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Attention Deficit Hyperactivity Disorder (ADHD) negatively impacts Quality of Life (QoL) in adults. Earlier studies on pharmacological treatment have shown short-term beneficial effects on QoL. No data are available on long-term effects on multimodal psychosocial and/or pharmacological interventions. 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 (Plac) (2 × 2 factorial design over a period of 52 weeks). Change of QoL was measured after three months of intensive treatment, after 26 weeks, and after one year of maintenance treatment, using the Quality of life enjoyment and satisfaction questionnaire (Q-LES-Q, eight subscales). A follow-up was performed 1.5 years after treatment completion. Q-LES-Q scores were analyzed descriptively (means and confidence intervals). A linear regression model was used to test for significant differences between the four treatment arms. The full analysis set comprised 419 patients. Q-LES-Q scores increased between baseline and the end of treatment across all Q-LES-Q subscales (with exception of stable scores in the physical health/activities subscale in the CM + Plac group) and remained stable improved at follow-up. Regression analyses did not show any significant differences between the four treatment conditions. COMPAS is the first study to demonstrate stable and long-term improvements of QoL after multimodal treatment regardless of medication with MPH or Placebo, and regardless of structured GPT or individual CM. Trial registration: ISRCTN54096201.

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.

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).

Background Multiple symptoms of suicide risk have been assessed based on visual and auditory information, including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment. Objective We aimed to examine measurements extracted from video interviews using open-source deep learning algorithms to quantify facial, vocal, and movement behaviors in relation to suicide risk severity in recently admitted patients following a suicide attempt. Methods We utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open-source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide risk with the Beck Scale for Suicide Ideation controlling for age and sex, using multiple linear regression. Results Suicide severity was associated with multiple visual and auditory markers, including speech prevalence (β=−0.68, P=.02, r2=0.40), overall expressivity (β=−0.46, P=.10, r2=0.27), and head movement measured as head pitch variability (β=−1.24, P=.006, r2=0.48) and head yaw variability (β=−0.54, P=.06, r2=0.32). Conclusions Digital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and linear associations with the severity of suicidal ideation.

Annals of General Psychiatry 19, 55 (2020). doi:10.1186/s12991-020-00305-3, Published by BioMed Central, [S.l.]

BackgroundMultiple symptoms of suicide risk are assessed based on visual and auditory information including flattened affect, reduced movement, and slowed speech. Objective quantification of such symptomatology from novel data sources can increase the sensitivity, scalability, and timeliness of suicide risk assessment.MethodsIn the current study we utilized video to quantify facial, vocal, and movement markers associated with mood, emotion, and motor functioning from a structured clinical conversation in 20 patients admitted to a psychiatric hospital following a suicide risk attempt. Measures were calculated using open source deep learning algorithms for processing facial expressivity, head movement, and vocal characteristics. Derived digital measures of flattened affect, reduced movement, and slowed speech were compared to suicide severity using the Beck Suicide Scale (BSS), controlling for age and gender using multiple linear regression.ResultsSuicide severity was associated with multiple visual and auditory markers including speech prevalence (β = −0.68; P =.017, r2 =.40, overall expressivity (β = −0.46; P = 0.10, r2 =.27), and head movement measured as head pitch variability (β = −1.24; P =.006, r2 =.48) and head yaw variability (β = −0.54; p =.055, r2 =.32).ConclusionsDigital measurements of facial affect, movement, and speech prevalence demonstrated strong effect sizes and significant linear associations with severity of suicidal ideation.

Zusammenfassung. Fragestellung: Ziel der Untersuchung ist die Erhebung von Daten zu psychischen Belastungen und deren Behandlung bei Kindern und Jugendlichen mit Fragilem-X-Syndrom (FRX). Methodik: Die Ergebnisse basieren auf einer strukturierten, prospektiven, offenen, nichtinterventionellen, registerbasierten Beobachtungsstudie in Deutschland (EXPLAIN), im Rahmen derer an 11 Zentren 34 Patienten jünger als 18 Jahre mit einem genetisch gesicherten FRX eingeschlossen wurden. Ergebnisse: Jedes dritte Indexkind hatte ein ebenfalls unter FRX leidendes Geschwisterkind. Die Belastung mit neurologischen und psychischen Symptomen war insgesamt hoch, wobei ataktische Symptome, epileptische Anfälle und autistische Symptome nur bei den Kindern (< 14 Jahre) berichtet wurden. Nahezu alle erfassten psychischen Symptome und Störungen, insbesondere die expansiven Symptome, wurden mit entsprechenden Psychopharmaka behandelt. Darüber hinaus kamen oft logopädische, ergotherapeutische und heilpädagogische Maßnahmen zum Einsatz. Trotz der hohen Symptombelastung lebten 96.3 % der unter 14-Jährigen und immer noch 57.1 % der 14- bis 18-Jährigen im elterlichen Haushalt. Schlussfolgerungen: Aufgrund der hohen Belastung mit neurologischen und psychischen Symptomen sollte frühzeitig eine dem Alter entsprechende kinder- und jugendpsychiatrische und neurologische Diagnostik und Therapie erfolgen.

