomized, double-blind, active-controlled, non-inferiority trial using ketamine and esketamine in TRD. Individuals diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders version IV and fulfilling TRD criteria were recruited from March 2017 to June 2018. Participants received a single subanesthetic dose of ketamine (0.5 mg/kg) or esketamine (0.25 mg/kg) for 40 min. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and symptom remission was defined as a MADRS score ≤7 and response defined as ≥50% reduction in depressive symptom severity, 24 h and 7 days after the infusion. Clinical variables were selected based on previous clinical trials. Stepwise backward logistic regression was used, considering a confidence level of 95%. RESULTS: 61 subjects were included: 39 (63.9%) were females with a mean age of 47.2 ± 14.9. Higher number of therapeutic failures (Odds Ratio (OR) = 0.677; 95% confidence interval (CI): 0.47-0.97) and higher severity of illness (OR = 0.912; 95% CI: 0.83-0.99) were associated with fewer remissions of depressive symptoms 7 days after intervention, and with fewer response in 24 h (OR = 0.583; 95% CI: 0,40; 0,84 and OR = 0.909; 95% CI: 0,83; 0,99, respectively). CONCLUSION: Number of treatment failures and severity of illness were predictors of fewer remissions and responses of depressive symptoms in this TRD population. Study of predictors of remission may contribute to better selection patients that may benefit from receiving ketamine.

Autonomy, procedural and substantive: a discussion of the ethics of cognitive enhancement.

As cognitive enhancement research advances, important ethical questions regarding individual autonomy and freedom are raised. Advocates of cognitive enhancement frequently adopt a procedural approach to autonomy, arguing that enhancers improve an individual's reasoning capabilities, which are quintessential to being an autonomous agent. On the other hand, critics adopt a more nuanced approach by considering matters of authenticity and self-identity, which go beyond the mere assessment of one's reasoning capacities. Both positions, nevertheless, require further philosophical scrutiny. In this paper, we investigate the ethics of cognitive enhancement through the lenses of political and philosophical arguments about autonomy and freedom. In so doing, we contend that a substantive, relational account of individual autonomy offers a more holistic understanding of the ethical concerns of cognitive enhancement.

Analysis of the superior temporal gyrus as a possible biomarker in schizophrenia using voxel-based morphometry of the brain magnetic resonance imaging: a comprehensive review.

The lack of predictive biomarkers for therapeutic responses to schizophrenia leads clinical procedures to be decided without taking into account the subjects' neuroanatomical features, a consideration, which could help in identifying specific pharmacological treatments for the remission of symptoms. Magnetic resonance imaging (MRI) is a technique widely used for radiological diagnosis and produces 3-dimensional images in excellent anatomical detail, and with a great capacity to differentiate soft tissue. Various MRI techniques of the human brain have emerged as a result of research, enabling structural tests that may help to in consolidate previous findings and lead to the discovery of new patterns of abnormality in schizophrenia. A literature review was undertaken to assess the superior temporal gyrus (STG) as a possible biomarker in schizophrenia with the use of voxel-based morphometry of the brain using MRI. Many findings in studies of schizophrenia using MRI have been inconclusive and, in some cases, conflicting, although interesting results have been obtained when attempting to correlate neuroimaging changes with aspects of clinical features and prognosis of the disease. The individuals affected by this mental illness appear to have smaller STG volumes when compared to healthy controls and also to subjects with a diagnosis of first-episode affective psychosis or groups of individuals at high risk of psychosis. However, the wide variety of definitions surrounding the STG found in a number of studies is a contributing factor to the lack of correlation between brain abnormalities and clinical symptoms. For instance, disagreements have arisen due to studies using regions of interest to analyze the STG whereas other studies prioritize the analysis of only STG subregions or specific supratemporal plane regions. It is necessary to standardize the nomenclature of the areas to be studied in the future, as this will enable more consistent results, allowing higher clinical and morphological correlations.

Intravenous arketamine for treatment-resistant depression: open-label pilot study.

We aimed to analyze the efficacy and safety of arketamine, the R(-)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6-27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.

KPTN gene homozygous variant-related syndrome in the northeast of Brazil: A case report.

