Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?

The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep ("rapid eye movement sleep instability"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders.

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.

Preventing COVID-19 outbreaks through surveillance testing in healthcare facilities: a modelling study.

BACKGROUND: Surveillance testing within healthcare facilities provides an opportunity to prevent severe outbreaks of coronavirus disease 2019 (COVID-19). However, the quantitative impact of different available surveillance strategies and their potential to decrease the frequency of outbreaks are not well-understood. METHODS: We establish an individual-based model representative of a mental health hospital yielding generalizable results. Attributes and features of this facility were derived from a prototypical hospital, which provides psychiatric, psychosomatic and psychotherapeutic treatment. We estimate the relative reduction of outbreak probability for three test strategies (entry test, once-weekly test and twice-weekly test) relative to a symptom-based baseline strategy. Based on our findings, we propose determinants of successful surveillance measures. RESULTS: Entry Testing reduced the outbreak probability by 26%, additionally testing once or twice weekly reduced the outbreak probability by 49% or 67% respectively. We found that fast diagnostic test results and adequate compliance of the clinic population are mandatory for conducting effective surveillance. The robustness of these results towards uncertainties is demonstrated via comprehensive sensitivity analyses. CONCLUSIONS: We conclude that active testing in mental health hospitals and similar facilities considerably reduces the number of COVID-19 outbreaks compared to symptom-based surveillance only.

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.

Psychological interventions for posttraumatic stress disorder involving primary care physicians: systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Evidence-based psychological interventions for posttraumatic stress disorder (PTSD) are available in specialized settings, but adequate care in primary care is often lacking. The aim of this systematic review was to determine the effectiveness of psychological interventions for PTSD involving primary care physicians (PCPs) and to characterize these interventions as well as their providers. METHOD: A systematic review and meta-analyses of randomized controlled trials (RCTs). Primary outcome were symptoms of PTSD. RESULTS: Four RCTs with a total of 774 patients suffering from PTSD symptoms were included, all applying cognitive behavioural based interventions. Three studies with psychological interventions being conducted by case managers were pooled in a meta-analysis. Interventions were not effective in the short term (0-6 months; SMD, - 0.1; 95% CI, - 0.24-0.04; I2 = 0%). Only two studies contributed to the meta-analysis for long term (12-18 months) outcomes yielding a small effect (SMD, - 0.23; 95% CI, - 0.38- -0.08; I2 = 0%). CONCLUSIONS: Psychological interventions for PTSD in primary care settings may be effective in the long term but number and quality of included studies was limited so the results should be interpreted with caution.

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression.

BACKGROUND: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. OBJECTIVE: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. METHODS: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of "well weeks" (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. RESULTS: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99-1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. CONCLUSIONS: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

Long-term outcome of a mental health promotion program in Germany.

Mental health promotion programs (MHP) seek to reduce sub-syndromal symptoms of mental distress and enhance positive mental health. This study evaluates the long-term effects of a mindfulness-based MHP program ('Life Balance') provided by health coaches in a multi-site field setting on mental distress, satisfaction with life and resilience. Using a controlled design, propensity score matching was used to select a control group for participants of the MHP. The total study sample (N = 3624) comprised 83% women, with a mean age of 50 years. Data was collected via mailings 1 year after study entry. Results suggest participants experience reduced emotional distress at 12-month follow-up, with a medium between-group effect size (d = 0.40) for those participants who showed clinically relevant symptoms of mental distress at study entry. The effects of the program were more pronounced in participants with higher initial distress scores. New cases of psychopathological symptoms were prevented in 1 of 16 participants. Satisfaction with life and resilience were enhanced significantly. Our data suggest 'Life Balance' shows long-term effectiveness and indicate it is possible to design MHP programs that serve as both primary and indicated prevention, and that these programs can be applied on a population basis.

The impact of childhood maltreatment on the differential efficacy of CBASP versus escitalopram in patients with chronic depression: A secondary analysis.

