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Background Physiological changes are induced by immersion, swimming and using diving equipment. Divers must be fit to dive. Using medication may impact the capacity to adapt to hyperbaric conditions. The aim of this systematic review is to assess the interaction of diving/hyperbaric conditions and medication and to provide basic heuristics to support decision making regarding fitness to dive in medicated divers. Methods This was a systematic review of human and animal studies of medications in the hyperbaric environment. Studies were subdivided into those describing a medication/hyperbaric environment interaction and those concerned with prevention of diving disorders. Studies without a relation to diving with compressed air, and those concerning oxygen toxicity, hyperbaric oxygen therapy or the treatment of decompression sickness were excluded. Results Forty-four studies matched the inclusion criteria. Animal studies revealed that diazepam and valproate gave limited protection against the onset of the high-pressure neurological syndrome. Lithium had a protective effect against nitrogen-narcosis and losartan reduced cardiac changes in repetitive diving. Human studies showed no beneficial or dangerous pressure-related interactions. In prevention of diving disorders, pseudoephedrine reduced otic barotrauma, vitamins C and E reduced endothelial dysfunction after bounce diving and hepatic oxidative stress in saturation diving. Discussion and conclusions Animal studies revealed that psycho-pharmaceuticals can limit the onset of neurologic symptoms and cardiovascular protective drugs might add a potential protective effect against decompression sickness. No evidence of significant risks due to changes in pharmacologic mechanisms were revealed and most medication is not a contraindication to diving. For improving decision making in prescribing medicine for recreational and occupational divers and to enhance safety by increasing our understanding of pharmacology in hyperbaric conditions, future research should focus on controlled human studies.

Referral to collaborative mental health care within the primary care setting is a service concept that has shown to be as effective as direct referral to specialized mental health care for patients with common mental disorders. Additionally it is more efficient in terms of lower mental health services use. This post-hoc analysis examines if treatment intensity during 1-year of follow-up can be predicted prospectively by baseline characteristics. With multilevel multivariate regression analyses baseline characteristics were examined as potential predictors of visit counts. Results showed that only the enabling factors service concept and referral delay for treatment had a significant association with mental health visit counts, when outcome was dichotomized in five or more visits. Inclusion of the outcome variable as a count variable confirmed the predictive value of service concept and referral delay, but added marital status as a significant predictor. Overall, enabling factors (service concept and referral delay) seem to be important and dominant predictors of mental health services use.

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 x 10(-5) and c.2702T > G [p.V901G], MAF 2.51 x 10(-3)). The CSPG4(A131T) mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4(V901G) mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05-13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4(A131T) mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 x 10(-8)), viability (P = 8.9 x 10(-7)), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4(A131T) (P = 0.006) and CSPG4(V901G) (P = 3.4 x 10(-4)) mutations. Finally, in vivo diffusion tensor imaging of CSPG4(A131T) mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 x 10(-5)). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.

Item does not contain fulltext Children of parents with a mental illness (COPMI) are at increased risk for developing psychiatric disorders, especially when parenting is compromised by multiple risk factors. Due to fragmented services, these families often do not get the support they need. Can coordination between services, as developed in the Preventive Basic Care Management (PBCM) program, improve parenting and prevent child behavioral problems? This randomized controlled clinical trial (RCT) compared the effectiveness of PBCM with a control condition. Ninety-nine outpatients of a community mental health center were randomized to intervention or control. Primary outcomes included parenting quality (assessed by the HOME instrument), parenting skills (parenting skills subscale of FFQ), and parenting stress (PDH). Secondary outcomes are child behavioral problems (SDQ). Outcomes were assessed at baseline and after 9 and 18 months. Effects were analyzed by Repeated Measures Analysis of Variance. Most families were single-parent families belonging to ethnic minorities. The results of the first RCT on effects of PBCM suggest that this intervention is feasible and has a positive effect on parenting skills. There was no evidence for effects on the quality of parenting and parenting stress, nor preventive effects on child behavioral problems. Replication studies in other sites, with more power, including monitoring of the implementation quality and studying a broader palette of child outcomes are needed to confirm the positive effects of PBCM. Long-term prospective studies are needed to investigate if improved parenting skills lead to positive effects in the children in the long run. 10 p.

Objective: We aimed to investigate the prevalence of the metabolic syndrome (MetS) and its individual components in subjects with bipolar disorder (BD) compared to those with major depressive disorder (MDD) and non-psychiatric controls.Methods: We examined 2431 participants (mean age 443 +/- 13.0,66.1% female), of whom 241 had BD; 1648 had MDD; and 542 were non-psychiatric controls. The MetS was ascertained according to NCEP ATP III criteria. Multivariable analyses were adjusted for age, sex, ethnicity, level of education, smoking status and severity of depressive symptoms, and in the case of BD subjects, also for psychotropic medication use.Results: Subjects with BD had a significantly higher prevalence of MetS when compared to subjects with MDD and non-psychiatric controls (28.4% vs. 20.2% and 16.5%, respectively, p Conclusion: This study confirms a higher prevalence of MetS in patients with BD compared to both MDD patients and controls. Specifically at risk are patients with a higher depression score and abdominal obesity. (C) 2015 Elsevier Inc. All rights reserved.

