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Background Shift work is commonly associated with health problems resulting from circadian misalignment and sleep restriction. About one in three shift workers is affected by insomnia and up to 90% report regular fatigue and/or sleepiness at the workplace. Epidemiological data shows that shift workers are at increased risk of cardiovascular disease, diabetes, obesity, breast cancer, mental-health problems, and shift-work disorder, which conditions typically lead to reduced work performance, processing errors, accidents at work, absenteeism, and reduced quality of life. Given these widespread and debilitating consequences, there is an urgent need for treatments that help improve the sleep, health, and functional performance of the shift-working population. The most common non-pharmacological recommendations are improved scheduling, bright-light exposure, napping, psychoeducation promoting sleep hygiene, and cognitive-behavioral techniques. The objectives of the present study are to investigate the effects of a multimodal shift-work intervention on perceived fatigue, sleepiness, physical and mental health, sleep parameters, and absenteeism. Methods A randomized controlled interventional study comparing the two groups each comprising at least 80 drivers of a public transport company, using self-report questionnaires and health checks completed at intake and after 3 and 6 months following the start of the intervention or waiting-list period. The intervention consists of (a) healthy scheduling taking into account shift-rotation direction and speed, chronotype, resting time, and napping; (b) an education program specifically developed for shift workers; and (c) a dedicated information campaign for shift planners. The primary outcome is symptomatic burden in terms of sleepiness, and the key secondary outcome is symptomatic burden in terms of fatigue. Supplementary secondary outcomes are sleep parameters, absenteeism, general and clinical health, changes in mood, and anxiety. Discussion Expected outcomes are significant improvements on all primary and secondary outcome parameters in the intervention group. To our knowledge, ours is the first randomized controlled study to systematically investigate the effects of a multimodal program on multiple health, sleep, and performance parameters in shift workers. Our research also aims at providing evidence-based practice guidelines for healthy scheduling in general and thus contribute to diminishing the serious health and economic burdens associated with shift work overall. Trial registration EDGE registration number: 000339. ClinicalTrials.gov NCT05452096

Purpose Bariatric surgery candidates are frequently treated with antidepressants. Several of these drugs have been associated with weight gain and could potentially interfere with weight loss after bariatric surgery. This cohort study aimed to investigate the short-term effects of antidepressants on weight loss during the first 24 months after a Roux-en-Y gastric bypass. Methods Patients with a fully documented antidepressant treatment status for at least 12 months were retrospectively included. Weight loss was expressed as the percentage excess BMI loss (%EBMIL) or percentage total weight loss (%TWL). A mixed linear effects model was used to determine the impact of continued and discontinued treatment with antidepressants on weight loss. Results A total of 751 patients were included in this study. At 24 months, patients had lost 77.38 ± 30.10 %EBMIL (30.63 ± 13.12 %TWL). In patients treated with antidepressants (n = 125), the %EBMIL and %TWL was reduced with − 2.81% (p = 0.025) and − 1.36% (p = 0.002) respectively, and with − 5.52 %EBMIL (p

Background: To examine the association between childhood trauma and work functioning, and to elucidate to what extent this association can be accounted for by depression and/or anxiety. Methods: Data of 1,649 working participants were derived from the Netherlands Study of Depression and Anxiety (NESDA, n = 2,981). Childhood trauma (emotional neglect, psychological, physical, and sexual abuse before age 16) was assessed with a structured interview and work functioning, in terms of absenteeism and presenteeism, with the Health and Labor Questionnaire Short Form (SF-HLQ) and the World Health Organization Disability Assessment Schedule II (WHODAS-II), respectively. Depressive and/or anxiety disorders were assessed with the Composite Interview Diagnostic Instrument (CIDI). Mediation analyses were conducted. Results: At baseline, 44.8% reported to have experienced childhood trauma. Workers with the highest childhood trauma level showed significantly (p p = 0.023 and p p = 0.020 and p PM = 0.23 and PM = 0.29, respectively). No significant mediating role in this relationship was found for current anxiety disorder and remitted depressive and/or anxiety disorder. Conclusions: Persons with childhood trauma have significantly reduced work functioning in terms of absenteeism and presenteeism. This seems to be largely accounted for by current depressive disorders and current comorbid depression-anxiety.