Alteration of the KPTN gene, responsible for the coding of kaptin (a protein involved in actin cytoskeletal dynamics), causes a syndrome characterized by macrocephaly, neurodevelopmental delay and epileptic seizures. We report the first Brazilian case of KPTN gene variation, previously described in nine subjects from four interlinked families from an Amish community in Ohio, two Estonian siblings and a 9-year-old boy from Kansas City. We report a case of KPTN-related syndrome in a 5-year-old child which presented macrocephaly, muscular hypotonia, and global development delay. The neurological examination revealed below-expected performance in coordination and balance tests, dyspraxia, and hand-mouth synkinesia. Expressive language was characterized by phono-articulatory imprecision, abundance of phonological processes and morphosyntactic immaturity. Neuropsychological assessment revealed intellectual disability with impairment of verbal and executive functions. Exome sequencing was performed. Analysis revealed a homozygous 2-nucleotide duplication c.597_598dup p.(Ser200Ilefs*55) in the KPTN gene, which is predicted to lead to a translational frameshift and formation of a premature stop codon. The phenotypic profile is similar to the cases described in the other families. Presence of macrocephaly and delayed development indicate the possibility of KPTN gene variation. Genetic testing should be carried out at an early stage in order to reach a timely diagnosis.

Prevalence of depression, anxiety, and substance-related disorders in parents of children with cerebral palsy: a systematic review.

AIM: To estimate the prevalence of mental illness in parents of children with cerebral palsy (CP). METHOD: This is a systematic review that follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols in the search for observational studies determining the prevalence of depression, anxiety, and substance abuse in parents of individuals with CP. The information sources used for this study were: PubMed, SciELO, Cochrane Library, Clinical Trials, and Biblioteca Virtual de Saúde. RESULTS: Fourteen articles were selected and included, investigating 1264 mothers and 105 fathers of children with CP. Data extracted for analysis were divided into three categories: study data, data about participants with CP, and data about parents. All studies included volunteer parents, of whom 95 per cent were female. INTERPRETATION: CP is related to a higher prevalence of symptoms of depression and anxiety in parents. Factors such as a child's degree of functionality and socioeconomic level may influence the frequency of mental disorders in parents. However, these studies have heterogeneous samples and applied different criteria to characterize their populations. WHAT THIS PAPER ADDS: Depression and anxiety are more prevalent for parents of children with cerebral palsy (CP) than parents of typically developing children. The child's illness severity is a risk factor for mental illness in parents of children with CP. The more time spent on child care, the higher the risk of mental illness among mothers of children with CP. There is a lack of reliable data in the literature on substance abuse in parents of children with CP.

PREVALENCIA DE DEPRESIÓN, ANSIEDAD Y TRASTORNOS RELACIONADOS AL USO DE SUSTANCIAS EN PADRES DE NIÑOS CON PARÁLISIS CEREBRAL: REVISIÓN SISTEMÁTICA: OBJETIVO: Calcular la prevalencia de enfermedad mental en padres de niños con parálisis cerebral (PC). METODO: Esta es una revisión sistemática que sigue la metodología para Protocolos de Revisiones Sistemáticas y Metaanálisis en la búsqueda de estudios observacionales que determinan la prevalencia de depresión, ansiedad y abuso de sustancias en padres de individuos con PC. Las fuentes de información utilizadas para este estudio fueron: PubMed, SciELO, LILACS, Biblioteca Cochrane, Clinical Trials, y Biblioteca Virtual de Saúde. RESULTADOS: Se seleccionaron e incluyeron 14 artículos, investigando 1.264 madres y 105 padres de niños con PC. Los datos extraídos para análisis fueron divididos en tres categorías: datos de estudio, datos sobre participantes con PC y datos sobre padres. Todos los estudios incluyeron padres voluntarios, de quienes el 95% fueron del sexo femenino. INTERPRETACIÓN: La PC está relacionada a una mayor prevalencia de síntomas de depresión y ansiedad en los padres. Factores como el grado de funcionalidad del niño y el nivel socioeconómico pueden influir en la frecuencia de trastornos cognitivos en los padres. Sin embargo, estos estudios tienen muestras heterogéneas y utilizaron diferentes criterios para caracterizar a las poblaciones.

