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2.
Psychiatr Serv ; 72(4): 415-420, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33557596

RESUMO

OBJECTIVE: Targeted, highly accessible early intervention for youths with emerging and complex psychiatric presentations is increasingly needed. The Youth Community Assessment and Treatment Team (YCATT) multidisciplinary service was established to provide intensive intervention for youths in Perth, Australia. METHODS: The authors conducted a retrospective evaluation to examine YCATT's impact on emergency department (ED) visits, psychiatric inpatient admissions, and provision of care for youths in the transition period between adolescent and adult psychiatric services. Demographic, clinical, and service utilization data for all referrals over the pilot period (2016-2017) were collected and analyzed with descriptive statistics. RESULTS: During the pilot period, 308 referrals were accepted. All referred youths had a trauma history and presented with acute or complex conditions, and most (66%) were between 16 and 18 years old. The admission rate to a psychiatric inpatient unit was <7%. Of 61 youths specifically referred to YCATT as an alternative to psychiatric admission, 90% were successfully diverted from psychiatric or ED admission. After discharge from YCATT, youths had improved scores on the Health of the Nations Outcome Scale and 10-item Kessler Psychological Distress Scale. CONCLUSIONS: These findings suggest that YCATT is an accessible and effective service for the population of transition-age youths. It appears that YCATT, in collaboration with other community services, contributed to diverting psychiatric inpatient admissions, facilitated outpatient treatment, and enabled continuity of care for vulnerable youths. The results underscore the need for more accessible, individualized treatment approaches for youths who transition to adulthood.

3.
J Psychiatr Res ; 136: 149-156, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33592386

RESUMO

Social media use (SMU) is an inherent element in the daily life and neurodevelopment of adolescents, but broad concerns exist regarding the untoward effects of social media on adolescents. We conducted a prospective, cross-sectional study that sought to examine the acute effects of SMU on clinical measures and biomarkers of stress in healthy and depressed adolescents. After at least 24 h of abstinence from social media, depressed adolescents (n = 30) and healthy control adolescents (n = 30) underwent baseline clinical assessment of their prior SMU, depressive symptom severity, self-esteem, and exposure to bullying. Participants provided salivary samples that were analyzed for α-amylase and cortisol levels. After 20 min of unsupervised SMU, saliva analyses and clinical assessments were repeated. After 20 min of SMU, salivary cortisol and α-amylase levels were significantly higher in adolescents with depression but not in healthy control adolescents. Furthermore, small but statistically significant changes in depressive symptom severity occurred in all participants. These changes in depressive symptoms were not clinically meaningful. SMU did not significantly change self-esteem measures among participants. Adolescents with depression appeared to have more physiological reactivity after SMU compared with healthy adolescents. Further research should characterize SMU as a clinical dimension and risk factor among adolescents with depression and other psychiatric disorders.

4.
Dev Med Child Neurol ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33634500

RESUMO

AIM: To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome. METHOD: Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment. RESULTS: The YGTSS score decreased from baseline after treatment (p<0.001; Cohen's d=2.9). All procedures were well-tolerated. INTERPRETATION: Robot-driven, neuronavigated bilateral rTMS of the SMA is feasible in children with Tourette syndrome and appears to reduce tic severity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33452433

RESUMO

Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians' ability to accurately predict a specific patient's eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% (p = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% (p = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming.

