Table_2_Psychotherapeutic Treatment for Anorexia Nervosa: A Systematic Review and Network Meta-Analysis.docx

<p>Background: The aim of the study was a systematic review of studies evaluating psychotherapeutic treatment approaches in anorexia nervosa and to compare their efficacy. Weight gain was chosen as the primary outcome criterion. We also aimed to compare treatment effects according to service level (inpatient vs. outpatient) and age group (adolescents vs. adults).</p><p>Methods:The data bases PubMed, Cochrane Library, Web of Science, Cinahl, and PsychInfo were used for a systematic literature search (until Feb 2017). Search terms were adapted for data base, combining versions of the search terms anorexia, treat^*/therap^* and controlled trial. Studies were selected using pre-defined in- and exclusion criteria. Data were extracted by two independent coders using piloted forms. Network-meta-analyses were conducted on all RCTs. For a comparison of service levels and age groups, standard mean change (SMC) statistics were used and naturalistic, non-randomized studies included.</p><p>Results: Eighteen RCTs (trials on adults: 622 participants; trials on adolescents: 625 participants) were included in the network meta-analysis. SMC analyses were conducted with 38 studies (1,164 participants). While family-based approaches dominate interventions for adolescents, individual psychotherapy dominates in adults. There was no superiority of a specific approach. Weight gains were more rapid in adolescents and inpatient treatment.</p><p>Conclusions: Several specialized psychotherapeutic interventions have been developed and can be recommended for AN. However, adult and adolescent patients should be distinguished, as groups differ in terms of treatment approaches considered suitable as well as treatment response. Future trials should replicate previous findings and be multi-center trials with large sample sizes to allow for subgroup analyses. Patient assessment should include variables that can be considered relevant moderators of treatment outcome. It is desirable to explore adaptive treatment strategies for subgroups of patients with AN. Identifying and addressing maintaining factors in AN remains a major challenge.</p

Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia

<div><p></p><p><i>Objectives.</i> Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. <i>Methods.</i> Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. <i>Results.</i> No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10^–8) in our GWA study, but 10 SNPs reached <i>P</i>-values less than 10^–6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. <i>Conclusions.</i> Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.</p></div

Effect of <i>NRGN</i> risk variant on brain function.

<p>Functional map illustrating increased neural activity in rs12541 TT homozygotes compared to C carriers. SSC, somatosensory cortex; CC, cingulate cortex. Results were cluster-corrected and z-values are represented according to the color code.</p

Effect of <i>NRGN</i> risk variant on cortical thickness and ACC volume.

<p>a) Cortical statistical map illustrating reduced cortical thickness for rs12807809 C carriers compared to TT homozygotes. The -log(CWP-value) is represented according to the color code. b) Boxplot showing mean and two standard errors of the standardized residuals for the effects of <i>NRGN</i> rs12807809 genotype on left rostal ACC volume controlled for intracranial volume, age, gender, diagnosis and scanner field strength.</p

Demographic variables of the MCIC sample.

<p>Means and standard deviations (SD) are given. HC = healthy control, SZ = patient with schizophrenia. Ethnicity was defined as described under Methods. WRAT3-RT = Wide Range Achievement Test 3 – Reading Test. Parental SES (socioeconomic status) was classified according to Hollingshead, and handedness determined using the Annett Scale of Hand Preference.</p>a<p>significantly different between HC and SZ on basis of Chi-Square (p<0.05).</p>b<p>significantly different between HC and SZ on basis of Welch (p<0.05).</p

Quantile-quantile plot for MCIC association results.

<p>The empirical and theoretical distributions are shown as dots and line, respectively.</p

DataSheet_1_Lipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals.xlsx

ContextThe bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.ObjectiveWe aimed to (i) detect variants in the lipocalin-2 gene (LCN2) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of LCN2 and MC4R variants on circulating lipocalin-2 level.MethodsSanger sequencing of the coding region of LCN2 in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. In-silico analyses to evaluate functional implications of detected LCN2 variants. TaqMan assays for rare non-synonymous variants (NSVs) in additional independent study groups. Serum levels of lipocalin-2 were measured by ELISA in 35 females with NSVs in either LCN2 or MC4R, and 33 matched controls without NSVs in the two genes.ResultsFourteen LCN2-variants (five NSVs) were detected. LCN2-p.Leu6Pro and p.Gly9Val located in the highly conserved signal peptide region may induce functional consequences. The secondary structure change of lipocalin-2 due to LCN2-p.Val89Ile may decrease solubility and results in a low lipocalin-2 level in a heterozygotes carrier (female recovered from AN). Lean individuals had lower lipocalin-2 levels compared to patients with obesity (p = 0.033).ConclusionLipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.</p

Linkage disequilibrium (LD) plot of all MCIC main hits on chromosome 19.

<p>LD is given based on r² estimated using the current dataset. Each diamond indicates the pairwise magnitude of LD, with dark grey/black indicating strong LD (r²>0.8). Figure prepared with <i>HaploView</i> (Barrett et al. 2005).</p

DataSheet_2_Lipocalin 2 – mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals.docx

ContextThe bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway.ObjectiveWe aimed to (i) detect variants in the lipocalin-2 gene (LCN2) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of LCN2 and MC4R variants on circulating lipocalin-2 level.MethodsSanger sequencing of the coding region of LCN2 in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. In-silico analyses to evaluate functional implications of detected LCN2 variants. TaqMan assays for rare non-synonymous variants (NSVs) in additional independent study groups. Serum levels of lipocalin-2 were measured by ELISA in 35 females with NSVs in either LCN2 or MC4R, and 33 matched controls without NSVs in the two genes.ResultsFourteen LCN2-variants (five NSVs) were detected. LCN2-p.Leu6Pro and p.Gly9Val located in the highly conserved signal peptide region may induce functional consequences. The secondary structure change of lipocalin-2 due to LCN2-p.Val89Ile may decrease solubility and results in a low lipocalin-2 level in a heterozygotes carrier (female recovered from AN). Lean individuals had lower lipocalin-2 levels compared to patients with obesity (p = 0.033).ConclusionLipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.</p

Genome-wide association results for SNPs associated with hippocampal volume in the MCIC sample.

<p>SNP IDs with chromosome (CHR), basepair position (BP), minor (A1) and major allele (A2), minor allele frequency (MAF), regression coefficient (BETA), coefficient (STAT) and asymptotic p-value for t-statistic, and corresponding gene regions: <i>KIF26B</i> (kinesin family member 26B), <i>TRPM8</i> (transient receptor potential cation channel, subfamily M, member 8), <i>LOC283089</i> (uncharacterized), <i>NR2F6</i> (nuclear receptor subfamily 2, group F, member 6), <i>USHBP1</i> (Usher syndrome 1C binding protein 1), and <i>BABAM1</i> (BRISC and BRCA1 A complex member 1). For additional information see Table S3 in File S1.</p