Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Exploring the efficacy of dialectical behaviour therapy and methylphenidate on emotional comorbid symptoms in adults with attention Deficit/Hyperactivity disorder: Results of the COMPAS multicentre randomised controlled trial.

This study evaluated the efficacy of dialectical behaviour group therapy (GPT) vs. individual clinical management (CM) and methylphenidate (MPH) vs. placebo (PLB) on emotional symptoms in adults with ADHD. This longitudinal multicentre RCT compared four groups (GPT+MPH, GPT+PLB, CM+MPH, and CM+PLB) over five assessment periods, from baseline to week 130. Emotional symptomatology was assessed using SCL-90-R subscales. Of the 433 randomised participants, 371 remained for final analysis. At week 13, the GPT+MPH group showed smaller reductions in anxiety symptoms than the CM groups, but the differences disappeared at subsequent assessments. Improvements in emotional symptom were significantly predicted by reductions in core ADHD symptoms in all groups except the GPT+MPH group. The unexpected lack of between-group differences may be explained by a "floor effect", different intervention settings (group vs. individual), and psychotherapy type. Multiple regression analyses suggest a more specific effect of combined interventions (GPT+MPH). Implications for clinical practice are discussed. Clinical trial registration: ISRCTN54096201 (Current Controlled Trials).

Left insular cortical thinning differentiates the inattentive and combined subtype of adult attention-deficit/hyperactivity disorder.

BACKGROUND: Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) demonstrated decreased global gray matter volume. In terms of surface parameters, most investigations focused on cortical thickness with a multi-center MEGA-analysis indicating cortical thinning in children, but not in adults with ADHD. In this single-scanner study, for the first time in adult ADHD, we additionally examined metrics beyond cortical thickness and surface area, namely sulcal depth and fractal dimension as measures of cortical alteration and complexity. Unlike most previous studies, ADHD subtypes were considered. METHODS: As part of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), surface parameters were analyzed in 131 adults with ADHD (66 combined, 60 inattentive and 5 hyperactive/impulsive subtype) and 95 healthy controls with the Computational Anatomy Toolbox (CAT12) using Statistical Parametric Mapping Software (SPM). RESULTS: Neither at the vertex- nor at the region of interest-level, the ADHD and control group differed significantly with regard to cortical thickness, gyrification index, sulcal depth or fractal dimension. Contrasting the combined and the inattentive subtype, patients of the combined subtype showed a significant thinning of the left anterior insular cortex. Thinner left pars opercularis cortical thickness was associated with symptoms of hyperactivity/restlessness. CONCLUSIONS: Resembling previous findings of a correlation of the left anterior insular gray matter volume with oppositional symptoms in adolescents with ADHD, we detected left anterior insular cortical thinning in the ADHD combined subtype. Left insular cortical thickness could represent a potential marker to distinguish the predominantly inattentive and the combined ADHD subtype in adulthood.

Multimodal treatment efficacy differs in dependence of core symptom profiles in adult Attention-Deficit/Hyperactivity Disorder: An analysis of the randomized controlled COMPAS trial.

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD.

Borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD) revisited - a review-update on common grounds and subtle distinctions.