The current article reports on perpetrator characteristics gathered in the first large-scale prevalence study on interpersonal violence against children in sport in the Netherlands and Belgium. Using retrospective web survey design, 4043 adults answered questions on their experiences in youth sport. The study looks at the number of perpetrators as well as individual descriptive characteristics (sex, age, and role in the sport organization) of perpetrators of psychological, physical and sexual violence as reported retrospectively by victim-respondents. This information was then clustered to provide an overview of the most common perpetrator profiles. Results show that in all types of interpersonal violence in sport, perpetrators are predominantly male peer athletes who frequently operate together in (impromptu) groups. Several differences between the three types of interpersonal violence are highlighted. While incidents of physical violence perpetrated by coaches tend to be less severe compared to those by other perpetrators, acts of sexual violence committed by a coach are significantly more severe. The presented findings shed new light on perpetrators of interpersonal violence in sport, nuancing the predominant belief that the male coach is the main perpetrator while providing nuanced information that can be utilized to improve prevention and child protection measures and other safeguarding initiatives in sport.

Background Although haloperidol is the most widely used drug in the treatment of delirium, evidence on the relevance of atypical antipsychotics (AAPs) is growing. Objective To review the literature on the efficacy and tolerability of AAPs in the treatment of delirium. Methods A systematic search of the literature published before April 2018 was performed on PubMed using the following search strings: “Delirium” and “Atypical antipsychotics”, “Novel antipsychotics”, “New antipsychotics”, “Quetiapine”, “Olanzapine”, “Aripiprazole”, “Risperidone”, “Paliperidone”, “Clozapine”, “Asenapine”, “Iloperidone”, “Amisulpiride”, “Ziprasidone”, “Zotepine”, “Sertindole”, “Lurasidone” or “Perospirone”. Results Twelve randomized controlled trials (RCTs) and 22 open trials were considered. Despite an overall lack of large-scale RCTs, there is some evidence supporting the efficacy of olanzapine and quetiapine in placebo controlled trials. In a recent and large RCT in elderly patients, risperidone and/or haloperidol were associated with a significantly worse outcome than placebo. While preliminary, the current comparative studies suggest that haloperidol and the AAPs olanzapine, quetiapine and risperidone are similarly effective, although treatment with AAPs is associated with a reduced incidence of extrapyramidal symptoms. Ziprasidone was not shown to be effective. No RCTs are available for other AAPs. Conclusions Although the current evidence of the efficacy and tolerability of AAPs in the treatment of delirium is limited and the heterogeneity of the data precluded a meta-analysis, olanzapine and quetiapine seem to be adequate alternatives to haloperidol, especially in patients who are vulnerable for extrapyramidal symptoms, who require sedation or who have a history of haloperidol intolerance. Evidently, larger-scale RCTs are urgently required.

Objective: The diagnoses of solvent-induced chronic toxic encephalopathy (CSE) can be supported by neuropsychological tests. However, since results not only reflect cognitive functioning but also the patients effort to perform well, this study examines to what extent underperformance impacts neuropsychological outcomes in individuals referred for suspected CSE. Methods: A retrospective study of 48 suspected CSE patients having completed ten neuropsychological tests assessing different domains of cognition. Underperformance was identified using the Amsterdam Short-Term Memory Test and the Rey 15-item Memory Test (FIT). Multiple linear regression was applied to examine the effect of insufficient effort on test performance. Results: A total of 54.1% of the patients were identified as having underperformed on one or both performance validity tests. Analyses showed a significant effect of underperformance on most tests barring letter-number sequencing. Conclusions: Most of the neuropsychological tests evaluated showed significant effects of underperformance. Performance on letter-number sequencing was not affected. In case of underperformance, the results of the neuropsychological assessment should be disregarded when weighing the final multi-disciplinary diagnosis, with the exception of letter-number sequencing.

