Long-term efficacy of a new 6-session cognitive behavioral therapy for adults with attention-deficit/hyperactivity disorder: A randomized, controlled clinical trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects about 2.8 % of the adult population. Cognitive behavioral therapy (CBT) has been demonstrated to be the most effective psychological intervention for ADHD. The aim of this study was to explore the efficacy of a new 6-session CBT program in comparison with a 12-session CBT program for adults with ADHD at short- and long-term. METHODS: 81 adults with ADHD (58 % males; mean age = 41.27±9.26 years old) were randomly assigned to each treatment condition (6- or 12-session CBT). Validated instruments were used to assess ADHD symptoms, comorbidities (anxiety and depression), and functional impairments at post treatment, and at 3- and 6-month follow-up. RESULTS: A significant improvement in ADHD severity, comorbidities (anxiety and depression) and functional impairments were found in both CBT programs after treatment. Furthermore, this improvement was also reported at 3- and 6-month follow-up. CONCLUSION: The current study highlights that a 6-session CBT program is as effective as a 12-session CBT program for ADHD improvement at post treatment and follow-up. The newly developed 6-session CBT program can be used to treat a larger number of patients, reducing the financial cost.

The impact of insomnia disorder on adult attention-deficit/hyperactivity disorder severity: A six-month follow-up study.

BACKGROUND AND OBJECTIVES: The longitudinal relationship between insomnia disorder and adult attention-deficit/hyperactivity disorder (ADHD) has been scarcely investigated. This study aimed to evaluate the relationship between the remission of insomnia disorder and adult ADHD clinical severity, psychiatric and medical comorbidities, and the health-related quality of life (HRQoL) in a 6-month follow-up. METHODS: Ninety-two adult patients with ADHD and insomnia disorder (52.2% males; mean age 39.5 ± 11.0 years) were comprehensively assessed at baseline, 3 months, and 6 months of a follow-up period. The evaluation included semi-structured interviews (for ADHD and comorbidity assessment), the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of ADHD and insomnia disorder was performed according to DSM-5 criteria. At baseline and follow-up, psychoeducation/sleep hygiene and, if necessary, pharmacological were prescribed for insomnia. RESULTS: Eighty-seven patients completed the 6-month follow-up. Insomnia disorder remission was reported in 72.4% of cases and was related to a greater improvement in ADHD symptoms and severity throughout the follow-up period. Additionally, an improvement in psychiatric comorbidities and better HRQoL were associated with insomnia disorder remission. CONCLUSION: The current study highlights that the treatment of insomnia disorder in ADHD adult patients may have an important role in the outcome of ADHD therapeutic approaches by reducing their severity.

Updated European Consensus Statement on diagnosis and treatment of adult ADHD.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

[The gut-brain axis in attention deficit hyperactivity disorder: the role of the microbiota]. / El eje intestino-cerebro en el trastorno por deficit de atencion/hiperactividad: papel de la microbiota.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) has a complex aetiology, mainly attributed to a number of susceptibility genes and environmental factors. Genetic association studies, however, have been inconsistent and have identified genetic variants with a moderate effect that explain a small proportion of the estimated inheritability of the disorder (< 10%). Recent studies suggest that the gut microbiota and diet play an important role in the development and symptoms of different mental disorders. Nevertheless, no clear evidence exists on the issue. This project proposes an alternative approach to identify mechanisms by which the intestinal microbial ecosystem and diet could contribute to the presence of ADHD. AIM: To identify biomarkers for ADHD by examining the gut microbiota. SUBJECTS AND METHODS: We conducted a cross-sectional study of adult patients with ADHD (n = 100) and control subjects (n = 100). Measures of ADHD evaluation and eating habits were performed in both groups. Samples of faecal material were obtained from which to extract bacterial DNA, then used to characterise the participants' gut microbiota. A meta-genomic association study was later performed to attempt to correlate the bacterial composition of the intestine with the clinical subtypes of the disorder. RESULTS AND CONCLUSIONS: Comparing the gut microbiota profiles of subjects with ADHD and controls is expected to help account for the clinical heterogeneity of the disorder and identify new mechanisms involved in its development.