BACKGROUND: Overlap in symptom domains particularly in the field of impulsivity and emotional dysregulation in attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have stimulated further research activities since our last review from 2014. MAIN BODY: Disentangling features of impulsivity in ADHD and BPD revealed that impulsivity is a feature of both disorders with patients suffering from both ADHD and BPD having highest impulsivity ratings. BPD individuals have more problems using context cues for inhibiting responses and their impulsivity is stress-dependent, whereas ADHD patients have more motor impulsivity and therefore difficulties interrupting ongoing responses. For emotion regulation difficulties the ranking order ranges from ADHD to BPD to the comorbid condition, again with the patients suffering from both, ADHD and BPD, having the most pronounced emotion regulation problems. Environmental influences namely adverse childhood events were shown to be linked to both ADHD and BPD. Traumatic experiences seem independently linked to impulsivity features. Thus, some authors point to the risk of misdiagnosis during childhood and the necessity to screen for traumatic experiences in both patient groups. Genetic research confirmed genetic overlap of BPD with bipolar disorder (BD) and schizophrenic disorders, as well as genetic overlap of BD and ADHD. A population-based study confirmed the high co-occurrence and familial co-aggregation of ADHD and BPD. Interesting questions in the field of gene-environment-interactions are currently dealt with by genetic and epigenetic research. Few studies have investigated treatment strategies for the comorbid condition, though the issue is highly important for the management of patients suffering from both disorders and presenting with the highest symptom scores. CONCLUSION: Research on the different impulsivity features might point to a necessity of disorder-specific treatment strategies in the field of impulse control. Future research is needed to base treatment decisions for the comorbid condition on an evidence basis.

Safety Profile of Methylphenidate Under Long-Term Treatment in Adult ADHD Patients - Results of the COMPAS Study.

INTRODUCTION: The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo (PLAC) in combination with cognitive behavioral group psychotherapy (GPT) or individual clinical management (CM) over the period of 1 year. Here, we report results on treatment safety. METHODS: MPH and PLAC were flexibly dosed. Among 433 randomized patients, adverse events (AEs) were documented and analyzed on an "as received" basis during week 0-52. Electrocardiogram data were recorded at baseline and week 24. RESULTS: Comparing 205 patients who received ≥1 dose of MPH with 209 patients who received PLAC, AEs occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8%), dry mouth (15 vs. 4.8%), palpitations (13 vs. 3.3%), gastrointestinal infection (11 vs. 4.8%), agitation (11 vs. 3.3%), restlessness (10 vs. 2.9%), hyperhidrosis, tachycardia, weight decrease (all 6.3 vs. 1.9%), depressive symptom, influenza (both 4.9 vs. 1.0%), and acute tonsillitis (4.4 vs. 0.5%). Syncope occurred significantly more often in the PLAC group (2.4 vs. 0%). Clinically relevant ECG changes occurred very rarely in both groups. Serious AEs were rare and without a significant group difference. The comparison of 206 patients treated with GPT versus 209 patients who received CM revealed no major differences. Serious AE classified as psychiatric occurred in 5 cases in the CM group and in 1 case in the GPT group. CONCLUSION: In this so far longest-running clinical trial, methylphenidate treatment was safe and well-tolerated.

Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study.

Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neurometabolic effects. Until now, no randomized and blinded clinical trials have been conducted addressing the neurometabolic signals of MPH administration in adults with ADHD. In the current study, the authors investigated how MPH intake and group psychotherapy (GPT) influence brain neurometabolism over the course of three months. The authors hypothesized a decrease in the anterior cingulate cortex (ACC) glutamate concentration following MPH administration. This study was part of a double-blind multicenter trial (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS)) investigating the effects of MPH and GPT in patients with adult ADHD. Using single-voxel magnetic resonance spectroscopy (MRS) of the pregenual ACC and the left cerebellar hemisphere (CHL), we investigated the concentration of glutamate plus glutamine (Glx), N-acetyl-aspartate, creatine, total choline containing compounds, and myo-inositol in patients before and after 12 weeks of treatment. Neither MPH nor GPT significantly influenced the Glx concentration or any of the other metabolite concentrations in the ACC and CHL after 12 weeks. Therefore, contrary to the hypothesis, no change in the prefrontal Glx signal was detected after MPH treatment. Given that MRS does not differentiate between glutamate in the synaptic cleft and in neuronal tissue, MPH-induced down-regulation of glutamatergic neurotransmission in the ACC might only affect the concentration of glutamate in the synaptic cleft, while the general availability of glutamate in the respective neuronal tissue might be unaffected by MPH intake. The observed lack of any MPH-induced normalization in metabolite concentrations is less surprising, considering that the baseline sample did not significantly differ from a healthy control group. Future studies of other regions, such as the basal ganglia, and the use of novel methods, such as whole brain MRS and multimodal imaging approaches, are necessary.

