To determine the efficacy of group cognitive-behavioral therapy (CBT) on adolescents with attention-deficit/hyperactivity disorder (ADHD) who were in pharmacological treatment but still had ...persistent symptoms.
We conducted a multicenter, randomized, rater-blinded, controlled trial between April 2012 and May 2014 in a cohort of 119 adolescents (15-21 years of age). Participants were randomly assigned to 12 manualized group CBT sessions (n = 45) or a waiting list control group (n = 44). Primary outcomes were assessed by a blinded evaluator (ADHD Rating Scale ADHD-RS, Clinical Global Impression Scale for Severity CGI-S, Global Assessment of Functioning GAF) before and after treatment, as well as by self-report and parent informant ratings.
Of the initial 119 participants enrolled, 89 completed treatment. A mixed-effects model analysis revealed that participants who were assigned to the group CBT sessions experienced significantly reduced ADHD symptoms compared to the control group (ADHD-RS Adolescent: -7.46, 95% CI = -9.56 to -5.36, p < .001, d = 7.5; ADHD-RS Parents: -9.11, 95% CI = -11.48 to -6.75, p < .001, d = 8.38; CGI-S Self-Report: -0.68, 95% CI = -0.98 to -0.39, p < .001, d = 3.75; CGI-S Clinician: -0.79, 95% CI = -0.95 to -0.62, p < .001; d = 7.71). Functional impairment decreased significantly in the CBT group according to parents (Weiss Functional Impairment Scale -4.02, 95% CI = -7.76 to -0.29, p < .05, d = 2.29) and according to the blinded evaluator (GAF: -7.58, 95% CI = -9.1 to -6.05, p < .001, d = 7.51).
Group CBT associated with pharmacological treatment is an efficacious intervention for reducing ADHD symptoms and functional impairment in adolescents. Clinical trial registration information-CBT Group for Adolescents With ADHD: a Randomized Controlled Trial; http://clinicaltrials.gov/; NCT02172183.
Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder ...(ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene's relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.
It has been hypothesized that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), although experimental data regarding the ...contribution of BDNF gene polymorphisms to this psychiatric disorder are controversial. Recently, changes in BDNF serum levels have been reported in children with ADHD, but there are no studies about the possible role of this neurotrophin in adults. A total of 54 Caucasoid ADHD adults, including the predominantly inattentive and combined types (aged 33.43 ± 8.99 yr) and 59 Caucasoid unrelated healthy controls (aged 35.52 ± 9.37 yr) were included in a study to evaluate BDNF levels in serum. Medical, neurological and psychiatric co-morbidities were excluded. Clinical data concerning ADHD diagnosis and blood samples for patients and controls were collected. BDNF serum levels were significantly lower in adults with ADHD compared to healthy controls (p < 0.0001). Although the combined type of ADHD subgroup displayed lower BDNF serum levels than the inattentive type, the differences did not reach statistical significance. No significant correlations were found between serum BDNF levels and scores on the Conners’ Adult ADHD Rating Subscales. These results suggest a role for BDNF in ADHD, at least in those patients whose disorder persists throughout life. Low BDNF levels may contribute to the neurodevelopmental deficits of ADHD and to the persistence of the disorder into adulthood. BDNF differences between ADHD subtypes should be further studied.
Abstract Attention-deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by inappropriate difficulties to sustain attention, control impulses and modulate activity level. ...Although ADHD is one of the most prevalent childhood psychiatric disorders, it also persists into adulthood in around 30–50% of the cases. Based on the effect of psychostimulants used in the pharmacological treatment of ADHD, dysfunctions in neuroplasticity mechanisms and synapses have been postulated to be involved in the pathophysiology of ADHD. With this background, we evaluated, both in childhood and adulthood ADHD, the role of several genes involved in the control of neurotransmitter release through synaptic vesicle docking, fusion and recycling processes by means of a population-based association study. We analyzed single nucleotide polymorphisms across 16 genes in a clinical sample of 950 ADHD patients (506 adults and 444 children) and 905 controls. Single and multiple-marker analyses identified several significant associations after correcting for multiple testing with a false discovery rate (FDR) of 15%: (i) the SYT2 gene was strongly associated with both adulthood and childhood ADHD ( p =0.001, OR=1.49 (1.18–1.89) and p =0.007, OR=1.37 (1.09–1.72), respectively) and (ii) STX1A was found associated with ADHD only in adults ( p =0.0041; OR=1.28 (1.08–1.51)). These data provide preliminary evidence for the involvement of genes that participate in the control of neurotransmitter release in the genetic predisposition to ADHD through a gene-system association study. Further follow-up studies in larger cohorts and deep-sequencing of the associated genomic regions are required to identify sequence variants directly involved in ADHD.