Childhood maltreatment (CM) has been indicated as a predictor of a differential response to antidepressant treatment with psychotherapy compared to medication. In this secondary analysis, we investigated whether the presence of CM results in a differential indication for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or escitalopram plus clinical management (ESC). Sixty patients with chronic depression were randomized to either 22 sessions of CBASP or ESC over the course of 8 weeks of acute and 20 weeks of extended treatment at 2 German treatment sites. CM was assessed using the Childhood Trauma Questionnaire and the clinician rated Early Trauma Inventory. Intention-to-treat analyses were used to examine the impact of CM on depression, global functioning, and quality of life. The presence of CM did not result in significant differences in treatment response to CBASP or ESC on any outcome measure after 28 weeks of treatment independent of the type of CM assessment. After 8 weeks, a significant CM × treatment interaction was found for scores on the Montgomery-Asberg Depression Rating Scale. Patients with a history of CM receiving CBASP had a significantly lower response rate compared to patients without CM and to those receiving ESC after 8 weeks. Conclusively, CBASP and ESC are equally effective treatment options for the difficult to treat subgroup of patients with chronic depression and a history of CM. CM may be a predictor of a longer latency of treatment response in the case of psychotherapy. KEY PRACTITIONER MESSAGE: CBASP and escitalopram are equally effective treatment options for chronic depression. Both treatments are also equally effective for the difficult to treat subgroup of patients with chronic depression and a history of childhood maltreatment. Childhood maltreatment may result in a longer latency of treatment response in the case of psychotherapy.

The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial.

BACKGROUND: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. METHODS: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. RESULTS: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. LIMITATIONS: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. CONCLUSION: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

[Overcoming treatment resistance in chronic depression : The role of inpatient psychotherapy]. / Überwindung der Therapieresistenz bei chronischer Depression : Die Bedeutung der stationären Psychotherapie.

BACKGROUND: Chronic depression poses a particular challenge for the psychiatric and psychotherapeutic care system. Owing to high rates of psychiatric comorbidities and multiple pharmacological and psychotherapeutic treatment resistance, novel treatment strategies are urgently required. AIM: In this article, we describe the clinical characteristics of chronic and treatment-resistant depression and review the pharmacological and psychotherapeutic treatment options currently available. We focus on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), the first specific psychotherapy approach to chronic depression. Finally, we discuss the role of psychotherapeutic inpatient programs and stepped care concepts in chronic and treatment-resistant depression.

Overcoming treatment resistance in chronic depression: a pilot study on outcome and feasibility of the cognitive behavioral analysis system of psychotherapy as an inpatient treatment program.

BACKGROUND: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP), initially developed as an outpatient treatment for chronic depression (CD), has been adapted as a multidisciplinary 12-week inpatient program for CD. METHODS: Seventy inpatients with CD and treatment resistance were included in a noncontrolled trial. The Hamilton Depression Rating Scale served as the primary outcome measure. Prospective naturalistic follow-up assessments were conducted 6 and 12 months after discharge. RESULTS: Dropout rate was 7.1%; 90.4% perceived the program as helpful. Pre-post comparisons yielded strong effect sizes; 75.7% of the intention-to-treat sample responded, and 40.0% remitted. Nonremission was associated with experiencing temporary deterioration of symptoms during treatment. After 6 months 75.0% and after 12 months 48.0% of patients sustained response. CONCLUSIONS: The CBASP program appears as a feasible acute treatment for treatment-resistant CD inpatients with promising outcome. However, the continuation of treatment after discharge should be optimized especially for patients with subjective deterioration during treatment.

Cognitive Behavioral Analysis System of Psychotherapy versus Escitalopram in Chronic Major Depression.

BACKGROUND: A specific psychotherapy for chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), was compared to escitalopram (ESC). METHODS: Sixty patients with chronic major depression were randomized to 'CBASP' (22 sessions) or 'ESC plus clinical management' (ESC/CM) at two treatment sites. The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS) after 8 weeks of acute treatment assessed by blinded raters. In the case of nonimprovement (<20% reduction in the MADRS score), the other condition was augmented for the following 20 weeks of extended treatment. Secondary end points were, among others, depressive symptoms, remission (MADRS score of ≤9) and response rates (reduction of MADRS score of ≥50%) 28 weeks after randomization. RESULTS: An intent-to-treat analysis revealed that clinician-rated depression scores decreased significantly after 8 and 28 weeks with no significant differences between the groups. The response rates after 28 weeks of treatment were high (CBASP: 68.4%, ESC/CM: 60.0%), and the remission rates were moderate (CBASP: 36.8%, ESC/CM: 50.0%) with neither group being superior. Nonimprovers to the initial treatment caught up with the initial improvers in terms of depression scores and response and remission rates by the end of the treatment after being augmented with the respective other condition. CONCLUSIONS: CBASP and ESC/CM appear to be equally effective treatment options for chronically depressed outpatients. For nonimprovers to the initial treatment, it is efficacious to augment with medication in the case of nonresponse to CBASP and vice versa.

