[ADHD in adulthood: Diagnostics and therapy]. / ADHS im Erwachsenenalter : Diagnostik und Therapie.

Traditionally, attention deficit hyperactivity disorder (ADHD) was assumed to be a childhood disorder. In the meantime a persistence of symptoms into adulthood has been shown in 60% of those affected. Besides the core symptoms of inattentiveness, hyperactivity and impulsivity, adults with ADHD often suffer from comorbid disorders and functional impairment in multiple domains. In recent years diagnostic guidelines and standardized questionnaires have been developed, which facilitate the diagnostics of ADHD. In addition various therapeutic approaches have emerged and randomized controlled studies have demonstrated the efficacy. The aim of the article is to present the current standard of knowledge with respect to the diagnostics and treatment of ADHD.

Altered cingulate and amygdala response towards threat and safe cues in attention deficit hyperactivity disorder.

BACKGROUND: Emotional dysregulation is becoming increasingly recognized as an important feature of attention deficit hyperactivity disorder (ADHD). In this study, two experiments were conducted investigating the neural response to either verbally instructed fear (IF) or uninstructed (classically conditioned) fear (UF) using the skin conductance response (SCR) and functional magnetic resonance imaging (fMRI). METHOD: In the conditioning phase of the UF experiment (17 ADHD and 17 healthy controls), subjects experienced an unconditioned stimulus (UCS, unpleasant electrodermal stimulation) paired with a former neutral conditioned stimulus (CS+), whereas a control stimulus (CS-) was never paired with the UCS. In the subsequent test phase, only the CS+ and the CS- were presented. In the IF experiment (13 ADHD and 17 healthy controls), subjects were only told that an independently experienced UCS might occur together with the CS+ but not the CS- during testing. No UCS was presented. RESULTS: Groups did not detectably differ in SCR or neural responses to UF. In IF, ADHD patients showed a trend-line decreased SCR and significantly decreased activation of the dorsal anterior cingulate cortex (dACC), a region prominently involved in fear responding, to the CS+. This was accompanied by higher amygdala activation to the CS-. CONCLUSIONS: During IF, ADHD patients showed deficits in regions centrally involved in fear learning and expression in terms of diminished CS+-related dACC and increased CS--related amygdala signals. This suggests an impaired processing of verbally transmitted aversive information, which is central for conveying fear information in social contexts. This result extends the growing literature on emotional alterations in ADHD.

Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Functional improvement and correlations with symptomatic improvement in adults with attention deficit hyperactivity disorder receiving long-acting methylphenidate.

BACKGROUND: Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated. METHOD: After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis. RESULTS: A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes. CONCLUSIONS: Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.

Effects of Acute Aerobic Exercise on Response Inhibition in Adult Patients with ADHD.

Previous studies suggest beneficial effects of aerobic exercise on executive functions, which are a core deficit in ADHD. The aim of the present fMRI study was to investigate acute effects of aerobic exercise on inhibitory control and related brain activation in adult patients with ADHD. 23 patients and 23 matched healthy controls performed on a Go/No-go task in an MRI scanner, following both, an exercise condition involving 30 min of cycling at moderate intensity, and a control condition. ADHD patients compared to healthy controls showed increased brain activation during successful inhibition in the exercise compared to the control condition in parietal, temporal, and occipital regions. Exercise did not improve behavioral performance in either group, but in ADHD patients, exercise-related increases in brain activation and behavioral task performance (i.e., correct inhibition rate) negatively correlated with correct inhibition rate in the control condition. Thus, patients with worse inhibition performance showed stronger exercise-related enhancements, indicating that the lack of improvements on the behavioral level for the whole patient group could be due to ceiling effects. Our findings might be an important step in understanding the neural basis of exercise effects and could, in the long term, help in developing alternative treatment approaches for ADHD.

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.

Reduced cingulate glutamate/glutamine-to-creatine ratios in adult patients with attention deficit/hyperactivity disorder -- a magnet resonance spectroscopy study.

BACKGROUND: The dopaminergic system is thought to be essentially involved in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). However, there is also evidence for abnormalities in the glutamatergic system and recent theories focus on a disturbed interaction between the two systems as the essential pathogenetic mechanism of ADHD. In the present study, we wanted to test the hypothesis that prefrontal glutamate signals indirectly indicate dopaminergic dysfunction in adult patients with ADHD. METHODS: Twenty-eight adult patients with ADHD and 28 group-matched healthy volunteers were studied clinically and using chemical-shift MR spectroscopy (MRS) of the prefrontal cortex covering the anterior cingulate gyrus. RESULTS: A significant reduction of the combined glutamate/glutamine to creatine ratio in the right anterior cingulate cortex in patients with ADHD was found. DISCUSSION: Glutamatergic alterations as measured with MRS might play a role in the pathogenesis of adult patients with ADHD.