Item does not contain fulltext TOPIC: The Preventive Basic Care Management (PBCM) program is a Dutch service coordination program for parents with mental illnesses, which focuses on organizing tailored support from various services for parents and their children from a preventive perspective. PURPOSE: The article discusses our efforts to make PBCM evidence-based, as well as the theoretical underpinnings, goals, the model of service coordination, and steps of the intervention. The main elements are systematic monitoring of parents' and children's vulnerabilities, strengths, and resources; strengthening parenting skills; facilitating access to a variety of services to address vulnerabilities; and overall planning and coordination of these preventive services. SOURCES USED: The theoretical underpinnings and intervention methodology of PBCM were developed in critical dialogues between practitioners and researchers about the focus and effective elements of service coordination for parents with mental illnesses. Data on feasibility and effectiveness came from pilot studies and retrospective interviews. Descriptive data about participants of an ongoing randomized controlled trial illustrate the needs of these families. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The service coordination program for parents with mental illnesses seems feasible and effective in tackling bottlenecks caused by fragmentation of the services supporting these families, who have varied and fluctuating needs. (PsycINFO Database Record (c) 2014 APA, all rights reserved). 6 p.

Life events induce stress, which is considered to negatively impact the course of disease in patients with bipolar disorder (BD), its effects being predominantly mediated by cortisol. Cortisol in scalp hair has been identified as a biomarker for assessing long-term cortisol levels, and allows clarifying the relation between life events, hair cortisol concentrations (HCC), and clinical course over time. In 71 BD patients, we analyzed the proximal 3 cm of hair, reflecting 3 months of cortisol production, and investigated the association between HCC, the number of life events, the amount of social support, and mood in the 3 months prior to the hair assessment and between HCC and mood in the subsequent 3 months. Although the total number of life events was not associated with HCC (p 0.05), the number of negative life events was associated with increased HCC (r(2)( )= 0.04, p = 0.02). Social support showed an inverse association with HCC in patients reporting negative life events (r(2)( )= 0.07, p = 0.03). HCC and mood were not associated in the 3 months prior to hair sampling or in the subsequent 3 months. This study indicates that patients who experienced recent negative life events have increased hair cortisol levels, which seem to be attenuated by social support.

Objective This study aims to determine the long-term effect of a stepped care cognitive behavioral therapy prevention program for depression in older people and the factors predicting or moderating outcome. Methods In a randomized controlled trial, 136 participants, aged 55 years or older, who had been treated for depression, received during 12 months a stepped care program (SCP) or care as usual (CAU) and were then followed up for a second year. Outcome was defined as the start of a new mental health treatment for depression in a specialized outpatient setting, as recorded in the patients' electronic medical records. Results Of the 123 patients, 38 required new mental health treatment. Survival analysis showed that participants in SCP (n = 27) required new treatment significantly more than patients receiving CAU (n = 11). Negative life events in the last year were predictive for new treatment in CAU but not in SCP. Conclusions An SCP seems to lower the threshold for new specialized mental health treatment for depression, whereas new treatment in CAU patients occurs more often in reaction to recent life events. Copyright © 2013 John Wiley & Sons, Ltd.

Background:Despite various studies, supportive evidence for the efficacy of exercise in treatment of mental illness is still weak.Objective:The aim of this study was to compare two forms of exercise, namely running therapy (RT) and physiotraining therapy (PT), on stationary devices.Methods:Patients in a day treatment programme for treatment of affective disorders were randomly allocated to one of the exercise groups or to a control group. Depression scores, self-efficacy, physical conditions and appreciations of the training programme were measured.Results:After 6 weeks, no significant differences were found between both the training groups and the control group; however, after 12 weeks, the physiotraining group showed significant improvement on scores for blind-rated Hamilton Rating Scale for Depression and on scores for self-rated Beck Depression Inventory 21-item version.Conclusions:Our results suggest that PT has advantages over RT. We speculate that an improved feeling of self-efficacy may be a mediating factor.

SummaryAlthough the Hamilton Rating Scale for Depression (HRSD) is the most frequently used rating scale for quantifying depressive states, it has been criticized for its reliability and its usability in clinical practice. This criticism is less applying to the Montgomery-Asberg Depression Rating Scale (MADRS). Goal of the present study is to investigate the reliability and validity, and clinical relationship between the HRSD and the MADRS. For 60 out-patients with diagnosed depression (DSM IV296.2x, 296.3x, 300.40 and 311.00), the HRSD and MADRS were scored at baseline and 6 weeks later by an independent rater according to a structured interview. Also the Clinical Global Impression (CGI) was assessed by a psychiatrist. Satisfying agreement was found between the totalscores (r= .75, p>.000 en r=.92, p>.000 respectively, at baseline and 6 weeks later). Furthermore agreement was found between the items of both scales, and these agree with the clinical impression. The reliability of the MADRS is more stable than the reliability of the HRSD (α = .6367 and α =.8900 vs α = .2193 and α = .8362 at baseline and at endpoint respectively). Considering the ease of scoring both scales in one interview and the widely international use of the HRSD, scoring both the HRSD and the MADRS to measure the severity of a depression seems to be an acceptabel covenant.