Does helping mothers in multigenerational ADHD also help children in the long run? 2-year follow-up from baseline of the AIMAC randomized controlled multicentre trial.

ADHD often affects multiple generations in a family. Previous studies suggested that children with ADHD benefit less from therapy if parents are also affected, since ADHD symptoms interfere with treatment implementation. This two-group randomised controlled trial examined whether targeting maternal ADHD boosts the efficacy of parent-child training (PCT) for the child's ADHD. Here, we report follow-up results 2 years from baseline. Mothers of 144 mother-child dyads (ADHD according to DSM-IV) were examined for eligibility (T1) and randomised to 12 weeks of intensive multimodal treatment comprising pharmacotherapy and DBT-based cognitive behavioural group psychotherapy (TG, n = 77) or clinical management comprising non-specific counselling (CG, n = 67) for Step 1 (concluded by T2). Subsequently, all dyads participated in 12 weekly PCT sessions for Step 2 (concluded by T3). In Step 3, participants received maintenance treatments for 6 months (concluded by T4). At 24 months after baseline (T5), we performed follow-up assessments. The primary endpoint was child ADHD/ODD score (observer blind rating). Outcomes at T5 were evaluated using ANCOVA. Assessments from 101 children and 95 mothers were available at T5. Adjusted means (m) of ADHD/ODD symptoms (range 0-26) in children did not differ between TG and CG (mean difference = 1.0; 95% CI 1.2-3.1). The maternal advantage of TG over CG on the CAARS-O:L ADHD index (range 0-36) disappeared at T5 (mean difference = 0.2; 95% CI - 2.3 to 2.6). Sensitivity analyses controlling for medication and significant predictors of follow-up participation showed unchanged outcomes. Within-group outcomes remained improved from baseline. At the 24-month follow-up, TG and CG converged. The superiority of intensive treatment regarding maternal symptoms disappeared. In general, cross-generational treatment seems to be effective in the long term. (BMBF grant 01GV0605; registration ISRCTN73911400).

Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial.

Borderline personality disorder (BPD) is characterized by severe interpersonal dysfunction with problems in social cognition, empathy and social approach. Although the neuropeptide oxytocin is known to regulate complex social cognition and behavior in healthy individuals and clinical populations, there is still a lack of evidence for a potential beneficial effect of oxytocin administration on social cognition and social approach in BPD. Fifty-one women with BPD and 51 matched healthy controls were randomized to a double-blind, placebo-controlled, between-subject experimental trial. We administered a single dose of 24 IU oxytocin or placebo intranasally prior to a standardized task measuring affective and cognitive empathy and approach motivation. All participants were free of hormonal contraception and tested in the mid-luteal phase of their menstrual cycle. In the placebo condition, patients with BPD showed reduced cognitive and affective empathy, and less approach behavior motivation than healthy controls. Intranasal oxytocin significantly increased affective empathy and approach motivation in both BPD patients and healthy controls compared to placebo. More importantly, oxytocin administration led to similar scores between BPD and healthy controls. These findings provide the first evidence for a beneficial effect of oxytocin on deficits in affective empathy and approach motivation of BPD. Our results indicate a beneficial effect of a single dose of oxytocin on affective empathy and approach motivation in women with BPD adapting their level of social functioning to healthy controls. Future clinical trials will need to investigate the long-term effects and effectiveness of oxytocin as an add-on treatment for social impairments in BPD.

Neurochemical sex differences in adult ADHD patients: an MRS study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients. METHODS: We studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach. RESULTS: For the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p = 0.033; t-Cho: p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex. CONCLUSION: This is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.