TITLE: El eje intestino-cerebro en el trastorno por deficit de atencion/hiperactividad: papel de la microbiota.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) presenta una etiologia compleja, atribuida principalmente a multiples genes de susceptibilidad y factores ambientales. No obstante, los estudios geneticos de asociacion han sido inconsistentes, identificando variantes geneticas de efecto moderado que explican una pequeña proporcion de la heredabilidad estimada del trastorno (< 10%). Recientes estudios sugieren que la microbiota intestinal y la dieta desempeñan un papel importante en el desarrollo y los sintomas de diferentes trastornos mentales. Sin embargo, en la actualidad no existe una claridad absoluta al respecto. El presente proyecto propone un abordaje alternativo para identificar mecanismos a traves de los cuales el ecosistema microbiano intestinal y la dieta podrian contribuir a la presencia del TDAH. Objetivo. Identificar biomarcadores para el TDAH a traves del estudio de la microbiota intestinal. Sujetos y metodos. Estudio transversal de pacientes adultos con TDAH (n = 100) y de individuos control (n = 100). En ambos grupos se tomaran medidas de evaluacion de TDAH y habitos alimentarios. Se obtendran muestras fecales para la extraccion del ADN bacteriano, que permitiran caracterizar la microbiota intestinal de los participantes, para posteriormente realizar un estudio de asociacion metagenomico e intentar correlacionar la composicion bacteriana intestinal con subtipos clinicos del trastorno. Resultados y conclusiones. Se espera que la comparacion de los perfiles de microbiota intestinal entre sujetos con TDAH y controles ayude a explicar la heterogeneidad clinica del trastorno e identificar nuevos mecanismos implicados en su desarrollo.

[Treatment of attention deficit hyperactivity disorder in adults using virtual reality through a mindfulness programme]. / Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder, which presents a high comorbidity with anxiety and affective signs and symptoms. It has repercussions on the functioning of those suffering from it, who also have low therapy compliance and generate a significant cost both at a personal level and for society. Mindfulness is a psychological treatment that has proved to be effective for ADHD. Virtual reality is widely used as treatment in cases of phobias and other pathologies, with positive results. AIMS: To develop the first treatment for ADHD in adults based on virtual reality and mindfulness, while also resulting in increased treatment adherence and reduced costs. PATIENTS AND METHODS: We conducted a pilot study with 25 patients treated by means of virtual reality, in four 30-minute sessions, and 25 treated with psychostimulants. Measures will be taken pre-treatment, post-treatment and at 3 and 12 months post-treatment, to evaluate both ADHD and also depression, anxiety, functionality and quality of life. Data will be later analysed with the SPSS v. 20 statistical program. An ANOVA of independent groups will be performed to see the differences between treatments and also a test-retest to detect whether the changes will be maintained. RESULTS AND CONCLUSIONS: It is necessary to use treatments that are effective, reduce costs and increase therapy adherence. Treatment with virtual reality is an interesting alternative to the classical treatments, and is shorter and more attractive for patients.

TITLE: Tratamiento del trastorno por deficit de atencion/hiperactividad en la edad adulta a traves de la realidad virtual mediante un programa de mindfulness.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es un trastorno del neurodesarrollo altamente prevalente, presenta una elevada comorbilidad con sintomatologia afectiva y ansiosa, afecta a la funcionalidad de la persona que lo padece, tienen una baja adhesion terapeutica y genera unos costes sociales y personales elevados. El mindfulness es un tratamiento psicologico que ha demostrado ser eficaz para el TDAH. La realidad virtual es un tratamiento altamente utilizado en fobias y extendido a otras patologias con resultados positivos. Objetivo. Desarrollar el primer tratamiento con realidad virtual y mindfulness para el TDAH en la edad adulta, que suponga un aumento en la adhesion terapeutica y reduzca costes. Pacientes y metodos. Estudio piloto de 25 pacientes tratados con realidad virtual, mediante cuatro sesiones de 30 minutos, y 25 mediante psicoestimulantes. Se tomaran medidas de evaluacion pretratamiento, postratamiento y postratamiento a los 3 y 12 meses, tanto de TDAH como de depresion, ansiedad, funcionalidad y calidad de vida. Se analizaran posteriormente con el programa SPSS v. 20 y se realizara un ANOVA de grupos independientes para ver las diferencias entre tratamientos y un test-retest para detectar el mantenimiento de los cambios. Resultados y conclusiones. Es necesaria la utilizacion de tratamientos que sean efectivos, supongan una reduccion en los costes y un aumento en la adhesion terapeutica. El tratamiento con realidad virtual se plantea como una alternativa a los tratamientos clasicos, que sea mas breve y atractiva para los pacientes.

