Showing papers in "Cns Spectrums in 2022"
TL;DR: The most relevant findings about the overlap between different kinds of feeding and eating disorders and the autism spectrum, taking into account the most recent hypotheses about the psychopathology of both these conditions, are summarized in this paper .
Abstract: In the last decades, increasing attention has been provided to socio-cultural and neurobiological factors involved in the psychopathology of feeding and eating disorders (FED), encouraging a multifactorial approach. In this framework, several authors stressed an association between FED and other kinds of psychiatric disorders from both a psychopathological and a neurobiological point of view. In particular, many promising contributions are focusing on the possible link between FED and autism spectrum disorder (ASD). Growing interest about this association rose from the frequently reported evidence of ASD-like traits amongst FED patients and abnormal eating behaviors amongst patients with ASD. This narrative review overview aims to summarize the most relevant findings about the overlap between different kinds of FED and the autism spectrum, taking into account the most recent hypotheses about the psychopathology of both these conditions. While most of the studies focused on anorexia nervosa, both ASD and autistic traits seem to be detectable also in other kinds of FED. In addition, the recently increased interest toward a dimensional approach to psychopathology led to progressively broadening the concept of ASD, focusing on its subthreshold and gender-specific manifestations and on its link with other psychiatric conditions, including FED. Globally the studies summarized here provide further support to theoretical models featuring a neurodevelopmental approach for mental disorders. In particular, FED have been conceptualized as a possible psychopathological trajectory of a neurodevelopmental alteration, toward which female gender would act as one of many predisposing factors.
15 citations
TL;DR: In this article , the authors compared the clinical features between males and females with Tourette syndrome and chronic tic disorder, and found that males had a statistically higher frequency of complex motor tics and earlier age at onset than females in the multivariate regression analysis.
Abstract: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder.We studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients.Age ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging.A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.
13 citations
TL;DR: A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.
Abstract: Abstract Background Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder. Methods We studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients. Results Age ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging. Conclusions A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.
12 citations
TL;DR: The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression, and prior to electroconvulsive therapy — while taking into account of patient preference, and is presented as a new specialist-consensus standard.
Abstract: This article is a clinical guide which discusses the “ state-of-the-art ” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of expe-rience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion — this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy — while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “ bridging ” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
8 citations
TL;DR: In this article , the authors present a clinical guide for the use of MAOIs in modern psychiatric practice, which provides practical clinical advice, and is the basis for the rational use of these drugs.
Abstract: Abstract This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
8 citations
TL;DR: In this article , the authors reported possible features of female ASD phenotypes, suggesting that ASD females would focus on different kinds of interests with respect to males, including fictions, celebrities, or fashion.
Abstract: Recently, increasing literature is focusing on sex differences in the manifestations of autism spectrum disorder (ASD), highlighting the presence of several possible female-specific features of this condition. 1 Some authors also pointed out that ASD diagnostic criteria would be tailored on the typical male presentations of the disorder, leading to an under-recognition of ASD among females. Subsequently ASD females, in particular those without language or intellectual impairment, would likely receive other kinds of diagnoses, with a consequent negative impact on the course of the disease and on the treatment outcome. 1,2 One of the first line of investigations in this field focused on anorexia nervosa (AN). Intriguingly, AN shows an opposite gender ratio when compared to ASD, featuring a strikingly higher prevalence among females but also a familiar aggregation with ASD. 3 Moreover, the strong interest in diet and weight, together with the ritualized behaviors related to food preparation and consumption typical of AN were noted to resemble an autistic-like pattern of stereotyped interests and behaviors, although focused on food. AN patients were also reported to share with ASD the presence of social difficulties, lack of socioemotional reciprocity, and an altered theory of mind. Several epidemiological studies, including longitudinal ones, highlighted significant overlaps between AN and ASD diagnoses, while more recently the presence of significant autistic traits was reported also in other feeding and eating disorders (FED), such as bulimia nervosa or the emerging condition of orthorexia nervosa. 3 These findings progressively provided support to the possibility of a reconceptualiza-tion of AN as a female phenotype of ASD, and, in parallel, increased the interest in investigating other sex-specific manifestations of the autism spectrum. Several authors reported possible features of female ASD phenotypes, suggesting that ASD females would focus on different kinds of interests with respect to males, including fictions, celebrities, or fashion. 2,3 In addition, ASD females would often show a milder impairment in
6 citations
TL;DR: In this paper , the authors systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
Abstract: Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
6 citations
TL;DR: In this article , the authors present an abstract for this content, full HTML content is provided on this page, and a PDF of this content is also available in through the ‘Save PDF’ action button.