Long-term Effects of Multimodal Treatment on Adult Attention-Deficit/Hyperactivity Disorder Symptoms: Follow-up Analysis of the COMPAS Trial.

Importance: Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. Objective: To evaluate the long-term efficacy of multimodal treatment for adult ADHD. Design, Setting, and Participants: This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 × 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. Interventions: After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. Main Outcomes and Measures: The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. Results: At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, which improved to adjusted means of 14.2 for the GPT arm and 14.7 for the CM arm at follow-up with no significant difference between groups (difference, -0.5; 95% CI, -1.9 to 0.9; P = .48). The adjusted mean decreased to 13.8 for the MPH arm and 15.2 for the placebo arm (difference, -1.4; 95% CI, -2.8 to -0.1; P = .04). As in the core study, MPH was associated with a larger reduction in symptoms than placebo at follow-up. These results remained unchanged when accounting for MPH intake at follow-up. Compared with participants in the CM arm, patients who participated in group psychotherapy were associated with less severe symptoms as measured by the self-reported ADHD Symptoms Total Score according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) of Conners Adult ADHD Rating Scale (AMD, -2.1; 95% CI, -4.2 to -0.1; P = .04) and in the subscale of reducing pure hyperactive symptoms, measured via the Diagnostic Checklist for the diagnosis of ADHD in adults (AMD, -1.3; 95% CI, -2.8 to 0.1; P = .08). Regarding the Clinical Global Impression scale assessment of effectiveness, the difference between GPT and CM remained significant at follow-up (odds ratio, 1.63; 95% CI, 1.03-2.59; P = .04). No differences were found for any comparison concerning depression as measured with the Beck Depression Inventory. Conclusions and Relevance: Results from COMPAS demonstrate a maintained improvement in ADHD symptoms for adults 1.5 years after the end of a 52-week controlled multimodal treatment period. The results indicate that MPH treatment combined with GPT or CM provides a benefit lasting 1.5 years. Confirming the results of the core study, GPT was not associated with better results regarding the primary outcome compared with CM. Trial Registration: isrctn.org Identifier: ISRCTN54096201.

Hyperactivity/restlessness is associated with increased functional connectivity in adults with ADHD: a dimensional analysis of resting state fMRI.

BACKGROUND: Adult attention-deficit/hyperactivity disorder (ADHD) is a serious and frequent psychiatric disorder of multifactorial pathogenesis. Several lines of evidence support the idea that ADHD is, in its core, a disorder of dysfunctional brain connectivity within and between several neurofunctional networks. The primary aim of this study was to investigate associations between the functional connectivity within resting state brain networks and the individual severity of core ADHD symptoms (inattention, hyperactivity, and impulsivity). METHODS: Resting state functional magnetic resonance imaging (rs-fMRI) data of 38 methylphenidate-naïve adults with childhood-onset ADHD (20 women, mean age 40.5 years) were analyzed using independent component analysis (FSL's MELODIC) and FSL's dual regression technique. For motion correction, standard volume-realignment followed by independent component analysis-based automatic removal of motion artifacts (FSL's ICA-AROMA) were employed. To identify well-established brain networks, the independent components found in the ADHD group were correlated with brain networks previously found in healthy participants (Smith et al. PNAS 2009;106:13040-5). To investigate associations between functional connectivity and individual symptom severity, sex, and age, linear regressions were performed. RESULTS: Decomposition of resting state brain activity of adults with ADHD resulted in similar resting state networks as previously described for healthy adults. No significant differences in functional connectivity were seen between women and men. Advanced age was associated with decreased functional connectivity in parts of the bilateral cingulate and paracingulate cortex within the executive control network. More severe hyperactivity was associated with increased functional connectivity in the left putamen, right caudate nucleus, right central operculum and a portion of the right postcentral gyrus within the auditory/sensorimotor network. CONCLUSIONS: The present study supports and extends our knowledge on the involvement of the striatum in the pathophysiology of ADHD, in particular, in the pathogenesis of hyperactivity. Our results emphasize the usefulness of dimensional analyses in the study of ADHD, a highly heterogeneous disorder. TRIAL REGISTRATION: ISRCTN12722296 ( https://doi.org/10.1186/ISRCTN12722296 ).