Background This study aimed to determine the feasibility and the effectiveness of a Stepped Care Program (SCP) for preventing relapse of depression in older people. Stepped care consisted of (1) watchful waiting; (2) bibliotherapy; (3) individual cognitive behavioral therapy; and (4) indicated treatment. Methods In a randomized controlled trial, persons 55 years and older (n = 136) who had suffered at least one episode of major depression in the past received a SCP or Care As Usual (CAU). The primary outcome measure was incidence of a new depressive episode. Results Of 1725 previously depressed persons, 175 were willing to partake in the study, 136 of whom were eligible. Treatment satisfaction for stepped care was high. At 12-month follow-up, no difference in incidence of depression between SCP and CAU was found. Medical patient records showed that missing data were often related to relapse. Conclusions In this study, SCP was not more effective in preventing relapse than CAU. Watchful waiting may harmfully delay actual preventive treatment. Prevention as an integral part of regular treatment might lead to higher participation rates. Copyright © 2011 John Wiley & Sons, Ltd.

Objectives: In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD). Methods: In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls. Results: A trend was found for a protective effect of the exon 9β polymorphism (p = 0.14) and the TthIIII polymorphism (p

Bipolar disorder (BD) is a chronic illness, and a great need has been expressed to elucidate factors affecting the course of the disease. Social support is one of the psychosocial factors that is assumed to play an important role in the course of BD, but it is largely unknown whether the depressive and/or manic symptoms also affect the patients' support system. Further, the perception of one's social support appears to have stronger effects on disease outcomes than one's enacted or received support, but whether this also applies to BD has not been investigated. The objective of this study is to examine temporal, bidirectional associations between mood states (depression and mania) and both enacted and perceived support in BD patients. The current study was conducted among 173 BD I and II outpatients, with overall light to mild mood symptoms. Severity of mood symptoms and social support (enacted as well as perceived) were assessed every 3months, for 2years (1146 data points). Multilevel regression analyses (linear mixed-models) showed that lower perceived support during 3months was associated with subsequent higher levels of depressive, but not of manic symptoms in the following 3months. Vice versa, depressive symptoms during 3months were associated with less perceived support in the following 3months. Further, manic symptoms during 3months were associated with less enacted support in the subsequent 3 months. The current study suggests that perceived, but not enacted, support is consistently related to depressive symptoms in a bidirectional way, while mania is specifically associated with a subsequent loss of enacted support. Clinical implications of the current findings are discussed.

IntroductionDifferentiating bipolar depression (BD) from unipolar depression (UD) is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the hypothalamic-pituitary-adrenal (HPA) axis or immunological activity. However, no previous study included assessments of both systems, which is problematic as they may influence each other. Therefore, this study aimed to explore whether cortisol indicators and inflammatory markers were a) independently associated with and/or b) showed effect modification in relation to a lifetime (hypo) manic episode in a large sample of depressed patients.MethodsData were derived from the Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM-IV depressive disorder at baseline, of which 124 (16.2%) had a lifetime (hypo) manic episode at the 2-year assessment, or a more recent episode at the 4-year or 6-year assessment. Baseline cortisol awakening response, evening cortisol and diurnal cortisol slope were considered as cortisol indicators, while baseline C-reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-alpha) were included as inflammatory markers.ResultsIn depressed men and women, none of the cortisol indicators and inflammatory markers were (independently) associated with a (hypo) manic episode. However, effect modification was found of diurnal cortisol slope and CRP in relation to a (hypo) manic episode. Further analyses showed that depressed men with high levels of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001) of having a (hypo) manic episode. No significant differences were found in women.ConclusionOur findings suggest that the combination of high diurnal cortisol slope and high CRP may differentiate between UD and BD. This stresses the importance of considering HPA-axis and immunological activity simultaneously, but more research is needed to unravel their interrelatedness.

Introduction Care for battle casualties demands special skills from medics, nurses, and tactical commanders. To date, no inventory has been performed evaluating the first responders (medics, nurses and tactical commanders) around battle casualties. Method This observational cohort study was conducted amongst the first responders (n = 195) who were deployed to Southern Afghanistan (2009-2010) in three Marine companies. The survey focused on four main topics: (1) participants general background, (2) exposure to combat (casualty) situations, (3) self-perceived quality of care (1 [low]-10 [high]) in the pre-hospital phase, and (4) the effects of combat stressors on professional skills and social environment using the Post Deployment Reintegration Scale (PDRS) and the Impact of Event Scale-Revised (IES-R). Results 71% of the eligible Dutch tactical commanders, medics, and nurses participated in this survey. Most (14/16) medics and nurses scored their pre-deployment training as sufficient The overall self-perceived quality of care score was above average (7.8). Most (80%) of the participants were exposed to battle casualties. There were no significant differences regarding rank, gender, age and military task using the impact of event scale and PDRS, except for a worse score on the work negative, family positive and personal positive subscales (p