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4 citations
TL;DR: In this paper , the authors evaluated the levels of TRP and metabolites of the kynurenine pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms.
Abstract: Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms.A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects.ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables.Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.
4 citations
TL;DR: In this article , a systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit.
Abstract: In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls.A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were "hoarding disorder," "cognition," "neuropsychology," "cognitive impairment," and "cognitive deficit." We included original studies assessing cognitive functioning in patients with HD.We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case-control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients.Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.
4 citations
TL;DR: In this article , the authors systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
Abstract: Abstract Background Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers. Methods We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy. Results We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence. Conclusions Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
TL;DR: There is a serious and concerning divide among ones with autism spectrum disorders living in underserved areas as compared to urban residents and there is an urgent need for corrective measures to address these highly modifiable problems.
Abstract: Abstract The rural areas have been at the receiving end amidst mental health disparity across the USA. There is a serious and concerning divide among ones with autism spectrum disorders (ASDs) living in underserved areas as compared to urban residents. With the higher than ever prevalence of ASD as per the recent reports of the Centers for Disease Control and Prevention; there is a need for a closer look at the prevailing issues. The trends are reflecting marked underdiagnosis, late diagnosis, lack of evidence-based diagnostic measures and interventions. These factors interplay in worsening the mental health crisis and there is an urgent need for corrective measures to address these highly modifiable problems.
TL;DR: Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls, and further work is needed to explore social cognition and the impact of emotion in cognitive performanceIn HD patients.
Abstract: Abstract Objective In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls. Methods A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were “hoarding disorder,” “cognition,” “neuropsychology,” “cognitive impairment,” and “cognitive deficit.” We included original studies assessing cognitive functioning in patients with HD. Results We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case–control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients. Conclusion Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.
TL;DR: In this paper , the authors have pointed out that there is a serious and concerning divide among ones with autism spectrum disorders living in underserved areas as compared to urban residents and there is an urgent need for corrective measures to address these highly modifiable problems.
Abstract: The rural areas have been at the receiving end amidst mental health disparity across the USA. There is a serious and concerning divide among ones with autism spectrum disorders (ASDs) living in underserved areas as compared to urban residents. With the higher than ever prevalence of ASD as per the recent reports of the Centers for Disease Control and Prevention; there is a need for a closer look at the prevailing issues. The trends are reflecting marked underdiagnosis, late diagnosis, lack of evidence-based diagnostic measures and interventions. These factors interplay in worsening the mental health crisis and there is an urgent need for corrective measures to address these highly modifiable problems.
TL;DR: In this article, the authors investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD, using a randomized double-blind, placebo-controlled study that involved the administration of a total of 20 sessions of RTMS (active/sham) to drug-naïve OCD patients.
Abstract: Abstract Background Obsessive–compulsive disorder (OCD) is a chronic psychiatric disorder that results in significant disability and substantial compromise in the quality of life. Until now, the role of repetitive transcranial magnetic stimulation (rTMS) has been primarily explored in individuals with treatment-resistant OCD. In this study, we investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD. Methods This is a randomized double-blind, placebo-controlled study that involved the administration of a total of 20 sessions of rTMS (active/sham) to drug-naïve OCD patients using a standard protocol (1-Hz; 20 trains [80 pulses/train]; 1600 pulses per session at 100% resting motor threshold) at supplementary motor area. All patients (active and sham) were started on escitalopram 10 mg/d, which was subsequently increased to 20 mg/d after 10 days. Results Out of the 24 patients, 13 received active and 11 received sham rTMS. At the end of rTMS therapy, there was a substantial reduction (P = .001) in total Yale-Brown Obsessive–Compulsive Scale, obsessions (P = .030) and compulsions (P = .001) between the groups. Only few patients (N = 8) reported mild side effect with rTMS, local pain, and headache being the commonest. The study revealed large effect size (Cohen’s d = 1.6) of rTMS as an early augmentation strategy in drug-free patients of OCD. Conclusions rTMS is a safe and effective early augmentation strategy in the management of OCD. Larger randomized controlled trials are required to establish the therapeutic role of rTMS as early augmentation in OCD.