Effectiveness of Psychotherapy in Adult ADHD: What Do Patients Think? Results of the COMPAS Study.

OBJECTIVE: In the multicenter study Comparison of Methylphenidate and Psychotherapy in Adult ADHD (COMPAS), the efficacy of treatments has been primarily evaluated by observer-rated symptom change. Here, we additionally analyzed the patients' subjective evaluation of therapy effects. METHOD: COMPAS compared ADHD-specific group therapy with unspecific clinical management with/without concomitant pharmacotherapy in a four-armed design. Evaluation through the patients' retrospective perspective was performed after 1 year (post-treatment) and after another 1.5 years (follow-up). RESULTS: In respect to patients' subjective ratings, ADHD-specific group psychotherapy outperformed unspecific management post-treatment ( z = 4.88, p < .0001) and at follow-up ( z = 2.90, p = .004). Rank correlations with rater-based symptom change were small to moderate (post-treatment: rs = 0.28, follow-up: rs = 0.16). CONCLUSION: Therapy evaluation based on the patients' perspective supports the concept of ADHD-specific group psychotherapy as a potentially useful therapy option in ADHD.

A multicentre randomized controlled trial on trans-generational attention deficit/hyperactivity disorder (ADHD) in mothers and children (AIMAC): an exploratory analysis of predictors and moderators of treatment outcome.

OBJECTIVE: We examined predictors and moderators of treatment outcome in mothers and children diagnosed with ADHD in a large multicentre RCT. METHOD: In total, 144 mother-child dyads with ADHD were randomly assigned to either a maternal ADHD treatment (group psychotherapy and open methylphenidate medication, TG) or to a control treatment (individual counselling without psycho- or pharmacotherapy, CG). After maternal ADHD treatment, parent-child training (PCT) for all mother-child dyads was added. The final analysis set was based on 123 dyads with completed primary outcome assessments (TG: n = 67, CG: n = 56). The primary outcome was the change in each child's externalizing symptoms. Multiple linear regression analyses were performed. RESULTS: The severity of the child's externalizing problem behaviour in the family at baseline predicted more externalizing symptoms in the child after PCT, independent of maternal treatment. When mothers had a comorbid depression, TG children showed more externalizing symptoms after PCT than CG children of depressive mothers. No differences between the treatment arms were seen in the mothers without comorbid depression. CONCLUSIONS: Severely impaired mothers with ADHD and depressive disorder are likely to need additional disorder-specific treatment for their comorbid psychiatric disorders to effectively transfer the contents of the PCT to the home situation (CCTISRCTN73911400).

Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial.

BACKGROUND: The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment. METHODS: The analysis included 143 mothers and children (aged 6-12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher). RESULTS: Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children's disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2). CONCLUSIONS: Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child's disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand. TRIAL REGISTRATION: ISRCTN registry ISRCTN73911400 . Registered 29 March 2007.

Please Don't Leave Me-Separation Anxiety and Related Traits in Borderline Personality Disorder.

PURPOSE OF REVIEW: In light of the apparent symptomatic resemblance of separation anxiety disorder (SAD) symptoms on the one hand and abandonment fears, anxiousness, and separation insecurity central to borderline personality disorder (BPD) on the other hand, a comprehensive overview of separation anxiety and related traits in BPD is provided. RECENT FINDINGS: Epidemiological, environmental, psychological, and neurobiological data connecting BPD to separation events, feelings of loneliness, insecure attachment styles, dimensional separation anxiety as well as SAD per se suggest a partly shared etiological pathway model underlying BPD and SAD. Differential diagnostic aspects and implications for treatment are discussed, highlighting separation anxiety as a promising transdiagnostic target for specific psychotherapeutic and pharmacological treatment approaches in BPD. This innovative angle on cross-disorder symptomatology might carry potential for novel preventive and therapeutic avenues in clinical practice by guiding the development of interventions specifically targeting separation anxiety and attachment-related issues in BPD.

