Increased brain activity to unpleasant stimuli in individuals with the 7R allele of the DRD4 gene.

The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) allele of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4-4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4-4R/7R genotype and 13 with the DRD4-4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4-4R/7R genotype versus participants with the DRD4-4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4-4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.

Efficacy of guanfacine extended release in the treatment of combined and inattentive only subtypes of attention-deficit/hyperactivity disorder.

BACKGROUND: Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6-17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. METHOD: Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. RESULTS: The full analysis set included 631 subjects aged 6-17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). CONCLUSIONS: The results support the use of GXR in the treatment of core ADHD symptoms as defined in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, including hyperactivity, impulsivity, and inattention.

Contrast of medical and nonmedical use of stimulant drugs, basis for the distinction, and risk of addiction: comment on Smith and Farah (2011).

Smith and Farah (2011) presented a scholarly review of critical areas related to their intriguing title "Are Prescription Stimulants 'Smart Pills'?" We contend that they accomplished the main goal of the article, to get the facts straight about possible cognitive enhancement via the nonmedical use of stimulant drugs by individuals without a diagnosis of attention-deficit/hyperactivity disorder (ADHD). At the same time, they justified their main conclusions that (a) individuals are seeking and engaging in nonmedical use of stimulant drugs with the expectations of cognitive enhancement despite uncertainty whether such expectations are valid and (b) on some tasks, there are small average benefits of nonmedical use, but the overall pattern is not clear (e.g., small beneficial effects across most individuals or large beneficial effects only in a few individuals, both of which result in small average effects). We offer comments in 3 areas to amplify key topics mentioned but not emphasized by Smith and Farah: (a) characterization of the cognitive effects of medical use of stimulants to contrast with the cognitive effects of nonmedical use; (b) justification of medical use of stimulants by placement on a normally distributed dimension of behavior rather than categorical diagnosis of ADHD, which varies widely across countries; and (c) evaluation of the potential risks of nonmedical use to individuals and to society (e.g., the likelihood of addiction to stimulant drugs in a small minority of the population) rather than just the potential benefits of cognitive enhancement.

ADHD medication reduces cotinine levels and withdrawal in smokers with ADHD.

Individuals with ADHD may self-medicate with nicotine, the main psychoactive ingredient in tobacco smoke, in order to reduce symptoms and negative moods associated with ADHD. ADHD medication (e.g., methylphenidate and atomoxetine) may mimic some of the effects of nicotine and may aid smoking cessation in smokers with ADHD. The present study examined if ADHD medication reduces smoking and withdrawal in non-treatment seeking smokers with ADHD. Fifteen adult smokers with ADHD participated in the study, which consisted of an experimental phase and field monitoring phase to examine the acute and extended effects, respectively, of ADHD medication. During the experimental phase, smokers were asked to complete a Continuous Performance Task (CPT) and the Shiffman-Jarvik smoking withdrawal questionnaire during the following four conditions: (1) ADHD medication+cigarette smoking, (2) ADHD medication+overnight abstinence, (3) placebo+cigarette smoking, and (4) placebo+overnight abstinence. During the field monitoring phase, participants were asked to provide salivary cotinine samples and complete electronic diaries about smoking, smoking urge, ADHD symptoms, and stress in everyday life for two days on ADHD medication and for two days on placebo. Results of the experimental phase showed that ADHD medication improved task performance on the CPT and reduced withdrawal during overnight abstinence. During the field monitoring phase, ADHD medication reduced salivary cotinine levels compared to placebo. In addition, the electronic diary revealed that ADHD medication improved difficulty concentrating during no smoking events and stress. The findings of the present study suggest that, along with other strategies, ADHD medication may be used to aid smoking withdrawal and cessation in smokers with ADHD.

Hyperactive-impulsive symptoms associated with self-reported sleep quality in nonmedicated adults with ADHD.