In a recent large-scale prevalence study of interpersonal violence (IV) against child athletes in the Netherlands and Belgium we found that 9% of adult respondents who participated in organized sports before the age of 18 had experienced severe psychological violence, 8% severe physical violence, and 6% severe sexual violence in various sport settings. While the general literature has repeatedly shown that exposure to IV during childhood is associated with mental health problems in adulthood and to a lesser extent with reduced quality of life (QOL), these relationships have not been demonstrated in (former) athletes. Thus, the current study aims to assess the association of severe childhood IV in sport and adult wellbeing. Depression, anxiety, and somatization were assessed in the same general population sample (N = 4043) using the Brief Symptom Inventory (BSI-18) and QOL with the World Health Organization Quality of Life questionnaire (WHOQOL-Bref). The association between severe IV in sport and adult wellbeing was investigated using multiple linear regression while controlling for demographics, recent life events, and relatives’ psychological problems. We found severe sexual, physical, and psychological childhood IV in sport to be associated with more adult psychological distress and reduced QOL. Polyvictimization shows the strongest correlation with poorer wellbeing and QOL. Recent life events, relatives’ psychological problems, marital status, and level of education were significant covariates in the psychological symptoms and QOL assessed. We hope that these new insights prompt sport administrators to implement broad spectrum child protection measures and raise the awareness of mental health professionals about the necessity to also screen for adverse childhood experiences in the sport context.

Quetiapine, an atypical antipsychotic drug, is recommended for the treatment of schizophrenia and mood disorders. In addition, given its sedative effects, a low dose of the agent is also widely used in the treatment of anxiety disorders, personality disorders, substance abuse, and sleep disturbances. In this case study, quetiapine was the first effective drug in reducing chronic insomnia in a male patient with a long treatment history. Because its effect declined over time, in the course of two years, a gradual dose increase led to a posology 50 times higher than the off-label dosage used to obtain sedation, i.e. 25100 mg quetiapine administered once daily. This case raises awareness of the ease with which dose escalation of quetiapine occurs. The risk of side effects and, possibly, dependence and abuse underlines the importance of regular and careful patient monitoring. Given the unexpected effectiveness of the agent and the absence of side effects in the described case, we argue that in treatment-resistant insomnia, a high dose of quetiapine may be justifiable in selected cases but also urge that further research on the long-term effects and potential adverse events of quetiapine for this indication is of the utmost importance.

Background It is not yet clear whether chronic fatigue syndrome (CFS) is associated with elevated levels of personality disorders. Purpose This study aims to determine the prevalence of DSM-IV axis II personality disorders among patients with CFS. Methods We examined the prevalence of personality disorders in a sample of 92 female CFS patients and in two well-matched control groups, i.e., normal community individuals (N = 92) and psychiatric patients (N = 92). Participants completed the assessment of DSM-IV personality disorders questionnaire (ADP-IV), which yields a categorical and dimensional evaluation of personality disorder features. Results The prevalence of personality disorders in CFS patients (16.3 %) was significantly lower than in psychiatric patients (58.7 %) and was similar to that in the community sample (16.3 %). Similar results were found for dimensional and pseudodimensional scores, except for the Depressive (DE) and ObsessiveCompulsive Personality Disorder (O-C) subscales. Patients with CFS had significantly higher levels of DE features compared to normal controls and similar dimensional scores on the O-C scale compared to psychiatric controls. Conclusions Although the CFS sample was characterized by depressive and obsessivecompulsive personality features, this study provides no evidence for the assumption that these patients generally show a higher prevalence of axis II pathology. Given the conflicting findings in this area, future studies using multiple measures to assess personality disorders in CFS are needed to substantiate these findings.

Most research points to cognitive slowing in chronic fatigue syndrome (CFS), although there have been negative reports. The present study is one of few that examines fine motor processing and the inhibition of automatic responses in a well-characterised CFS population. A total of 35 female CFS patients without current major depression and 25 female controls performed two computerised figure-copying tasks. The cognitive and fine motor processing of visualspatial information was measured by recording reaction time (RT) and movement time (MT), respectively. The inhibition of automatic responses was assessed by introducing conflicting patterns (i.e., patterns that were difficult to draw from the preferred left to right). A multivariate general linear model was adopted for the statistical analysis of the movement recordings. As a result, CFS was significantly associated with longer RT and MT in the pooled and in the task-specific analyses. However, there was no interaction between disease status and conflicting character of the patterns. In conclusion, these performance data on the figure-copying tasks provide confirmatory evidence for psychomotor slowing in CFS, but not for a disturbed inhibition of automatic responses. Computerised figure-copying tasks may be promising tools for use in neurobiological research and clinical trials in CFS.

