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Medicina Sep 2023Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently... (Review)
Review
Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroaggression crises. Serotonin reuptake inhibitors, to decrease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As specific entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism..
Topics: Humans; Autistic Disorder; Stereotyped Behavior; Anxiety; Anxiety Disorders; Autism Spectrum Disorder
PubMed: 37714122
DOI: No ID Found -
Psychiatry Research Aug 2023Evidence supports the antidepressant effects of resistance exercise training (RET); however, findings among young adults at-risk for elevated depressive symptoms are... (Randomized Controlled Trial)
Randomized Controlled Trial
Evidence supports the antidepressant effects of resistance exercise training (RET); however, findings among young adults at-risk for elevated depressive symptoms are limited. This randomized controlled trial examined the effects of eight weeks of ecologically-valid, guidelines-based RET, compared to a wait-list control, on depressive symptoms among 55 young adults (26±5y; 36 female) with and without subclinical, or analogue, Generalized Anxiety Disorder (AGAD; Psychiatric Diagnostic Screening Questionnaire GAD subscale ≥6 and Penn State Worry Questionnaire ≥45) and Major Depressive Disorder (AMDD). Following a three-week familiarization period, participants completed one-on-one, twice-weekly RET sessions. The 16-item, self-reported Quick Inventory of Depressive Symptomatology (QIDS) assessed depressive symptoms. RM-ANCOVAs examined between-group differences, and significant interactions were decomposed with simple effects analysis. Hedges' d effect sizes (95%CI) quantified the magnitude of differences in change between groups across time. Stratified analyses were conducted among subsamples with AMDD and AGAD. There were no baseline depressive symptom differences between groups. Attendance was 83%, and compliance was 80%. RET induced statistically significant, clinically-meaningful, large-magnitude reductions in depressive symptoms from baseline to week eight in the total (d = 1.01; [95%CI: 0.44-1.57]), AMDD (d = 1.71; [95%CI: 0.96-2.46]), and AGAD (d = 1.39; [95%CI: 0.55-2.24]) samples. These findings support guidelines-based RET as a promising treatment for mild depression.
Topics: Humans; Female; Young Adult; Depression; Resistance Training; Depressive Disorder, Major; Exercise; Anxiety Disorders
PubMed: 37429171
DOI: 10.1016/j.psychres.2023.115322 -
JAMA Psychiatry Aug 2023The microbiota-gut-brain axis is a promising target for novel treatments for mood disorders, such as probiotics. However, few clinical trials have been conducted, and... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The microbiota-gut-brain axis is a promising target for novel treatments for mood disorders, such as probiotics. However, few clinical trials have been conducted, and further safety and efficacy data are needed to support this treatment approach.
OBJECTIVE
To provide acceptability and tolerability data and estimates of intervention effect size for probiotics as adjunctive treatment for patients with major depressive disorder (MDD).
DESIGN, SETTING, AND PARTICIPANTS
In this single-center, double-blind, placebo-controlled pilot randomized clinical trial, adults aged 18 to 55 years with MDD taking antidepressant medication but having an incomplete response were studied. A random sample was recruited from primary and secondary care services and general advertising in London, United Kingdom. Data were collected between September 2019 and May 2022 and analyzed between July and September 2022.
INTERVENTION
Multistrain probiotic (8 billion colony-forming units per day) or placebo daily for 8 weeks added to ongoing antidepressant medication.
MAIN OUTCOMES AND MEASURES
The pilot outcomes of the trial were retention, acceptability, tolerability, and estimates of putative treatment effect on clinical symptoms (depression: Hamilton Depression Rating Scale [HAMD-17] and Inventory of Depressive Symptomatology [IDS] scores; anxiety: Hamilton Anxiety Rating Scale [HAMA] and General Anxiety Disorder [GAD-7] scores) to be used as indicators for a definitive trial.
RESULTS
Of 50 included participants, 49 received the intervention and were included in intent-to-treat analyses; of these, 39 (80%) were female, and the mean (SD) age was 31.7 (9.8) years. A total of 24 were randomized to probiotic and 25 to placebo. Attrition was 8% (1 in the probiotic group and 3 in the placebo group), adherence was 97.2%, and there were no serious adverse reactions. For the probiotic group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 11.00 (5.13) and 8.83 (4.28), respectively; IDS, 30.17 (11.98) and 25.04 (11.68); HAMA, 11.71 (5.86) and 8.17 (4.68); and GAD-7, 7.78 (4.12) and 7.63 (4.77). For the placebo group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 14.04 (3.70) and 11.09 (3.22), respectively; IDS, 33.82 (9.26) and 29.64 (9.31); HAMA, 14.70 (5.47) and 10.95 (4.48); and GAD-7, 10.91 (5.32) and 9.48 (5.18). Standardized effect sizes (SES) from linear mixed models demonstrated that the probiotic group attained greater improvements in depressive symptoms according to HAMD-17 scores (week 4: SES, 0.70; 95% CI, 0.01-0.98) and IDS Self Report scores (week 8: SES, 0.64; 95% CI, 0.03-0.87) as well as greater improvements in anxiety symptoms according to HAMA scores (week 4: SES, 0.67; 95% CI, 0-0.95; week 8: SES, 0.79; 95% CI, 0.06-1.05), but not GAD-7 scores (week 4: SES, 0.57; 95% CI, -0.01 to 0.82; week 8: SES, 0.32; 95% CI, -0.19 to 0.65), compared with the placebo group.