Objectives Units deployed to armed conflicts are at high risk for exposure to combat events. Many battle casualties (BCs) have been reported in the recent deployment to Afghanistan. The long-term impact of these combat injuries, at their five-year end point, is currently unknown. To date, no systematic inventory has been performed of an identified group of BCs in comparison to non-injured service members from the same operational theatre. Design Observational cross-sectional cohort study. Setting Open online survey among Dutch BCs that deployed to Afghanistan (2006–2010). Participants The Dutch BCs (n = 62) were compared to two control groups of non-injured combat groups (battle exposed [n = 53], and non-battle exposed [n = 73]). Main Outcome Measures Participants rated their impact of trauma exposure (Impact of Events [IES]), post deployment reintegration (Post Deployment Reintegration Scale [PDRS]), general symptoms of distress (Symptom Checklist 90 [SCL-90]), as well as their current perceived quality of life (EuroQol-6D [EQ-6D]). Also cost effectiveness (Short From health survey [SF-36]) and care consumption were assessed (Trimbos/iMTA questionnaire). Results Over 90% of BCs were still in active duty. The mean scores of all questionnaires (IES, EQ-6D, SF-36, and SCL-90) of the BC group were significantly higher than in the control groups (p

Background The objective of this study was to estimate the prevalence of Seasonal Affective Disorder (SAD) in adults with lifetime Attention-Deficit/Hyperactivity Disorder (ADHD). Method Patients eligible for this study had lifetime impairing symptoms of ADHD and a current and/or past co-morbid mood disorder according to their medical record. The Seasonal Pattern Assessment Questionnaire (SPAQ) was administered by a telephone interview to assess seasonality. Results The overall rate of SAD in this clinical population of adults with ADHD was estimated at 27%. Females were more at risk to develop SAD than men. Limitations The SPAQ is a screening, not a diagnostic instrument. Conclusions SAD symptoms are frequently comorbid with ADHD in adults. These results have clinical relevance for the recognition and treatment of SAD with bright light therapy in adults with ADHD.

Background:Sleep disorders are widespread among patients with schizophrenia and contribute to adverse clinical outcomes. Antipsychotic drugs exert varying effects on sleep, and the effects of atypical agents may differ from those of conventional neuroleptics.Objective:To review the literature on the effects of atypical medication on subjective and objective sleep quality in patients with schizophrenia.Methods:A non-systematic literature review of Medline was performed in August 2003 searching the period from January 1985 to August 2003 for studies of the effects of atypical antipsychotics on sleep.Results:We found published studies of clozapine, olanzapine, and risperidone, but none on quetiapine or ziprasidone. Studies with clozapine showed that it increased total sleep time, sleep efficiency, stage-2 non-rapid eye movement sleep and rapid eye movement (REM) sleep density, and decreased stage-4 sleep, slow wave sleep (SWS) and stage-1 sleep. Single-dose studies with olanzapine have shown that it increases SWS, sleep continuity, total sleeping time, subjective sleep quality, and delta sleep. Long-term studies with risperidone have shown improvements in total sleep, sleep efficiency, sleep continuity, SWS, and stage-2 sleep, and reductions in sleep latency, number of awakenings, and proportion of time awake. These benefits were paralleled by improvements in subjective sleep assessment and psychopathology, and psychosocial functioning.Conclusions:The evidence presented in this review suggests that atypical antipsychotics exert favorable effects on sleep profile compared with conventional agents, including improvement of subjective sleep quality and modification of specific sleep stages known to be associated with better clinical outcome.

A stepwise hypnosis-training model for psychiatric residents is presented as used in the Netherlands. Hypnosis is presented to residents as an intervention that can be incorporated into the treatment of various types of disorders in structured, time-limited units. The model takes into account the usual reluctance and insecurity of the psychiatric resident, who is usually encountering hypnosis for the first time.

Background: The severity of bipolar disorder can be assessed using the daily prospective National Institute of Mental Health's Life Chart Method (LCM-p). Also for scientific research the LCM-p, has been used frequently. However, processing and analyzing the LCM-p for research purposes, are challenging because of the multitude of complex measures that can be derived from the data. In the current paper we review the different LCM-p course variables (mood episodes, average severity, proportion of time ill and mood switches) and their definitions. Strengths and limitations and the impact of the use of different LCM-p course measures and definitions on the research results are described. Method: A systematic review of original papers on the LCM was conducted using 9 electronic databases for literature between January 1996 and December 2014. Papers using other prospective charting procedures were not evaluated in the current study. Results: The initial literature search led to 1352 papers of which 21 were eventually selected. A relatively wide variety of definitions of LCM-p course variables was used across the studies. Especially for the calculation of number of episodes and mood switch no univocal definition seems to exist. Across studies several different durations and severity criteria are applied to calculate these variables. We describe which variables and definitions are most suitable for detecting specific bipolar disease course characteristics and patterns. Conclusion: In the absence of a golden standard for the calculation of LCM-p course variables, researchers should report the exact method they applied to their LCM-p data, and clearly motivate why this is their method of first choice considering their research aim. (C) 2015 Elsevier B.V. All rights reserved.