The etiopathogenesis of chronic fatigue syndrome (CFS) remains poorly understood. Although neuroendocrine disturbances and hypothalamicpituitaryadrenal (HPA) axis hypofunction in particular have been found in a large proportion of CFS patients, it is not clear whether these disturbances are cause or consequence of the illness. After a review of the available evidence we hypothesize that that HPA axis hypofunction in CFS, conceptualized within a system-biological perspective, primarily reflects a fundamental and persistent dysregulation of the neurobiological stress system. As a result, a disturbed balance between glucocorticoid and inflammatory signaling pathways may give rise to a pathological cytokine-induced sickness response that may be the final common pathway underlying central CFS symptoms, i.e. effort/stress intolerance and pain hypersensitivity. This comprehensive hypothesis on HPA axis hypofunction in CFS may stimulate diagnostic refinement of the illness, inform treatment approaches and suggest directions for future research, particularly focusing on the neuroendocrineimmune interface and possible links between CFS, early and recent life stress, and depression.

The current article reports on the first large-scale prevalence study on interpersonal violence against children in sport in the Netherlands and Belgium. Using a dedicated online questionnaire, over 4,000 adults prescreened on having participated in organized sport before the age of 18 were surveyed with respect to their experiences with childhood psychological, physical, and sexual violence while playing sports. Being the first of its kind in the Netherlands and Belgium, our study has a sufficiently large sample taken from the general population, with a balanced gender ratio and wide variety in socio-demographic characteristics. The survey showed that 38% of all respondents reported experiences with psychological violence, 11% with physical violence, and 14% with sexual violence. Ethnic minority, lesbian/gay/bisexual (LGB) and disabled athletes, and those competing at the international level report significantly more experiences of interpersonal violence in sport. The results are consistent with rates obtained outside sport, underscoring the need for more research on interventions and systematic follow-ups, to minimize these negative experiences in youth sport.

Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma.Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses.Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients.We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.

Studies on the impact of childhood trauma on postpartum depression show inconsistencies and methodological limitations. The present study examines the effect of childhood trauma on depression 12 and 24 weeks after childbirth, while controlling for history of depression, depression symptoms during pregnancy and type D personality. During the third trimester of pregnancy, 210 women completed self-report questionnaires assessing depression (current and/or past episodes), childhood trauma and type D personality, of whom 187 participated in the postpartum follow-up, with depression symptoms being reassessed at 12 and 24 weeks after delivery with three depression outcome measures. Eventually, 183 participants were retained for analysis. Results indicated no predictive value of childhood trauma on postpartum depression in the univariate analyses, nor after controlling for previous depression, depression symptoms during pregnancy and type D personality. However, past depression and depression symptoms during pregnancy did independently and convincingly predict postpartum depression, especially at 12 weeks and to a lesser extent at 24 weeks following childbirth. Overall, we found no significant association between childhood trauma and postpartum depression. Past depression and depression symptoms during pregnancy are more relevant factors to assess before childbirth.

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=0.02) and genotype (p=0.02) association with an SNP in the promoter region (NR3C1-1); in the Swedish sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with the R23K SNP. The haplotype association studies showed modest evidence for an involvement of the 5' region of the NR3C1 gene in the genetic vulnerability for MDD. This study suggests that polymorphisms in the 5' region of the NR3C1 gene may play a role in the genetic vulnerability for MDD.

The clinical presentation of panic disorder (PD) is known to be highly heterogeneous, complicating research on its etiology, neurobiological pathways, and treatment. None of the attempts to identify PD subtypes have been independently reproduced, rendering the current literature inconclusive.Using a data-driven, case-centered approach (factor mixture modeling) on a broad range of anxiety symptoms assessed with the Beck anxiety inventory, the present study identifies PD disorder subtypes in a large (n = 658), well-documented mixed-population sample from the Netherlands Study of Depression and Anxiety (NESDA), with subtypes being validated and detailed using a variety of clinical characteristics.A three-class, one-factor model proved superior to all other possible models (Bayesian information criterion = 13,200; Lo-Mendel-Rubin = 0.0295; bootstrapped likelihood ratio test ≤ 0.0001), with the first class, a cognitive-autonomic subtype, accounting for 29.8%, the second class, the autonomic subtype, for 29.9%, and a third class, the aspecific subtype, for 40.3% of the population. The cognitive-autonomic and autonomic subtypes showed significant differences compared to the aspecific subtype (e.g., comorbidity and suicide attempts) but on severity differed between themselves only.Three qualitatively different PD subtypes were identified: a severe cognitive-autonomic subtype, a moderate autonomic subtype, and a mild aspecific subtype. Qualitative and quantitative differences were related to severity and clinical properties such as comorbidity, suicide attempts, sleep, and sense of mastery.