Patient compliance and effect of orthopaedic shoes.

Orthopaedic shoes are individually handmade after a prescription from an orthopaedic surgeon, hence relatively expensive. Bad compliance is mentioned in the literature but not investigated. In order to evaluate patient compliance and the effect of orthopaedic shoes, 85 patients who were prescribed orthopaedic shoes at the authors' department during a 3 year period received a questionnaire concerning relief of symptoms and daily use of the shoes. The answers from 74 patients were correlated to the prescription procedure and the degree of medical follow-up. Only 60 of 74 patients used their shoes. Some 51 patients had some benefit while 23 had no effect or even worse symptoms. Some patients even used their shoes despite no symptomatic relief. However, patients who felt they were well informed about the purpose and function of their shoes had more benefit than the rest. Only 12 patients of the 74 were checked by the orthopaedic surgeon after delivery of the shoes. In conclusion the authors believe there is a great need for information to be given to the patients about the functions and limitations of orthopaedic shoes and that every patient should be offered a control check-up by the surgeon. Further investigations of the effect of orthopaedic shoes should be carried out to optimise the use of these expensive devices.

[Primary assessment of X-ray images in a casualty department]. / Primaer bedømmelse af røntgenbilleder på en skadestue.

During a period of three months, the primary diagnoses made by the duty officer in the casualty department on x-rays taken on patients with orthopaedic conditions were compared with the definitive diagnoses made after a conference with the radiological department. The consequences of possible erroneous diagnoses were also recorded. A total of 634 regions were examined in 555 patients. Incorrect diagnoses were made in 55 regions (8.5%). In 21 of these, alterations in the primary treatment were required. All of the treatments could be corrected by telephone (7) or an additional visit by the patient (14). X-rays of the cranium and the spine are known to be difficult to evaluate by inexperienced doctors. This was also found to be the case in the present investigation.

Long-term (1 year) safety and efficacy of methylphenidate modified-release long-acting formulation (MPH-LA) in adults with attention-deficit hyperactivity disorder: a 26-week, flexible-dose, open-label extension to a 40-week, double-blind, randomised, placebo-controlled core study.

INTRODUCTION: Previously, in a 40-week, randomised, double-blind, placebo-controlled core study comprising three phases (9-week dose confirmation, 5-week open-label dose optimisation and 6-month maintenance of effect) in adults with attention-deficit/hyperactivity disorder (ADHD), methylphenidate modified-release long-acting formulation (MPH-LA) at 40-80 mg/day controlled ADHD symptoms as well as decreased functional impairment with a good tolerability profile (NCT01259492). Here, we report the long-term efficacy and safety from a 26-week, open-label extension phase of the same study (NCT01338818). METHODS: Patients in the extension study (n = 298) initiated treatment with MPH-LA (20 mg/day), up-titrated in increments of 20 mg/week to reach individual patient's daily optimal dose of 40-80 mg. Adverse events (AEs) and serious adverse events (SAEs) were reported at the end of extension study for events monitored from (1) maintenance of effect phase baseline (core study; 12 months) and (2) extension study baseline (6 months). Mean changes in DSM-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores are reported for both the timelines. Efficacy was also evaluated using clinician-rated instruments, namely Clinical Global Impression-Improvement Scale (CGI-I) and Clinical Global Impression-Severity Scale (CGI-S). RESULTS: No unexpected AEs were reported in the extension study. Incidence of SAEs reported during 6 months and 12 months were similar (0.7 %), and no deaths were reported. No SAEs were considered attributable to the drug at the end of 12 months. There were no reports of patients with QT, QTcB or QTcF >500 ms. The mean improvement in DSM-IV ADHD RS and SDS total scores at the end of 12 months were 0.9 and 1.4 points, respectively; and at the end of 6 months were 7.2 and 4.8, respectively. The proportion of patients with improvement in CGI-S scale was 31.4 % and 52.1 % at the end of 12 and 6 months, respectively. Overall, 69.4 % of patients showed clinical improvement in CGI-I scale at the end of 6 months. CONCLUSIONS: In adult patients with ADHD, use of MPH-LA up to 1 year continued to be well tolerated while maintaining the clinical efficacy.

Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes.