TL;DR: In this article , the authors investigated a motor pattern of compulsive rituals with respect to corresponding ordinary behaviors and found that such a motor structure is independent from obsessive-compulsive psychopathology, whereas it results specifically associated with prepsychotic symptoms of schizophrenia.
Abstract: Abstract Background Studies investigating obsessive-compulsive disorder from an ethological approach have highlighted a specific motor pattern of compulsive rituals with respect to corresponding ordinary behaviors. Particularly, compulsive motor profile is built through the repetition of acts, with prevalence of nonfunctional ones and redirection of attention to its basic structural units. These formal features would characterize ritual behavior throughout evolution, from nonhuman animals to human cultures. However, no study to date has investigated a possible relationship between such motor profile and underlying psychopathology. Therefore, the first objective of the study was to confirm previous findings on a larger sample size of obsessive patients; the second objective was to elucidate whether motor profile might be associated with obsessive-compulsive psychopathology and/or prepsychotic symptoms of schizophrenia. Methods Twenty-one obsessive-compulsive outpatients provided a videotape of their rituals. An equal number of healthy controls, matched for sex and age, were registered for corresponding ordinary acts. Obsessive patients were administered the Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, and the Frankfurt Complaint Questionnaire. Results The results of the present study confirm that ritual compulsions present a specific motor structure characterized by repetition of both functional and nonfunctional acts and their longer duration. Such a motor pattern is independent from obsessive-compulsive psychopathology, whereas it results specifically associated with prepsychotic symptoms of schizophrenia. Conclusions We argue that this association may reflect the adaptive significance of ritual behavior across evolution, that is, its homeostatic function in conditions of unpredictability.
TL;DR: Relmada Therapeutics, Inc. as mentioned in this paper developed the Symptoms of Depression Questionnaire (SDQ), a patient-reported measure, was developed to capture the heterogeneity of symptoms of major depressive disorder (MDD).
Abstract: Major depressive disorder (MDD) is the second leading cause of disability and chronic disease burden in the United States. The importance of improving functional outcomes in MDD is increasingly recognized. The Symptoms of Depression Questionnaire (SDQ), a patient-reported measure, was developed to capture the heterogeneity of symptoms of MDD. REL-1017 (esmethadone HCl; d-methadone), is a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker and potential rapid antidepressant currently in Phase 3 development. In a Phase 2a trial, REL-1017 showed robust, rapid, and sustained antidepressant efficacy as adjunctive treatment in patients with MDD. The objective of this study was to assess the effects of REL-1017 on SDQ subscales to better characterize the functional implications of its therapeutic effects.A double-blind, placebo-controlled, inpatient, two-doses, 25 and 50 mg, three-arm, 1:1:1, randomized, phase 2a trial of REL-1017 was conducted at 10 centers in the United States. Least square (LS) mean scores and Cohen's effect sizes of the total score of a 44-item of SDQ and its 5 subscales: lassitude, mood, cognitive/social functioning (SDQ-1); anxiety, agitation, anger, and irritability (SDQ-2); desire to be dead (SDQ-3); disruptions in sleep quality (SDQ-4); changes in appetite and weight (SDQ-5) were compared between REL-1017 and placebo.A total of 62 adult male and female patients (18-65 years of age) diagnosed with MDD participated in the trial. On day 14, the last day of efficacy measurement, the difference from placebo of the LS mean (90% CI) for REL-1017 25 mg and REL-1017 50 mg groups, respectively, showed improvement for both tested doses on SDQ total score (-23.2; P = .0066 [effect size: 0.9]; -26.8 P = .0014 [effect size: 1.1]). Additionally, for SDQ subscales, REL-1017 25 mg and REL-1017 50 mg groups, respectively, showed significant improvement as compared with placebo: SDQ-1 (-13.9; P = .0025 [effect size: 1.0]; -15.0; P = .0009 [effect size: 1.1]), SDQ-2 (-4.6; P = .0398 [effect size: 0.7]; -7.2; P = .0012 [effect size: 1.1]) and SDQ-4 (-2.7; P = .0055 [effect size: 1.0]; -2.8; P = .0029 [effect size: 1.0]). No significant differences were observed between the treated groups and placebo in the SDQ-3 and SDQ-5 subscales.In patients with MDD, aside from improving the overall CFB compared to placebo in SDQ total score, REL-1017 resulted in clinically meaningful and statistically significant improvements in cognitive/motivational, anxiety/irritability, and sleep-specific domains. The robust, rapid, and sustained efficacy of REL-1017 for MDD is not limited to improving mood, but potentially extends to cognitive, motivational, sleep, and social functions, with potentially meaningful therapeutic and socioeconomic implications. These results may signal disease-modifying effects of esmethadone for MDD that may offer potential advantages over symptomatic treatment with standard antidepressants.Relmada Therapeutics, Inc.
TL;DR: In this paper , the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia was investigated in patients with depression and mania, and schizophrenia patients with high cognitive impairment.
Abstract: Abstract Objective To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia. Methods Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance. Results In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=−0.5 [P<.001]; 3 mg/d=−0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=−1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; −2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073). Conclusion These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.
TL;DR: The role of the endogenous opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects as mentioned in this paper .
Abstract: Abstract Background The endogenous opioid system affects metabolism, including weight regulation. Evidence from preclinical and clinical studies provides a rationale for targeting this system to mitigate weight-related side effects of antipsychotics. This review describes the role of the opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects. Methods A PubMed literature search was conducted to identify representative opioid antagonists and associated preclinical and clinical studies examining their potential for the regulation of weight and metabolism. Results The mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) types have overlapping but distinct patterns of central and peripheral expression, and each contributes to the regulation of body weight and metabolism. Three representative opioid antagonists (eg, naltrexone, samidorphan, and LY255582) were identified for illustration. These opioid antagonists differed in their receptor binding and pharmacokinetic profiles, including oral bioavailability, systemic clearance, and half-life, and were associated with varying effects on food intake, energy utilization, and metabolic dysregulation. Conclusions Preclinical and clinical data suggest that antagonism of the endogenous opioid system is a mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. However, evidence suggests that the differing roles of MOR, DOR, and KOR in metabolism, together with the differences in receptor binding, pharmacokinetic, and functional activity profiles of the opioid receptor antagonists discussed in this review, likely contribute to their differential pharmacodynamic effects and clinical outcomes observed regarding antipsychotic-associated weight gain.
TL;DR: The potential for use of psilocybin and psilocin as a treatment agent in neuropsychiatry has been investigated in this article , where the potential for harm is also assessed.
Abstract: Abstract Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.
TL;DR: The potential for use of psilocybin and psilocin as a treatment agent in neuropsychiatry has been investigated in this article and the potential for harm is also assessed.
Abstract: Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward. need for clinical supervision of hallucinogenic experiences. 7 Other limitations include drug safety concerns. This review investigates the pharmacology, risks, and benefits of psilocybin and scope the suitability of this agent as a future pharmacological treatment for a multitude of neuropsychiatric conditions.
TL;DR: In this paper , a randomized, placebo-controlled, double-blind trial was conducted to investigate whether a single intravenous dose of hydrocortisone administered within 6 hours after exposure to trauma would reduce the incidence of PTSD at the 13-month follow-up.