6.
Neuropsychopharmacology ; 46(2): 462-469, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919400

RESUMO

Treatment-resistant depression (TRD) is prevalent and associated with a substantial psychosocial burden and mortality. There are few prior studies of interventions for TRD in adolescents. This was the largest study to date examining the feasibility, safety, and efficacy of 10-Hz transcranial magnetic stimulation (TMS) for adolescents with TRD. Adolescents with TRD (aged 12-21 years) were enrolled in a randomized, sham-controlled trial of TMS across 13 sites. Treatment resistance was defined as an antidepressant treatment record level of 1 to 4 in a current episode of depression. Intention-to-treat patients (n = 103) included those randomly assigned to active NeuroStar TMS monotherapy (n = 48) or sham TMS (n = 55) for 30 daily treatments over 6 weeks. The primary outcome measure was change in the Hamilton Depression Rating Scale (HAM-D-24) score. After 6 weeks of blinded treatment, improvement in the least-squares mean (SE) HAM-D-24 scores were similar between the active (-11.1 [2.03]) and sham groups (-10.6 [2.00]; P = 0.8; difference [95% CI], - 0.5 [-4.2 to 3.3]). Response rates were 41.7% in the active group and 36.4% in the sham group (P = 0.6). Remission rates were 29.2% in the active group and 29.0% in the sham group (P = 0.95). There were no new tolerability or safety signals in adolescents. Although TMS treatment produced a clinically meaningful change in depressive symptom severity, this did not differ from sham treatment. Future studies should focus on strategies to reduce the placebo response and examine the optimal dosing of TMS for adolescents with TRD.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33271210

RESUMO

OBJECTIVES: In recent decades, the diagnostic and therapeutic implications of the microbiome changes and the impact of probiotic supplementation have increased rapidly. However, the potential for clinical translation of microbiome research for children and adolescents with psychiatric disorders is unclear. This review examined available evidence related to gut microbiota as well as the impact of probiotic supplementation on psychiatric disorders in the pediatric population reported to date. METHODS: We performed a literature search for the gut microbiota in child and adolescent population (0-18 years old) with mental health disorders from July 1999 through July 2019 in several databases: ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science. RESULTS: A total of 7 studies met inclusion criteria consisting of randomized controlled trials and cohort studies that examined various associations between psychiatric disorders and gut microbiota in youth. Six studies examined the effects of various treatment interventions such as probiotic supplementation on microbiota composition and behaviors. One study showed an increase in prosocial behavior in children with Autism Spectrum Disorder (ASD) and an increase in the Lachnospiraceae family following prebiotic supplementation. Another study suggested that prebiotic supplementation increased bifidobacterial populations for ASD and healthy controls. A study evaluating infant supplementation of prebiotics showed both a decreased likelihood of developing Attention Deficit Hyperactivity Disorder (ADHD) or ASD and decreased gut Bifidobacterium. One study did not find significant differences in microbiome composition after micronutrient treatment. CONCLUSION: The main goal of this systematic review was to comprehensively examine and summarize the current evidence focused on the potential effect of the relationship between microbiota gut composition as well as the effects of probiotic supplementation on psychiatric disorders in children and adolescents. This is a relatively new area of research and the number of included studies is limited. More studies are needed to determine whether gut dysbiosis leads to the development and/or contributes to the severity of mental disorders or whether gut dysbiosis is a result of other processes that accompany mental disorders. CLINICAL SIGNIFICANCE: A better understanding of the specific bacteria contributions, gut-brain pathways, and role in pathophysiological mechanisms in neuropsychiatric disorders in the child and adolescent populations can possibly provide alternative tools for a clinical psychiatrist. Moreover, it may ultimately aid the clinician with intervention strategies, or detect populations at risk for developing neuropsychiatric disorders.

8.
J Affect Disord ; 280(Pt A): 305-314, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33221716

RESUMO

BACKGROUND: The phenomenology and neurobiology of depressive symptoms in anxious youth is poorly understood. METHODS: Association networks of anxiety and depressive symptoms were developed in adolescents with generalized anxiety disorder (GAD; N=52, mean age: 15.4±1.6 years) who had not yet developed major depressive disorder. Community analyses were used to create consensus clusters of depressive and anxiety symptoms and to identify "bridge" symptoms between the clusters. In a subset of this sample (n=39), correlations between cortical thickness and depressive symptom severity was examined. RESULTS: Ten symptoms clustered into an anxious community, 5 clustered into a depressive community and 5 bridged the two communities: impaired schoolwork, excessive weeping, low self-esteem, disturbed appetite, and physical symptoms of depression. Patients with more depressive cluster burden had altered cortical thickness in prefrontal, inferior and medial parietal (e.g., precuneus, supramarginal) regions and had decreases in cortical thickness-age relationships in prefrontal, temporal and parietal cortices. LIMITATIONS: Data are cross-sectional and observational. Limited sample size precluded secondary analysis of comorbidities and demographics. CONCLUSIONS: In youth with GAD, a sub-set of symptoms not directly related to anxiety bridge anxiety and depression. Youth with greater depressive cluster burden had altered cortical thickness in cortical structures within the default mode and central executive networks. These alternations in cortical thickness may represent a distinct neurostructural fingerprint in anxious youth with early depressive symptoms. Finally, youth with GAD and high depressive symptoms had reduced age-cortical thickness correlations. The emergence of depressive symptoms in early GAD and cortical development may have bidirectional, neurobiological relationships.