Effectiveness of a brief psychoeducational group intervention for relatives on the course of disease in patients after inpatient depression treatment compared with treatment as usual--study protocol of a multisite randomised controlled trial.

BACKGROUND: Relapses and rehospitalisations are common after acute inpatient treatment in depressive disorders. Interventions for stabilising treatment outcomes are urgently needed. Psychoeducational group interventions for relatives were shown to be suitable for improving the course of disease in schizophrenia and bipolar disorders. A small Japanese monocentre randomised controlled trial also showed promising results for depressive disorders. However, the evidence regarding psychoeducation for relatives of patients with depressive disorders is unclear. METHODS/DESIGN: The study is conducted as a two-arm multisite randomised controlled trial to evaluate the incremental effect of a brief psychoeducational group intervention for relatives as a maintenance treatment on the course of disease compared to treatment as usual. Primary outcome is the estimated number of depression-free-days in patients within one year after discharge from inpatient treatment. 180 patients diagnosed with unipolar depressive disorders as well as one key relative per patient will be included during inpatient treatment and randomly allocated to the conditions at discharge. In the intervention group, relatives will participate in a brief psychoeducational group intervention following the patient's discharge. The intervention consists of four group sessions lasting 90 to 120 min each. Every group session contains informational parts as well as structured training in problem-solving. In both study conditions, patients will receive treatment as usual. Patients as well as relatives will be surveyed by means of questionnaires at discharge and three, six, nine and twelve months after discharge. In addition to the primary outcome, several patient-related and relative-related secondary outcomes will be considered and health economics will be investigated. DISCUSSION: Our study will provide evidence on the incremental effect of a brief psychoeducational intervention for relatives as a maintenance treatment after inpatient depression treatment. Positive results may have a major impact on health care for depression. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00006819; Trial registration date: 2014 Oktober 31; Universal Trial Number (UTN): U1111-1163-5391.

Life Balance - a mindfulness-based mental health promotion program: conceptualization, implementation, compliance and user satisfaction in a field setting.

BACKGROUND: Mental health disorders account for a large percentage of the total burden of illness and constitute a major economic challenge in industrialized countries. Several prevention programs targeted at high-risk or sub-clinical populations have been shown to decrease risk, to increase quality of life, and to be cost-efficient. However, there is a paucity of primary preventive programs aimed at the general adult population. "Life Balance" is a program that employs strategies borrowed from well-established psychotherapeutic approaches, and has been made available to the public in one federal German state by a large health care insurance company. The data presented here are the preliminary findings of an ongoing field trial examining the outcomes of the Life Balance program with regard to emotional distress, life satisfaction, resilience, and public health costs, using a matched control group design. METHODS: Life Balance courses are held at local health-care centers, in groups of 12 to 15 which are led by laypeople who have been trained on the course materials. Participants receive instruction on mindfulness and metacognitive awareness, and are assigned exercises to practice at home. Over an 8-month period in 2013-2014, all individuals who signed up for the program were invited at the time of enrollment to take part in a study involving the provision of psychometric data and of feedback on the course. A control group of subjects was invited to complete the questionnaires on psychometric data but did not receive any intervention. RESULTS: Of 4,898 adults who attended Life Balance courses over the specified period, 1,813 (37.0 %) provided evaluable study data. The average age of study participants was 49.5 years, and 83 % were female. At baseline, participants' self-reported symptoms of depression and anxiety, life satisfaction, and resilience were significantly higher than those seen in the general German population. Overall, evaluations of the course were positive, and 83 % of participants attended at least at 6 of the 7 sessions. Some sociodemographic correlations were noted: men carried out the assigned exercises less often than did women, and younger participants practiced mindfulness less frequently than did older ones. However, satisfaction and compliance with the program were similar across all sociodemographic categories. CONCLUSIONS: While the Life Balance program is publicized as a primary prevention course that is not directed at a patient population, the data indicate that it was utilized by people with a significant mental health burden, and that the concept can be generalized to a broad population. As data from the control group are not yet available, conclusions about effectiveness cannot yet be drawn. TRIAL REGISTRATION: German Clinical Trials Registration ID: DRKS00006216.