Abstract: A blunted response of the hypothalamic-pituitary-adrenal axis immediately after exposure to traumatic events has been proposed as a risk factor for posttraumatic stress disorder (PTSD). Accordingly, administration of hydrocortisone in the aftermath of a traumatic event is indicated. This study consisted of a randomized, placebo-controlled, double-blind trial investigating whether a single intravenous dose of hydrocortisone administered within 6 hours after exposure to trauma would reduce the incidence of PTSD at the 13-month follow-up.A total of 118 consented patients with acute stress symptoms were administered a single intravenous bolus of hydrocortisone/placebo within 6 hours of the traumatic event. Blood samples were taken before hydrocortisone administration.At 13 months, the hydrocortisone group did not differ from the placebo group regarding PTSD prevalence or symptom severity. However, a significant interaction between time of the trauma (ie, night, when cortisol's level is low) and treatment was found. Specifically, a lower prevalence of PTSD was found at the 13-month follow-up in the hydrocortisone night group.Administration of hydrocortisone within 6 hours of the traumatic event was not effective in preventing PTSD compared to placebo. However, nocturnal administration (when cortisol levels are low) may suggest a new venue for research.
TL;DR: The role of repetitive transcranial magnetic stimulation (rTMS) has been primarily explored in individuals with treatment-resistant OCD as mentioned in this paper , where the authors investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD.
Abstract: Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that results in significant disability and substantial compromise in the quality of life. Until now, the role of repetitive transcranial magnetic stimulation (rTMS) has been primarily explored in individuals with treatment-resistant OCD. In this study, we investigated the safety and efficacy of rTMS as an early augmentation strategy in drug-free patients with OCD.This is a randomized double-blind, placebo-controlled study that involved the administration of a total of 20 sessions of rTMS (active/sham) to drug-naïve OCD patients using a standard protocol (1-Hz; 20 trains [80 pulses/train]; 1600 pulses per session at 100% resting motor threshold) at supplementary motor area. All patients (active and sham) were started on escitalopram 10 mg/d, which was subsequently increased to 20 mg/d after 10 days.Out of the 24 patients, 13 received active and 11 received sham rTMS. At the end of rTMS therapy, there was a substantial reduction (P = .001) in total Yale-Brown Obsessive-Compulsive Scale, obsessions (P = .030) and compulsions (P = .001) between the groups. Only few patients (N = 8) reported mild side effect with rTMS, local pain, and headache being the commonest. The study revealed large effect size (Cohen's d = 1.6) of rTMS as an early augmentation strategy in drug-free patients of OCD.rTMS is a safe and effective early augmentation strategy in the management of OCD. Larger randomized controlled trials are required to establish the therapeutic role of rTMS as early augmentation in OCD.
TL;DR: The estimated societal burden of schizophrenia in the USA in 2019 was $330.6B, which represented a 93.5% increase from 2013 to 2019, after accounting for inflation.
Abstract: Abstract Background Schizophrenia is associated with health, social, and financial burdens for patients, caregivers, and society. Major systemic changes, reforms, and technological advances have happened in the USA since the prior estimate of the societal cost of schizophrenia, $155.7B in 2013. This study analyzes the most recent data and literature to update this estimate. Methods Direct and indirect costs associated with schizophrenia in the US in 2019 were estimated using a prevalence-based approach (ICD-10 codes: F20, F25). Direct healthcare costs were assessed retrospectively using a matched cohort design in the IBM Watson Health MarketScan Commercial, Medicare, and Medicaid databases from October 1, 2015, through December 31, 2019. Patients were matched to controls on demographics, insurance type, and index year. Direct nonhealthcare costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life years lost. Cost offsets were applied to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD. Results The estimated excess economic burden of schizophrenia in the US in 2019 was $330.6B, including $62.3B in direct healthcare costs (19%), $19.7B in direct nonhealthcare costs (5%), and $251.9B in excess indirect costs (76%). The largest drivers of indirect costs were caregiving ($112.3B), premature mortality ($77.9B), and unemployment ($54.2B). Conclusions The estimated societal burden of schizophrenia in the USA in 2019 was $330.6B, which represented a 93.5% increase from 2013 to 2019, after accounting for inflation. This study underscores the increasing and apparent burden of schizophrenia not only on the patient, but also on caregivers and society. Funding Sunovion Pharmaceuticals
TL;DR: It is described how Aripiprazole may have caused a worsening of psychiatric symptoms by blocking the antipsychotic effects of Paliperidone due to its strong binding affinity for the D2 receptor.