Background Antidepressant-induced hyponatremia can cause significant morbidity and mortality. It is mostly associated with the use of selective serotonin reuptake inhibitors (SSRIs), but its frequency and class specificity are uncertain. Objectives To determine the relationship between hyponatremia and antidepressants and to define the incidence and odds ratios for antidepressant classes. Methods A review of the literature prior to March 2013 was performed using Web of Science and PubMed by employing combinations of search strings “antidepressants” and antidepressant class and generic drug names with “hyponatr(a)emia,” “SIADH,” or “inappropriate ADH.” Results Overall, 21 effect studies and more than 100 case reports were considered, most concerning SSRIs. Because of variations in study designs, populations, and cutoff values, incidence rates diverged between 0.06% and 40% for SSRIs and 0.08% and 70% for venlafaxine. Although based on less solid evidence, incidence figures for mirtazapine and tricyclic antidepressants were lower. Regarding classes, odds ratios for SSRIs (1.5–21.6) were consistently higher than for tricyclic antidepressants (TCAs) (1.1–4.9). The risks associated with monoamine oxidase inhibitors, reboxetine, and bupropion could not be established owing to insufficient information. Patient risk factors included older age (odds ratios = 6.3) and concomitant use of (thiazide) diuretics (odds ratios = 11.2–13.5). Conclusion Hyponatremia is a potentially dangerous side effect of antidepressants and is not exclusive to SSRIs. Current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine, especially when combined with patient risk factors, warranting clinicians to be aware of this complication. The risks associated with mirtazapine are moderate, supporting this antidepressant as an alternative treatment for patients with (an increased risk of) hyponatremia.

Objective. Maladaptive response styles to negative affect have been shown to be associated with prospective (postpartum) depression. Whether maladaptive styles to positive affect are also critically involved is understudied, even though anhedonia (a correlate of low positive affectivity) is a cardinal symptom of depression. The present study is the first to investigate the predictive value of cognitive response styles to both negative (depressive rumination) and positive affect (dampening) for postpartum depressive symptoms. Methods. During the third trimester of pregnancy, 210 women completed self-report instruments assessing depression (symptom severity and current and/or past episodes) and scales gauging the presence of depressive rumination and dampening. Of these women, 187 were retained for postpartum follow-up, with depressive symptoms being reassessed at 12 (n = 171) and 24 (n = 176) weeks after delivery. Results. Regression analyses showed that higher levels of dampening of positive affect during pregnancy predicted higher levels of depressive symptoms at 12 and 24 weeks postpartum, irrespective of initial symptom severity, past history of depression and levels of rumination to negative affect. Prepartum trait levels of rumination, however, did not predict postpartum symptomatology when controlled for baseline symptoms and history of major depressive episode(s). Conclusions. The results of this investigation suggest that the way women cognitively respond to positive affect contributes perhaps even more to the development of postpartum depression than maladaptive response styles to negative affect. publisher: Elsevier articletitle: Turning the pink cloud grey: Dampening of positive affect predicts postpartum depressive symptoms journaltitle: Journal of Psychosomatic Research articlelink: http://dx.doi.org/10.1016/j.jpsychores.2014.04.003 content_type: article copyright: Copyright © 2014 Elsevier Inc. All rights reserved. ispartof: Journal of Psychosomatic Research vol:77 issue:1 pages:64-69 ispartof: location:England status: published

