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Objective Tinnitus can be regarded as a chronic stressor, leading to dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. There is important comorbidity with anxiety, particularly panic, potentially associated with differences in HPA axis functioning and methylation patterns of HPA axis-related genes. This study examines DNA methylation of the glucocorticoid receptor gene (NR3C1) exon 1F in adults with chronic subjective tinnitus and the possible differential effect of panic. Methods In a well characterized tinnitus sample (n = 22, half of which had co-occurring panic attacks), and unaffected controls (n = 31) methylation patterns of the CpG sites were determined using pyrosequencing and compared between groups through linear mixed models. Gene expression was determined using quantitative PCR on mRNA. Results Comparing the combined tinnitus groups to the control group, no DNA methylation differences were observed; however, the tinnitus group with panic attacks showed consistently higher mean methylation values across all CpGs compared to the tinnitus-only and the control group (P = 0.03 following Tukey correction), which became even more pronounced when accounting for childhood trauma (P = 0.012). Moreover, a significant positive correlation was found between methylation of the CpG7 site and the Beck Anxiety Inventory total score (P = 0.001) in the total population. NR3C1-1F expression was not significantly different between the three groups. Conclusion Panic is associated with higher DNA methylation of the NR3C1 exon 1F in adults with chronic subjective tinnitus, consistent with the reduced negative glucocorticoid feedback and HPA axis hyperfunction observed in individuals with panic disorder.

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: One out of seven individuals who have suffered a traumatic brain injury (TBI) develops a posttraumatic stress disorder (PTSD), which is often associated with neurocognitive impairment. The present study explores the impact of neurocognitive functioning after mild, moderate, and severe TBI on the course of PTSD symptoms. Methods: The data of 671 adults admitted to hospital for a TBI was drawn from the Collaborative European Neurotrauma Effectiveness Research (CENTER-TBI) study. After six- and 12-months post-injury, participants completed the PTSD Checklist-5 (PCL-5), from which change scores were calculated. At six months, participants also completed a neurocognitive assessment including the Rey Auditory Verbal Learning Test, the Trail Making Test, and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regressions were performed to identify associations between cognitive functioning and PCL-5 change scores. Results: Overall, mean PCL-5 change scores showed no clear change (−0.20 ± 9.88), but 87 improved and 80 deteriorated by a change score of 10 or more. CANTAB Rapid Visual Information Processing scores were significantly associated with PCL-5 change scores. Conclusions: Strong sustained attention was associated with improvement in PTSD symptoms. Assessing cognitive performance may help identify individuals at risk of developing (persisting) PTSD post-TBI and offer opportunities for informing treatment strategies.

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.

The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of childhood trauma. In a single-blind randomized placebo-controlled crossover study, 21 women with remitted recurrent MDD and 18 healthy controls were exposed to psychosocial stress (Trier social stress test) or inflammatory stress (typhoid vaccine), or both, to investigate the effects of childhood trauma on the neuroendocrine and inflammatory responses. Childhood trauma was assessed using the Childhood Trauma Questionnaire and participants were dichotomized into a traumatized and non-traumatized group. Serum adrenocorticotropic hormone (ACTH), cortisol, interferon (IFN)-&gamma, tumor necrosis factor (TNF)-&alpha, and interleukin (IL)-6 were measured at regular intervals after each intervention. The effects of trauma, time, and intervention on these parameters were modeled by fitting linear mixed models. Childhood trauma in itself did not have a main effect on the outcome measurements. However, an interactional effect of trauma with stressor type was found in the remitted MDD group: trauma was associated with higher cortisol levels only after adding immunological to psychosocial stress, and with lower TNF-&alpha, levels in response to vaccination. This suggests the existence of a vulnerable trauma-associated MDD endophenotype.

Background 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. Methods 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. Results 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. Conclusion 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.

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.

Profiling sexual offenders in sport based on a victim survey Based on the reports of 578 Flemish and Dutch athletes, the current article reports on perpetrator characteristics of childhood sexual violence in sport. Using retrospective web survey design, information was gathered about the number as well as individual descriptive characteristics (sex, age, and role in the sport organization) of sexual perpetrators as retrospectively reported by the victim-respondents. This information was then clustered to provide an overview of the most common perpetrator profiles. Perpetrators are predominantly male peer athletes or other known persons in the sport organization, and not the coach. However, acts of sexual violence committed by a coach are significantly more severe than those committed by peer athletes. The presented findings shed new light on sexual offenders in sport, nuancing the predominant belief that the male coach as the main perpetrator while providing nuanced information that can be utilized to improve child protection and safeguarding initiatives in sport.

Uit een recent grootschalig onderzoek naar grensoverschrijdend gedrag ten aanzien van kinderen in de sport in Vlaanderen en Nederland bleek dat 9% van de volwassenen ervaringen rapporteerde met ernstig psychisch geweld, 8% met ernstig fysiek geweld en 6% met ernstig seksueel geweld in de sport [1]. De negatieve impact van jeugdtrauma op tal van psychische en fysieke problemen in de volwassenheid werd reeds herhaaldelijk aangetoond, echter nog niet eerder binnen de sport. Deze studie onderzocht het verband tussen geweldservaringen in de jeugdsport en het mentale welzijn en de levenskwaliteit in de volwassenheid in een steekproef van 4043 Vlamingen en Nederlanders. De geweldservaringen werden gerapporteerd aan de hand van de Grensoverschrijdend gedrag ten aanzien van kinderen in de sport vragenlijst die voor deze prevalentiestudie ontwikkeld werd. Psychische klachten in de volwassenheid werden gemeten aan de hand van de Brief Symptom Inventory-18, een screeningsinstrument voor psychopathologie en levenskwaliteit werd bevraagd aan de hand van de WHOQOL-Bref, de levenskwaliteit vragenlijst van de Wereld Gezondheidsorganisatie. Het verband tussen ernstige geweldservaringen in de jeugdsport en welzijn in de volwassenheid werd aan de hand van multipele lineaire regressies gemeten, rekening houdend met beïnvloedende factoren zoals demografie, recente stressvolle gebeurtenissen en familiale voorgeschiedenis met psychische problemen. We vonden een negatief verband tussen seksueel, fysiek en psychisch geweld en mentale gezondheid en levenskwaliteit. Ervaringen met meerdere types van ernstig geweld in de jeugdsport leidde tot meer psychische klachten en een sterkere afname van de levenskwaliteit. Deze nieuwe inzichten kunnen beleidsmakers in de sport aanzetten om sterker in te zetten op de preventie van grensoverschrijdend gedrag in de sport en versterken de noodzaak bij professionals in de gezondheidszorg om ook te screening op jeugdtrauma in de sportcontext.