Abstract: Abstract Background Aripiprazole has high binding affinity for the dopamine D2 receptor, which is thought to be responsible for the antipsychotic effect, though aripiprazole is not the most potent of the second-generation antipsychotics. Theoretically, aripiprazole could displace or outcompete more potent antipsychotics, prompting decreased antipsychotic effect. We describe a case of aripiprazole potentially worsening psychiatric symptoms by blocking paliperidone. Case Ms. A is a 43-year-old woman with schizophrenia, multiple inpatient hospitalizations, and a history of court-ordered treatment. She historically has had good response to oral and long-acting formulations of risperidone and paliperidone. Ms. A requested a medication change and was transitioned to aripiprazole lauroxil injection with plan for bimonthly administration. Approximately 1 month after receiving her aripiprazole lauroxil injection, Ms. A presented to our CPEP due to symptoms of psychosis and was admitted to our inpatient unit. She was restarted on oral paliperidone, titrated up to her previously effective dose, and was transitioned to paliperidone palmitate LAI. In contrast to prior admissions, she did not respond well to paliperidone and displayed continued and worsened psychosis. Discussion Prior studies have examined how adding aripiprazole to another, more potent D2 antagonist can cause a relapse in psychotic symptoms; however, few studies have investigated the inverse relationship or mechanism. Those that have proposed mechanisms typically refer to aripiprazole’s partial agonist activity as the causative factor, rather than an impediment to antipsychotic binding which we have described. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of aripiprazole to avoid this phenomenon. Funding No Funding
TL;DR: In this article , the authors examined the efficacy of adjunctive deep transcranial magnetic stimulation (dTMS) in ameliorating the symptoms of OCD and the effect of dTMS on activation of brain regions while performing the Stroop task using functional magnetic resonance imaging (fMRI).
Abstract: Obsessive-compulsive disorder (OCD) is one of the most common neuropsychiatric disorders with lifetime prevalence higher than that of schizophrenia and bipolar disorders. Inadequate response to available pharmacological and psychotherapeutic interventions is common in OCD. Adjunctive brain stimulation methods to address the inadequate treatment response in OCD have found a special interest in research. This study aimed to examine the efficacy of adjunctive deep transcranial magnetic stimulation (dTMS) in ameliorating the symptoms of OCD and the effect of dTMS on activation of brain regions while performing the Stroop task using functional magnetic resonance imaging (fMRI).A total of 41 patients were assessed for the study out of which 15 OCD patients received 10 sessions of high-frequency dTMS using the H7 coil to target the anterior cingulate cortex and the medial prefrontal cortex over a period of 2 weeks. The Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used for the pre- and post-stimulation clinical assessment. fMRI was used to measure the activation of brain regions while performing the Stroop task.There was a significant improvement in the obsessive-compulsive, anxiety, and depressive symptoms after the 2 weeks of the dTMS treatment. A significant decrease in the activation of left caudate nucleus and adjacent white matter was noted while performing the Stroop task after the dTMS treatment.The study provides preliminary evidence for functional correlates of effectiveness of dTMS as an adjunctive treatment modality for OCD.
TL;DR: In this article , the authors compared the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among treatment-resistant depression patients.