Objective. Although the remission criteria for generalized anxiety are well defined, there is not much data available on the point prevalence of remission. The Measuring Impact of Remission in Anxiety Disorders in Belgium (MIRABEL) study is a naturalistic study designed to document the point prevalence of remission in patients treated for general anxiety and potential factors affecting this prevalence. Methods. The study population consisted of 618 adult outpatients being treated for generalized anxiety. The sample is defined by the key symptoms of generalized anxiety disorder rather than by fulfilling the exact DSM-IV-TR diagnostic criteria. Remission was defined as a Hamilton Anxiety Scale (HAM-A) score of less than or equal to 7. To reduce the interrater reliability, the HAM-A was assessed by the attending physicians who had no specific training. Factors investigated as possibly related to remission included sociodemographic, disease and treatment characteristics. Results. The point prevalence of remission in the study population was estimated at 13.3%. Remission prevalence varied with occupational status and severity of the current anxiety episode. Remission prevalence was lower in the presence of comorbidity and was proportional to the number of comorbid symptoms. Remitters took fewer medications but were treated longer. Remission prevalence was higher in patients who were taking antidepressants, but was lower in patients who were taking sedatives. Conclusions. These findings underline the poor prognosis of generalized anxiety.

We have read the important article on the premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort[1][1] with a lot of interest. The authors reported that parental physical abuse, childhood gastrointestinal symptoms and parental reports of many colds were independently

INTRODUCTION: In the following article CAPRI presents its current research projects. SUBJECTS AND METHOD: The team leaders were asked to present and summarize the project they had been working on. The fields in which research was conducted are: Child and Adolescent Psychiatry, Cognitive and Psychomotor Dysfunctions in Schizophrenia, fMRI in Schizophrenia, Cognitive and Psychomotor Dysfunctions in Major Depressive Disorder, Chronic Fatigue Syndrome, Addiction Medicine and Forensic Psychiatry. RESULTS: An overview of recent and ongoing research projects is provided and the main results are summarized.

Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between polymorphisms in CRF-BP gene and bipolar disorder in an isolated Swedish population. One hundred and eighty-two patients with bipolar I disorder and 333 controls from Northern Sweden were included in the study. Five single nucleotide polymorphisms and a deletion polymorphism in the CRF-BP gene were genotyped. The haplotype block structure of the gene was considered and the expectation maximization algorithm was adopted to estimate the haplotype frequencies. As a result, there were no significant associations of the different polymorphisms in the CRF-BP gene with bipolar disorder. In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder.

There is evidence for a hypofunction of the hypothalamic-pituitary-adrenal (HPA) axis in a proportion of the patients with chronic fatigue syndrome (CFS), despite the negative studies and methodological difficulties. In this review, we focus on challenge studies and on the role of the HPA axis in the pathogenesis of CFS. Mild hypocortisolism, blunted adrenocorticotropin response to stressors and enhanced negative feedback sensitivity to glucocorticoids are the main findings. Several underlying mechanisms have been proposed. Currently, it is a matter of debate whether these disturbances have a primary role in the pathogenesis of CFS. However, even if the HPA axis dysfunctions are secondary to other factors, they are probably a relevant factor in symptom propagation in CFS.