Objective: One third of patients with a major depressive episode also experience manic symptoms or, even, a (hypo) manic episode. Retrospective studies on the temporal sequencing of symptomatology suggest that the majority of these patients report depressive symptoms before the onset of manic symptoms. However, prospective studies are scarce and this study will, therefore, prospectively examine the onset of either manic symptoms or a (hypo) manic episode in patients with a major depressive disorder. In addition, we will consider the impact of a large set of potential risk factors on both outcomes.Methodology: Four-year follow-up data were used to determine the onset of manic symptoms as well as a CIDI-based (hypo) manic episode in a large sample (n = 889, age: 18-65 years) of outpatients with a major depressive disorder and without manic symptoms at baseline. Baseline vulnerability (i.e., sociodemographics, family history of depression, childhood trauma, life-events) and clinical (i.e., isolated manic symptoms, depression characteristics, and psychiatric comorbidity) factors were considered as potential risk factors.Results: In our sample of depressed patients, 15.9% developed manic symptoms and an additional 4.7% developed a (hypo) manic episode during four years. Baseline isolated manic symptoms and comorbid alcohol dependence predicted both the onset of manic symptoms and a (hypo) manic episode. Low education only predicted the onset of manic symptoms, whereas male gender, childhood trauma and severity of depressive symptoms showed strong associations with, especially, the onset of (hypo) manic episodes.Conclusions: A substantial proportion (20.6%) of patients with a major depressive disorder later developed manic symptoms or a (hypo) manic episode. Interestingly, some identified risk factors differed for the two outcomes, which may indicate that pathways leading to the onset of manic symptoms or a (hypo) manic episode might be different. Our findings indirectly support a clinical staging model.

Background Life events are assumed to be triggers for new mood episodes in bipolar disorder (BD). However whether life events may also be a result of previous mood episodes is rather unclear. Method 173 bipolar outpatients (BD I and II) were assessed every three months for two years. Life events were assessed by Paykel׳s self-report questionnaire. Both monthly functional impairment due to manic or depressive symptomatology and mood symptoms were assessed. Results Negative life events were significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction (life events as a result of mood/functional impairment), we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events. Limitations The use of a self-report questionnaire for the assessment of life events makes it difficult to determine whether life events are cause or consequence of mood symptoms. Second, the results can only be generalized to relatively stable bipolar outpatients, as the number of severely depressed as well as severely manic patients was low. Conclusions Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.

Outcome studies of patients suffering from depression indicate high relapse rates and a tendency towards chronicity. The present study describes the long-term outcome of 95 depressed outpatients in a third-level referral centre. and examines the relationship between baseline-variables (age, sex, level of psychopathology, age at onset of first psychiatric disorder, duration of illness at baseline, diagnosis) and outcome variables. After 3.5 years, 34 patients (36%) had a chronic course, 24 patients (25%) had at least one recurrence and 37 patients (39%) had a non-recurrent course. Chronicity was significantly correlated with an early age of onset of the first psychiatric disorder, a high level of psychopathology and a high level of depressive symptoms at baseline. The duration of depression at index did not differentiate chronic course from recurrent or non-recurrent course. After 1 year of follow-up, patients with recurrence were significantly more likely to stop antidepressant treatment. The results confirm the great chance for chronicity and recurrence in depression and the need to develop long-term treatment programs to prevent relapse.

SummaryIn a three phase sequential treatment strategy study involving 119 depressed outpatients, a total of 31 patients (26.7%) stopped treatment prematurely due to side-effects (21/31), aggravation of symptoms (3/31), non-compliance (4/31), and non-treatment related events (3/31). At baseline, no significant differences were found on sociodemographic and psychiatric data between patients who did or did not drop out. As predictors of dropout eight domains of data concerning psychiatric history, premorbid history, symptomatology, personality, and social adjustment were used. Using a logistic linear regression analysis, only three variables were related to dropout. Patients with a history of alcohol use or poor social functioning according to axis V of the Diagnostic and Statistical Manual (DSM)-III-R had a higher chance to drop out, while patients with a sleep disturbance according to the Symptom Checklist (SCL)-90 had a smaller chance to drop out.

A relatively small number of studies have been dedicated to the differential effects of the current mood state on cognition in patients with a bipolar disorder (BD). The aim of the current study was to investigate the effect of current mood state on divided attention (DA) performance, and specifically examine possible beneficial effects of the (hypo-) manic state. Over a maximum period of 24 months, medication use, divided attention test (a subtest of the Test for Attentional Performance (TAP)) was assessed every 6 months in 189 outpatients with BD. Data were analyzed with multilevel regression analysis (i.e. linear mixed models). DA performance varied considerable over time within patients. Corrected for psychotropic medication a significant quadratic relationship between manic symptoms and DA performance was found, with mild hypomanic symptoms having a positive influence on divided attention scores and moderate to severe manic symptoms having a negative influence. No association between depressive symptoms and DA performance was found. In future research on mania and cognition as well as in the clinical practice both the beneficial and negative effects of mania should be taken into account.

Background: Bipolar disorders often remain unrecognized in clinical practice, which may be a consequence of imprecise recall of manic symptoms earlier in life. This study will therefore examine the validity oldie widely used Mood Disorder Questionnaire (MDQ) in detecting a (hypo)manic episode and explore the impact of recall bias.Methods: As an indication of impairments in recalling manic symptoms, we examined the long-term reliability of the MDQ after two years of follow-up in a sample of 2087 persons. Then, the validity of he MDQ was tested against the gold standard of a CIDI-based DSM-IV (hypo)manic episode Its performance was compared for detecting a lifetime episode (at T1) versus a recent episode in the past two years (at T2).Results: The long term reliability of the MDQ was limited as the coned recall of individual items ranged horn 44.6% to 68.8% after two years. The overall validity of the MDQ in detecting a lifetime (hypo)manic episode was limited and no adequate cut-off point with acceptable sensitivity and specificity could be identified. However, the MDQ accurately detected a recent episode with a sensitivity of 0.83 and a specificity of 0.82 for the standard and optimal cut-off point of Taking into account two additional MDQ questions on clustering in time and severity of problems decreased its validity.Limitations: Patients with a primary, clinical diagnosis of bipolar disorder were excluded.Conclusions: The MDQ accurately detected recent (hypo)manic episodes, but imprecise recall may result in a limited performance for episodes earlier in life. (C) 2013 Elsevier B.V. All rights reserved.