Abstract: Ketamine, an N-methyl-d-aspartate receptor antagonist, has been "repurposed" as a rapid-acting antidepressant for treatment-resistant depression (TRD). The s-enantiomer of ketamine, "esketamine," was FDA approved for TRD and depressive symptoms in adults with major depressive disorder with suicidal ideations/behaviors. Intravenous (IV) ketamine, although financially less expensive, is often not covered by insurance and intranasal (IN) esketamine, although covered by insurance can be expensive. There is a paucity of literature on efficacy data comparing subanesthetic IV ketamine and IN esketamine for TRD in a real-world scenario. Thus, we conducted this study comparing the efficacy and the number of treatments required to achieve remission/response with repeated use of subanesthetic IV ketamine/IN esketamine among TRD patients.This was an observational study where we included adults (≥18 years) with TRD who provided consent and had received up to 6 IV ketamine infusions (0.5 mg/kg, infused over 40 minutes) or up to 8 intranasal (IN) esketamine (56/84 mg) treatments for TRD at the Mayo Clinic Depression Center. Depression symptoms were measured utilizing the self-report 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale before and 24 hours after ketamine/esketamine treatment. Remission and response were defined as QIDS-SR 16 score ≤5 and ≥50% change in QIDS-SR 16, respectively. Continuous variables are reported as means ± SD and categorical variables as counts and percentages. The Wilcoxon rank-sum test was used to compare continuous variables. Chi-square and Fisher's exact tests were used to compare categorical variables. The number of treatments to remission/response was calculated.Sixty-three adults with TRD, middle-aged (47.0 ± 12.1 years), predominantly female (65%), of which 76% (n = 48) and 24% (n = 15) received IV ketamine and IN esketamine, respectively. Mean (SE) change in QIDS-SR 16 score was -8.7 ± 0.7 (P < .001), a significant reduction (improvement) from baseline (mean ± SD = 17.6 ± 3.7). Overall remission and response rates were 36.5% and 55.6%, respectively in the acute phase. Response (56.3% vs 53.3%) and remission rates (39.6% vs 26.7%) were similar among patients who received IV ketamine or IN esketamine, respectively (P > .05). The mean number of treatments received to achieve response (2.5 ± 1.6 vs 4.6 ± 2.1) and remission (2.4 ± 1.3 vs 6.3 ± 2.4) were significantly lower among patients who received IV ketamine compared to IN esketamine (P < .005). Most patients tolerated both treatments well.Intravenous ketamine and intranasal esketamine showed similar response/remission in TRD patients but the number of treatments required to achieve response/remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions.No funding.
TL;DR: Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.
Abstract: BACKGROUND
Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.
AIM
To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.
METHODS
This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.
RESULTS
A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.
CONCLUSIONS
Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.
TL;DR: In this paper , a reward-based value-modulated attentional capture task was completed by a sample of nonclinical student participants-44 with high (HOC) and 48 with low (LOC) levels of OC symptoms.
Abstract: Recently, a novel approach to obsessive-compulsive disorder has emerged, implicating altered reward functioning in the disorder. Yet, no study to date has directly examined the attentional aspect of reward functioning in participants with obsessive-compulsive (OC) symptoms, with past research mostly relying on reaction-time-based tasks.A reward-based value-modulated attentional capture task was completed by a sample of nonclinical student participants-44 with high (HOC) and 48 with low (LOC) levels of OC symptoms. We measured the extent to which high and low reward-signaling distractors captured attention and impaired performance on the task, resulting in a lower possibility of obtaining a monetary reward. Attentional capture was indexed via fixation data, and further explored using saccade data.Both groups performed more poorly when a high-reward signaling distractor was present, compared to when a low-reward signaling distractor was present. Importantly, this difference was significantly greater in the HOC group, and was found to be driven by the specific effects of reward-signaling distractors. Similar results emerged when exploring saccade data, and remained significant after controlling for both addiction-related compulsivity and depressive symptoms.Current findings suggest that attentional reward-related functioning may be associated with OC symptoms. Different aspects of reward functioning, including attention, should be further explored and incorporated into future research and clinical endeavors.
TL;DR: In this paper , Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient.
Abstract: Background. Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown. Methods. In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores. Results. Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginalgyrus(SMG),especiallybetweenvermisVIandtheSMGintheattentionnetworks, andlowerRSFCbetweentherightsupplementarymotorareaandrightlateralparietalarea.Lower graymatter(GM)volumeintheSMGwasalsofound.RSFCwassignificantlycorrelatedwith clinicalratingscalescoresforallpatientswithEDduetoADHDorMDD.GMchangewas correlatedwithEDandMDDratingscalescores. Discussion. The cerebellum and attention networks might play major roles in ED pathophys-iology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.