BACKGROUND: Visceral fat plays an important role in the development of metabolic disease independently of the effect of overall abdominal fat. Ultrasonography is an accessible method of accurately assessing abdominal fat distribution in epidemiological studies, but few details about the reproducibility of this method have been published. OBJECTIVE: The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes. DESIGN AND METHODS: Ultrasonography was used to estimate visceral and subcutaneous abdominal fat. Intra- and interobserver variation, short-term variation and variation between estimates in the fasting and non-fasting state were examined in three samples of 30, 33 and 23 participants from the ADDITION-PRO study. A variance components model was used to calculate intra- and interobserver variation, and Bland-Altman plots were drawn for all three substudies. RESULTS: Coefficients of variation for intra- and interobserver variation were in the range 3.4-6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient of variation of 15%. The effect of a meal was primarily on the visceral estimates and did not extend beyond the first postprandial hour. Non-fasting visceral estimates were larger than fasting estimates. CONCLUSION: Both visceral and subcutaneous fat can be estimated with ultrasonography with adequate intra- and interobserver reproducibility by clinical researchers with limited training, making it a feasible method of assessing abdominal fat distribution in epidemiological studies.

Risky decision making in adults with ADHD.

BACKGROUND AND OBJECTIVES: Risky decision making and disadvantageous choices constitute core characteristics of patients with attention-deficit/hyperactivity disorder (ADHD). Consequences include negative psychosocial and health-related outcomes. However, risky decision making and its interrelations with emotional states in ADHD are poorly understood. Therefore, the authors investigated risky decision making without and after boredom induction in adults with and without ADHD. METHODS: In study 1, ADHD patients (n = 15) and age/education matched controls (CG; n = 16) were compared on the Game of Dice Task (GDT), an established task measuring decision making in unambiguous situations. In study 2, ADHD patients (n = 14) and CG (n = 13) underwent boredom induction prior to the GDT. RESULTS: In study 1, ADHD patients selected the disadvantageous alternatives significantly more often than CG. In study 2, no significant group differences were found due to an increase in risky decision making in CG following the boredom induction. LIMITATIONS: Even if severity of depression did not affect our results, it may be necessary to compare GDT responses in ADHD patients with and without current depression. CONCLUSIONS: Risk as a motor of disadvantageous decision making needs to be taken into account in therapeutic contexts as a maintenance factor of dysfunctional behaviour. The findings of study 2 are in line with postulated alterations of emotional state adjustment in ADHD. The link between decisions making and emotional regulation in ADHD needs further attention in research.

German validation of the Conners Adult ADHD Rating Scales (CAARS) II: reliability, validity, diagnostic sensitivity and specificity.

BACKGROUND: The German version of the Conners Adult ADHD Rating Scales (CAARS) has proven to show very high model fit in confirmative factor analyses with the established factors inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional lability, and problems with self-concept in both large healthy control and ADHD patient samples. This study now presents data on the psychometric properties of the German CAARS-self-report (CAARS-S) and observer-report (CAARS-O) questionnaires. METHODS: CAARS-S/O and questions on sociodemographic variables were filled out by 466 patients with ADHD, 847 healthy control subjects that already participated in two prior studies, and a total of 896 observer data sets were available. Cronbach's-alpha was calculated to obtain internal reliability coefficients. Pearson correlations were performed to assess test-retest reliability, and concurrent, criterion, and discriminant validity. Receiver Operating Characteristics (ROC-analyses) were used to establish sensitivity and specificity for all subscales. RESULTS: Coefficient alphas ranged from .74 to .95, and test-retest reliability from .85 to .92 for the CAARS-S, and from .65 to .85 for the CAARS-O. All CAARS subscales, except problems with self-concept correlated significantly with the Barrett Impulsiveness Scale (BIS), but not with the Wender Utah Rating Scale (WURS). Criterion validity was established with ADHD subtype and diagnosis based on DSM-IV criteria. Sensitivity and specificity were high for all four subscales. CONCLUSION: The reported results confirm our previous study and show that the German CAARS-S/O do indeed represent a reliable and cross-culturally valid measure of current ADHD symptoms in adults.

German validation of the Conners Adult ADHD Rating Scales-self-report (CAARS-S) I: factor structure and normative data.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S). METHODS: Eight hundred and fifty healthy German control subjects were recruited to fill out the CAARS-S and to answer questions on sociodemographic variables. Explorative and confirmative factor analyses were conducted to obtain the factor structure for the German model and to replicate the factor structure of the original American model. Analyses on gender, age, and education level were calculated for normative data. RESULTS: The explorative factor analysis of the German sample results in a six-factor solution that explained 52% of the variance. A confirmative analysis that was based on the 42 items of the original American model showed a high model-fit. Analyses of normative data showed significant influences of age, gender, and education level on the emerging subscales. CONCLUSION: Even though the explorative factor analysis yields a solution different from the American original, the confirmative factor analysis results in such a high model-fit that use of the American version is justified with respect to international multicenter studies, for which this instrument will be highly valuable.

