Effect of managed transition on mental health outcomes for young people at the child-adult mental health service boundary: a randomised clinical trial.

BACKGROUND: Poor transition planning contributes to discontinuity of care at the child-adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC). METHODS: A two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial. RESULTS: The mean difference in HoNOSCA scores between the MT and UC arms at 15 months was -1.11 points (95% confidence interval -2.07 to -0.14, p = 0.03). The cost of delivering the intervention was relatively modest (€17-€65 per service user). CONCLUSIONS: MT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.

The ACCEPT-study: design of an RCT with an active treatment control condition to study the effectiveness of the Dutch version of PEERS® for adolescents with autism spectrum disorder.

BACKGROUND: Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit. Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention. METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28). CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect. TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures.

BACKGROUND: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. METHODS: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. DISCUSSION: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. TRIAL REGISTRATION: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Long-term effects of theta/beta neurofeedback on EEG power spectra in children with attention deficit hyperactivity disorder.

OBJECTIVE: Neurofeedback has been proposed as an effective alternative for pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD), with potentially long-term and delayed benefits. However, the specificity of such long-term behavioral improvements remains inconclusive and therefore additional research into the neurophysiological effects of neurofeedback is needed. We compared long-term effects of theta/beta neurofeedback (NFB) to methylphenidate (MPH) and physical activity (PA, semi-active control intervention) on electroencephalogram (EEG) power spectra. Based on the vigilance stabilization model, we hypothesized further reductions in theta and alpha power in the NFB compared to the control groups. METHOD: EEG power spectra (theta, alpha and beta) during resting and task conditions were recorded at pre-, post-intervention and 6-months follow-up in 67 children, aged 7-13 (NFB: n = 24, MPH: n = 23, or PA: n = 20). RESULTS: Analyses revealed no power spectra differences at follow-up between MPH and NFB (range p = .165-.905) and PA and NFB (range p = .172-.822). CONCLUSIONS: No evidence was found for the specificity of theta/beta NFB at follow-up. SIGNIFICANCE: This was the first study into long-term neurophysiological effects of theta/beta NFB. Future studies are encouraged to explore both specific and non-specific mechanisms of NFB. CLINICAL TRIALS REGISTRATION: Train Your Brain? Exercise and neurofeedback intervention for ADHD, https://clinicaltrials.gov/show/NCT01363544, Ref. No. NCT01363544.

Correction to: Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

Following publication of the original article [1], the authors reported they wanted to reinstate a co-author, who previously declined his authorship due to a misinterpretation of authorship limitations per research center.

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

BACKGROUND: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. METHODS: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. DISCUSSION: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network. METHODS: Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands. RESULTS: We found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (ηp2=0.06) and increased leaf fraction (ηp2=0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network. CONCLUSIONS: The finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs. SIGNIFICANCE: This study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD.

Life course analysis of the impact of mammary cancer and pyometra on age-anchored life expectancy in female Rottweilers: Implications for envisioning ovary conservation as a strategy to promote healthy longevity in pet dogs.

Mammary cancer and pyometra are important health hazards associated with ovary conservation in pet dogs. Early ovariohysterectomy may reduce the incidence of these two diseases, but an estimate of the extent to which the development of mammary cancer or pyometra adversely influences overall longevity is missing. As a first step toward addressing this knowledge gap, the results of a historical cohort study of Rottweilers that lived in North America are reported. Questionnaires completed by owners and veterinarians were used to obtain lifetime health and medical information on 242 female Rottweilers, including years of lifetime ovary exposure, age at death, and cause of death. To determine the extent to which longevity was shortened in females that developed these ovary-associated diseases, age-anchored life expectancy-defined as the median number of remaining years until death for females alive at specified ages during the life course-and years of life lost, a measure of premature mortality, were estimated. Mammary carcinoma was diagnosed in 19 (7.9%) females; median age at diagnosis was 8.5 years; case fatality was 37%. Pyometra was diagnosed in 16 (6.6%) females; median age at diagnosis was 5.4 years; case fatality was 7%. Median lifetime ovary exposure for the study population was 4.3 years. Although risk for developing both diseases increased with longer ovary exposure, longer ovary exposure (≥4.3 years) was also associated with an overall longevity advantage-a 33% decrease in mortality, living 17 months longer than females with shorter ovary exposure (P=0.002). Analysis of age-anchored life expectancy showed that at no time points during the life course was the current or future diagnosis of mammary carcinoma or pyometra associated with shortened survival compared to females who never developed these conditions. This lack of longevity disadvantage is an expected result for diseases with late-onset, moderate (<50%) case fatality (mammary carcinoma) or low (<10%) case fatality (pyometra). These findings fail to support the notion that a strategy, such as elective ovariohysterectomy, implemented to reduce the incidence of mammary carcinoma and pyometra will beneficially impact overall longevity. It follows that future efforts to find and implement effective longevity-promoting interventions should look beyond reducing the incidence of a particular disease to considering trade-offs.