Key Points Question What are the long-term results of multimodal treatment for adult attention-deficit/hyperactivity disorder (ADHD) when comparing cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) in combination with either methylphenidate or placebo? Findings In this follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, 256 adults participated in follow-up 1.5 years after the intervention ended. The severity of ADHD symptoms improved in all 4 prior treatment groups, with no significant difference found between GPT and CM, but methylphenidate was associated with a larger improvement in symptoms compared with placebo. Meaning Results from the COMPAS trial demonstrate an improvement of ADHD symptoms over 1.5 years in adults with ADHD after 1 year of treatment with methylphenidate plus either GPT or CM., This follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, evaluates the long-term efficacy of multimodal treatment for attention-deficit/hyperactivity disorder (ADHD)., 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

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs. In the current study, we have analyzed circadian rhythms in daily activity and sleep, and the circadian gene expression in a cohort of healthy controls (N = 22), ADHD participants not using ADHD-medication (N = 17), and participants with ADHD and current use of ADHD medication (N = 17). Rhythms of sleep/wake behavior were assessed via wrist-worn actigraphy, whilst rhythms of circadian gene expression were assessed ex-vivo in primary human-derived dermal fibroblast cultures. Behavioral data indicate that patients with ADHD using ADHD-medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency, more nocturnal activity but not more nocturnal wakenings than both controls and ADHD participants without medication. At the molecular level, there were alterations in the expression of PER2 and CRY1 between ADHD individuals with no medication compared to medicated ADHD patients or controls, whilst CLOCK expression was altered in patients with ADHD and current medication. Analysis of fibroblasts transfected with a BMAL1:luc reporter showed changes in the timing of the peak expression across the three groups. Taken together, these data support the contention that both ADHD and medication status impact on circadian processes.

Abstract. 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).

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. Open-Access-Publikationsfonds 2018

Anliegen: Ziel der Untersuchung ist die Erhebung von Daten zu psychischen Belastungen und deren Behandlung beim fragilen X-Syndrom (FRX). Methode: Die Ergebnisse basieren auf einer Beobachtungsstudie (EXPLAIN). Ergebnisse: Die Belastung mit psychischen Symptomen war insgesamt hoch. Betroffene unter 18 Jahren wiesen mehr expansive, erwachsene Patienten dagegen mehr internalisierende Storungen auf. Trotz der hohen Symptombelastung lebten 90,6 % der unter 18-Jahrigen und immer noch 50 % der Erwachsenen im elterlichen Haushalt. Schlussfolgerungen: Aufgrund der hohen Belastung mit psychischen Symptomen sollte eine dem Alter entsprechende Diagnostik und Therapie erfolgen.

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

Background As data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients. Methods EXPLAIN-FXS is a prospective observational (non- interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years. Results Seventy- five patients (84.0 % males, mean age 16.7 ± 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 ± 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 ± 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 ± 14.6 points (median 90; range 50 – 100). Conclusions This report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient’s needs. Trial registration The ClinTrials.gov identifier is NCT01711606. Registered on 18 October 2012.

