Manuel Föcker

Fetal alcohol spectrum disorders

Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse.

Leptin-Mediated Neuroendocrine Alterations in Anorexia Nervosa: Somatic and Behavioral Implications

Hypoleptinemia is a key endocrinological feature of anorexia nervosa (AN). Several symptoms in acute AN are related to the low circulating leptin levels including amenorrhea and semi-starvation-induced hyperactivity. The drop in leptin levels results from the loss of fat mass; once leptin levels fall below specific thresholds the hypothalamic-pituitary-gonadal and -thyroid axes are down-regulated; in contrast, the hypothalamic-pituitary-adrenal axis is up-regulated. Hypoleptinemia is the major signal underlying both somatic and behavioral adaptations to starvation. Because the mechanisms involved in this adaptation are similar in rodents and humans, rodent models can be used to investigate the relevant central pathways which underly the respective starvation-induced symptoms. During therapeutically induced weight gain, leptin levels can intermittently increase above normal concentrations. This hyperleptinemia could predispose to renewed weight loss.

Are bidirectional associations of obesity and depression already apparent in childhood and adolescence as based on high-quality studies? A systematic review

Our aim was to evaluate bidirectional associations of obesity and depression in cross‐sectional and longitudinal studies with initial assessments in childhood or adolescence. The clarification of these relationships may support the development of innovative interventions, e.g. based on nutrition and mental health. A systematic literature search was conducted in MEDLINE. Main inclusion criteria were (i) assessment of subjects <18 years at baseline, (ii) use of validated psychometric instruments and (iii) elicitation of objectively measured anthropometric data at least at one time point. Twenty‐four studies met our inclusion criteria. Out of 19, 14 cross‐sectional studies confirmed a significant association of obesity and depression. Three out of eight longitudinal studies reported associations between obesity and subsequent depression in female children and adolescents only, and three out of nine studies obtained evidence in favour of the other direction with two studies revealing significant results only for female and one only for male children and adolescents. Evidence is mixed, and secure conclusions are hampered by the methodological variance of the included studies. Relationships are seemingly more readily detectable in female children adolescents and in the cross‐sectional compared with the longitudinal analyses. Possibly, the joint development of obesity and depression in predisposed subjects accounts for the latter discrepancy.

Vitamin D and mental health in children and adolescents

While vitamin D is known to be relevant for bone health, evidence has recently accumulated for an impact on mental health. To identify the potential benefits and limitations of vitamin D for mental health, an understanding of the physiology of vitamin D, the cut-off values for vitamin D deficiency and the current status of therapeutic trials is paramount. Results of a systematic PUBMED search highlight the association of vitamin D levels and mental health conditions. Here, we focus on children and adolescents studies as well as randomized controlled trials on depression in adults. 41 child and adolescent studies were identified including only 1 randomized controlled and 7 non-controlled supplementation trials. Overall, results from 25 cross-sectional studies as well as from 8 longitudinal studies suggest a role of vitamin D in the pathogenesis of mental disorders in childhood and adolescence. Findings from supplementation trials seem to support this hypothesis. However, randomized controlled trials in adults revealed conflicting results. Randomized controlled trials in childhood and adolescents are urgently needed to support the potential of vitamin D as a complementary therapeutic option in mental disorders. Study designs should consider methodological challenges, e.g., hypovitaminosis D at baseline, appropriate supplementation doses, sufficient intervention periods, an adequate power, clinically validated diagnostic instruments, and homogenous, well-defined risk groups.

Comparison of metabolic profiles of acutely ill and short-term weight recovered patients with anorexia nervosa reveals alterations of 33 out of 163 metabolites