A work time study analysing differences in resource use between psychiatric inpatients.

PURPOSE: Judgement about the adequacy of reimbursement schemes requires an understanding of differences in resource use between patient groups. The aim of this study was to analyse staff time allocation of psychiatrists, psychologists and nurses in inpatient mental health care and to use these data to analyse differences in per diem resource use between patient groups. METHODS: A self-reporting work-sampling study was carried out at a psychiatric teaching hospital. All of 36 psychiatrists, 23 psychologists and 106 nurses involved in clinical care during the study period participated in a two-week measurement of their work time. RESULTS: A total of 20,380 observations were collected, representing about 10,190 h of work or 6.2 full-time-equivalent years. The average resource use in minutes of staff time per patient day was 227 min, representing 138 of staff costs. The most resource intensive care was provided at the Psychiatric Intensive Care Unit and for geriatric patients with 334 and 266 min per patient day (192 and 162 ), respectively. The least resource intensive care was provided for patients with substance-related disorders (197 min, 116 ). Substantial shares of clinical work time were dedicated to tasks without patient contact (58 %). Nursing time was the main driver of total resource use, representing 70 % of staff time and 60 % of costs. CONCLUSION: Presented differences in per diem resource use should inform discussions about the adequacy of reimbursement schemes. Tasks in the absence of the patient, such as documentation and administration, should be reduced to free resources for direct patient care.

Provision of group psychoeducation for relatives of persons in inpatient depression treatment--a cross-sectional survey of acute care hospitals in Germany.

BACKGROUND: Depressive disorders are often recurrent and place a high burden on patients and their relatives. Psychoeducational groups for relatives may reduce relatives' burden, help prevent relapses in patients, and are recommended by the German "National Disease Management Guideline Unipolar Depression". Since there is limited knowledge on the provision of psychoeducational groups for relatives of persons in inpatient depression treatment, we conducted a survey among acute care hospitals in Germany. METHODS: We conducted a two-step cross-sectional survey. Step I consisted of a questionnaire asking the heads of all psychiatric/psychosomatic acute care hospitals in Germany (N = 512) whether psychoeducational groups for relatives were provided within depression treatment, and if not, the reasons for not implementing them. In group offering hospitals the person responsible for conducting psychoeducational groups received a detailed questionnaire on intervention characteristics (step II). We performed descriptive data analysis. RESULTS: The response rate was 50.2% (N = 257) in step I and 58.4% in step II (N = 45). 35.4% of the responding hospitals offered psychoeducational groups for relatives of patients with depressive disorders. According to the estimates of the respondents, relatives of about one in five patients took part in psychoeducational groups in 2011. Groups were mostly provided by two moderators (62.2%) as continuous groups (77.8%), without patients' participation (77.8%), with up to ten participants (65.9%), consisting of four or fewer sessions (51.5%) which lasted between one and one and a half hours each (77.8%). The moderators in charge were mostly psychologists (43.9%) or physicians (26.8%). Approximately one third used published manuals. Reasons for not conducting such psychoeducational groups were lack of manpower (60.1%), time (44.9%) and financial constraints (24.1%). 25.3% mentioned adequate concepts of intervention as a required condition for initiating such groups. CONCLUSIONS: Only a small proportion of relatives of patients with depressive disorders participated in psychoeducational groups in 2011 in Germany. Mostly short interventions were favoured and main implementation barriers were scarce resources. Brief interventions that fit with healthcare routine should be developed and tested within randomised controlled trials. This could promote the provision of psychoeducational groups for relatives as evidence-based practice in inpatient depression treatment in Germany.

Psychiatric side-effects of bilateral deep brain stimulation for movement disorders.