[Transitional psychiatry in the Netherlands: experiences and views of mental health professionals]. / Transitiepsychiatrie in Nederland: ervaringen en opvattingen van ggz-professionals.

BACKGROUND: Psychopathology manifests itself primarily in late adolescence and continues into adulthood. Continuity of care is essential during this phase of life. The current care service distinguishes between child/adolescent (CAMHS) and adult mental health services (AMHS). The separation of services can interfere with the continuity of care.
AIM: To map professionals' experiences of and views on the transition and associated problems that young people can experience as they are transferred from CAMHS to AMHS.
METHOD: We distributed an online questionnaire among professionals providing mental health care to young people (aged 15-25) with psychiatric problems.
RESULTS: The questionnaire was completed by 518 professionals. Decisions relating to transition were generally based on the professional's own deliberations. The preparation consisted mainly of discussing changes with the adolescent and his or her parents. The majority of transition-related problems were experienced in CAMHS, particularly with regard to collaboration with AMHS. Respondents were of the opinion that the developmental age ought to be the determining factor in the decision-making process with regard to transition and they considered it important that developmentally appropriate services should be available in order to bridge the gap.
CONCLUSION: Professionals in CAMHS and AMHS are encountering problems in preparing the transitional phase and in organising the required structural collaboration between the two separate services. The problems relate mainly to coordination, communication and rules and regulations. Professionals are keen to improve the situation and want to see greater flexibility. In their view, there should be a wider range of specialised facilities for young people, enabling them to benefit from transitional psychiatry.

An ERP source imaging study of the oddball task in children with Attention Deficit/Hyperactivity Disorder.

OBJECTIVE: Children with ADHD have difficulties attending to task-relevant events, which has been consistently associated with reductions in the amplitude of the P3b event-related potential (ERP) component. However, the underlying neural networks involved in this P3b reduction remain elusive. Therefore, this study explored source localization of P3b alterations in children with ADHD, aiming at a more detailed account of attentional difficulties. METHODS: Dense array ERPs were obtained for 36 children with ADHD and 49 typically developing children (TD) using an auditory oddball task. The P3b component (310-410 ms) was individually localized with the LAURA distributed linear inverse solution method and compared between groups. RESULTS: The ADHD group showed reduced P3b amplitudes in response to targets compared to the TD group. Differences were located primarily in frontopolar (cinguloopercular network, BA10) and temporoparietal regions (ventral attention network, BA39 and 19) in the left hemisphere. Reductions in P3b amplitudes were related to more inattention and hyperactivity/impulsivity problems in the ADHD group. CONCLUSIONS: The results show alterations in both top-down and bottom-up attention-related brain areas, which may underlie P3b amplitude reductions in children with ADHD. SIGNIFICANCE: This study provides novel data on both temporal and spatial aspects of dysfunctional attention processes in ADHD.

Teacher characteristics, social classroom relationships, and children's social, emotional, and behavioral classroom adjustment in special education.