PREVALÊNCIA DE DEPRESSÃO, ANSIEDADE, E DESORDENS RELACIONADAS AO USO DE SUBSTÂNCIAS EM PAIS DE CRIANÇAS COM PARALISIA CEREBRAL: UMA REVISÃO SISTEMÁTICA: OBJETIVO: Estimar a prevalência de doença mental em pais de crianças com paralisia cerebral (PC). MÉTODO: Esta é uma revisão sistemática que segue o protocol Itens preferenciais para reportar em revisões sistemáticas e metanálises na busca por estudos observacionais que determinassem a prevalência de depressão, ansiedade, e abuso de substâncias nos pais de indivíduos com PC. As fontes de informação usadas para este estudo foram: PubMed, SciELO, LILACS, Cochrane Library, Clinical Trials, e Biblioteca Virtual de Saúde RESULTADOS: Quatorze artigos foram selecionados e incluídos, investigando 1264 mães e 105 pais de crianças com PC. Os dados extraídos para análise foram divididos em três categorias: dados dos estudos, dados sobre os participantes com PC, e dados sobre os pais. Todos os estudos incluíram pais voluntários, dos quais 95 por cento eram mulheres. INTERPRETAÇÃO: A PC se relaciona com maior prevalência de sintomas de depressão e ansiedade em pais. Fatores como grau de funcionalidade da criança e nível socioeconomico podem infuenciar a frequência de desordens cognitivas nos pais. No entanto, estes estudos têm amostras heterogêneas e aplicaram diferentes critérios para caracterizar suas populações.

Esketamine Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder: A Retrospective Chart Review.

OBJECTIVE: Converging evidence supports the role of the glutamate, an excitatory amino acid neurotransmitter, in the pathophysiology of obsessive-compulsive disorder (OCD). Ketamine and esketamine, both noncompetitive N -methyl- d -aspartate antagonists, have emerged as a promising medication for this psychiatric disorder, given its possible efficacy with faster onset and good tolerability. The purpose of this retrospective chart review is to evaluate whether unbiased clinical documentation supports formal clinical trials of esketamine for an OCD indication. METHODS: A retrospective chart review of patients with treatment-resistant OCD receiving a single dose of esketamine (0.5mg/kg) added to standard therapy was conducted. The Yale-Brown Obsessive-Compulsive Scale and the Montgomery-Åsberg Depression Rating Scale were used to evaluate OCD and depressive symptoms respectively at baseline, 24 hours, and 7 days after esketamine administration. Descriptive statistics were used to analyze the data. RESULTS: Eight subjects were identified in this retrospective chart review: esketamine was administered subcutaneously in 7 and intravenously in 1. One week after infusion, 25% of the sample met criteria for treatment response and 50% for partial response. Major depressive disorder was a comorbid diagnosis in 75% of the sample and 2 of these subjects showed a positive antidepressant response. CONCLUSIONS: Our findings provide preliminary evidence that esketamine may reduce obsessive-compulsive symptoms in a subset of treatment-resistant OCD patients.

Hikikomori Syndrome and Digital Technologies: A Systematic Review.

ABSTRACT: Hikikomori syndrome (HS) is a voluntary prolonged social isolation associated with personal and community impact. Previous evidence pointed out a possible relationship between this syndrome with addiction to digital technologies. Here we aim to understand the relationship between HS and digital technology use, overuse, and addictive behaviors, as well as potential therapeutic approaches.We conducted a systematic review of observational and intervention studies available in PubMed/MEDLINE, LILACS, IBECS, Embase, PsycINFO, and SciELO databases, following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA 2020) criteria. The risk of bias was assessed with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and Consensus-based Clinical Case Reporting Guideline Development (CARE). Eligibility criteria were pre-, at-risk populations, or those with HS diagnosis, and any kind of technological overuse. Seventeen studies were included in the review, of which eight were cross-sectional, eight were case reports, and one was quasi-experimental. Hikikomori syndrome was associated with addition to digital technologies; no cultural differences were found. Environmental factors, such as a history of bullying, low self-esteem, and grief were identified as precursors of addictive behaviors. The included articles addressed addiction to digital technologies, electronic games, and social networks, among others, in HS. HS is cross-culturally associated with such addiction. The management of these patients remains challenging, and no target evidence-based treatments have been developed. The studies included in this review had several limitations, and more studies with a higher level of evidence are needed to support the results.

Taking modern psychiatry into the metaverse: Integrating augmented, virtual, and mixed reality technologies into psychiatric care.