We have read the article by Neigh and Nemeroff with a lot of interest [1xReduced glucocorticoid receptors: consequence or cause of depression?. Neigh, G.N. and Nemeroff, C.B. Trends Endocrinol. Metab. 2006; 17: 124–125Abstract | Full Text | Full Text PDF | PubMed | Scopus (33)See all References[1]. The authors discussed the study by Ridder et al. [2xMice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. Ridder, S. et al. J. Neurosci. 2005; 25: 6243–6250Crossref | PubMed | Scopus (239)See all References[2] as a starting point to review the current status of the glucocorticoid receptor (GR) hypothesis of major depressive disorder (MDD). In their excellent paper, they argue that GR dysfunction might not be the primary source of the hypothalamic–pituitary–adrenal (HPA) axis dysfunction in MDD. Although we agree that several molecular mechanisms might lead to HPA axis dysfunction, we would like to draw the attention to some recent genetic studies in humans. Concerning the causal involvement of the GR in the pathogenesis of MDD, it is important to mention two studies that have been published very recently [3xGlucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression. van West, D. et al. Neuropsychopharmacology. 2006; 31: 620–627Crossref | PubMed | Scopus (107)See all References, 4xPolymorphisms of the glucocorticoid receptor gene and major depression. van Rossum, E.F. et al. Biol. Psychiatry. 2006; 59: 681–688Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References]. Both studies are related to the ground breaking work by van Rossum et al. that was reviewed previously in Trends in Endocrinology and Metabolism [5xGenetic polymorphisms and multifactorial diseases: facts and fallacies revealed by the glucocorticoid receptor gene. van Rossum, E.F. et al. Trends Endocrinol. Metab. 2005; 16: 445–450Abstract | Full Text | Full Text PDF | PubMed | Scopus (37)See all References[5].Our research group examined whether genetic variations in the GR-encoding gene (NR3C1, gene ID 2908) were associated with MDD, using a gene-based association analysis of single nucleotide polymorphisms (SNPs) [3xGlucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression. van West, D. et al. Neuropsychopharmacology. 2006; 31: 620–627Crossref | PubMed | Scopus (107)See all References[3]. In a Belgian sample, we observed a significant association of MDD with a SNP in the promoter region (NR3C1–1, rs10482605). In a Swedish sample, there was a significant association between MDD and SNP R23K (rs6190). The two SNPs were located close to each other in the 5′ region of the gene. Interestingly, SNP R23K was shown to be associated with resistance to glucocorticoids [6xA polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. van Rossum, E.F. et al. Diabetes. 2002; 51: 3128–3134Crossref | PubMedSee all References[6], a major feature in MDD [7xThe corticosteroid receptor hypothesis of depression. Holsboer, F. Neuropsychopharmacology. 2000; 23: 477–501Crossref | PubMed | Scopus (1358)See all References, 8xGlucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Pariante, C.M. and Miller, A.H. Biol. Psychiatry. 2001; 49: 391–404Abstract | Full Text | Full Text PDF | PubMed | Scopus (667)See all References]. The proposed underlying molecular mechanism of the GR resistance caused by the R23K polymorphism is a change in balance between two translocational variants of the GR proteins (GR-A and GR-B). More precisely, R23K leads to a reduced production of the transcriptionally more active GR-B and to an increased production of the less active GR-A [9xIncreased expression of the glucocorticoid receptor-A translational isoform as a result of the ER22/23EK polymorphism. Russcher, H. et al. Mol. Endocrinol. 2005; 19: 1687–1696Crossref | PubMed | Scopus (69)See all References[9].Almost simultaneously, van Rossum et al. [4xPolymorphisms of the glucocorticoid receptor gene and major depression. van Rossum, E.F. et al. Biol. Psychiatry. 2006; 59: 681–688Abstract | Full Text | Full Text PDF | PubMed | Scopus (223)See all References[4] reported a significant association between the R23K SNP and MDD in a German population. In this study, patients who were heterozygote for the R23K SNP responded more quickly to antidepressant treatment. The authors also observed an association of MDD with BclI, a restriction length polymorphism associated with hypersensitivity to glucocorticoids. The latter finding does not match with the GR hypothesis for MDD, although the authors emphasized the tissue-specific effects of BclI. More specifically, they suggested that increased GR activation in the limbic system might also contribute to the development of MDD. Clearly, this issue requires further investigation.Taken together, these two studies on the association between polymorphisms in the GR-encoding gene and MDD provide further evidence for a role of the GR receptor in the vulnerability for MDD. It seems likely that, at least in a proportion of MDD patients, GR dysfunction is the primary source of HPA axis abnormalities.

Contains fulltext : 56819.pdf (Publisher’s version ) (Closed access) Background Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is a prominent neurobiological finding during a major depressive episode, reflecting a state dependent factor. An issue under investigation is whether the dysfunction of the HPA axis has also a role to play as a state-independent or trait factor for major depressive disorder (MDD). In relation to this, it is important to examine HPA axis function in patients who are clinically remitted from depression. Methods Twenty-three remitted outpatients with recurrent MDD and 23 age- and gender-matched control individuals without a history of MDD participated in the sensitive combined dexamethasone/corticotropin-releasing factor (DEX/CRF) test. Results Free salivary cortisol responses were not significantly different between the two groups, although three patients (13%) displayed extremely elevated cortisol responses after CRF. Limitations Limited sample size. All but one patient were under treatment with an antidepressant. Conclusions This study shows no evidence for a disturbed DEX/CRF test as a state-independent factor in recurrent MDD on a group level. However, MDD is a complex and heterogenic disorder. Probably, there is a subgroup of patients who show a disturbed DEX/CRF test due to an inherited and/or acquired predisposition or as a biological scar after previous depressive episodes. 5 p.