The goal of this study was to explore relations between teacher characteristics (i.e., competence and wellbeing); social classroom relationships (i.e., teacher-child and peer interactions); and children's social, emotional, and behavioral classroom adjustment. These relations were explored at both the individual and classroom levels among 414 children with emotional and behavioral disorders placed in special education. Two models were specified. In the first model, children's classroom adjustment was regressed on social relationships and teacher characteristics. In the second model, reversed links were examined by regressing teacher characteristics on social relationships and children's adjustment. Results of model 1 showed that, at the individual level, better social and emotional adjustment of children was predicted by higher levels of teacher-child closeness and better behavioral adjustment was predicted by both positive teacher-child and peer interactions. At the classroom level, positive social relationships were predicted by higher levels of teacher competence, which in turn were associated with lower classroom levels of social problems. Higher levels of teacher wellbeing were directly associated with classroom adaptive and maladaptive child outcomes. Results of model 2 showed that, at the individual and classroom levels, only the emotional and behavioral problems of children predicted social classroom relationships. At the classroom level, teacher competence was best predicted by positive teacher-child relationships and teacher wellbeing was best predicted by classroom levels of prosocial behavior. We discuss the importance of positive teacher-child and peer interactions for children placed in special education and suggest ways of improving classroom processes by targeting teacher competence.

Developmental links between disobedient behavior and social classroom relationships in boys with psychiatric disorders in special education.

In mainstream education, positive relationships with teachers and peers have been found to positively influence children's behavioral development. However, high levels of classroom behavior problems may hinder the formation of such positive relationships. Therefore, findings from mainstream education cannot be generalized to special education. The present study investigated the developmental links between disobedience and positive as well as negative relationships with teachers and peers among boys in restrictive special educational settings. At three assessment waves across one school year, teacher-reports of teacher-child closeness and conflict, and peer-reports of peer acceptance, rejection and disobedience were collected among 340 boys (mean age = 10.1 years, SD = 1.58, range = 5-13) with psychiatric disorders receiving special education. Autoregressive cross-lagged models were fitted to explore the nature of these developmental links. The impact of boys' age was examined using multiple group analyses. Findings supported the importance of teacher-child conflict, but not closeness, and positive and negative peer relationships for the development of boys' disobedience, with a stronger effect of negative than positive relationships. However, teacher-child and peer relationships were not longitudinally related and the effect of boys' age was minimal. This study extends prior research by suggesting that, despite differences in educational setting and severity of behavior problems between children in mainstream and special education, reducing negative classroom interactional patterns is most important in preventing the development of problematic classroom behavior in boys with severe social-emotional and behavioral difficulties.

Exceptional longevity in female Rottweiler dogs is not encumbered by investment in reproduction.

To better understand the potential trade-off between female reproductive investment and longevity in an emerging model of human healthspan, we studied pet dogs to determine whether intensity of reproduction (total number of offspring) encumbered the likelihood of exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, including complete reproductive histories, for a cohort of canine "centenarians"--exceptionally long-lived Rottweiler dogs that lived more than 30% longer than the breed's average life expectancy. Reproductive intensity (number of litters, total number of pups) and tempo of reproductive effort (age at first reproduction, mean interbirth interval, age at last reproduction) in 78 exceptionally long-lived female Rottweilers (>13 years old) were compared to a cohort of 97 female Rottweilers that had usual longevity (age at death 8.0-10.75 years). We found no evidence that a mother's physiological investment in offspring was associated with disadvantaged longevity. Instead, similar to some studies in women, our data showed an inverted U-shaped trend, suggesting that moderate investment in reproduction may promote longevity. Late reproductive success, a much-studied surrogate of maternal fitness in women, was not a strong predictor of longevity in this canine cohort. Instead, independent of reproductive investment, the duration of lifetime ovary exposure was significantly associated with highly successful aging. Our results from exceptionally long-lived pet dogs provide rationale for further investigative efforts to understand the ovary-sensitive biological factors that promote healthy longevity in women and pet dogs.

Probing the perils of dichotomous binning: how categorizing female dogs as spayed or intact can misinform our assumptions about the lifelong health consequences of ovariohysterectomy.