Abstract Attention Deficit Hyperactivity Disorder (ADHD) commonly affects children, although the symptoms persist into adulthood in approximately 50% of cases. Structural imaging studies in children ...have documented both cortical and subcortical changes in the brain. However, there have been only a few studies in adults and the results are inconclusive. Method Voxel-based morphometry (VBM) was applied to 44 adults with ADHD, Combined subtype, aged 18-54 years and 44 healthy controls matched for age, sex and IQ. Results ADHD patients showed reduced grey matter (GM) volume in the right supplementary motor area (SMA). Using more lenient thresholds we also observed reductions in the subgenual anterior cingulate (ACC) and right dorsolateral prefrontal (DLPFC) cortices and increases in the basal ganglia, specifically in the left caudate nucleus and putamen. There was a positive correlation between the cumulative stimulant dose and volume in the right SMA and DLPFC clusters. Conclusions The findings suggest that adults with ADHD show brain structural changes in regions belonging to the so-called cool executive function network. Long-term stimulant medication may act to normalize these GM alterations.
The aim of the present study was to assess the efficacy of psychoeducation as compared with cognitive behavioral group therapy in adults with attention deficit hyperactivity disorder (ADHD) who still ...had significant symptoms and were in pharmacological treatment. This is the first study on psychoeducation in adults with ADHD. Thirty-two individuals were randomized to two treatment conditions: 15 were in the psychoeducation group and 11 were in the cognitive behavioral group therapy. A total of 30 completed treatment, and 26 completed the follow-up assessments. The results indicated that both treatments were associated with statistically significant improvements on inattention, hyperactivity, impulsivity, and self-esteem. The patients in both groups showed a decrease in anxiety symptoms and obtained significantly lower scores in depression. Measures on functional impairment showed statistically significant differences on improved quality of life and on lower global severity as perceived in self-report and assessed by clinician report. Psychoeducation demonstrated to be an effective treatment in reducing ADHD core symptoms.
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. At least 30% of patients diagnosed in childhood continue to suffer from ADHD during adulthood ...and genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. To date, genome-wide association studies (GWAS) of ADHD have been completed in seven independent datasets, six of which were pediatric samples and one on persistent ADHD using a DNA-pooling strategy, but none of them reported genome-wide significant associations. In an attempt to unravel novel genes for the persistence of ADHD into adulthood, we conducted the first two-stage GWAS in adults with ADHD. The discovery sample included 607 ADHD cases and 584 controls. Top signals were subsequently tested for replication in three independent follow-up samples of 2104 ADHD patients and 1901 controls. None of the findings exceeded the genome-wide threshold for significance (PGC<5e-08), but we found evidence for the involvement of the FBXO33 (F-box only protein 33) gene in combined ADHD in the discovery sample (P=9.02e-07) and in the joint analysis of both stages (P=9.7e-03). Additional evidence for a FBXO33 role in ADHD was found through gene-wise and pathway enrichment analyses in our genomic study. Risk alleles were associated with lower FBXO33 expression in lymphoblastoid cell lines and with reduced frontal gray matter volume in a sample of 1300 adult subjects. Our findings point for the first time at the ubiquitination machinery as a new disease mechanism for adult ADHD and establish a rationale for searching for additional risk variants in ubiquitination-related genes.
Objective: Functional imaging studies have found reduced frontal activity, mainly in dorso/ventro-lateral regions and reduced task-related de-activation of the default mode network in childhood ADHD. ...Adult studies are fewer and inconclusive. We aimed to investigate the potential neural bases of executive function in ADHD adults, examining brain activity during N-back task performance, and to explore the potential corrective effects of long-term methylphenidate treatment. Method: We recruited a large adult ADHD-combined sample and a matched control group and obtained functional magnetic resonance imaging (fMRI) images during task. ADHD participants were subdivided in a group under long-term treatment with methylphenidate (washed out for the scan) and a treatment-naive group. Results: ADHD participants showed deficient de-activation of the medial prefrontal cortex during 2-back task, implying default mode network dysfunction. We found no relationship between blunted de-activation and treatment history. Conclusion: As de-activation failure in the medial frontal cortex is linked to lapses of attention, findings suggest a potential link to ADHD symptomatology.
Background:
Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. ...However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress.
Methods:
Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded.
Results:
No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027).
Conclusions:
Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life.
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