OBJECTIVE: Individuals with ADHD often report sleep problems. Though most studies on ADHD and sleep examined children or nonclinically diagnosed adults, the present study specifically examines nonmedicated adults with ADHD to determine whether inattentive and hyperactive-impulsive symptoms are associated with sleep problems. METHOD: A total of 22 nonmedicated adults diagnosed with ADHD are assessed with a DSM-IV-based interview and the Pittsburg Sleep Quality Index (PSQI). RESULTS: The number of hyperactive-impulsive symptoms indicate a positive correlation with sleep duration, habitual sleep efficiency, and global PSQI score. No significant associations are found between inattentive symptoms and sleep quality. CONCLUSION: The results show that sleep problems are associated with hyperactive and impulsive symptoms in nonmedicated adults with ADHD. These findings provide information on the nature of sleep problems without the confounding effects of medication associated with ADHD. Treatment of sleep problems, especially in those with hyperactive-impulsive symptoms, may help ameliorate ADHD symptomatology.

Effects of transdermal nicotine on symptoms, moods, and cardiovascular activity in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder.

The aim of the study was to test the self-medication hypothesis by examining the effects of nicotine in the everyday lives of smokers and nonsmokers with attention-deficit/hyperactivity disorder (ADHD). Fifty-two adults with ADHD (25 abstinent smokers and 27 nonsmokers) participated in a double-blind placebo controlled study with one nicotine patch condition and one placebo patch condition in counterbalanced order. Each condition continued for two consecutive days in which patches were administered each morning. The effects of nicotine on ADHD symptoms, moods, and side effects were assessed with electronic diaries. Cardiovascular activity was recorded with ambulatory blood pressure monitors and physical activity was monitored with actigraphs. Nicotine reduced reports of ADHD symptoms by 8% and negative moods by 9%, independent of smoking status. In addition, nicotine increased cardiovascular activity during the first 3 to 6 hours after nicotine patch administration. The results support the self-medication hypothesis for nicotine in adults with ADHD and suggest that smoking cessation and prevention efforts for individuals with ADHD will need to address both the symptom reducing and mood enhancing effects of nicotine.

Special considerations in diagnosing and treating attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent chronic condition that affects people of all ages, including young children, school-aged children, adolescents, and adults. Symptoms can be noted as early as preschool age, tend to progress into functional impairment and behavioral problems in later childhood, and typically persist into adulthood. Contrary to previous belief, the disorder does not resolve with puberty for the majority of children; rather, the symptoms are manifested differently throughout the lifecycle. Presentation in adults is heavily biased toward inattentive symptoms, which are less likely to draw notice than hyperactive or impulsive symptoms and may contribute to the underrecognition of ADHD in this patient population. Diagnosis is particularly difficult due in large part to the pronounced comorbidity of psychiatric disorders in this patient population. Identification may be even more difficult in adults than children as the diagnostic criteria are not as clear, adults have difficulty remembering symptoms prior to 7 years of age, and there is a high prevalence of comorbid psychiatric disorders in adults. Early identification and treatment of symptoms of ADHD in preschool-age children is essential to effective long-term management of the disorder. Both medication and behavioral treatments appear to alleviate the symptoms of ADHD, and evidence suggests that discontinuation of treatment leads to the reemergence of the condition. Efforts are currently continuing toward understanding the genetic underpinnings of ADHD. This expert review supplement will address the prevalence, comorbidity, treatment issues, and special considerations surrounding ADHD management throughout each stage of the lifecycle beginning with ADHD in preschool-aged children, continuing with school-aged children and adolescents, and ending with adulthood.

The laboratory school protocol: its origin, use, and new applications.

OBJECTIVE: ADHD is the most common childhood psychiatric disorder, with impairments seen in home and academic settings. To investigate such impairments in a school-like setting, the laboratory school protocol (LSP) was developed at the University of California, Irvine. METHOD: This model provides a rigorously controlled environment to examine pharmacodynamic and pharmacokinetic aspects of responses to treatment. A key principle of this methodology is to exercise tight control of the timing and context of measurements by establishing a cycle of activities repeated across each study day. In addition, the LSP approach has been extended to both younger and older populations than the typically studied school-aged group. This extension requires corresponding modifications in measures to characterize drug efficacy and to allow evaluation of ADHD symptoms in a highly standardized setting. RESULTS: This article provides guidelines for employing the LSP for the assessment of medication effects for both preschool and adolescent/adult populations. CONCLUSION: The LSP can be modified to form either an Adult Workplace Environment or a Preschool Assessment Laboratory.