H¹-MR-spectroscopy of cerebellum in adult attention deficit/hyperactivity disorder.

INTRODUCTION: Neurobiological research has implicated the cerebellum as one possible site of neurophysiological dysfunction in ADHD. Latest theoretical conceptualizations of the cerebellum as core site of the brain to model motor as well as cognitive behavior puts further weight to the assumption that it might play a key role in ADHD pathophysiology. METHODS: 30 medication free adult ADHD patients and 30 group matched (gender, age and education) healthy controls were investigated using the method of chemical shift imaging (CSI) of the cerebellum. The vermis, left and right cerebellar hemispheres were processed separately. RESULTS: We found significantly increased glutamate-glutamine (Glx) to creatine (Cre) ratios in the left cerebellar hemisphere. No other differences in measured metabolite concentrations were observed. DISCUSSION: To our knowledge this is the first evidence for neurochemical alterations in cerebellar neurochemistry in adult ADHD. They relate well to recent hypotheses that the cerebellum might control mental activities by internal models.

[Multimodal treatment of adult attention-deficit hyperactivity disorder]. / Multimodale Therapie der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter.

The indication for treatment of adult attention-deficit hyperactivity disorder (adult ADHD) is derived not from the diagnosis itself but results from the severity of symptoms, comorbidities, psychosocial consequences, and a lack of defined resources for ADHD. The basis of therapy is psychoeducation that includes teaching about symptoms, models of the disorder, and options for treatment. The combination of pharmacotherapy and psychotherapy is recommended. Methylphenidate is considered the first-line therapy, because of its strong effect and modest side effects, but is not authorized in Germany ("off-label use"). Atomoxetine, which is authorized for continuing treatment into adulthood, is indicated if methylphenidate is insufficient or has unacceptable side effects and in case of comorbid substance use. Various psychotherapeutic interventions using available ADHD-typical resources have demonstrated positive effects. Psychosocial support and self-help groups complete the treatment concept. Persistence of the treatment indication has to be reevaluated at regular intervals. Disorder-specific multimodal therapy of adult ADHD conforms to the complex, primarily neurobiologic etiology and the psychosocial consequences.

[Clinical teaching with simulated patients in psychiatry and psychotherapy. A controlled pilot study]. / Einsatz von Simulationspatienten in den Lehrfächern Psychiatrie und Psychotherapie. Eine kontrollierte Pilotstudie.

Because of the new medical licensure act in Germany, much more bedside teaching than before is needed. For many of the relevant clinical pictures, few patients can be expected to undergo study lessons. That is why many universities use simulated patients (SP). In contrast to other disciplines such as internal medicine or surgery, there is not much literature about SP in psychiatry and psychotherapy. The objective of this pilot study was to evaluate if SP used for clinical teaching in addition to real patients are well accepted for simulation of psychiatric illnesses and clinical teaching. After randomization, one half of the 139 study medical students were taught using real patients and the other half using real patients and SP. The amounts of patient contact were equal in both groups. Using a questionnaire, pre- and postanalysis was carried out of answers about communication skills, the capability of addressing difficult subjects such as suicidality, and interest in psychiatry. The acceptance rate of SP was very high. Students' ratings of clinical teaching and their own performance, and their interest in future psychiatric work were significantly higher in the SP group. The results of this pilot study are very encouraging and indicate that the systematic use of SP in clinical psychiatric teaching is not only an appropriate alternative to real patients but also can lead to higher quality.

Photographic screening for strabismus among mentally retarded children.

The prevalence of squint among mentally retarded children is much higher than in the general population. A photographic screening method based on the positioning of the 1st and 4th Purkinje image was applied to 80 mentally retarded children. The method was validated against orthoptic examination of the children. Totally 320 exposures were taken. Fourth Purkinje image was visible on 73% of these. Five children were not evaluable from the 4th Purkinje image. The photographic technique was simple and easy to handle, but comparison between the clinical and photographic diagnoses were inconsistent in 12 out of 80 cases, which made the method unreliable. In some cases the clinical assessments also varied from time to time. A combination of clinical orthoptic assessment and the photographic method is suggested.