Alan Apter

Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity.

The importance of environment in the regulation of brain, behaviour and physiology has long been recognized in biological, social and medical sciences. Animals maintained under enriched conditions have clearly been shown to have better learning abilities than those maintained under standard conditions. However, the effects of environmental enrichment (EE) on immunity and emotionality have been less documented and remain questionable. Therefore, we investigated the effect of EE on natural killer (NK) cell activity, psychological stress responses and behavioural parameters. Male C3H mice were housed either in enriched or standard conditions for 6 weeks. Behaviour was then examined by the grip‐strength test, staircase and elevated plus maze, and corticosterone levels and NK cell activity were measured. Furthermore, animals exposed to the stress paradigm, achieved by electric shock with reminders, were tested for freezing time in each reminder. Corticosterone levels were also measured. The EE mice showed decreased anxiety‐like behaviour and higher activity compared to standard mice, as revealed by a greater percentage of time spent in the open arms of the elevated plus maze, and a higher rate of climbing the staircase. A shorter freezing time in the stress paradigm and no corticosterone level reactivity were measured in EE mice. In addition, NK cell activity in spleens of EE mice was higher than that demonstrated in those of standard mice. Thus, EE has a beneficial effect on anxiety‐like behaviour, stress response and NK cell activity. The effect on NK cell activity is promising, due to the role of NK cells in host resistance.

Weight Gain Associated With Olanzapine and Risperidone in Adolescent Patients: A Comparative Prospective Study

OBJECTIVE To evaluate weight gain associated with olanzapine, risperidone, and haloperidol treatment and its clinical risk factors in adolescent patients. METHOD The study was conducted at three adolescent psychiatric departments in two mental health centers in the Tel Aviv area. All patients were Jewish Israelis. Weight and body mass index (BMI) of hospitalized adolescents treated with olanzapine (n = 21), risperidone (n = 21), or haloperidol (n = 8) were prospectively monitored on a weekly basis for the first 12 weeks of treatment. Various clinical risk factors were tested for association with weight gain. RESULTS The olanzapine and risperidone groups experienced significant weight gain between baseline and endpoint (p < .01), whereas the average weight of the haloperidol group did not change. Average weight gain was significantly higher for the olanzapine group (7.2 +/- 6.3 kg, 11.1% +/- 7.8%) than for the risperidone (3.9 +/- 4.8 kg, 6.6% +/- 8.6%) and haloperidol (1.1 +/- 3.3 kg, 1.5% +/- 6.0%) groups. Extreme weight gain (>7%) was recorded in 19 patients (90.5%), 9 patients (42.9%), and 1 (12.5%) patient, respectively Gender (males), low concern about gaining weight (females), low baseline BMI, and paternal BMI were positively correlated with weight gain, whereas previous neuroleptic history, neuroleptic dosage, response to treatment, and illness duration were not. CONCLUSIONS Olanzapine and risperidone are associated with extreme weight gain in adolescents, much higher than that reported in adults. This side effect should be taken into consideration before prescribing these medications, especially in patients at high risk.

An Epidemiological Study of Obsessive-Compulsive Disorder and Related Disorders in Israeli Adolescents

Five hundred and sixty-two, 16- to 17-year-old consecutive inductees into the Israeli Army, constituting a random sample of their cohort, were screened for obsessive-compulsive disorder (OCD), Tourettes syndrome, transient tics (TT), chronic multiple tics (CMT), and attention-deficit hyperactive disorder (ADHD). Two child psychiatrists interviewed the subjects, using screening items from structured interviews that implement DSM-III-R diagnostic criteria. For OCD, a point prevalence of 3.6% was found, 3.9% for ADHD, 1.8% for CMT, and 1.6% for TT. For ADHD, TT, and CMT, but not for OCD, there was a significantly higher prevalence for males than for females. Among the OCD individuals, there was an elevation of TT, CMT, and Tourettes syndrome relative to the population rates.

Correlation of Suicidal and Violent Behavior in Different Diagnostic Categories in Hospitalized Adolescent Patients

OBJECTIVE To determine the relative importance of aggression and depression in adolescent suicide within different diagnostic categories. METHOD One hundred sixty-three consecutive admissions to an adolescent psychiatric inpatient unit were assessed using a semistructure diagnostic instrument, the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Scores for depression, suicidal behaviors, and violent behaviors were calculated from this assessment. RESULTS Anorexia nervosa and conduct disorder patients had the highest suicidal behavior scores. In addition, patients with conduct disorder were significantly more violent than patients with major depressive disorder, and scores on the Violent Behavior Scale correlated with suicidal symptoms but not with depressive symptoms. CONCLUSION Aggression may be as important in some kinds of suicidal behaviors as is depression. Thus it seems that there are hypothetically at least two types of suicidal behaviors during adolescence: a wish to die (depression) and a wish not to be here for a time (impulse control). The first type of suicidal behavior characterizes that seen in disorders with prominent depression such as major depressive disorder and anorexia nervosa, and the second characterizes disorders of impulse control such as conduct disorder.

Aggression, Impulsivity, and Suicide Behavior: A Review of the Literature

This article reviews the literature on the association between impulsivity aggression and suicide. The key words impulsivity, aggression, and suicide were entered into the pubmed, psychlit, and proqest databases. Significant articles were scrutinized for relevant information. Impulsivity and aggression are highly correlated with suicidal behavior across psychiatric samples, nosological borders, and non-psychiatric populations. Impulsivity and aggression are related but the nature of this relationship remains unclear. The literature is confusing and contradictory. This is probably due to the difficulty in defining and separating out these concepts and the fact that there is much overlap between them. Future research should aim at clarifying and refining these concepts as well as their link to all the different forms of suicidal behavior.

Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome

The study of neurogenetic microdeletion syndromes provides an insight into the developmental psychopathology of psychiatric disorders. The aim of the study was to evaluate the prevalence of psychiatric disorders, especially obsessive‐compulsive disorder (OCD), in patients with velocardiofacial syndrome (VCFS), a 22q11 microdeletion syndrome. Forty‐three subjects with VCFS of mean age 18.3 ± 10.6 years were comprehensively assessed using semi‐structured psychiatric interview and the Yale–Brown obsessive compulsive scale (Y‐BOCS). Best estimate diagnoses were made on the basis of information gathered from subjects, parents, teachers, and social workers. Fourteen VCFS subjects (32.6%) met the DSM‐IV criteria for OCD. OCD had an early age of onset and generally responded to fluoxetine treatment. It was not related to mental retardation. The most common obsessive‐compulsive symptoms were contamination, aggression, somatic worries, hoarding, repetitive questions, and cleaning. Sixteen of the 43 patients (37.2%) had attention‐deficit/hyperactivity disorder (ADHD), and 7 (16.2%) had psychotic disorder. The results of our study suggest that there is a strong association between VCFS and early‐onset OCD. This finding may be significant in the understanding of the underlying genetic basis of OCD.

Suicidal behavior, depression, and conduct disorder in hospitalized adolescents.

Abstract A childhood version of the Schedule for Affective Disorders and Schizophrenia (K-SADS) was used to assess 140 consecutive admissions to an adolescent psychiatric inpatient unit. Depression scale scores were correlated with the suicidality scale scores. Suicidality scores on the K-SADS were higher in adolescents diagnosed as having conduct disorder (CD) than in those diagnosed as having major depressive disorder (MDD), even though the CD patients were less depressed than the MDD patients. Aggression and impulsivity may be factors as important as depression in some kinds of suicidal behaviors. A hypothesis is suggested to explain the interrelationship among depression, aggression, and suicidal behavior.

Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk

BACKGROUND  Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. METHODS  Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. RESULTS  Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. CONCLUSIONS Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models.

School-based suicide prevention programmes: the SEYLE cluster-randomised, controlled trial

BACKGROUND Suicidal behaviours in adolescents are a major public health problem and evidence-based prevention programmes are greatly needed. We aimed to investigate the efficacy of school-based preventive interventions of suicidal behaviours. METHODS The Saving and Empowering Young Lives in Europe (SEYLE) study is a multicentre, cluster-randomised controlled trial. The SEYLE sample consisted of 11,110 adolescent pupils, median age 15 years (IQR 14-15), recruited from 168 schools in ten European Union countries. We randomly assigned the schools to one of three interventions or a control group. The interventions were: (1) Question, Persuade, and Refer (QPR), a gatekeeper training module targeting teachers and other school personnel, (2) the Youth Aware of Mental Health Programme (YAM) targeting pupils, and (3) screening by professionals (ProfScreen) with referral of at-risk pupils. Each school was randomly assigned by random number generator to participate in one intervention (or control) group only and was unaware of the interventions undertaken in the other three trial groups. The primary outcome measure was the number of suicide attempt(s) made by 3 month and 12 month follow-up. Analysis included all pupils with data available at each timepoint, excluding those who had ever attempted suicide or who had shown severe suicidal ideation during the 2 weeks before baseline. This study is registered with the German Clinical Trials Registry, number DRKS00000214. FINDINGS Between Nov 1, 2009, and Dec 14, 2010, 168 schools (11,110 pupils) were randomly assigned to interventions (40 schools [2692 pupils] to QPR, 45 [2721] YAM, 43 [2764] ProfScreen, and 40 [2933] control). No significant differences between intervention groups and the control group were recorded at the 3 month follow-up. At the 12 month follow-up, YAM was associated with a significant reduction of incident suicide attempts (odds ratios [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and severe suicidal ideation (0·50, 0·27-0·92; p=0·025), compared with the control group. 14 pupils (0·70%) reported incident suicide attempts at the 12 month follow-up in the YAM versus 34 (1·51%) in the control group, and 15 pupils (0·75%) reported incident severe suicidal ideation in the YAM group versus 31 (1·37%) in the control group. No participants completed suicide during the study period. INTERPRETATION YAM was effective in reducing the number of suicide attempts and severe suicidal ideation in school-based adolescents. These findings underline the benefit of this universal suicide preventive intervention in schools. FUNDING Coordination Theme 1 (Health) of the European Union Seventh Framework Programme.

Emotional reactivity and cognitive regulation in anxious children

Recent models of anxiety disorders emphasize abnormalities in emotional reactivity and regulation. However, the empirical basis for this view is limited, particularly in children and adolescents. The present study examined whether anxious children suffer both negative emotional hyper-reactivity and deficits in cognitive emotion regulation. Participants were 49 children aged 10-17 with generalized anxiety disorder, social anxiety, or separation anxiety disorder as their primary diagnosis, as well as 42 age- and gender-matched non-anxious controls. After completing a diagnostic interview and self-report questionnaires, participants were presented with pictures of threatening scenes with the instructions either to simply view them or to use reappraisal, a cognitive emotion regulation strategy, to decrease their negative emotional response. Emotion ratings, content analysis of reappraisal responses, and reports of everyday use of reappraisal were used to assess negative emotional reactivity, reappraisal ability, efficacy and frequency. Relative to controls, children with anxiety disorders (1) experienced greater negative emotional responses to the images, (2) were less successful at applying reappraisals, but (3) showed intact ability to reduce their negative emotions following reappraisal. They also (4) reported less frequent use of reappraisal in everyday life. Implications for the assessment and treatment of childhood anxiety disorders are discussed.