In 2009, we reported findings from the first study evaluating the relationship between canine longevity and number of years of lifetime ovary exposure. All previous studies examining gonadal influences on canine longevity relied upon categorizing females as "intact" or "spayed" based on gonadal status at the time of death. Our study of Rottweilers generated a novel result: Keeping ovaries longer was associated with living longer. This result challenged previous assumptions that spayed females live longer. In the present investigation, we explored a methodological explanation for the apparent contradiction between our results and those of others, so we might better understand the impact that timing of spaying has on longevity. We hypothesized that naming female dogs as "spayed" or "intact" based upon gonadal status at time of death - a method we refer to as dichotomous binning - inadequately represents important biological differences in lifetime ovary exposure among bitches spayed at different ages. This hypothesis predicts that a strong relationship between years of lifetime ovary exposure and longevity in a population could be obscured by categorizing females as spayed or intact. Herein, we provide support for this hypothesis by reanalyzing longevity data from 183 female Rottweilers. In this study population, there was a three-fold increased likelihood of exceptional longevity (living ≥ 13 yr) associated with the longest duration of ovary exposure. However, categorizing females in this population as spayed or intact yielded the spurious, contradictory assertion that spayed females (presumed to have the least ovary exposure) are more likely to reach exceptional longevity than those that are intact. Thus, by ignoring the timing of spaying in each bitch, the inference from these data was distorted. It follows from this new understanding that dichotomous binning-naming females as spayed or intact-is inadequate for representing lifetime ovary exposure, introducing misclassification bias that can generate misleading assumptions regarding the lifelong health consequences of ovariohysterectomy.

Increased brain membrane fluidity in schizophrenia.

Recent findings showing significant correlations between phospholipase A2 (PLA2) activity and structural changes in schizophrenic brains contribute to the membrane hypothesis of schizophrenia, which was hampered because a clean functional link between elevated PLA2 activity and brain structure was missing (Neuroimage, 2010; 52: 1314-1327). We measured membrane fluidity parameters and found that brain membranes isolated from the prefrontal cortex of schizophrenic patients showed significantly increased flexibility of fatty acid chains. Our findings support a possible link between elevated PLA2 activity in cortical areas of schizophrenic patients and subsequent alterations of the biophysical parameters of neuronal membranes leading to structural changes in these areas.

AFM for diagnosis of nanocrystallization of steels in hardening processes.

INTRODUCTION: The aim of this study is to investigate the nanocrystallization of steels caused by the transformation from the austenitic to the martensitic phase induced by a severe plastic deformation (SPD) treatment. In this framework, we applied an air blast shot peening treatment, which is a simple protocol widely used for industrial purposes. METHODS: AISI 286 and AISI 316 specimens were peened for different times and polished using diamond pastes in order to remove corrugations higher than 1 mum. The characterization of the steel surfaces was performed by atomic force microscopy (AFM) operating in contact mode. Additional EDXD measurements were performed to confirm the phase transition. RESULTS AND DISCUSSION: An AFM-based characterization at nanometric level of the steel surfaces is provided. When the peening exceeds a threshold time that, as expected, depends on the steel composition, a uniform nanostructuration is detected. It is well known that such rearrangement is associated to the growth of a martensitic phase. To date, AFM has been employed in this field only for few applications and to solve specific problems. On the other hand, our results demonstrate that this is a useful technique for the characterization of hardened surfaces, especially when non-destructive sample preparation treatments are required. Moreover, we show that AFM can be a useful tool also for in situ industrial diagnostics of metallic parts.

Fluoxetine versus trimipramine in the treatment of depression in geriatric patients.

INTRODUCTION: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and trimipramine, a tricyclic antidepressant (TCA), were compared in terms of efficacy and tolerability in a six-week, parallel group, double-blind pilot study in 41 geriatric patients with major depression (61 - 85 years old). METHOD: The Hamilton Rating Scale for Depression (HAMD-17), the Montgomery-Asberg Rating Scale (MADRS), the Adjective Mood Scale (Bf-S), the Clinical Global Impression (CGI), and the Patients Global Impression (PGI) were used to measure changes in depressive symptoms. RESULTS: Improvement with treatment was found on all scales. Efficacy and tolerability were similar in both groups. No statistically significant differences were found. CONCLUSION: These findings suggest that fluoxetine and trimipramine are comparable in terms of efficacy and tolerability in the treatment of major depression in geriatric patients.