SummaryIntroduction: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is hypothesized to a role in the pathogenesis of bipolar disorder (BD). Conflicting results have been reportedwhen saliva or serum was used to measure cortisol levels. A recently developed method is tomeasure cortisol in scalp hair, with 1 cm of scalp hair representing 1 month. We studied whetherthere aredifferencesinlong-termhaircortisollevelsbetweenBDpatientsandhealthyindividuals whether there are associations between hair cortisol and disease characteristics.Methods: Hair samples were collected in 100 BD patients and 195 healthy controls. Long-termcortisol levels were determined in 3 cm hair segments. Saliva samples were collected on twoconsecutive evenings. Documented disease characteristics were disease state, age of onset andpsychiatric co-morbidity.Results: Hair cortisol levels were not statistically different in BD patients compared to healthycontrols (p = 0.233) and were not associated with the disease state at the moment of samplecollection (p = 0.978).Inthesubgroupofpatientswithageofonset 30years,haircortisollevelswere significantly elevated compared to thesubgroup with age ofonset

Contains fulltext : 354944-20180306181137-19938508695a9ecbc9a313d3.02118576-1.pdf (Publisher’s version ) (Closed access) This is a qualitative pilot study of congruence in narrative reconstruction of interpretations of life events by patients in a clinical psychiatric setting. It is based on the assumption that a coherent interpretive structure means that the interpretation of contingent life events by a person must be congruent with the conflict between these everyday events and the person’s embedded ultimate life goal. The pilot study confirms the assumption, provided the interpretation is based on ultimate life goals in order to integrate experience, severe mental disorder in these patients, with the person’s life story. If there is no clear embedded ultimate life goal, the person does not have a congruent angle on the contingent life event to assign it a position in her life story. As a result self-realisation, with or without a context of religious significance, becomes problematic. Whether patients with a severe mental disorder differ from persons without a disorder remains an open question and can not be answered by this study. 26 p.

Background and Objectives: Switching antipsychotics (APs) in the treatment of mental ilnesses such as schizophrenia is common practice for clinicians as well as a transitional moment associated with the possibility of adverse events and recurrence of psychoses. As in recent years, AP switching strategies have received more attention, a number of authors have recommended transitions with overlapping drug dosage regimens in time (such as tapering, cross-tapering, plateau switching) over abrupt switches. However, there is a paucity of data documenting how clinicians are switching APs in real life. Moreover, the question if recently recommended switching strategies are converted into everyday practice is still very much unanswered. The present investigation aims to study if indeed there is a preference for tapered approaches over abrupt switching. Methods: In a retrospective longitudinal descriptive study, electronic prescription data from a large clinical psychiatric setting in the Netherlands were collected for the year 2007. Timelines of medication regimens were constructed for individual patients, enabling to identify transitions between APs. As patients could have been subjected to multiple switches in a given time period, transitions were expressed as episodes. Abrupt switches were defined as switches having no overlap in time. Results: From a total of 5322 AP prescriptions involving 1465 patients, a total of 180 episodes (associated with 158 patients) were identified where APs were switched. Of these 180 episodes, 110 (61%) involved abrupt transitions. 70 episodes (39%) had overlap in time with an average taper length of 16.1 (SEM 1.6) days. Conclusions: In the majority of cases in the studied clinical setting, APs are switched abruptly.

The predictive value of eight domains or sets of variables including sociodemographic aspects, premorbid history, symptomatology, personality, social and diagnostic data are evaluated in depressed outpatients with a Hamilton Rating Scale for Depression (HRSD) score of at least 14. Patients were treated using a three-phase sequential treatment strategy. Of the 119 patients, 88 completed the trial. The HRSD-score at the end of phases I, II or III was used as an outcome measure. Patients with an initially high HRSD-score and an obsessive-compulsive personality had a greater chance of recovery, while patients with somatization and a passive-aggressive personality had less of a chance of recovery. Variables involving psychiatric history, premorbid history or symptomatology of the depression, were not significantly related to outcome. The endogenous/non-endogenous distinction was not a predictor of response.

Depressed outpatients (n = 51) resistant to treatment with maprotiline were treated in a blind, randomized, single-centre study, for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor (MAO-A-I), brofaromine or lithium addition to maprotiline. The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period. No significant differences in efficacy were found between the two treatment regimes. In the patients who completed the trial, brofaromine was well tolerated with the exception of insomnia. Anticholinergic effects as well as thyroid dysfunctions (17 out of 20) were more frequent in the maprotiline/lithium group.

Introduction: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD. Methods: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N3635, Bc1I, and 9 beta polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics. Results: Seasonal patterns of hypomania are related to the Bc1I haplotype and the TthIIII + 9 beta haplotype of the GR gene (respectively, crude p = .007 and crude p = .005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p = .004, after adjustment p = .016). No evidence for a role of the MR in modifying clinical manifestations was found. Conclusion: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset. (C) 2011 Elsevier Ltd. All rights reserved.

