Dataset Information

Integrative DNA Methylation and Gene Expression Analysis of Cognitive Behavioral Therapy Response in Children and Adolescents with Obsessive-Compulsive Disorder; a Pilot Study.

ABSTRACT:

Purpose

Here, we propose an integrative analysis of genome-wide methylation and gene expression to provide new insight into the biological mechanisms of Cognitive behavioral therapy (CBT) in pediatric obsessive-compulsive disorder (OCD).

Patients and methods

Twelve children and adolescents with OCD receiving CBT for the first time were classified as responders or non-responders after eight weeks of CBT. Differentially methylated positions (DMPs) and gene co-expression modules were identified using specific R software packages. Correlations between the DMPs and gene co-expression modules were investigated.

Results

Two genes were enriched with significant DMPs (Δβ > ± 0.2, FDR-adjusted p-value < 0.05): PIWIL1 and MIR886. The yellowgreen module of co-expressed genes was associated with CBT response (FDR-adjusted p-value = 0.0003). Significant correlations were observed between the yellowgreen module and the CpGs in PIWIL1 and MIR886 (p < 0.008). Patients showing hypermethylation in these CpGs presented an upregulation in the genes in the yellowgreen module.

Conclusion

Taken together, the preliminary results of this systems-level approach, despite the study limitations, provide evidence that the epigenetic regulation of ncRNAs could be a predictor of CBT response.

Limitations

The sample size limited the statistical power, and given that the study was hypothesis-driven, our results should be seen as preliminary.

SUBMITTER: Rodriguez N

PROVIDER: S-EPMC8254600 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND AND OBJECTIVES:This study examined the occurrence of sudden gains (or reversal of gains) among children with obsessive-compulsive disorder (OCD) during the course of cognitive-behavioral therapy (CBT), as well as the association of sudden gains with treatment response, treatment group, and pre-treatment clinical characteristics. METHODS:The sample consisted of 136 youth (ages 7-17) with a primary diagnosis of OCD who were randomized in a double-blinded fashion to 10 sessions of CBT with augmentation of either d-cycloserine or placebo. Sudden gain status was determined based on clinician-rated obsessive-compulsive symptom severity, which was collected on 9 occasions across the study period. RESULTS:42.6% of youth experienced at least one sudden gain, which tended to occur either after starting exposure and response prevention or towards the end of treatment. After applying the Benjamini-Hochberg procedure for multiple comparisons, there were no significant pre-treatment predictors of sudden gains and only reduced insight predicted the reversal of gains. Individuals with at least one sudden gain had improved overall treatment outcomes, measured both by reduction in OCD symptom severity, and by global illness severity. LIMITATIONS:Several clinical constructs were not examined. Symptomatology was not assessed at every treatment session. Differences in those who achieved sudden gains and those who did not may be obscured. There is the possibility that a sudden gain reflected a scoring error generated by an optimistic or inaccurate report. Finally, a relatively homogenous sample may limit the generalizability of results. CONCLUSIONS:The course of CBT for pediatric OCD is variable with many children experiencing sudden gains, but a sizable percentage experience a reversal of gains which was related to reduced insight. Sudden gains tended to occur after starting exposure and response prevention and towards the end of treatment. TRIALSREGISTRATION:ClinicaltrialsgovRegistry:NCT00864123. https://www.clinicaltrials.gov/ct2/show/NCT00864123.

Project description:ObjectivesObsessive-compulsive disorder (OCD) in childhood and adolescence often leads to significant impairment in various areas of life and has a high risk of becoming chronic. Cognitive behavioral therapy (CBT) is the recommended first-line treatment, but it is too rarely implemented in accordance with guidelines and is often not available close to the patient's home. Importantly, internet-based CBT could help to reduce this gap in care. Having previously successfully demonstrated the feasibility of an internet-based CBT approach, we aimed to assess its effectiveness in a waiting list controlled randomized trial.MethodsChildren and adolescents aged 6-18 years with a principal diagnosis of OCD received 14 sessions of therapist-delivered CBT via videoconference distributed over 16 weeks. After inclusion, participants were randomly assigned to either the treatment or waiting list group. Participants in the treatment group began treatment immediately after baseline diagnostics, and participants in the waiting list group began treatment after a 16-week waiting period. The primary outcome was a pre-post comparison of OCD symptoms as measured with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Additionally, remission was an important outcome measure. Follow-up assessments were conducted for all measures 16 and 32 weeks after completion of treatment.ResultsA total of 60 children and adolescents were included into the analyses. Over the course of the treatment, OCD symptoms according to the CY-BOCS significantly decreased in the treatment group compared to the waiting-list control group. Cohen's d between groups was 1.63. After the patients in the waiting list group also received the treatment, the OCD symptoms decreased significantly in this group as well. This improvement of symptoms increased over the course of the follow-up assessments. Remission rate peaked at the 32-week follow-up, with 68% in the treatment group and 79% in the waiting list group. Importantly, patient satisfaction with treatment was high to very high.ConclusionIn our study, OCD symptoms decreased significantly and remission rate was high after internet-based CBT. Those effects were comparable to those found in studies of face-to-face treatment. Although further evidence is needed, these are early indications that our approach may be a viable way to provide access to adequate treatment for children and adolescents affected by OCD.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT05037344].