9.
J Child Adolesc Psychopharmacol ; 30(10): 599-605, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33179961

RESUMO

Objectives: Prior studies demonstrate elevated cortical glutamate (Glu) in patients with bipolar disorder (BD). Studies assessing neurochemistry in early stages of bipolar illness before the emergence of manic symptoms are lacking. This study aimed to examine neurochemical correlates measured by proton magnetic resonance spectroscopy (1H-MRS) and a dimensional measure of bipolarity in a sample of depressed adolescents. Methods: Adolescent participants (aged 13-21 years) underwent a semistructured diagnostic interview and clinical assessment, which included the General Behavior Inventory Parent Version (P-GBI), a 73-item, parent-rated assessment of symptoms and behaviors. 1H-MRS scans of a left dorsolateral prefrontal cortex (L-DLPFC) voxel (8 cm3) were collected using a two-dimensional J-averaged sequence to assess N-acetylaspartate (NAA), Glu, Glx (glutamate + glutamine), and NAA/Glx concentrations. We used generalized linear models to assess the relationships between P-GBI scores and metabolite levels in L-DLPFC. Results: Thirty-six participants (17 healthy controls, 19 depressed) underwent 1H-MRS scans and clinical evaluation with the P-GBI. There was a significant negative relationship between P-GBI score and L-DLPFC NAA/Glx in the whole sample. However, the magnitude of the effect was small and statistical significance was lost after correcting for multiple comparisons. Conclusions: These preliminary results suggest that NAA/Glx may have utility as a marker of bipolar traits in healthy and depressed adolescents. If replicated, 1H-MRS measures of glutamatergic metabolism anomalies might have a role in identifying depressed adolescents at risk for mixed symptom presentations or BD. Identifying bipolarity in the early stages of the disease would have a significant impact on treatment planning and prognosis. Further longitudinal studies should examine neurochemical correlates of mood state during the developmental emergence of BD.

10.
Depress Anxiety ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001549

RESUMO

BACKGROUND: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated. METHODS: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline. RESULTS: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC. CONCLUSIONS: TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.

11.
BMC Pediatr ; 20(1): 467, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023527

RESUMO

BACKGROUND: Suicide is the leading cause of death among Japanese adolescents. However, knowledge gaps regarding contemporary demographics and factors associated with suicidality among Japanese adolescents are a major concern. This study examined the prevalence of suicidality among Japanese adolescents and investigated associated factors. METHODS: A population-based questionnaire survey investigating general health was administered to 22,419 adolescents aged 13-18 years. The 29-item questionnaire covered emotional status, family function, cyberbullying, suicidality, and stressors (e.g., relationships with parents/friends, school performance, and sexual identity). We conducted multiple logistic regression analysis to identify factors associated with suicidality in this population. RESULTS: The prevalence of suicidal ideation was 21.6% in males and 28.5% in females, and that of attempted suicide was 3.5% in males and 6.6% and in females. Bullying and stress related to family relationships had the strongest associations with suicidality. Exposure to cyberbullying had the highest odds ratio for both junior high (3.1, 95% confidence interval [CI] 2.1-4.4) and high school students (3.6, 95% CI 2.5-5.3). Other factors significantly associated with suicidality were sex, emotional status, and stress about relationships with friends, sexual identity, school records, and academic course. Adolescents accessed a variety of resources to cope with stressors, with the Internet being the most common resource consulted. CONCLUSIONS: Suicidality is commonly experienced among Japanese adolescents. Although there are many associated risk factors, cyberbullying is of particular concern. Recognition of factors associated with adolescent suicidality will inform further research and suicide prevention efforts for healthcare providers and families.

