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The effect of personality disorder symptoms on response to treatment with methylphenidate transdermal system in adults with attention-deficit/hyperactivity disorder.

ABSTRACT: This trial was designed to prospectively explore the relationship among personality disorder (PD) symptoms, attention-deficit/hyperactivity disorder (ADHD), and treatment response in a randomized, double-blind, crossover clinical trial of methylphenidate transdermal system (MTS) and to confirm results of a prior exploratory study.67 adults who met the Utah and/or DSM-IV-TR criteria for ADHD were recruited with no attempt to include or exclude patients with PD. Responders were defined by a 50% improvement on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the primary outcome measure. Personality disorder was diagnosed by the clinicians using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders Questionnaire, several self-report scales, and clinical observations. Subjects were categorized as: no PD (PD-negative), 1 PD (PD-positive), and 2 or more PDs (PD-plus). The study was conducted from February 2007 to December 2009 at the Mood Disorders Clinic at the University of Utah School of Medicine, Salt Lake City.37% (n = 25) were PD-positive, and another 27% (n = 18) were PD-plus. In those with a PD, 65% (n = 28) had a cluster C diagnosis, 44% (n = 19) cluster B, and 5% (n = 12) cluster A. PD-plus subjects had significantly higher levels of oppositional defiant disorder (ODD) symptoms (P = .007) and emotional dysregulation (P = .004). 71% (15/21) of the PD-positive and PD-negative subjects were responders in the MTS arm (P < .001) as opposed to 38% (6/16) of the PD-plus subjects (P = .24). Conversely, the interaction between treatment (placebo versus MTS) and the 3 PD groups was not statistically significant (P = .46) when the total WRAADDS was used as the outcome measure.Personality disorder status was associated with more complex ADHD, especially high levels of emotional dysregulation and ODD symptoms. There was a significant treatment effect for PD-positive and PD-negative, but not PD-plus subjects.ClinicalTrials.gov identifier: NCT00506285.

SUBMITTER: Olsen JL

PROVIDER: S-EPMC3583767 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The effect of personality disorder symptoms on response to treatment with methylphenidate transdermal system in adults with attention-deficit/hyperactivity disorder.

Olsen John L JL Reimherr Frederick W FW Marchant Barrie K BK Wender Paul H PH Robison Reid J RJ

The primary care companion for CNS disorders 20121011 5

<h4>Objective</h4>This trial was designed to prospectively explore the relationship among personality disorder (PD) symptoms, attention-deficit/hyperactivity disorder (ADHD), and treatment response in a randomized, double-blind, crossover clinical trial of methylphenidate transdermal system (MTS) and to confirm results of a prior exploratory study.<h4>Method</h4>67 adults who met the Utah and/or DSM-IV-TR criteria for ADHD were recruited with no attempt to include or exclude patients with PD. Re ...[more]

PMID: 23469326

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Project description:BACKGROUND:Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts. METHODS:An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed. RESULTS:One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92% were associated with methylation quantitative trait loci, and 68% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia. CONCLUSIONS:Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.

Dataset Information

The effect of personality disorder symptoms on response to treatment with methylphenidate transdermal system in adults with attention-deficit/hyperactivity disorder.

Publications

The effect of personality disorder symptoms on response to treatment with methylphenidate transdermal system in adults with attention-deficit/hyperactivity disorder.

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