IL-6 and TNF-α in unmedicated adults with ADHD: Relationship to cortisol awakening response.

There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-α between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-α and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-α between groups. Pearson correlations were used to study associations between IL-6, TNF-α, and CAR. There were no significant differences in serum IL-6 or TNF-α levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0.386, p=0.020), TNF-α (r=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between IL-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-α, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-α and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies.

Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder.

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

Exome chip analyses in adult attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.

Preliminary evidence for association of genetic variants in pri-miR-34b/c and abnormal miR-34c expression with attention deficit and hyperactivity disorder.

Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by impairment to sustain attention and inability to control impulses and activity level. The etiology of ADHD is complex, with an estimated heritability of 70-80%. Under the hypothesis that alterations in the processing or target binding of microRNAs (miRNAs) may result in functional alterations predisposing to ADHD, we explored whether common polymorphisms potentially affecting miRNA-mediated regulation are involved in this psychiatric disorder. We performed a comprehensive association study focused on 134 miRNAs in 754 ADHD subjects and 766 controls and found association between the miR-34b/c locus and ADHD. Subsequently, we provided preliminary evidence for overexpression of the miR-34c-3p mature form in peripheral blood mononuclear cells of ADHD subjects. Next, we tested the effect on gene expression of single-nucleotide polymorphisms within the ADHD-associated region and found that rs4938923 in the promoter of the pri-miR-34b/c tags cis expression quantitative trait loci for both miR-34b and miR-34c and has an impact on the expression levels of 681 transcripts in trans, including genes previously associated with ADHD. This gene set was enriched for miR-34b/c binding sites, functional categories related to the central nervous system, such as axon guidance or neuron differentiation, and serotonin biosynthesis and signaling canonical pathways. Our results provide preliminary evidence for the contribution to ADHD of a functional variant in the pri-miR-34b/c promoter, possibly through dysregulation of the expression of mature forms of miR-34b and miR-34c and some target genes. These data highlight the importance of abnormal miRNA function as a potential epigenetic mechanism contributing to ADHD.

Cortisol awakening response in adults with attention deficit hyperactivity disorder: Subtype differences and association with the emotional lability.

Cortisol awakening response (CAR) has been studied in children with ADHD, and some authors have reported morning cortisol differences among ADHD subtypes. Despite, only half of the children with ADHD continue to exhibit the disorder into adulthood, CAR has not been studied in adults so far. One hundred and nine adults with ADHD according to the DSM-IV criteria (46 inattentive and 63 combined) ranging in age from 18 to 55 years, and 27 healthy controls were included. Psychiatric and organic comorbidities were excluded. Salivary cortisol samples were obtained at 0, 30, 45 and 60 minutes after awakening. CAR was present in 84% of the healthy controls but in only 64% of the adults with ADHD (68% of the inattentive and 61% of the combined were CAR-positive). There were no significant differences in any of the morning cortisol measures between patients and controls or between the combined and inattentive subtypes of ADHD. Among the inattentive subtype but not in the combined patients, significant positive correlations were observed between the CAR and emotional lability (p=0.05), or self-concept (p=0.014) CAARS subscales, as well as with the cognitive impulsivity subscale of the Barratt impulsiveness scale (p=0.028). These results suggest that adults with ADHD exhibit normal cortisol responses upon awakening and thus cannot be defined in terms of hypo-arousal. Neurobiological differences between the combined and inattentive subtypes involving cortisol, are discussed.

Early-age clinical and developmental features associated to Substance Use Disorders in Attention-Deficit/Hyperactivity Disorder in Adults.