INTRODUCTION: The effects of deep brain stimulation (DBS) on cognitive functions, and its psychiatric side-effects, are still controversial. The present study investigated psychiatric comorbidity and postoperative effects of DBS of different targets on mood and psychological functions in 81 patients with a mean follow-up of 37 months. METHODS: A total of 109 patients underwent implantation of DBS electrodes between 2001 and 2006; it was possible to evaluate 81 patients by a psychiatric test battery using the "Neuropsychiatric Inventory". To evaluate the possible influence of the target, we analyzed the data without 16 patients with DBS surgery for other diseases (e.g., epilepsia, cluster headache) or unilateral implantation only. The resulting population (n = 65, mean age 61 years, range 23-78 years, male:female 42:23) consisted of 43 Parkinson's disease patients stimulated in the subthalamic nucleus, ten dystonia patients stimulated in the globus pallidus internus, and 12 tremor patients in the ventral intermediate nucleus. RESULTS: There was a high rate of preoperative psychiatric comorbidity, which is reflected by a high rate of patients with preoperative medication of neuroleptic drugs (18.4 %, especially clozapin 14.7 %) and antidepressive drugs (16.5 %). Depression was the most common psychiatric side-effect after DBS, occurring in 47.7 % of all patients (31/65 patients), without significant preference to a specific target (STN: 42 %, Gpi: 60 %, VIM: 58 %). Delusion (n = 5 out of 43 PD patients, 11.6 %), euphoria (n = 1, 2.3 %) and disinhibition (n = 3, 7.0 %) were seen in the PD patients only. CONCLUSION: A wide range of behavioural changes may be seen following DBS. Depression was the most common side-effect after DBS, and occurred independently of the target. PD patients, in contrast to dystonia and tremor patients, developed complications in all tested subgroups, with varying frequencies. Preoperative evaluation for psychiatric and cognitive dysfunction is crucial to identify patients who are at specific risk for psychiatric complications.

Mortality With and Without Whole-Body CT in Severely Injured Children.

BACKGROUND: The choice of imaging modality-the use of whole-body computed tomography (WB-CT) versus a step-wise diagnostic procedure-in injured children is controversial. In this study we availed ourselves of data from the TR-DGU, the trauma registry of the German Society for Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie), to investigate whether the use of WB-CT improves the outcome. METHODS: The TR-DGU data from the period 2012-2021 were evaluated. A three-stage analysis began with comparison of children with adults aged ≤ 50 years. As a second step, the observed and expected mortality in children with WB-CT was compared with the mortality in children without WB-CT. Finally, predictors of the use of WB-CT were identified so that a propensity score analysis of matched pairs could be performed. RESULTS: A total of 65 092 patients were included, 4573 children (7%) and 60 519 adults (93%), with differences in accident type and injury pattern. Comparison of the ratio of observed to expected mortality revealed no difference between the two groups of children (standardized mortality ratio 0.97 with WB-CT, 0.95 without WB-CT). In adults, however, there was an advantage for the WB-CT group. The propensity score analysis of 1101 matched pairs showed identical mortality in the two groups (3.9% with WB-CT, 4.0% without WB-CT). CONCLUSION: The TR-DGU data show no benefit of WB-CT compared with step-wise diagnosis in the care of severely injured children. In view of the radiation exposure involved, with the danger of inducing malignancy, the benefits and risks of the use of WB-CT in children should be weighed up carefully in team discussions.

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).

Early life stress stimulates hippocampal reelin gene expression in a sex-specific manner: evidence for corticosterone-mediated action.

Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reelin, a master molecule for development and differentiation of the hippocampus. From postnatal day 1 (P1) to P14, mouse pups were subjected to one of the following treatments: nonhandling (NH), handling (H), maternal separation (MS), and early deprivation (ED) followed by immediate (P15) or delayed (P70) real time RT-PCR analysis of reelin mRNA expression. We show that at P15, reelin mRNA levels were significantly increased in male H and ED groups when compared with the NH group. In contrast, no stress-induced alterations of reelin mRNA expression were found in female animals. This sex difference in stress-mediated stimulation of reelin expression was maintained into adulthood, since at P70 intergroup differences were still found in male, but not in female mice. On the cellular level, however, we did not find any significant differences in cell densities of Reelin-immunolabeled neurons between treatment groups or sexes, but an overall reduction of Reelin-expressing neurons in the adult hippocampus when compared to P15. To address the question whether corticosterone mediates the stress-induced up-regulation of reelin gene expression, we used age-matched hippocampal slice cultures derived from male and female mouse pups. Quantitative determination of mRNA levels revealed that corticosterone treatment significantly up-regulated reelin mRNA expression in male, but not in female hippocampi. Taken together, these results show a sex-specific regulation of reelin gene expression by early life experience, most likely mediated by corticosterone.