Starvation represents an extreme physiological state and entails numerous endocrine and metabolic adaptations. The large-scale application of metabolomics to patients with acute anorexia nervosa (AN) should lead to the identification of state markers characteristic of starvation in general and of the starvation specifically associated with this eating disorder. Novel metabolomics technology has not yet been applied to this disorder. Using a targeted metabolomics approach, we analysed 163 metabolite concentrations in 29 patients with AN in the acute stage of starvation (T0) and after short-term weight recovery (T1). Of the 163 metabolites of the respective kit, 112 metabolites were quantified within restrictive quality control limits. We hypothesized that concentrations are different in patients in the acute stage of starvation (T0) and after weight gain (T1). Furthermore, we compared all 112 metabolite concentrations of patients at the two time points (T0, T1) with those of 16 age and gender matched healthy controls. Thirty-three of the metabolite serum levels were found significantly different between T0 and T1. At the acute stage of starvation (T0) serum concentrations of 90 metabolites differed significantly from those of healthy controls. Concentrations of controls mostly differed even more strongly from those of AN patients after short-term weight recovery than at the acute stage of starvation. We conclude that AN entails profound and longer lasting alterations of a large number of serum metabolites. Further studies are warranted to distinguish between state and trait related alterations and to establish diagnostic sensitivity and specificity of the thus altered metabolites.

Eating-related Psychopathology and Food Addiction in Adolescent Psychiatric Inpatients

OBJECTIVE Our aims were to investigate the relationship between food addiction and mental disorders including eating disorders (ED), eating-related psychopathology and body mass index-standard deviation score in a sample of adolescent psychiatric inpatients. METHODS Food addiction was assessed with the Yale Food Addiction Scale (YFAS). Eating-related psychopathology was measured with the Three-Factor Eating Questionnaire (TFEQ). Psychiatric diagnoses were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The sample consisted of n = 242 adolescent psychiatric inpatients, of which n = 37 (15.3%) met criteria for an ED. Multiple regression analysis was used to examine the association between YFAS symptom count, TFEQ scales and ED controlling for age and gender. RESULTS Food addiction frequency was 16.5%, and the mean YFAS symptom count was 2.39 (SD: 1.60). In patients with food addiction, TFEQ scale scores were significantly higher than patients without food addiction. Frequency of ED was 42.9% in patients with and 9.9% in patients without food addiction. The TFEQ subscales disinhibition and hunger as well as diagnosis of ED were associated with YFAS symptom count. DISCUSSION Food addiction in adolescent psychiatric inpatients occurs with rates higher than those seen in community samples of children, adolescents and adults. Food addiction might be associated with eating styles related to susceptibility to hunger and feelings of loss of control. The implications of high-YFAS scores in restricting-type anorexia nervosa warrant further investigations to explore which and how the respective items are interpreted in this ED subgroup. Copyright

Hair Cortisol Concentrations in Adolescent Girls with Anorexia Nervosa are Lower Compared to Healthy and Psychiatric Controls.

OBJECTIVE In anorexia nervosa (AN) hypercortisolism has been described using urine, plasma and saliva samples as short-term markers for the hypothalamic-pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol concentration (HCC) as a marker for long-term integrated cortisol secretion in female patients with AN compared to female healthy controls (HC) and female psychiatric controls (PC). METHODS HCC was assessed in 22 female adolescent psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of the same age range. For further analyses we examined the associations of age and body mass index (BMI) with HCC. RESULTS Log HCC was lower in AN-patients compared to HC (p = 0.030). BMI-standard deviation scores (SDS) but not age correlated with log HCC (BMI-SDS: r = 0.19, bias corrected accelerated 95% confidence interval: [.04, .34], p = 0.015; age: r = 0.10, bias corrected accelerated 95% confidence interval: [-.07, .25], p = 0.213) when combining AN, HC and PC samples. DISCUSSION We find lower HCC in AN, compared to HC and PC, respectively. Based on the relationship between HCC and BMI-SDS across AN, HC and PC, we argue that HCC might not capture endocrine alterations because of AN pathology-related processes but rather shows consistent relationships with BMI, which extent even to the very low range of BMI values, as present in AN patients. Alternatively, incorporation of cortisol into the hair follicle might have been compromised because of trophic hair follicle disturbances that had been reported in AN patients, previously. Copyright

Clinical Problems Encountered in the Treatment of Adolescents with Anorexia Nervosa 1Both authors contributed equally.