Project description:ImportanceTherapist-guided, internet-delivered cognitive behavioral therapy is an effective treatment option for children and adolescents with obsessive-compulsive disorder, but to our knowledge, its cost-effectiveness compared with traditional in-person treatment has not been established.ObjectiveTo evaluate the cost-effectiveness of guided internet-delivered cognitive behavioral therapy implemented within a stepped-care model compared with in-person cognitive behavioral therapy for young people with obsessive-compulsive disorder.Design, setting, and participantsThis economic evaluation of a randomized noninferiority trial conducted at 2 specialist obsessive-compulsive disorder clinics in Sweden enrolled 152 children and adolescents aged 8 to 17 years with obsessive-compulsive disorder, mainly through clinician referrals (110 [72%]). Recruitment began October 6, 2017, and ended May 24, 2019. Follow-up ended April 14, 2020.InterventionsParticipants were randomly assigned to receive either guided internet-delivered cognitive behavioral therapy or in-person cognitive behavioral therapy during a 16-week period. At the 3-month follow-up, nonresponders in both groups were offered additional in-person cognitive behavior therapy sessions.Main outcomes and measuresHealth outcomes were treatment response rates (primary outcome), remission rates, and quality-adjusted life-years. Cost data were collected before treatment, after treatment, at 3-month follow-up, and at 6-month follow-up (primary end point) and are presented in 2020 US dollars. The differences in incremental costs and health outcomes were compared between the groups and presented from the health care professional, health care sector, and societal perspectives.ResultsA total of 152 participants (94 girls [62%]; mean [SD] age, 13.4 [2.5] years) were randomized; 151 (99%) completed the trial. At the 6-month follow-up, 50 of 74 participants (68%) in the stepped-care group and 52 of 77 participants (68%) in the in-person cognitive behavioral therapy group were classified as treatment responders (odds ratio, 1.00 [95% CI, 0.51-1.98]; P = .99). Health economic analyses showed that the stepped-care group used fewer therapist resources than the in-person cognitive behavioral therapy group, resulting in a mean cost savings of $2104 (95% CI, $1202-$3006) per participant for the full study period of 10 months, corresponding to a relative savings of 39%. The cost savings remained largely comparable when taking wider health care sector and societal perspectives.Conclusions and relevanceThis study suggests that, for young people with obsessive-compulsive disorder, a low-cost digital intervention followed by in-person treatment for nonresponders was cost-effective compared with in-person cognitive behavior therapy alone.

Project description:IntroductionObsessive-compulsive disorder (OCD) is characterized by recurrent distressing thoughts and repetitive behaviors, or mental rituals performed to reduce anxiety. Recent neurobiological techniques have been particularly convincing in suggesting that cortico-striatal-thalamic-cortico (CSTC) circuits, including orbitofrontal cortex (OFC) and striatum regions (caudate nucleus and putamen), are responsible for mediation of OCD symptoms. However, it is still unclear how these regions are affected by OCD treatments in adult patients. To address this yet open question, we conducted a systematic review of all studies examining neurobiological changes before and after first-line psychological OCD treatment, i.e., cognitive-behavioral therapy (CBT).MethodsStudies were included if they were conducted in adults with OCD and they assessed the neurobiological effects of CBT before and after treatment. Two databases were searched: PsycINFO and PubMed for the time frame up to May 2022.ResultsWe obtained 26 pre-post CBT treatment studies performed using different neurobiological techniques, namely functional magnetic resonance imaging (fMRI), Positron emission tomography (PET), regional cerebral blood flow (rCBF), 5-HT concentration, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), Electroencephalography (EEG). Neurobiological data show the following after CBT intervention: (i) reduced activations in OFC across fMRI, EEG, and rCBF; (ii) decreased activity in striatum regions across fMRI, rCBF, PET, and MRI; (iii) increased activations in cerebellum (CER) across fMRI and MRI; (iv) enhanced neurochemical concentrations in MRS studies in OFC, anterior cingulate cortex (ACC) and striatum regions. Most of these neurobiological changes are also accompanied by an improvement in symptom severity as assessed by a reduction in the Y-BOCS scores.ConclusionCognitive-behavioral therapy seems to be able to restructure, modify, and transform the neurobiological component of OCD, in addition to the clinical symptoms. Nevertheless, further studies are necessary to frame the OCD spectrum in a dimensional way.