Julia Huemer

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Mental health issues in unaccompanied refugee minors.

Previous studies about unaccompanied refugee minors (URMs) showed that they are a highly vulnerable group who have greater psychiatric morbidity than the general population. This review focuses on mental health issues among URMs. Articles in databases PsycINFO, Medline and PubMed from 1998 to 2008 addressing this topic were reviewed. The literature had a considerable emphasis on the assessment of PTSD symptoms. Results revealed higher levels of PTSD symptoms in comparison to the norm populations and accompanied refugee minors. In several studies, age and female gender predicted or influenced PTSD symptoms. The existing literature only permits limited conclusions on this very hard to reach population. Future research should include the analysis of long-term outcomes, stress management and a more thorough analysis of the whole range of psychopathology. Additionally, the development of culturally sensitive norms and standardized measures for diverse ethnic groups is of great importance.

Additive Gene–Environment Effects on Hippocampal Structure in Healthy Humans

Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).

Reduced default mode network suppression during a working memory task in remitted major depression

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.

Responses to conflict, family loss and flight: posttraumatic stress disorder among unaccompanied refugee minors from Africa

ObjectiveTo investigate African unaccompanied refugee minors (URMs) living in Austria for posttraumatic stress disorder (PTSD) prevalence and related symptoms, comorbidity, demographics and coping strategies.Method“UCLA PTSD Index and inventories” and “Scales for Children Afflicted by War and Persecution (SCWP)” were used to assess 41 African URMs.ResultsThe study revealed lower PTSD rates than measured among URMs in previous studies. Girls were more likely to develop PTSD. PTSD was significantly correlated with single war-related traumatic events. The depression score for the sample was above the clinical cut-off value.ConclusionsTrauma-specific psychopathology was less severe than reported in other studies. These findings could be explained by concepts of resilience. Other implications, such as response bias, are discussed.ZusammenfassungAnliegenUnbegleitete minderjährige Flüchtlinge sind oftmals als Patienten vorstellig in kinder- und jugendpsychiatrischen Einrichtungen. Neben vorhandenen sprachlichen Barrieren existieren in der Literatur wenige Daten zu dieser heterogenen Patientenpopulation. Vorliegende Studie fokussiert die aus Afrika stammenden, unbegleiteten, minderjährigen Flüchtlinge (URMs) in Österreich und untersucht das Vorhandensein etwaiger psychischer Störungen, insbesondere jener einer posttraumatischen Belastungsstörung (PTBS) und etwaiger begleitender Symptome und Komorbiditäten. Auch werden in diesem Zusammenhang Coping-Strategien erfasst.MethodeBei den insgesamt 41 afrikanischen URMs, die innerhalb von Österreich rekrutiert werden konnten, wurden neben „UCLA PTSD Index und Inventare“ auch „Scales for Children Afflicted by War and Persecution (SCWP)“ als Untersuchungsinstrumente eingesetzt.ErgebnisseIm Vergleich mit vorhandenen Daten in der Literatur zeigten sich in vorliegender Studie niedrigere PTBS Werte. Die Vulnerabilität für PTBS war für Mädchen erhöht. Die Diagnose einer PTBS stand in einem signifikanten Zusammenhang mit einmaligen kriegsbezogenen traumatischen Ereignissen. Die Depressions-Skala für das Sample befand sich über den klinischen Cut-off Werten.SchlussfolgerungenDie traumaspezifische Psychopathologie war unterhalb der in anderen Studien aufgezeigten Werte. Diese Ergebnisse könnten durch eine mögliche erhöhte Resilienz erklärt werden. Weiterführende Erklärungsmodelle werden diskutiert.

Effect of Obesity on Plasma Clusterin: A Proposed Modulator of Leptin Action

Clusterin, a protein constituent of HDL, was recently shown to bind plasma leptin in vitro and has been proposed to modulate leptin activity. To gain insight into a possible role for plasma clusterin in human obesity, we measured plasma clusterin, leptin, soluble leptin receptor (sObR), and lipoproteins in 70 obese adolescents (12.4 ± 1.6 y; BMI-SD score (SDS-BMI) 2.35 ± 0.47) before and after 3 wk of weight reduction in a dietary camp and in 44 normal weight controls. Binding of plasma leptin to HDL or clusterin was studied using ultracentrifugation and immunoaffinity chromatography. During weight reduction, clusterin decreased from 14.6 ± 4.1 to 10.3 ± 2.9 mg/dL, p < 0.001) in obese adolescents, whereas sObR increased. However, baseline plasma clusterin in obese adolescents did not differ from controls. Clusterin did not correlate with SDS-BMI, weight loss, leptin, or lipoproteins. Only ∼1% of plasma leptin was associated with clusterin/apoA-I complexes or with HDL. Our results do not support a role for plasma clusterin as an important leptin-binding protein or modulator of leptin action. The decrease of plasma clusterin during weight reduction may be an effect of the hypocaloric diet rather than being directly linked to weight loss.

Unaccompanied refugee children

1 Leydesdorff L, Wagner CS. International collaboration in science and the formation of a core group. J Informetrics 2008; 2: 317–25. 2 US Offi ce of Research Integrity and the University of Minnesota. Conference on Challenges and Tensions in International Research Collaborations. Minneapolis, Minnesota, USA. Oct 2–3, 2008 http://www.international. umn.edu/oriconf/index.html (accessed Oct 20, 2008). 3 Committee on International Collaborations in Social and Behavioral Sciences Research, US National Committee for the International Union of Psychological Science, National Research Council. International collaborations in behavioral and social sciences: report of a workshop. 2008 http://books.nap.edu/openbook.php?record_id=12053&page=4 (accessed Oct 20, 2008).

Perception of Autonomy and Connectedness Prior to the Onset of Anorexia Nervosa and Bulimia Nervosa

OBJECTIVE This study examines retrospective correlates of nonshared family environment prior to onset of disease, by means of multiple familial informants, among anorexia and bulimia nervosa patients. METHODS A total of 332 participants was included (anorexia nervosa, restrictive type (AN-R): n = 41 plus families); bulimic patients (anorexia nervosa, binge-purging type; bulimia nervosa: n = 59 plus families). The EATAET Lifetime Diagnostic Interview was used to establish the diagnosis; the Subjective Family Image Test was used to derive emotional connectedness (EC) and individual autonomy (IA). RESULTS Bulimic and AN-R patients perceived significantly lower EC prior to onset of disease compared to their healthy sisters. Bulimic patients perceived significantly lower EC prior to onset of disease compared to AN-R patients and compared to their mothers and fathers. A low family sum - sister pairs sum comparison - of EC had a significant influence on the risk of developing bulimia nervosa. Contrary to expectations, AN-R patients did not perceive significantly lower levels of IA compared to their sisters, prior to onset of disease. Findings of low IA in currently ill AN-R patients may represent a disease consequence, not a risk factor. CONCLUSIONS Developmental child psychiatrists should direct their attention to disturbances of EC, which may be present prior to the onset of the disease.

Migraine in Patients With Eating Disorders: A Study Using a Sister-Pair Comparison Design

(Headache 2011;51:220‐225)

Psychopathology among parents of children and adolescents with separation anxiety disorder

SummaryObjectiveTo examine psychopathology among parents of children and adolescents with separation anxiety disorder (SAD).MethodA case-control design was applied: parents of children and adolescents suffering from SAD (n = 30; age: 10.7 ± 1.8 a) were compared with parents of youth without any psychiatric disease (n = 30; age: 11.2 ± 1.8 a). The SCID-I, a structured clinical interview to assess psychopathology, was applied among the parents group.ResultsParents of children and adolescents suffering from SAD exhibited a significantly higher prevalence of psychopathology, mainly anxiety disorders and mood disorders, in comparison with the control group. Within anxiety disorders, mothers predominantly suffered from social phobia and specific phobia. Fathers most frequently suffered from obsessive-compulsive disorder and social phobia. Maternal anxiety disorder (current and lifetime) and maternal affective disorder (lifetime) proved to be significant predictors of SAD in youth.ConclusionsThe associations between parents’ psychopathology and the development of SAD in their children are discussed in the light of clinical implications, both in terms of psychotherapeutic care as well as treatment outcome.ZusammenfassungZielIn dieser Studie wird die Psychopathologie der Eltern von Kindern und Jugendlichen mit einer diagnostizierten Emotionalen Störung mit Trennungsangst untersucht.MethodeIn diesem Studiendesign werden Eltern und Jugendliche, welche die diagnostischen Kriterien einer Emotionalen Störung mit Trennungsangst erfüllten (n = 30; Alter: 10,7 ± 1,8 a) und gesunde Probanden (n = 30; Alter: 11,2 ± 1,8 a) verglichen. Das SKID-I, ein strukturiertes klinisches Interview für psychische Störungsbilder, wird für die Evaluierung der psychopathologischen Auffälligkeiten der Eltern verwendet.ErgebnisseDie Eltern von Kindern und Jugendlichen mit einer diagnostizierten Emotionalen Störung mit Trennungsangst haben verglichen mit der Kontrollgruppe eine signifikant höhere Prävalenz für psychiatrische Erkrankungen, vor allem im Bereich der Angststörungen und der affektiven Störungen.Bezüglich der Angststörungen erfüllen hierbei die Mütter häufig die diagnostischen Kriterien für Soziale Phobie und Spezifische Phobie. Die Väter hingegen zeigen zum Untersuchungszeitpunkt häufiger Zwangserkrankungen und Soziale Phobien. Mütterliche Angststörungen (current und lifetime) und affektive Erkrankungen (lifetime) haben sich als signifikante Prädiktoren erwiesen.SchlussfolgerungDer Zusammenhang zwischen elterlicher Psychopathologie und der Entwicklung einer Emotionalen Störung mit Trennungsangst wird hinsichtlich der psychotherapeutischen Interventionsmöglichkeiten und des damit zusammenhängenden Behandlungserfolges diskutiert.