Following a high-profile case of child sexual abuse in sport in 1996, the Netherlands Olympic Committee and the Netherlands Sports Confederation (NOC*NSF) established a telephone ‘helpline’ service on sexual harassment and abuse (SHA). In order to expand their understanding of this problem, NOC*NSF maintained written records of incidents reported to the helpline. These records revealed 323 separate incidents for the period 2001 to 2010. This paper presents a descriptive analysis of this data and discusses the findings. We conclude that whilst there are major limitations to working with information gathered in this way, a sustainable telephone ‘helpline’ can provide a valuable service for the sports community. Whilst official sources of data are known to under represent the scale of sexual abuse, through collaboration with researchers, such services can also generate important information for policymakers.

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.

Over the past decade, the international agenda on the prevention of child sexual harassment and abuse in sport has been strengthened by a number of general policy recommendations. Despite a growing body of literature and research about sexual harassment and abuse in sport, there is hardly any evidence-based policy and preven- tion research to guide the policy implementation process. By using the Flemish sport 15 system as its empirical focus, this article investigates the feasibility of the so-called Flag System to translate policy into practice. The Flag System is a didactic tool created to assist sport stakeholders in the assessment of sexual behaviour involving children. It is in the process of being implemented in Flanders, and preliminary findings suggest a high level of feasibility at all levels of organized sports. Demonstrating that a number 20 of inhibiting forces have effectively been reduced in Flanders, the current analysis of the process of planned change suggests that the Flag System has potential in bridging the gap between policy and practice and may also be suitable for implementation in other Western countries.

Recent prevalentieonderzoek bij een steekproef van 4.000 Nederlandse en Vlaamse volwassenen toont aan dat 1 op de 7 volwassenen die in kindertijd of jeugd sportten, op zn minst eenmalig seksueel grensoverschrijdend gedrag heeft ervaren in de sport. Sinds 2012 maakt de Vlaamse sportwereld werk van de preventie van seksueel grensoverschrijdend gedrag in de sport. Dit artikel beschrijft een stand van zaken van het preventiebeleid en licht een veelbelovend instrument Sport met grenzen toe. De auteurs doen tevens een oproep aan de sportarts om een actieve rol op te nemen bij het ontwikkelen, installeren en uitdragen van een preventief en curatief beleid in de sportvereniging.

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.

ResumenPropósitoLos datos indican que los antipsicóticos clásicos pueden agravar la catatonía no maligna (CNM) y la catatonía maligna (CM). Los antipsicóticos atípicos tienen menos posibilidades de causar trastornos del movimiento que los antipsicóticos clásicos, y se prescriben con frecuencia en los trastornos que se pueden asociar con la catatonía. Por tanto, la pregunta importante que se plantea es si los antipsicóticos atípicos tienen un papel que desempeñar en el tratamiento de la catatonía.Materiales y métodosSe realizó una búsqueda en Medline para localizar artículos sobre el uso de antipsicóticos atípicos en la catatonia publicados entre 1970 y el 31 de diciembre de 2004.ResultadosLas publicaciones sobre el uso de antipsicóticos atipicos en la catatonía consisten en informes clínicos y estudios retrospectivos. En la mayoría de los casos de CNM se informa de una reducción de los síntomas catatónicos con el tratamiento con antipsicóticos atípicos. Los casos de CM se relacionan sobre todo con el síndrome neuroléptico maligno (SNM), que se considera como una variante estuporosa yatrógena de CM causada por los antipsicóticos.ConclusiónHay indicaciones de que los antipsicóticos atípicos pueden ser útiles en la CNM. Como consecuencia, deberíamos centramos no sólo en los posibles efectos secundarios extrapiramidales y neurovegetativos de estos farmacos, sino también en los posibles efectos beneficiosos en ciertas funciones cerebrales y en los síntomas catatónicos. Sin embargo, se necesitan ensayos controlados distribuidos al azar para evaluar el efecto de estos medicamentos, y la prudencia es aconsejable, ya que se ha asociado casos de SNM con el tratamiento con antipsicóticos atípicos. No hay datos para prescribir antipsicóticos atípicos en la CM.

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.

Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is a core neurobiological feature of major depression. The responsible mechanisms are unclear. Hyperactivity is arguably a causal factor of depression, and not an epiphenomenon. It can be that the antidepressants used in clinical practice are efficacious through their effect on the HPA axis. Several drugs directly targeting the HPA axis are in development, but currently none of these has shown satisfactory efficacy and tolerability in large-scale trials.

Background: 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 identifyPD subtypes have been independently reproduced, rendering the current literature inconclusive. Methods: 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), welldocumented mixed-population sample from the Netherlands Study of Depression and Anxiety (NESDA), with subtypes being validated and detailed using a variety of clinical characteristics. Results: 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. Conclusion: 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.

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.