The landscape of psychiatry is ever evolving and has recently begun to be influenced more heavily by new technologies. One novel technology which may have particular application to psychiatry is the metaverse, a three-dimensional digital social platform accessed via augmented, virtual, and mixed reality (AR/VR/MR). The metaverse allows the interaction of users in a virtual world which can be measured and manipulated, posing at once exciting new possibilities and significant potential challenges and risks. While the final form of the nascent metaverse is not yet clear, the immersive simulation and holographic mixed reality-based worlds made possible by the metaverse have the potential to redefine neuropsychiatric care for both patients and their providers. While a number of applications for this technology can be envisioned, this article will focus on leveraging the metaverse in three specific domains: medical education, brain stimulation, and biofeedback. Within medical education, the metaverse could allow for more precise feedback to students performing patient interviews as well as the ability to more easily disseminate highly specialized technical skills, such as those used in advanced neurostimulation paradigms. Examples of potential applications in brain stimulation and biofeedback range from using AR to improve precision targeting of non-invasive neuromodulation modalities to more innovative practices, such as using physiological and behavioral measures derived from interactions in VR environments to directly inform and personalize treatment parameters for patients. Along with promising future applications, we also discuss ethical implications and data security concerns that arise when considering the introduction of the metaverse and related AR/VR technologies to psychiatric research and care.

Efficacy and safety of transcranial direct current stimulation over the left dorsolateral prefrontal cortex in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, triple-blinded, sham-controlled, crossover trial.

Introduction: Although pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) has demonstrated efficacy, several individuals persist in experiencing social and academic impairment. Additionally, the occurrence of significant side effects may render the use of psychotropic medications untenable. However, Transcranial Direct Current Stimulation (tDCS), a non-invasive brain stimulation technique, shows promising results in treating ADHD. Objectives: To investigate the efficacy and safety of tDCS on the performance of children and adolescents with ADHD in neuropsychological tests involving visual attention, visual and verbal working memory, and inhibitory control. Methodology: This study was a triple-blind, randomized, sham-controlled, crossover clinical trial. The intervention consisted of a daily session of tDCS (2 mA) or sham targeting the left dorsolateral prefrontal cortex (L-DLPFC), for 30 min, on five consecutive days. The primary outcome was change in the Visual Attention Test, Fourth Edition (TAVIS-4) before and after each intervention. Subjects were also evaluated pre and post-tDCS using the Digit Span subtest of the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), the Developmental Neuropsychological Assessment, Second Edition (NEPSY-II) Inhibiting Response (IR) subtest, and the Corsi Block-Tapping Task. Results: Fifteen individuals were included, and no statistically significant difference was observed when comparing the results of the TAVIS-4, the IR of NEPSY-II, and the intragroup Digit Span subtest of WISC-V undertaken before and after the procedure. Adverse events were mainly self-limiting and transient. The participants did not perceive any benefit from tDCS when measured on the Patient Global Impression of Improvement (PGI-I) Scale. Conclusion: This study did not meet its primary endpoint and found no performance enhancement in any investigated neuropsychological outcomes relating to the intervention group.

Psychopathological symptoms in parents and siblings of people on the autism spectrum: A systematic review and meta-analysis.

Parents and siblings of children on the autism spectrum experience significant distress, and for this reason, it is essential to understand the most prevalent psychopathological symptoms among this population. This work aims to establish the prevalence of psychopathological symptoms in parents and siblings of individuals on the autism spectrum, following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) criteria. Searches were carried out using the PubMed/Medline, Embase, PsycINFO, SciELO, and Biblioteca Virtual em Saúde (BVS) databases. Twenty-three articles were included in this review. Depressive symptoms were the most frequently reported conditions, with a higher prevalence in mothers of children on the autism spectrum. In the meta-analysis, mothers of children on the autism spectrum scored higher by 0.42 standard deviations on the symptom scales (SMD 0.42; CI 0.25-0.59), with low statistical heterogeneity (I2 0%, p = 0.5) when compared with mothers of children with atypical development. The psychopathological symptoms of relatives should be investigated as part of the follow-up procedures for the child on the autism spectrum to facilitate their treatment.

Arketamine for bipolar depression: Open-label, dose-escalation, pilot study.

There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.

Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial.

OBJECTIVES: Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). METHODS: Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. RESULTS: There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. CONCLUSION: There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion.

Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.

BACKGROUND: Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD), and conflicting evidence suggests that induced dissociation by these drugs can be a clinical predictor of esketamine/ketamine's efficacy. METHODS: This study is a secondary analysis from a bi-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of esketamine (.25 mg/kg) or racemic ketamine (.50 mg/kg) over 40 minutes. Dissociative symptoms were assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes following the beginning of the infusion. The variation in depression scores was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hrs, 72 hrs, and 7 days following infusion. RESULTS: Sixty-one patients were included in the analysis. Examining CADSS scores of 15 or below, for every 1-point increment in the CADSS score, there was a mean change of -0.5 (SD = 0.25; p-value 0.04) of predicted MADRS score from baseline to 24 hrs. The results for 72 hrs and 7 days following infusion were not significant. Limitations: This study was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, therefore confounding variables for this relationship were not controlled. CONCLUSION: We suggest a positive relationship between dissociation intensity, measured by CADSS, and antidepressant effect 24 hours after ketamine and esketamine infusion for a CADSS score of up to 15 points.

Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study.

BACKGROUND: Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. METHODS: This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. RESULTS: Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LIMITATIONS: This was a pilot study with a small sample and underpowered. CONCLUSIONS: Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

A Novel PACS1 Variant Associated With Schuurs-Hoeijmakers Syndrome Phenotype in an Indigenous Descendant in Brazil: A Case Report.

Schuurs-Hoeijmakers syndrome, an autosomal dominant disorder associated with mutations in the PACS1 gene, was initially identified in two unrelated children of European descent from a cohort of individuals with intellectual disabilities. This gene alteration significantly reduced cranial cartilaginous structures, inducing craniofacial alterations predominantly in a dominant-negative fashion. In this paper, we report a novel variant of PACS1 associated with Schuurs-Hoeijmakers syndrome: a boy aged two years and nine months of indigenous descent presenting with motor stereotypies, atypical sensory searches, language delay, and low socio-interactional reciprocity. Whole exome sequencing confirmed the presence of a heterozygous missense mutation c.943C>T p. (Arg315Trp) in the PACS1 gene. The phenotypic profile identified was similar to the other cases of Schuurs-Hoeijmakers syndrome described in the literature. This report highlights the importance of considering the possibility of PACS1 gene alterations and a diagnosis of Schuurs-Hoeijmakers syndrome in patients presenting craniofacial alterations associated with autistic features, psychomotor and language development delay.

Metabolomics of Major Depressive Disorder: A Systematic Review of Clinical Studies.

Although the understanding of the pathophysiology of major depressive disorder (MDD) has advanced greatly, this has not been translated into improved outcomes. To date, no biomarkers have been identified for the diagnosis, prognosis, and therapeutic management of MDD. Thus, we aim to review the biomarkers that are differentially expressed in MDD. A systematic review was conducted in January 2022 in the PubMed/MEDLINE, Scopus, Embase, PsycINFO, and Gale Academic OneFile databases for clinical studies published from January 2001 onward using the following terms: "Depression" OR "Depressive disorder" AND "Metabolomic." Multiple metabolites were found at altered levels in MDD, demonstrating the involvement of cellular signaling metabolites, components of the cell membrane, neurotransmitters, inflammatory and immunological mediators, hormone activators and precursors, and sleep controllers. Kynurenine and acylcarnitine were identified as consistent with depression and response to treatment. The most consistent evidence found was regarding kynurenine and acylcarnitine. Although the data obtained allow us to identify how metabolic pathways are affected in MDD, there is still not enough evidence to propose changes to current diagnostic and therapeutic actions. Some limitations are the heterogeneity of studies on metabolites, methods for detection, analyzed body fluids, and treatments used. The experiments contemplated in the review identified increased or reduced levels of metabolites, but not necessarily increased or reduced the activity of the associated pathways. The information acquired through metabolomic analyses does not specify whether the changes identified in the metabolites are a cause or a consequence of the pathology.

Botulinum Toxin Type A in the Spasticity of Cerebral Palsy Related to Congenital Zika Syndrome: An Observational Study.

PURPOSE: Investigate the effect of botulinum toxin type-A (BoNT-A) on spasticity and motor performance in children with Cerebral Palsy (CP) related to Congenital Zika Syndrome (CZS). METHODS: Prospective longitudinal observational study of 34 children with CP referred for BoNT-A treatment. Outcomes were evaluated with a muscle tone assessment scale (Modified Ashworth Scale - MAS) and the Patients' Global Impression of Improvement (PGI-I) scale. RESULTS: Mean age was 32.06 ± 3.07 months and 85% were classified as Gross Motor Function Classification System (GMFCS) V. Primitive reflexes were present in 56% of the sample. The majority of the parents (97.9%) reported improvement in range of motion or reduction in spasticity after treatment with botulinum toxin. No side effects were recorded. When compared to the baseline, median reduction in the MAS was 0.5 (IQR = 0). CONCLUSIONS: The findings of this study suggest that BoNT-A may effectively promote functional improvements and reduce muscle tone, improving the child's and family's quality of life.