Major depressive disorder (MDD) is characterized by a dysregulation of the stress response system. A corticotropin-releasing factor (CRF) hyperdrive is a consistent and well-documented finding. CRF-binding protein (CRF-BP) may play a role in the pathogenesis of MDD. CRF-BP reduces the availability of CRF by binding free CRF and inhibits CRF function at the pituitary level. Moreover, CRF-BP expression increases in the pituitary and amygdala in response to acute stress, providing an additional feedback mechanism to maintain the homeostasis of the stress response. There are different regulatory elements of the expression of CRF-BP gene that are implicated in the pathophysiology of MDD, including CRF, glucocorticoids, cytokines and estrogens. A specific haplotype within the CRF-BP gene has been associated with MDD, but confirmation of this finding is necessary. Currently, the possible role of CRF-BP in the pathophysiology of conditions that have been associated with a hypofunction of the CRF system and immune dysfunctions is unclear. Implications of the function of CRF-BP for therapeutic strategies in MDD are being discussed. An important advantage of ligands that target CRF-BP is that concentrations of free CRF can be altered without acting directly on the transmission of CRF through its receptor.

PurposeEvidence indicates that classical antipsychotics may aggravate non-malignant and malignant catatonia (MC). Atypical antipsychotics are less likely to cause movement disorders than classical antipsychotics and they are being frequently prescribed in disorders that can be associated with catatonia. Therefore, the important question that arises is whether atypical antipsychotics have a role to play in the treatment of catatonia.Materials and methodsA Medline search was performed to locate papers on the use of atypical antipsychotics in catatonia published between 1970 and 31st December 2004.ResultsThe literature on the use of atypical antipsychotics in catatonia consists of case reports and retrospective studies. In most cases of non-MC a reduction of the catatonic symptoms is reported upon treatment with atypical antipsychotics. Cases of MC relate mainly to the neuroleptic malignant syndrome (NMS), which is considered as an iatrogenic stuporous variant of MC caused by antipsychotics.ConclusionThere are indications that atypical antipsychotics may be useful in non-MC. As a consequence, one should not only focus on the possible extrapyramidal and autonomic side effects of these drugs, but also on the possible beneficial effects on certain brain functions and on the catatonic symptomatology. However, randomized controlled trials are needed to evaluate the effect of these drugs, and caution is advisable, since cases of NMS have been linked to treatment with atypical antipsychotics. There is no evidence to prescribe atypical antipsychotics in MC.

BackgroundDissociative disorders encompass a range of symptoms varying from severe absent-mindedness and memory problems to confusion about one's own identity. Recent studies suggest that these symptoms may be the by-products of a labile sleep-wake cycle.MethodsIn the current study, we explored this issue in patients suffering from insomnia (N = 46). We investigated whether these patients have raised levels of dissociative symptoms and whether these are related to objective sleep parameters. Patients stayed for at least one night in a specialized sleep clinic, while sleep EEG data were obtained. In addition, they completed self-report measures on dissociative symptoms, psychological problems, and sleep characteristics.ResultsDissociative symptom levels were elevated in patients suffering from insomnia, and were correlated with unusual sleep experiences and poor sleep quality. Longer REM sleep periods and less time spent awake during the night were predictive of dissociation.ConclusionsThis is the first study to show that insomnia patients have raised dissociative symptom levels and that their dissociative symptoms are related to objective EEG parameters. These findings are important because they may inspire sleep-related treatment methods for dissociative disorders.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe and prolonged fatigue, along with a set of nonspecific symptoms and signs, such as sore throat, muscle pain, headaches, and difficulties with concentration or memory. OBJECTIVE: The study examined whether CFS is associated with specific dimensions of Cloningers psychobiological model of personality. METHOD: Personality profiles were compared between 38 CFS patients and 42 control subjects by means of the Temperament and Character Inventory (TCI). RESULTS: The CFS group showed significantly higher scores on Harm-Avoidance and Persistence. CONCLUSION: The current study shows a significant association between specific personality characteristics and CFS. These personality traits may be implicated in the onset and/or perpetuation of CFS and may be a productive focus for psychotherapy.