CONCLUSIONS AND RELEVANCE
The acceptability, tolerability, and estimated effect sizes on key clinical outcomes are promising and encourage further investigation of probiotics as add-on treatment for people with MDD in a definitive efficacy trial.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03893162.
Topics: Adult; Humans; Female; Male; Depressive Disorder, Major; Depression; Antidepressive Agents; Anxiety Disorders; Double-Blind Method; Treatment Outcome
PubMed: 37314797
DOI: 10.1001/jamapsychiatry.2023.1817 -
Neuroscience and Biobehavioral Reviews Aug 2023Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies... (Meta-Analysis)
Meta-Analysis Review
Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n > 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n = 550,748; no ADHD n = 14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for ADs, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.
Topics: Adult; Female; Humans; Male; Anxiety; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Comorbidity; Depressive Disorder, Major; Substance-Related Disorders
PubMed: 37149075
DOI: 10.1016/j.neubiorev.2023.105209 -
JAMA Psychiatry Mar 2024Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified.
OBJECTIVE
To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD.
DATA SOURCES
MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD.
STUDY SELECTION
RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion.
DATA EXTRACTION AND SYNTHESIS
This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results.
MAIN OUTCOMES AND MEASURES
Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated.
RESULTS
Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21).
CONCLUSIONS AND RELEVANCE
Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.
Topics: Humans; Anxiety Disorders; Cognitive Behavioral Therapy; Network Meta-Analysis; Psychotherapy; Randomized Controlled Trials as Topic
PubMed: 37851421
DOI: 10.1001/jamapsychiatry.2023.3971 -
Medicine Oct 2023The coronavirus disease-2019 (COVID-19) pandemic has resulted in a surge in stress, anxiety, and depression worldwide. Ashwagandha, an ayurvedic adaptogen has been... (Randomized Controlled Trial)
Randomized Controlled Trial
A standardized Ashwagandha root extract alleviates stress, anxiety, and improves quality of life in healthy adults by modulating stress hormones: Results from a randomized, double-blind, placebo-controlled study.
BACKGROUND
The coronavirus disease-2019 (COVID-19) pandemic has resulted in a surge in stress, anxiety, and depression worldwide. Ashwagandha, an ayurvedic adaptogen has been traditionally used to manage stress, anxiety, and general well-being.
OBJECTIVE
We assessed the effect of Ashwagandha root extract (ARE-500 mg) standardized for 2.5% withanolides as per USP protocol with piperine (5 mg of 95% piperine) once daily for 60 days (12.5 mg withanolides/day) to alleviate stress and anxiety in healthy individuals with mild to moderate symptoms.
METHODS
A randomized, double-blind, placebo-controlled study was conducted for 60 days using ARE (n = 27) and placebo (n = 27) once daily at night at Narayana Institute of Cardiac Sciences, Bangalore, and Vijaya Super Specialty Hospital, Nellore, in India. The objectives of this study were to assess an improvement in perceived stress scale (PSS), generalized anxiety disorder (GAD-7), quality of life (QOL), cognitive scores in the Cambridge Neuropsychological Test Automated Battery (CANTAB), changes in salivary cortisol, urinary serotonin, dopamine, serum levels of nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) from baseline to end of the study. Safety was evaluated by laboratory parameters, and by monitoring any incidence of adverse events.
RESULTS
54 individuals were randomized and 50 of them completed the study. The PSS, GAD-7, and QOL scores improved significantly in all the participants taking ARE compared to the placebo. The CANTAB analysis revealed a significant improvement in multitasking, concentration, and decision taking time in ARE compared to placebo. ARE was also associated with a greater reduction in the morning salivary cortisol and an increase in urinary serotonin compared to placebo. Serum levels of NO, GSH, and MDA were not significantly different. Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study.
CONCLUSION
The results of the study suggest that ARE with 2.5% withanolides can effectively improve stress and anxiety by reducing cortisol and increasing serotonin in healthy individuals with mild to moderate symptoms.