OBJECTIVE: The main objective was to explore early-age conditions associated to Substance Use Disorders (SUD) in adults with Attention Deficit/Hyperactivity Disorder (ADHD); secondly, to determine which of those conditions are specific to ADHD subjects; and finally, to compare ADHD and non-ADHD subjects in terms of SUD lifetime prevalence and professional, social and personal adjustment. METHOD: Comparison between ADHD adults with (n=236) and without lifetime SUD (n=309) regarding clinical characteristics of ADHD, externalization disorders, temperamental traits, environmental factors, academic history and family psychiatric history; secondly, ADHD subjects were compared to a non-ADHD group (n=177) concerning those variables. RESULTS: The following variables were found to be positively associated to SUD in ADHD subjects: ADHD severity, CD and ODD comorbidities, temperamental characteristics ("fearful", "accident prone" and "frequent temper tantrums"), "sexual abuse", "be suspended from school", family history of SUD and ADHD, and male gender; ADHD inattentive subtype and "fearful" were inversely associated to SUD. From those variables, "frequent temper tantrums" was also associated to SUD in non-ADHD subjects. ADHD subjects had higher prevalence of lifetime SUD and greater professional, social and personal impairment than non-ADHD subjects. CONCLUSION: Findings suggest a significant association between ADHD, SUD and early-age conditions, such as CD and ODD comorbidity; other variables from childhood, namely, ADHD subtype, temper characteristics ("fearful", "accident prone"), "sexual abuse", "be suspended from school" and family history of ADHD are associated to SUD in ADHD subjects, but not in non-ADHD subjects. Moreover, this study confirms both the higher prevalence of lifetime SUD and greater professional, social and personal impairment in ADHD subjects than in non-ADHD subjects.

Neuroanatomía del trastorno por déficit de atención/hiperactividad en el adulto: hallazgos de neuroimagen estructural y funcional / The neuroanatomy of attention deficit hyperactivity disorder in adults: structural and functional

Este trabajo tiene como objetivo revisar la bibliografía existente sobre los hallazgos de resonancia magnética estructural, funcional y conectividad. Durante mucho tiempo, se ha pensado que los niños superaban el trastorno por déficit de atención/hiperactividad (TDAH) al llegar a la adolescencia. Sin embargo, actualmente se sabe que hasta un 70% de los niños que presentaban TDAH en la infancia continúa presentando síntomas en la esfera conductual y cognitiva en la edad adulta. Estudios de neuroimagen realizados en adultos con TDAH han mostrado alteraciones cerebrales a nivel estructural, funcional y en conectividad. Estos hallazgos se han observado principalmente en el córtex frontal inferior y prefrontal dorsolateral, así como en regiones estriatales, del cíngulo anterior, parietotemporales y cerebelares. Sin embargo, se han encontrado algunas inconsistencias, posiblemente relacionadas con la presencia de comorbilidad, historia de medicación, diferencias por género y el reducido tamaño de la muestra utilizada en algunos estudios. También se han observado diferencias en relación con los estudios realizados en niños con TDAH. De ahí la importancia para futuros estudios de evitar que existan variables que puedan afectar los hallazgos en el TDAH en adultos y, además, poder comprobar si los déficits anatómicos y funcionales persisten en la edad adulta (AU)

The objective of this work is to review the existing literature on findings from structural and functional magnetic resonance and connectivity. For a long time it was thought that children ‘grew out’ of attention deficit hyperactivity disorder (ADHD) on reaching adolescence. Yet, it is now known that up to 70% of children who present ADHD in childhood go on to present symptoms in the behavioural and cognitive sphere in adulthood. Neuroimaging studies conducted in adults with ADHD have shown alterations in the brain at the structural and functional levels, and also in terms of connectivity. These findings have been observed mainly in the inferior frontal and dorsolateral prefrontal cortex, as well as in striatal, anterior cingulate, parietotemporal and cerebellar regions. However, certain inconsistencies have also been found, which may be related with the presence of comorbidity, a history of medication, gender-related differences and the small size of the sample used in some studies. Differences have also been noted in relation to studies carried out in children with ADHD. Hence the importance for future studies of avoiding the existence of variables that can affect the findings in ADHD in adults and, moreover, of being able to determine whether the anatomical and functional déficits continue into adulthood (AU)

Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable developmental disorder characterized by a persistent impairing pattern of inattention and/or hyperactivity-impulsivity. Using families from a genetic isolate, the Paisa population from Colombia, and five independent datasets from four different populations (United States, Germany, Norway and Spain), a highly consistent association was recently reported between ADHD and the latrophilin 3 (LPHN3) gene, a brain-specific member of the LPHN subfamily of G-protein-coupled receptors that is expressed in ADHD-related regions, such as amygdala, caudate nucleus, cerebellum and cerebral cortex. To replicate the association between LPHN3 and ADHD in adults, we undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single- and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P = 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P = 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan.