Dysregulation of the hypothalamic-pituitary-adrenal axis, one of the stress-response systems, is one of the key neurobiological features of major depression (MDD). Data supporting the notion that glucocorticoid-mediated feedback inhibition is impaired in MDD come from a multitude of studies demonstrating nonsuppression of cortisol secretion following administration of the synthetic glucocorticoid dexamethasone. We examined whether genetic variations in the glucocorticoid receptor gene (Nuclear Receptor Subfamily 3, Group C, Member 1; NR3C1) could be associated with increased susceptibility for MDD using a whole gene-based association analysis of single nucleotide polymorphisms (SNPs). Four SNPs were identified in NR3C1 and genotyped in two well-diagnosed samples of patients with MDD ascertained in Belgium and northern Sweden, and matched control samples. In total, 314 MDD patients and 354 control individuals were included in the study. In the Belgian sample, we observed significant allele (p ¼ 0.02) and genotype (p ¼ 0.02) association with an SNP in the promoter region (NR3C1-1); in the Swedish sample, we observed significant allele (p ¼ 0.02) and genotype (p ¼ 0.02) association with the R23K SNP. The haplotype association studies showed modest evidence for an involvement of the 5 0 region of the NR3C1 gene in the genetic vulnerability for MDD. This study suggests that polymorphisms in the 5 0 region of the NR3C1 gene may play a role in the genetic vulnerability for MDD.

Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P¼0.02) and genotype (P¼0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P¼0.04). In both patient-control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.

Research suggests that motor impairment is highly prevalent in some psychiatric conditions, particularly ASD and ADHD. However, future work is necessary to draw sound conclusions.

Some evidence suggests that the HPA axis may be dysfunctional in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate whether a different pattern of HPA axis activity is found between the inattentive (I) and combined (C) subtypes of ADHD, in comparison with healthy control children. A total of 100 prepubertal subjects [52 children with ADHD combined type (ADHD-C), 23 children with ADHD predominantly inattentive type (ADHD-I), and 25 healthy control subjects] were studied. The effects of stress were studied by comparing cortisol responses to a psychosocial stressor, consisting of a public speaking task. Children with ADHD-I showed an elevated cortisol response to the psychosocial stressor, in contrast to children with ADHD-C who showed a blunted cortisol response to the psychosocial stressor. When a distinction was made between responders and non-responders (a subject was classified as a responder when there was an increase in cortisol reactivity), hyperactivity symptoms were clearly related to a lower cortisol reactivity to stress. The results indicate that a low-cortisol responsivity to stress may be a neurobiological marker for children with ADHD-C, but not for those with ADHD-I. Directions for future research and clinical implications are discussed.

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Fibromyalgia is a form of non-articular rheumatism characterised by long term (>3 months) and widespread musculoskeletal aching, stiffness and pressure hyperalgesia at characteristic soft tissue sites, called soft tissue tender points. The biophysiology of fibromyalgia, however, has remained elusive and the treatment remains mainly empirical. This article reviews the neuroendocrine-immune pathophysiology of fibromyalgia. There is no major evidence that fibromyalgia is accompanied by activation of the inflammatory response system, by immune activation or by an inflammatory process. There is some evidence that fibromyalgia is accompanied by some signs of immunosuppression, suggesting that immunomodifying drugs could have potential in the treatment of fibromyalgia. Recent trials with cytokines, such as interferon-alpha, have been undertaken in patients with fibromyalgia. Immunotherapy with these agents, however, may induce symptoms reminiscent of fibromyalgia and depression in a considerable number of patients. Lowered serum activity of prolyl endopeptidase (PEP), a cytosolic endopeptidase that cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass, may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides, e.g. substance P. Trials with PEP agonists could be worthwhile in fibromyalgia. The muscle energy depletion hypothesis of fibromyalgia is supported by findings that this condition is accompanied by lowered plasma levels of branched chain amino acids (BCAAs), i.e. valine, leucine and isoleucine. Since there is evidence that BCAA supplementation decreases muscle catabolism and has ergogenic values, a supplemental trial with BCAAs in fibromyalgia appears to be justified.

Many patients who visit a centre for hereditary metabolic diseases remarkably also suffer from a child psychiatric disorder. Those child psychiatric disorders may be the first sign or manifestation of an underlying metabolic disorder. Lack of knowledge of metabolic disorders in child psychiatry may lead to diagnoses being missed. Patients therefore are also at risk for not accessing efficacious treatment and proper counselling. To search the literature for the co-occurrence of child psychiatric disorders, such as ADHD, autism, psychosis, learning disorders and eating disorders and metabolic disorders. A search of the literature was conducted by performing a broad search on PubMed, using the terms “ADHD and metabolic disorders”, “autism and metabolic disorders”, “psychosis and metabolic disorders”, “learning disorders and metabolic disorders”, and “eating disorders and metabolic disorders”. Based on inclusion criteria (concerning a clear psychiatric disorder and concerning a metabolic disorder) 4441 titles and 249 abstracts were screened and resulted in 71 relevant articles. This thorough literature search provides child and adolescent psychiatrists with an overview of metabolic disorders associated with child psychiatric symptoms, their main characteristics and recommendations for further investigations.