The conceptualization of anorexia nervosa (AN) depends on the diagnostic criteria. Most patients with teenage onset AN seem to remit within 3-10 years depending on the definitions of recovery. The mortality of adolescent onset anorexia nervosa (AN) has fortunately decreased over the last two decades. Based on randomized controlled trials, we review different treatments including individual and group psychotherapy, family therapy, psychopharmacology, and hormone therapy. Treatment settings vary over time for any individual patient. Despite high rates of inpatient treatment, the respective evidence for effectiveness is meager. In underage patients with severe AN clinical, ethical and legal aspects need to be dealt with systematically if intermittent compulsory treatment is deemed necessary. The prolonged and frequently chronic course of AN often entails therapeutic discontinuity; the transition into adulthood requires a graded therapeutic concept that considers the severity of the disorder, developmental and chronological age, and parental involvement. Finally, we consider future clinical and research options to improve treatment and outcome of this eating disorder.

Low 25(OH)-vitamin D concentrations are associated with emotional and behavioral problems in German children and adolescents

Background Evidence has accumulated for the association between low vitamin D serum concentrations and mental health disorders in both children and adults. We performed a cross-sectional analysis in a population-based sample of children and adolescents to detect associations between 25(OH)-vitamin D serum [25(OH)D] concentrations and scores of the five Strengths and Difficulties Questionnaire (SDQ) subscales and the total difficulties score in different age groups (age ≥3-<12 years and ≥12-<18 years). Methods 9068 participants of the population-based, nation-wide German Health Interview and Examination Survey for Children and Adolescents (KIGGS) with information on mental health status assessed by the SDQ and 25(OH)D levels were included in the analysis. For statistical analysis we used linear regression models stratified by gender based on different adjustment sets. For the younger subsample the analysis was additionally adjusted for the frequency of playing outside. We compared the associations based on parent- and self-ratings of the SDQ for children and adolescents aged ≥12-<18 years. Results We found inverse associations between 25(OH)D concentrations and the subscales emotional problems, peer relationship problems and the total difficulties score in both genders after adjustment for potential confounders. The strongest associations were observed in the older subsample for parent-ratings in boys and self-ratings in girls. In the younger subsample the associations were less strong and no longer evident after adjustment for potential confounders such as migration background, socioeconomic status and frequency of playing outside. Conclusion Based on the large-scale cross-sectional study in a German population-based sample of children and adolescents we detected inverse associations between 25(OH)D concentrations and both parent- and self-rated SDQ scores of the total difficulties scale and different subscales with the strongest association in the subsample aged ≥12-<18 years for both genders. Migration background and socioeconomic status were detected as relevant confounders. Further studies–particularly in countries with comparatively low mean 25(OH)D concentrations–in childhood and adolescence are warranted. Longitudinal studies are also necessary to infer direction of effects. Finally, RCTs in children and adolescents are required to determine whether Vitamin D is beneficial for mental health.

The role of genetic variation of human metabolism for BMI, mental traits and mental disorders.

Objective The aim was to assess whether loci associated with metabolic traits also have a significant role in BMI and mental traits/disorders Methods We first assessed the number of single nucleotide polymorphisms (SNPs) with genome-wide significance for human metabolism (NHGRI-EBI Catalog). These 516 SNPs (216 independent loci) were looked-up in genome-wide association studies for association with body mass index (BMI) and the mental traits/disorders educational attainment, neuroticism, schizophrenia, well-being, anxiety, depressive symptoms, major depressive disorder, autism-spectrum disorder, attention-deficit/hyperactivity disorder, Alzheimers disease, bipolar disorder, aggressive behavior, and internalizing problems. A strict significance threshold of p < 6.92 × 10−6 was based on the correction for 516 SNPs and all 14 phenotypes, a second less conservative threshold (p < 9.69 × 10−5) on the correction for the 516 SNPs only. Results 19 SNPs located in nine independent loci revealed p-values < 6.92 × 10−6; the less strict criterion was met by 41 SNPs in 24 independent loci. BMI and schizophrenia showed the most pronounced genetic overlap with human metabolism with three loci each meeting the strict significance threshold. Overall, genetic variation associated with estimated glomerular filtration rate showed up frequently; single metabolite SNPs were associated with more than one phenotype. Replications in independent samples were obtained for BMI and educational attainment. Conclusions Approximately 5–10% of the regions involved in the regulation of blood/urine metabolite levels seem to also play a role in BMI and mental traits/disorders and related phenotypes. If validated in metabolomic studies of the respective phenotypes, the associated blood/urine metabolites may enable novel preventive and therapeutic strategies.