Objective: This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective.Methods: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs).Results: Escitalopram was associated with a cost savings per patient of 263 versus venlafaxine XR and 1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram.Conclusion: Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands. (Clin Ther. 2012; 34:1364-1378) (C) 2012 Published by Elsevier HS Journals, Inc.

This study aimed to determine the feasibility and the effectiveness of a Stepped Care Program (SCP) for preventing relapse of depression in older people. Stepped care consisted of (1) watchful waiting; (2) bibliotherapy; (3) individual cognitive behavioral therapy; and (4) indicated treatment.In a randomized controlled trial, persons 55 years and older (n = 136) who had suffered at least one episode of major depression in the past received a SCP or Care As Usual (CAU). The primary outcome measure was incidence of a new depressive episode.Of 1725 previously depressed persons, 175 were willing to partake in the study, 136 of whom were eligible. Treatment satisfaction for stepped care was high. At 12-month follow-up, no difference in incidence of depression between SCP and CAU was found. Medical patient records showed that missing data were often related to relapse.In this study, SCP was not more effective in preventing relapse than CAU. Watchful waiting may harmfully delay actual preventive treatment. Prevention as an integral part of regular treatment might lead to higher participation rates.

This article presents the results of a large efficacy study comparing different forms of therapy for major depressive disorder (MDD), including interpersonal psychotherapy (IPT) and pharmacotherapy. Patients were randomized to either IPT, IPT in combination with anti-depressant medication, IPT in combination with pill-placebo or medication only. The primary outcome measure was the Hamilton Rating Scale for Depression (HAMD). Patients were treated for 12 to 16 weeks. Ratings were performed at baseline, after 6 weeks of treatment and at the end of treatment. Ethnic minority patients (EMP) had higher scores on the HAMD than non-EMP for every rating period. However, the rate of improvement was the same for EMP and non-EMP. The higher mean scores of EMP on the HAMD could not be explained as solely due to higher scores on somatic items of the rating scales. The attrition rate in EMP (45.9%) was significantly higher than in non-EMP (24.4%), even in the structured treatment format studied. The results suggest that standard antidepressant therapy, be it medication, psychotherapy or both, may be effective for depressed minority patients but therapists should focus on enhancing adherence to treatment.

Objective: This study compared the effectiveness of treating common mental disorders in a collaborative care program in a primary care setting and the effectiveness of treating such disorders through traditional referral of patients to mental health services. Methods: In a cluster randomized controlled trial, 27 general practitioner practices in the Netherlands were designated to provide either collaborative care or usual care. In the collaborative care condition, a mental health care professional worked on site at the primary care practice and was available to provide patients a maximum of five appointments if they were referred by the general practitioner. If indicated, referral to specialized mental health services followed. In the usual care condition, if indicated, general practitioners would refer patients to off-site specialized mental health services. The study included 165 patients. At baseline and at three, six, and 12 months, the study assessed patients’ psychopathology, patients’ quality of life, and patients’ and general practitioners’ satisfaction with the treatment provided. Delay in seeing a mental health provider, duration of treatment, number of appointments, and related treatment costs were assessed at 12 months. The data were analyzed with hierarchical linear models. Results: Level of patients’ psychopathology and quality of life significantly improved over time, and there were no significant differences between models of care. There was no significant difference in patients’ satisfaction with care in either condition. The collaborative care condition resulted in significantly higher satisfaction with services among general practitioners, shorter referral delay, reduced time in treatment, fewer appointments, and consequently lower treatment costs. Conclusions: Collaborative care for a heterogeneous group of persons with common mental disorders seems to be as effective as the usual practice of referral to mental health services for reducing psychopathology, but it is significantly more efficient regarding referral delay, duration of treatment, number of appointments, and related treatment costs. (Psychiatric Services 60:74–79, 2009)

Background Prediction of treatment outcome has important clinical consequences. Personality factors have rarely been tested as predictors of acute outcome. Personality, demographic and illness-related characteristics were assessed at baseline for prediction of outcome of treatment in depressed out-patients. Methods One hundred and ninety-three patients with major depressive disorder (MDD) were enrolled in a 12 to 16 week trial. The treatment consisted of nefazodone, nefazodone in combination with interpersonal psychotherapy (IPT), IPT in combination with placebo and IPT alone. Demographic and illness related variables were collected at baseline. Personality was assessed using the NEO-FFI. This instrument measures five dimensions of personality. A hierarchical logistic regression was carried out to test for significant predictors of remittance. Further a multiple regression analysis was used to investigate variables predictive of changes on the Hamilton Depression Rating Scale as dependent variable. Results Univariate analysis showed a significant relationship of outcome with severity, duration of index episode, and use of medical services (UMS). None of the personality variables was predictive of outcome. Regression analyses showed that these disease related variables each uniquely predicted outcome, but that personality factors did not significantly contribute to the prediction model. Limitations The study was carried out in secondary and tertiary care centers and may not be generalizable to other populations. Personality dimensions were assessed with a self-report instrument and may be prone to bias. Conclusions Severity and duration of the index episode, and to a lesser extent, UMS, and not personality factors, predict outcome in the short term treatment of MDD.