13.
J Am Acad Child Adolesc Psychiatry ; 59(9): 1007-1009, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32615152

RESUMO

Approximately 89% of adolescents have access to a smartphone, with 70% checking social media (eg, Snapchat, Instagram) multiple times per day.1 Psychiatric hospitalizations for adolescents commonly involve suicidal crises with underlying interpersonal stressors, often inextricably embedded in the digital milieu. Upon psychiatric hospitalization, adolescents typically leave their smartphones with caregivers or in a locked area of the unit and enter into a social media "deprivation" period (inclusive of all digital social communication, such as texting). Generally, adolescents are reintroduced to smartphones after discharge. In many cases, they may be flooded with access to social media at this time, without the guidance of their clinical team. It is currently unclear to what extent absolute deprivation is helpful vs harmful for recovering youth. There are strong arguments for prohibiting digital media access, including the following: limiting exposure to online stressors (eg, cybervictimization) or inappropriate/risky content (eg, sexting, self-injury triggers), protecting patient privacy and safety, maintaining focus on treatment, and avoiding significant liability/logistical challenges (eg, monitoring use and information disseminated, ensuring that property is protected, ensuring equal access across patients, and need for knowledgeable staff). However, the aim of this letter is to consider potential risks of current norms of smartphone use within adolescent psychiatric hospitals. Preliminary clinical guidance and future research directions are outlined, with the goal of expanding precision medicine approaches to the reintroduction of social media to adolescents during and after psychiatric hospitalization.

14.
eNeuro ; 7(4)2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669346

RESUMO

Prior research suggests that the neurobiological underpinnings of depression include aberrant brain functional connectivity, neurometabolite levels, and hippocampal volume. Chronic restraint stress (CRS) depression model in rats has been shown to elicit behavioral, gene expression, protein, functional connectivity, and hippocampal volume changes similar to those in human depression. However, no study to date has examined the association between behavioral changes and brain changes within the same animals. This study specifically addressed the correlation between the outcomes of behavioral tests and multiple 9.4 T magnetic resonance imaging (MRI) modalities in the CRS model using data collected longitudinally in the same animals. CRS involved placing young adult male Sprague Dawley rats in individual transparent tubes for 2.5 h daily over 13 d. Elevated plus maze (EPM) and forced swim tests (FSTs) confirmed the presence of anxiety-like and depression-like behaviors, respectively, postrestraint. Resting-state functional MRI (rs-fMRI) data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. Proton magnetic resonance spectroscopy revealed decreased sensorimotor cortical glutamate (Glu), glutamine (Gln), and combined Glu-Gln (Glx) levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32661820

RESUMO

Pictorial mood assessments reduce the barriers of age, culture, gender and language fluency in the course of psychiatric assessments. This study sought to validate the Ottawa Mood Scales, a pictorial form of mood assessment questionnaire among non-native English speaking young adults in Malaysia. Since the Ottawa Mood Scales has not been previously validated, the convergent validity of the Ottawa Mood Scales was measured against the Positive and Negative Affect Scale (PANAS), an established mood assessment instrument. A total of 129 young adults (aged 18-34) were recruited and completed an online survey with the Ottawa Mood Scales and PANAS questionnaires. Exploratory factor analysis indicated that the Ottawa Mood Scales has a one-dimensional structure and that a four-item model demonstrated higher reliability than the original 5-item model. Scores on the Ottawa Mood Scales items positively and significantly correlated with scores on the negative PANAS subscale, which supports the validity of the Ottawa Mood Scales in measuring the negative effect. The Cronbach's α was .793 for the four-item model of the Ottawa Mood Scales indicating acceptable reliability in this Malaysian young adult sample. It was concluded that the Ottawa Mood Scales could have utility in assessing mood disorder symptoms in young adults.