Objective Similar to patients with a metabolic syndrome, patients with major depression are at increased risk of developing cardiovascular disorders. Interestingly, both disorders share a specific endocrine syndrome that promotes the accumulation of visceral fat, which again is considered a marker of increased cardiovascular morbidity and mortality. Methods Intra-abdominal fat was measured in 22 postmenopausal depressed women and 23 age-matched healthy women by computer tomography at the level of lumbar vertebrae 1 (L1) and 4 (L4). Saliva was taken in patients and control subjects at 08:00 hours over a period of 7 drug-free days for the measurement of free cortisol. In patients only we performed an oral glucose tolerance test. Results Compared with control subjects, depressed patients with elevated free cortisol concentrations showed similar visceral fat depots at L1 (113.0 +/- 41.6 vs. 94.3 +/- 53.2 cm(2)). Hypercortisolemic depressed patients also showed greater fat depots in this area (74.5 +/- 55.5 cm(2), p =.04) than the normocortisolemic patients. However, a comparison of all patients with control subjects revealed no difference in fat accumulation at either L1 or L4. Finally, glucose concentrations during the glucose tolerance test were higher in hypercortisolemic than in normocortisolemic patients, whereas their insulin levels showed only a tendency toward being increased. Conclusions Hypercortisolemic depressed patients suffer from resistance to insulin and increased visceral fat. The fact that hypercortisolemia reverses depression-related fat loss, particularly in the visceral area, might partially explain why major depression can be considered a risk factor for cardiovascular disorders.

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.

There is preclinical evidence that CRH is released in response to a glutamatergic stimulation. However, it is not clear, whether glutamate plays a role in the physiological stress response. We tested whether the antiglutamatergic drug riluzole dampens the response of the hypothalamus-pituitary-adrenocortical (HPA) system to both a mental and a physical stressor. Nine male elderly healthy subjects received placebo and 150 mg riluzole for 2 days in a randomized balanced order. Blood was withdrawn every 15 min for estimation of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, the subjects were subjected to a cognitive challenge paradigm. Further, between 19.02 and 19.15 an individually adapted physical stress test was performed. After riluzole treatment, baseline ACTH and cortisol concentrations were unchanged when compared to placebo treatment. Also, after the mental stressor, there was no difference between both treatment conditions. In contrast, the cortisol (riluzole vs. placebo: 148 ± 60 vs. 183 ± 98 nmol/l) and ACTH response (20.2 ± 11.9 vs. 40.7 ± 61.9 pmol/l) to the physical stressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system activity under baseline and cognitive-stress-induced conditions in elderly subjects. However, a trend for dampening the endocrine response to physical stress emerged.

Hyperactivity of the HPA-system in major depression is reflected by an increased secretion of adrenal hormones especially cortisol and dehydroepiandrosterone (DHEA). In women for whom androgenicity is associated with cardiovascular disorders the dominant source of androstenedione and testosterone secretion are the adrenal glands. To date, there is only sparse information about the regulation of androstenedione, testosterone and dihydrotestosterone (DHT) concentrations in women with severe major depression.Therefore, 11 pre- and postmenopausal, severely depressed, hypercortisolemic women (Hamilton Depression Scale, 31.3+/-5.9; age, 28-77 yrs; mean, 48. 1+/-18.1 yrs) and 11 age-matched healthy female controls (age, 24-81 yrs; mean, 47.9+/-21.5 yrs) underwent a 24 hour (h) blood sampling starting at 0800 h with 30-minute sampling intervals. By applying multivariate analysis of covariance with age as covariate, androstenedione, testosterone and DHT plasma levels at 0900 h show a trend for elevated concentrations in depressed women compared to controls (F(1,19)=2.7; P=0.057). Univariate F tests reveal a significant difference between the groups for androstenedione (4. 19+/-1.571 vs 2.584+/-1.257 nmol/l; P

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) regulates glucocorticoid activity by converting cortisol into cortisone and vice versa. Frequent signs of major depression are elevated concentrations of circulating cortisol and ACTH. However, no information is available about the activity of 11-beta-HSD in this disorder. Therefore, we compared diurnal plasma concentrations of cortisol and cortisone and their ratios, reflecting 11-beta-HSD activity, in 25 severely depressed patients (Hamilton Depression Scale, 29 +/- 6; 14 men, 11 women, age 22-77 yr; mean, 47 +/- 16) and 30 control persons (20 men, 10 women age 23-85 yr; mean, 51 +/- 19). Cortisol and cortisone were measured at 0900 h, 1100 h, 1300 h, 2000 h, 2200 h, 0100 h, 0300 h, and 0700 h with specific RIAs after extraction. Both cortisol and cortisone concentrations were significantly increased in patients compared with controls (cortisol, 251.7 +/- 113.1 vs. 160 +/- 96.6 nmol/L; cortisone, 32.8 +/- 10.9 vs. 21.9 +/- 10.9 nmol/L). The calculated ratios of cortisol to cortisone were similar in controls and patients. Similar to cortisol, the circadian variation of cortisone was flattened in patients with the ratio of maximal cortisone to minimal cortisone being 1.9-fold higher in controls than in patients. There was no gender-specific difference in cortisone values neither in patients nor in controls. We conclude that in major depression increased cortisol is not due, at least partly, to an altered 11-beta-HSD activity or to a decrease in cortisone.

BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on the X chromosome, is the most common inherited form of intellectual disability and autism spectrum disorders. Comprehensive data are lacking, however, on the characteristics and management patients with FXS in Germany. METHODS/DESIGN: EXPLAIN is a prospective, observational, longitudinal registry with a non-probability sampling approach. It collects data on patient characteristics, therapeutic interventions, psychosocial parameters (including those of family members and caregivers), quality of life of caregiver and patient, caregiver burden, and health economic parameters, such as hospitalisation time. It is designed to include data from 300 patients in ambulatory care from about 50 centres that employ psychiatrists, paediatricians, neurologists, and other relevant specialists, in Germany. The study was initiated in March, 2013. Patients will be followed for at least two years. DISCUSSION: The registry is expected to provide much-needed data on the characteristics and management of patients with FXS in Germany. It will also allow comparisons with other countries, and will enable gap analyses based on current guidelines for management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov identifier is NCT01711606.

The present study aimed to investigate glutamate concentrations in patients with unipolar depression in the midcingulate cortex (MCC) as compared to the left dorsolateral prefrontal cortex (DLPFC). We hypothesized a dissociation of glutamate levels with unchanged levels in DLPFC and abnormally changed levels in MCC as well as differential effects of antidepressant pharmacotherapy. Glutamate was determined using magnetic resonance spectroscopy at 3 T in DLPFC and MCC in fourteen depressed patients and matched healthy volunteers. A follow-up measurement was performed after 4 weeks of antidepressant treatment. The main finding is a region-specific pattern of glutamate concentrations with increased MCC glutamate concentrations and no significant differences in DLPFC glutamate concentrations in unipolar depressive patients compared to healthy controls. Response and non-response to antidepressant pharmacotherapy were predicted by high glutamate at baseline in DLPFC and MCC, respectively. In addition, treatment responders showed a further increase in DLPFC glutamate levels after successful antidepressant treatment. Findings indicate altered region-specific glutamate concentrations in DLPFC and MCC that are predictive of response and non-response, respectively, to antidepressant pharmacotherapy. These findings might serve as a starting point for future studies in which the value of this metabolite pattern for treatment response prediction should be investigated.

Figure 1 (A) Posteroanterior chest roentgenog and a mass abutting the right cardiophrenic ang mography scan shows a large cystic lesion m abutting the heart border with a radiodensity of 1 view of the cyst (asterisk). Note the inflamed app the cyst looking down to the pericardium (asteris with chronic inflammatory infiltrates and no original magnification 100). Funding: None. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Emil Missov, MD, PhD, Division of Cardiology, University of Minnesota Medical Center, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail address: misso001@umn.edu

Studies in normal human subjects and animals suggest that the neuropeptide growth hormone-releasing hormone (GHRH) is a common regulator of the sleep EEG and nocturnal hormone secretion. In healthy volunteers GHRG prompts an increase in the amount of slow wave sleep (SWS) and in growth hormone (GH) secretion and blunting of cortisol release. Inhibition of GHRH may contribute to sleep-endocrine aberrances during depression. We tested the effects of pulsatile application of 4 × 50 μg GHRH on the sleep EEG and simultaneously investigated nocturnal hormone secretion in 10 inpatients (4 females, 6 males) with the acute episode of major depression. In contrast to the effects of placebo, after GHRH GH secretion increased distinctly and rapid-eye-movement (REM) density decreased during the second half of night. No other significant changes in sleep-endocrine activity, including SWS, cortisol and ACTH secretion, could be observed. We assume that hypothalamic-pituitary-adrenocorticol system activity and slow wave sleep are inert to the influence of GHRH during acute depression. Cortisol and ACTH remained unchanged even in a subsample of five younger (aged 19-28 years) patients. This observation is in contrast to our recent finding that cortisol secretion is blunted in young normal volunteers after GHRH. But on the other hand, GHRH is capable of stimulating GH and inducing a decrease in REM density in these subjects.