Background: Although several forms of effective therapy exist for outpatients suffering from major depressive disorder, many patients do not profit from treatment. Combining psychotherapy and medication may be an effective strategy. However, earlier studies have rarely found a clear advantage for the combination. Where an advantage was found, a possible placebo effect of adding 2 types of treatment could not be ruled out as cause for the superior effect of the combination. Methods: A total of 353 patients were screened, of whom 193 were randomized over 4 conditions: nefazodone plus clinical management, interpersonal psychotherapy (IPT), the combination of the two or the combination of IPT and pill-placebo. All patients suffered from major depressive disorder and had a score of at least 14 on the 17-item Hamilton Rating Scale (HAMD). The patients were treated for 12–16 weeks. At baseline, at 6 weeks and on completion of treatment, ratings were performed by independent raters. The primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. Results: Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. Conclusions: The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.

Objective To examine whether positive and negative life events precede bipolar mood symptoms or whether bipolar mood symptoms precede life events in bipolar I and bipolar II outpatients. Method 173 bipolar outpatients with a diagnosis of bipolar disorder type 1 (BD I) or 2 (BD II) were assessed every three months for a total of two years. Life events were assessed by Paykel's self-report questionnaire. The NIMH monthly retrospective life chart method (LCM-r) was used to assess monthly functional impairment due to manic or depressive symptomatology. Mood symptoms were assessed every six months with the Quick Inventory of Depressive Symptomatology- Self Report (QIDS) and the Young Mania Rating Scale (YMRS). Results Multilevel regression analyses (linear mixed-models) showed that negative life events are significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction, we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events. Conclusions Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.

Introduction Dysregulation of the hypothalamic-pituitary-adrenal (HPA-)axis is hypothesized to play a role in the pathogenesis of bipolar disorder (BD). Conflicting results have been reported when saliva or serum was used to measure cortisol levels. A recently developed method is to measure cortisol in scalp hair, with one cm of scalp hair representing one month. We studied whether there are differences in long-term hair cortisol levels between BD patients and healthy individuals and whether there are associations between hair cortisol, life events and disease characteristics. Methods Hair samples were collected in 100 BD patients and 195 healthy controls. Long-term cortisol levels were determined in 3 cm hair segments. Saliva samples were collected on two consecutive evenings. Documented disease characteristics were disease state, age of onset, psychiatric co-morbidity, and life events. Results Hair cortisol levels were not statistically different in BD patients compared to healthy controls (p=0.233) and were not associated with the disease state at the moment of sample collection (p=0.978). Clinical characteristics, such as age of onset ≥30 years (p=0.004) and psychiatric co-morbidity (44.87 versus 31.41 pg/mg hair; p=.021), appeared to associate with higher hair cortisol levels. Panic disorder associated with decreased cortisol levels (22.13 versus 34.67 pg/mg hair; p=0.019). The occurrence of recent negative major life events, but not of positive major life events, was associated with an increase in HCC in BD patients.

The authors conducted an open-label study of the efficacy and tolerability of venlafaxine and of lithium augmentation in outpatients with depression who were not responding to venlafaxine. Outpatients aged 18 to 70 years were eligible if they had a minimum baseline score of 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were started on venlafaxine 37.5 mg twice daily for 1 week. For weeks 2 through 4, the dose of venlafaxine was increased to 75 mg twice daily, and for weeks 5 through 7, the dose was further increased to 75 mg three times daily. At the end of the 7-week treatment period, patients with a50% decrease in their HAM-D scores from baseline were given lithium carbonate 600 mg once daily. The dose of lithium carbonate was adjusted to maintain plasma levels in the range of 0.6 to 1.0 mmol/mL. Efficacy was assessed with the 17-item HAM-D, Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions Scale. Data were analyzed on an intent-to-treat basis. At the end of the 7-week treatment period, 35% of patients showed aor = 50% decrease in their HAM-D scores from baseline. Lithium augmentation was initiated in 23 patients. The results showed that the addition of lithium was well-tolerated and led to a further decrease in the HAM-D scores, with eight patients responding and two of them presenting a remission. The addition of lithium to venlafaxine was found to be a well-tolerated strategy in treatment-resistant patients.

Thirty-three patients with depression treated with 225 mg venlafaxine were genotyped for the polymorphic enzyme, debrisoquine 4-hydroxylase (CYP2D6). The relationship between drug and metabolite levels and between genotype and clinical response were investigated. Although the number of responders in this study is insufficient for definite conclusions to be drawn, a target therapeutic concentration ranging from 195-400 microg/L for the sum of venlafaxine and O-desmethylvenlafaxine is suggested. The ratio of O-desmethylvenlafaxine to venlafaxine in the serum concentrations is a measure of metabolic turnover, and can be used to distinguish between ultrarapid and poor metabolizers. All but one of the nonresponders in this study had lower ratios than the responders. Three patients (9%) had homozygous defective CYP2D6 alleles and did not readily metabolize venlafaxine to O-desmethylvenlafaxine, pointing to poor metabolism. In these patients, N-desmethylation was increased. Two out of four patients detected by the ratio as potentially ultrarapid metabolizers were shown to have multiple copies of a functional CYP2D6 gene.