16.
Depress Anxiety ; 37(9): 926-934, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579280

RESUMO

BACKGROUND: Psychiatrists frequently struggle with how to sequence treatment for depressed adolescents who do not respond to an adequate trial of a selective serotonin reuptake inhibitor (SSRI). This study leveraged recent statistical and computational advances to create Bayesian hierarchal models (BHMs) of response in the treatment of SSRI-resistant depression in adolescents study to inform treatment planning. METHODS: BHMs of individual treatment trajectories were developed and estimated using Hamiltonian Monte Carlo no u-turn sampling. From the Monte Carlo pseudorandom sample, 95% credible intervals, means, posterior tail probabilities, and so forth, were determined. Then, for the random effects model, posterior tail probabilities were used to create Bayesian two-tailed p values to evaluate the null hypotheses: no difference in efficacy between SSRIs and venlafaxine. The robustness of the results was examined using the fixed effects model of treatment comparisons. RESULTS: In patients not receiving cognitive behavioral therapy (CBT; n = 168), SSRIs produced greater and faster improvement in depressive symptoms compared to venlafaxine (p = .015). No differences in response or trajectory of response for symptoms of anxiety were detected between SSRIs and venlafaxine (p = .168). For patients receiving CBT (n = 162), SSRIs and venlafaxine produced similar improvements in symptoms of anxiety and depression. CONCLUSIONS: Findings from this novel computational approach suggest that a second trial of an SSRI is warranted for depressed adolescents who fail to respond to initial SSRI treatment.

17.
Depress Anxiety ; 37(8): 747-759, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32419335

RESUMO

BACKGROUND: Pediatric anxiety disorders such as generalized anxiety disorder (GAD) are common, impairing, and often undertreated. Moreover, many youth do not respond to standard, evidence-based psychosocial or psychopharmacologic treatment. An increased understanding of the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems has created opportunities for novel intervention development for pediatric GAD. METHODS: This narrative review examines potential candidates for pediatric GAD: eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine. RESULTS: The pharmacology, preclinical data, clinical trial findings and known side effects of eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine, are reviewed, particularly with regard to their potential therapeutic relevance to pediatric GAD. CONCLUSION: Notwithstanding numerous challenges, some of these agents represent potential candidate drugs for pediatric GAD. Further treatment development studies of agomelatine, eszopiclone, pimavanserin and riluzole for pediatric GAD also have the prospect of informing the understanding of GABAergic and glutamatergic function across development.

18.
Front Pharmacol ; 11: 467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32390836

RESUMO

Background: Epimutations secondary to gene-environment interactions have a key role in the pathophysiology of major psychiatric disorders. In vivo and in vitro evidence suggest that mood stabilizers can potentially reverse epigenetic deregulations found in patients with schizophrenia or mood disorders through mechanisms that are not yet fully understood. However, their activity on epigenetic processes has made them a research target for therapeutic approaches. Methods: We conducted a comprehensive literature search of PubMed and EMBASE for studies investigating the specific epigenetic changes induced by non-antipsychotic mood stabilizers (valproate, lithium, lamotrigine, and carbamazepine) in animal models, human cell lines, or patients with schizophrenia, bipolar disorder, or major depressive disorder. Each paper was reviewed for the nature of research, the species and tissue examined, sample size, mood stabilizer, targeted gene, epigenetic changes found, and associated psychiatric disorder. Every article was appraised for quality using a modified published process and those who met a quality score of moderate or high were included. Results: A total of 2,429 records were identified; 1,956 records remained after duplicates were removed and were screened via title, abstract and keywords; 129 records were selected for full-text screening and a remaining of 38 articles were included in the qualitative synthesis. Valproate and lithium were found to induce broader epigenetic changes through different mechanisms, mainly DNA demethylation and histones acetylation. There was less literature and hence smaller effects attributable to lamotrigine and carbamazepine could be associated overall with the small number of studies on these agents. Findings were congruent across sample types. Conclusions: An advanced understanding of the specific epigenetic changes induced by classic mood stabilizers in patients with major psychiatric disorders will facilitate personalized interventions. Further related drug discovery should target the induction of selective chromatin remodeling and gene-specific expression effects.

