Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

Trajectories of attention-deficit/hyperactivity disorder dimensions in adults.

OBJECTIVE: There is a lack of available information on the trajectories of attention-deficit/hyperactivity disorder (ADHD) dimensions during adulthood. This study investigates the course and the predictors of change for each ADHD domain in a clinical sample of adults with ADHD. METHOD: Adults with ADHD (n = 344) were followed up for 7 years, with a final retention rate of 66.0%. Trajectories of inattention, hyperactivity, and impulsivity and their potential predictors were examined. RESULTS: On average, symptoms declined in all ADHD domains during follow-up. Despite this, rises in inattentive, hyperactive, and impulsive symptoms were observed in approximately 13%, 25%, and 17% of patients respectively. Different predictors influenced the trajectory of each ADHD dimension. Oppositional defiant disorder and social phobia were associated with the maintenance of symptoms, while alcohol use disorder was associated with both maintenance and rise of symptoms. CONCLUSION: Unexpectedly, a rise in the symptoms after 7 years was not uncommon in adults with ADHD. Prevalent comorbidities have the potential to influence the neurodevelopment and the trajectory of ADHD. Therefore, such predictors should be investigated in population cohorts to better characterize the course of ADHD. Additionally, these findings may be relevant in prevention studies and in strategies for ADHD treatment.

Persistence and remission of ADHD during adulthood: a 7-year clinical follow-up study.

BACKGROUND: Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment. METHOD: A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence. RESULTS: Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54-25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04-1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20-8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12-11.47, p = 0.03). CONCLUSIONS: Despite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.

The burdened life of adults with ADHD: impairment beyond comorbidity.

Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.