Effects of mindfulness and psychoeducation on working memory in adult ADHD: A randomised, controlled fMRI study.

Adult attention-deficit/hyperactivity disorder (ADHD) is a serious mental disorder associated with impaired neurocognitive performance related to working memory function. Recent clinical trials have suggested that mindfulness is a promising intervention in adults with ADHD. We performed a randomised controlled clinical trial to investigate working memory (WM) with an n-back task in adults with ADHD during fMRI before and after an 8-week mindfulness intervention (MAP) compared with psychoeducation (PE). ADHD symptoms were assessed using the self- and observer-rated Conners Adult ADHD Rating Scales (CAARS). The complete pre-post data of 21 MAP and 19 PE participants were analysed. We found no group difference in ADHD symptoms or task performance at the pre-measurement, but there was a significant decrease in ADHD symptoms and significant improvement in task performance in both groups at the post-measurement. Furthermore, we found a significant increase in task-related activation in the right parietal lobe, with no difference between groups. Exploratory two-sample paired t-tests revealed significant increased brain activation after MAP in the bilateral inferior parietal lobule, right posterior insula and right precuneus. A decrease in self-rated 'Inattention/Memory Problems' after MAP compared to baseline was associated with stronger activation in parts of the left putamen, globus pallidus and thalamus.

Does the efficacy of parent-child training depend on maternal symptom improvement? Results from a randomized controlled trial on children and mothers both affected by attention-deficit/hyperactivity disorder (ADHD).

Multimodal treatment of children with ADHD often includes parent-child training (PCT). However, due to the high heritability, parents of children with ADHD are frequently also affected by the disorder, which is likely to constitute a significant barrier to successful treatment of the child. This secondary analysis of our randomized controlled multicentre AIMAC trial (ADHD in mothers and children) investigates whether children's outcomes following parent-child training in combination with maternal ADHD treatment depend on maternal symptom improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers of mother-child dyads were randomized to multimodal ADHD treatment (group psychotherapy plus methylphenidate) or clinical management (mainly supportive counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother-child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS-O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were analysed using a general linear model, controlling for baseline scores, study centre, and maternal treatment group. 125 mother-child dyads were analysed. Mothers showed significant improvements in ADHD symptoms and overall psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE 0.58, p < 0.0001), maternal improvement had no effect on children's outcomes after Bonferroni-Holm correction for multiple testing. The findings do not support our hypothesis that children's outcomes following PCT for ADHD depend on maternal symptom improvements.Trial register CCT-ISRCTN73911400.

The Impact of Depressive Symptoms and Traumatic Experiences on Quality of Life in Adults With ADHD.

OBJECTIVE: We assessed factors influencing quality of life (QoL) in adults with ADHD. METHOD: QoL, traumatic childhood experiences, and depression were assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Childhood Trauma Questionnaire (CTQ), and Beck Depression Inventory (BDI), respectively, in 60 adult ADHD outpatients and 60 age- and gender-matched controls. RESULTS: Emotional neglect or abuse had occurred significantly more often during childhood in adults with ADHD. Depressive symptoms were rated significantly higher by ADHD patients. QoL was significantly lower in adults with ADHD, and the variables depression, ADHD symptom severity, and traumatic load, accounted for ~60% of variance in overall QoL. CONCLUSION: QoL is significantly reduced in adult ADHD patients. Depressive symptoms and traumatic childhood experiences influence QoL. Treatment for adult ADHD patients should take the high interdependence of depressive symptoms, childhood trauma, and QoL into consideration.