Intergenerational Transmission of Depression: Test of an Interpersonal Stress Model in a Community Sample

An interpersonal stress model of depression transmission was tested in a community sample of nearly 800 depressed and never-depressed women and their 15-year-old children. It was hypothesized that maternal depression (and depression in the maternal grandmother) contributed to chronic interpersonal stress in the mothers, affecting quality of parenting and youths' social competence. In turn, poor social functioning and interpersonal life events caused at least in part by the youths were predicted to be the proximal predictors of current depressive symptoms and diagnoses. Structural equation modeling confirmed the predicted associations among variables and the link between youth chronic and episodic interpersonal stress and depression. Additionally, the association between maternal and child depression was entirely mediated by the predicted family and interpersonal stress effects

Psychometric properties of the Farsi translation of the kiddie schedule for affective disorders and schizophrenia-present and lifetime version

BACKGROUND: Semi-structural clinical interviews are very important in the area of mental health research and services. There were no studies of the reliability and validity of the Farsi (Persian) version of Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) in Iran. This study compares the results of face-to-face, semi-structural interview and clinical interview by a child and adolescent psychiatrist. METHOD: Subjects were 109 children and adolescents recruited to the child and adolescent psychiatry outpatient clinic of Hafez Hospital. Order of interview (in-psychiatrist or the semi-structural interview) was determined using random assignment within a counterbalanced framework. After, translation and back translation of K-SADS-PL, the Farsi version of K-SADS-PL was provided and used in the study. The interviewer was unaware of the child and adolescent psychiatrist diagnosis at the time of making the interview. Consensual validity, test-retest and inter-rater reliability, sensitivity, specifity, positive and negative predictive validity for the disorders were studied. RESULTS: Consensual validity of all of the psychiatric disorders was good to excellent. It was highest for panic disorder, conduct disorder, and simple phobia. Consensual validity of anorexia nervosa was 0.49. There was sufficient validity and test-retest and inter-rater reliability and good to excellent sensitivity and specifity and positive and negative predictive validity for nearly all of the disorders. Test-retest reliabilities of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and tic disorder were 0.81, 0.67, and 0.56; respectively. Inter-rater reliabilities of ADHD, and ODD were 0.69 and 0.69. Tic disorder, post traumatic disorder, panic disorder, and ADHD had the highest positive predictive validities. CONCLUSION: The Farsi version of K-SADS-PL is a valid and reliable interview instrument for use in assessing and diagnosising child and adolescent psychiatric disorders

Parent-child interactions and adolescent anxiety: a systematic review

Parental behaviours have been implicated in the development and maintenance of anxiety in children and young people; however the degree to which findings apply to adolescents specifically remains unclear. We conducted a systematic review of studies examining the evidence for an association between parental behaviours and adolescent anxiety. Twenty two studies were identified. The results of this systematic review provide fairly consistent preliminary evidence for an association between anxiety and perceived parental control and anxious rearing in adolescence. The findings relating to an association between adolescent anxiety and perceived parental rejection and lack of warmth are somewhat less consistent. Methodological shortcomings in the studies mean that these results should be interpreted with caution. Future research should be conducted using observational and experimental design with adolescents from referred, clinical populations to help identify the critical parental processes and clarify the direction of effects

Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

<p>Abstract</p> <p>Background</p> <p>The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH.</p> <p>Methods</p> <p>Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67).</p> <p>Results</p> <p>Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 ± 31.9 mg, 74.8 ± 26.2 mg, and 95.4 ± 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N = 36) on placebo.</p> <p>Conclusion</p> <p>Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH.</p> <p>Trial Registration</p> <p>The trial of OROS-MPH was registered at clinicaltrials.gov, number NCT00181571.</p

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a Prospective follow-up study

BACKGROUND: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed. METHODS: This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years). RESULTS: We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another. CONCLUSION: These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach

Understanding the sex difference in vulnerability to adolescent depression: an examination of child and parent characteristics

This study examined sex differences in risk factors associated with adolescent depression in a large sample of boys and girls. Moderation and mediation explanatory models of the sex difference in likelihood of depression were examined. Findings indicate that the factors associated with depression in adolescent boys and girls are quite similar. All of the variables considered were associated with depression, but sex did not moderate the impact of vulnerability factors on likelihood of depression diagnosis. However, negative self-perceptions in the domains of achievement, global self-worth, and physical appearance partially mediated the relationship between sex and depression. Further, girls had higher levels of positive self-perceptions in interpersonal domains that acted as suppressors and reduced the likelihood of depression in girls. These findings suggest that girls' higher incidence of depression is due in part to their higher levels of negative self-perceptions, whereas positive interpersonal factors serve to protect them from depressive episodes

Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls

<p>Abstract</p> <p>Background</p> <p>The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (<it>NOS1AP</it>) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of <it>NOS1AP </it>in these psychiatric conditions, but only a limited number explored the sequence variability of <it>NOS1AP</it>.</p> <p>Methods</p> <p>We analyzed the coding sequence of <it>NOS1AP </it>in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93).</p> <p>Results</p> <p>Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions.</p> <p>Conclusions</p> <p>Coding variations of <it>NOS1AP </it>are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human <it>NOS1AP </it>gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.</p

Evidence for genetic association of RORB with bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (<it>DBP</it>) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, <it>RAR</it>-related orphan receptors alpha (<it>RORA</it>) and beta (<it>RORB</it>), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in <it>RORA </it>and <it>RORB</it>.</p> <p>Methods</p> <p>We genotyped 355 <it>RORA </it>and <it>RORB </it>SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching.</p> <p>Results</p> <p>We report that four intronic <it>RORB </it>SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three <it>RORB </it>haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any <it>RORA </it>SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any <it>RORA </it>or <it>RORB </it>SNPs.</p> <p>Conclusion</p> <p>Our findings suggest that clock genes in general and <it>RORB </it>in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.</p