Olanzapine versus flupenthixol in the treatment of inpatients with schizophrenia: a randomized double-blind trial.

OBJECTIVE: The atypical antipsychotic olanzapine has extensively been compared with haloperidol, whereas studies vs. other (conventional) neuroleptics are scarce. This exploratory double-blind 4-week study was designed to compare the efficacy and the safety of olanzapine (OLA) and flupenthixol (FLU) which have recently been considered as a "partially atypical" antipsychotics. METHODS: Twenty-eight inpatients with schizophrenia (DSM-IV) were randomly assigned for treatment with OLA (N = 15, 5-20 mg/d) or FLU (N = 13, 5-20 mg/d). The Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS), plus the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales, were used to assess the efficacy of both compounds; safety was determined by using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS) and by assessing treatment-emergent adverse events. Non-parametric statistics were applied. RESULTS: BPRS and NSRS scores improved in both groups (exploratory tests; all p < or = 0.02). Similar results were observed for CGI-Severity, CGI- and PGI-Improvement. There were no significant group differences. Responder rates (at least 40 % decrease in BPRS total) were 9/13 OLA patients (69 %) and 9/12 FLU patients (75 %). EPS events were reported only in the FLU group (p < 0.01); FLU patients needed significantly more anticholinergic medication. Weight gain was higher in OLA patients (p < 0.01). Overall, fewer patients with adverse events were observed in the OLA group (p = 0.04). No significant changes were noted on SAS and AIMS scores. CONCLUSION: Findings from this study suggest that overall and negative symptomatology improved in both treatment groups, while the safety and tolerability profiles differed for both substances.

Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age.

BACKGROUND: In recent years, a growing number of studies has focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to attention-deficit/hyperactivity disorder (ADHD). While their results are contradictory, the reason for this inconsistency remains as yet unclear. METHOD: The present study sought to examine the association between ADHD and the DRD4 exon III polymorphism during child development using longitudinal data from a high-risk community sample (n = 265, 129 females, 126 males) who have been followed from birth to 11 years of age. RESULTS: Higher rates of ADHD were observed in boys with the 7 repeat allele of exon III than in boys with other alleles at the ages of 4 1/2 (Fisher's exact test, p = .061), 8 (p = .026), and 11 years (p = .005). Boys with this allele also exhibited higher rates of persistent disorder (p = .024). In girls, a trend towards an association (p = .055) with the 7 repeat allele emerged only at preschool age. CONCLUSIONS: These findings provide additional evidence for the role of the dopamine D4 receptor in ADHD during the course of child development.

[Role of androgens in externalizing behavior problems in adolescents]. / Bedeutung von Androgenen für externalisierende Verhaltensauffälligkeiten Jugendlicher.

OBJECTIVE: While an association between androgens and different types of aggression has been well documented in male offenders, the influence of androgens on externalizing behavior in adolescents at risk for antisocial behavior has not been investigated so far. METHODS: Plasma levels of the main androgen metabolites testosterone (T) and 5a-dihydrotestosterone (DHT) were measured in N = 119 14-year-olds (51 boys, 68 girls) from a prospective longitudinal study of children at risk. The Achenbach Child Behavior Checklist (CBCL) and the Youth Self Report Form (YSR) were used to assess externalizing behavior at age 14. RESULTS: The CBCL revealed significant positive correlations between DHT levels and the subscales "externalizing problems" and the problem scales "aggressive behavior" and "delinquent behavior" in male adolescents. Only the YSR subscale "delinquent behavior" exhibited a marginally significant association with DHT. Neither scale showed any significant correlations between androgen levels and externalizing behavior in female adolescents. CONCLUSIONS: Earlier findings of androgen effects on aggressive and antisocial behavior in male offenders were confirmed for male adolescents from a general population sample. The results stress the importance of the androgen metabolite DHT.