Topics: Humans; Adult; Quality of Life; Hydrocortisone; Serotonin; Withanolides; COVID-19; India; Anxiety Disorders; Anxiety; Double-Blind Method
PubMed: 37832082
DOI: 10.1097/MD.0000000000035521 -
Frontiers in Immunology 2023Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have...
BACKGROUND
Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study.
METHODS
The summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons.
RESULTS
After FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(β=-0.289, 95%CI=0.044~0.194, =0.002), reduced PB/PC AC in GAD patients (β=-0.270, 95% CI=0.77~0.92, =0.000), and diminished PB/PC on lymphocytes (β=-0.315, 95% CI=0.77~0.93, =0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (β=-0.155,95%CI=0.78~0.94,=0.002), CD20-%B cell (β= -0.105,95% CI=0.77~0.94, =0.002), IgD-CD38br%lymphocyte(β=-0.305, 95%CI=0.79~0.95, =0.002), FSC-A level on granulocytes (β=0.200, 95%CI=0.75~0.91, =8.35×10), and CD4RA on TD CD4+(β=-0.150, 95% CI=0.82~1.02, =0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,=1.237×10),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, =8.085×10).
CONCLUSION
The study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Anxiety Disorders; Granulocytes; B-Lymphocytes
PubMed: 38264647
DOI: 10.3389/fimmu.2023.1338083 -
Behaviour Research and Therapy Sep 2023Considerable work has advanced understanding of the nature, causes, management, and prevention of anxiety disorders in children and adolescents over the past 30 years.... (Review)
Review
Considerable work has advanced understanding of the nature, causes, management, and prevention of anxiety disorders in children and adolescents over the past 30 years. Prior to this time the primary focus was on school refusal and specific phobias. It is now recognised that children and adolescents experience the full gamut of anxiety disorders in very similar ways to adults and that anxiety disorders in the paediatric years can predict a lifelong mental-health struggle. Given the vast array of specific studies in this field, the current review summarises current knowledge about these high prevalence disorders, points to overarching limitations, and suggests potentially important future directions. Following a brief historical overview, the review summarises knowledge about demographic and epidemiological characteristics, distal and proximal risk factors, current treatment directions, and prevention. There is still a great deal to learn about the causes and treatments of child and adolescent anxiety disorders. By amalgamating our current knowledge, this review provides a window to the research directions that are likely to lead to future advances.
Topics: Adult; Child; Humans; Adolescent; Anxiety Disorders; Phobic Disorders; Risk Factors; Prevalence
PubMed: 37499294
DOI: 10.1016/j.brat.2023.104376 -
Neurobiology of Learning and Memory Oct 2023Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative... (Review)
Review
Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative learning depending on type, intensity, and persistence of the stressor, the subject's sex, the context that the stress and behavior is experienced in, and the type of associative learning taking place. In some cases, stress can cause or exacerbate the maladaptive behavior that underlies numerous psychiatric conditions including anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, substance use disorder, and others. Therefore, it is critical to understand how the varied effects of stress, which may normally facilitate adaptive behavior, can also become maladaptive and even harmful. In this review, we highlight several findings of associative learning and decision-making processes that are affected by stress in both human and non-human subjects and how they are related to one another. An emerging theme from this work is that stress biases behavior towards less flexible strategies that may reflect a cautious insensitivity to changing contingencies. We consider how this inflexibility has been observed in different associative learning procedures and suggest that a goal for the field should be to clarify how factors such as sex and previous experience influence this inflexibility.
Topics: Humans; Adaptation, Psychological; Anxiety Disorders; Conditioning, Classical; Stress Disorders, Post-Traumatic
PubMed: 37598745
DOI: 10.1016/j.nlm.2023.107812 -
Science Bulletin Oct 2023The persistence of pathological memory is the basis of several psychiatric disorders. Memory retrieval induces "reconsolidation", a time interval during which the... (Review)
Review
The persistence of pathological memory is the basis of several psychiatric disorders. Memory retrieval induces "reconsolidation", a time interval during which the original memory becomes labile and destabilized. Time- and retrieval-dependent processes and memory reconsolidation are critical periods for memory interference. Modulating memory reconsolidation has received considerable research attention as a treatment protocol for several psychiatric conditions such as posttraumatic stress disorder, addiction, anxiety, and trauma-related disorders. This specific time window provides an opportunity for intervention regarding mental diseases. This article reviews the effect of modulating memory reconsolidation using behavioral-, brain stimulation-, and pharmacological-based interventions, which may help bridge the gap between intervention in laboratories and application in clinical practice. The potential advantages, limitations, challenges, and opportunities for memory reconsolidation manipulations were discussed.
Topics: Humans; Extinction, Psychological; Memory; Anxiety Disorders; Stress Disorders, Post-Traumatic; Psychiatry
PubMed: 37689533
DOI: 10.1016/j.scib.2023.08.050