19.
Neuroimage Clin ; 27: 102260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388347

RESUMO

BACKGROUND: Individuals with autism spectrum disorder (ASD) often present with executive functioning (EF) deficits, including spatial working memory (SWM) impairment, which impedes real-world functioning. The present study examined task-related brain activity, connectivity and individual variability in fMRI-measured neural response during an SWM task in older youth and young adults with autism and clinically significant EF impairment. METHODS: Neuroimaging was analyzed in 29 individuals with ASD without intellectual disability who had clinically significant EF impairment on the Behavior Rating Inventory of Executive Function, and 20 typically developing controls (participant age range=16-34). An SWM N-Back task was performed during fMRI. SWM activity (2-Back vs. 0-Back) and task-related dorsolateral prefrontal cortex (DLPFC) connectivity was examined within and between groups. Variability of neural response during SWM was also examined. RESULTS: During SWM performance both groups activated the expected networks, and no group differences in network activation or task-related DLPFC-connectivity were found. However, greater individual variability in the pattern of SWM activity was found in the ASD versus the typically developing control group. CONCLUSIONS: While there were no group differences in SWM task-evoked activity or connectivity, fronto-parietal network engagement was found to be more variable/idiosyncratic in ASD. Our results suggest that the fronto-parietal network may be shifted or sub-optimally engaged during SWM performance in participants with ASD with clinically significant EF impairment, with implications for developing targeted interventions for this subgroup.

20.
Brain Stimul ; 13(3): 539-547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32289673

RESUMO

BACKGROUND: In youth and young adults with autism spectrum disorder (ASD), executive function (EF) deficits may be a promising treatment target with potential impact on everyday functioning. OBJECTIVE: To conduct a pilot randomized, double-blind, parallel, controlled trial evaluating repetitive transcranial magnetic stimulation (rTMS) for EF deficits in ASD. METHOD: In Toronto, Ontario (November 2014 to June 2017), a 20-session, 4-week course of 20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) (90%RMT) was compared to sham stimulation in 16-35 year-olds with ASD (28 male/12 female), without intellectual disability, who had impaired everyday EF performance (n = 20 active/n = 20 sham). Outcome measures evaluated protocol feasibility and clinical effects of active vs. sham rTMS on EF performance. The moderating effect of baseline functioning was explored. RESULTS: Of eligible participants, 95% were enrolled and 95% of randomized participants completed the protocol. Adverse events across treatment arms were mild-to-moderate. There was no significant difference between active vs. sham rTMS on EF performance. Baseline adaptive functioning moderated the effect of rTMS, such that participants with lower baseline functioning experienced significant EF improvement in the active vs. sham group. CONCLUSIONS: Our pilot RCT demonstrated the feasibility and acceptability of using high frequency rTMS targeting DLPFC in youth and young adults with autism. No evidence for efficacy of active versus sham rTMS on EF performance was found. However, we found promising preliminary evidence of EF performance improvement following active versus sham rTMS in participants with ASD with more severe adaptive functioning deficits. Future work could focus on examining efficacy of rTMS in this higher-need population. CLINICAL TRIAL REGISTRATION: Repetitive Transcranial Magnetic Stimulation (rTMS) for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure: A Pilot Study; https://clinicaltrials.gov/ct2/show/NCT02311751?term = ameis&rank = 1; NCT02311751. The trial was funded by: an American Academy of Child and Adolescent Psychiatry (AACAP) Pilot Research Award, the Innovation Fund from the Alternate Funding Plan of the Academic Health Sciences Centres of Ontario, and an Ontario Mental Health Foundation (OMHF) Project A Grant and New Investigator Fellowship.


Assuntos
Transtorno do Espectro Autista/terapia , Função Executiva , Estimulação Magnética Transcraniana/métodos , Adolescente , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/efeitos adversos
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