Systematic review on the effects of medication under hyperbaric conditions: consequences for the diver.

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.

Text Analysis of Electronic Medical Records to Predict Seclusion in Psychiatric Wards: Proof of Concept.

Aim: With the introduction of "Electronic Medical Record" (EMR) a wealth of digital data has become available. This provides a unique opportunity for exploring precedents for seclusion. This study explored the feasibility of text mining analysis in the EMR to eventually help reduce the use of seclusion in psychiatry. Methods: The texts in notes and reports of the EMR during 5 years on an acute and non-acute psychiatric ward were analyzed using a text mining application. A period of 14 days was selected before seclusion or for non-secluded patients, before discharge. The resulting concepts were analyzed using chi-square tests to assess which concepts had a significant higher or lower frequency than expected in the "seclusion" and "non-seclusion" categories. Results: Text mining led to an overview of 1,500 meaningful concepts. In the 14 day period prior to the event, 115 of these concepts had a significantly higher frequency in the seclusion category and 49 in the non-seclusion category. Analysis of the concepts from days 14 to 7 resulted in 54 concepts with a significantly higher frequency in the seclusion-category and 14 in the non-seclusion category. Conclusions: The resulting significant concepts are comparable to reasons for seclusion in literature. These results are "proof of concept". Analyzing text of reports in the EMR seems therefore promising as contribution to tools available for the prediction of seclusion. The next step is to build, train and test a model, before text mining can be part of an evidence-based clinical decision making tool.

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.

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 × 10-5 and c.2702T > G [p.V901G], MAF 2.51 × 10-3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G 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 CSPG4A131T 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 × 10-8), viability (P = 8.9 × 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 CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10-4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 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.

The characteristics of psychotic features in bipolar disorder.

BACKGROUND: In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors. METHODS: In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models. RESULTS: A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (ß = -0.09, t = -3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (ß = 0.09, t = 3.04, p = 0.002). CONCLUSIONS: In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

An Internet-based Acceptance and Commitment Therapy intervention for older adults with anxiety complaints: study protocol for a cluster randomized controlled trial.

BACKGROUND: Anxiety is among the most prevalent and disabling mental health problems in older adults. Few older adults with mild to moderately severe anxiety symptoms receive adequate interventions, putting them at risk for developing anxiety disorders, depression, and various somatic problems. Effective, low-threshold interventions should be developed. Blended care, in which a web-based intervention is combined with a limited amount of face-to-face contacts with a mental healthcare counselor at the general practice, is a promising option. The online self-help intervention "Living to the Full"-an Acceptance and Commitment Therapy (ACT) intervention-has been proven to reduce depression and anxiety in several patient groups, but has not yet been investigated in older adults. The aim of this study is to evaluate the (cost-)effectiveness of a blended form of "Living to the Full" in reducing anxiety symptoms in adults aged 55 to 75 years. Furthermore, moderators and mediators of the treatment effect are investigated. METHODS/DESIGN: The (cost-)effectiveness of the ACT intervention will be investigated in a cluster single-blind randomized controlled trial (RCT). The blended intervention will be compared to treatment-as-usual. Thirty-six mental health counselors working at general practices in the Netherlands will be randomized to deliver blended care or treatment as usual. A total of 240 participants (aged 55-75 years) with mild to moderately severe anxiety complaints (defined as a total score of 5-15 on the GAD-7) will be recruited. There are four measurements consisting of online questionnaires (primary outcome: GAD-7) and a telephone interview: before the start of the intervention; directly following the intervention (14 weeks after baseline); and six and twelve months after baseline. Possible mediator variables will be assessed multiple times basis during the intervention. DISCUSSION: This RCT will evaluate the effectiveness of a blended ACT intervention for older adults with anxiety symptoms. If the intervention is shown to be effective, it will be implemented, thereby improving the accessibility and quality of preventive interventions for older adults with anxiety problems. TRIAL REGISTRATION: Netherlands Trial Register, NTR6270 . Registered on 21 March 2017.

Prediction of Mental Health Services Use One Year After Regular Referral to Specialized Care Versus Referral to Stepped Collaborative Care.

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.

Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity Differentiating between Unipolar and Bipolar Depressive Episodes.

INTRODUCTION: Differentiating 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. METHODS: Data 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-α) were included as inflammatory markers. RESULTS: In 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. CONCLUSION: Our 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.

Metabolic syndrome in patients with bipolar disorder: comparison with major depressive disorder and non-psychiatric controls.

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 44.3±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<0.001), also when adjusted for sociodemographic and lifestyle factors (OR 1.52, 95% CI: 1.09-2.12, p=0.02 compared to MDD; OR 1.79, 95% CI: 1.20-2.67, p=0.005 compared to non-psychiatric controls). The differences between BD subjects with controls could partly be ascribed to a higher mean waist circumference (91.0 cm vs. 88.8, respectively, p=0.03). In stratified analysis, the differences in the prevalence of MetS between patients with BD and MDD were found in symptomatic but not in asymptomatic cases. 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.

Effects of preventive family service coordination for parents with mental illnesses and their children, a RCT.

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.

Long-term impact of battle injuries; five-year follow-up of injured Dutch servicemen in Afghanistan 2006-2010.

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<0.05). The PDRS showed a significantly lower (p<0.05) outcome in the negative subscales. The mean consumption of care was triple that of both control groups. A lower score on quality of life was related to higher levels of distress and impact of trauma exposure. CONCLUSIONS: This study showed a clear long-term impact on a wide range of scales that contributes to a reduced quality of life in a group of BCs. Low perceived cost effectiveness matched with high consumption of care in the BC group in comparison to the control groups. These results warrant continuous monitoring of BCs.

Impact of combat events on first responders: experiences of the armed conflict in Uruzgan, Afghanistan.

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<0.05) in the PDRS for the first responders in comparison to the armed forces norm score. CONCLUSION: The quality of care in the pre-hospital phase was considered adequate, symptoms of post-traumatic stress in this group was low. Active involvement of co-combatants and the social support network are essential in adaption after exposure to combat events. Further research is necessary to identity predisposing preventable high stress factors, and to compose a "waterproof" aftercare programme.

Recent negative life events increase hair cortisol concentrations in patients with bipolar disorder.

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.

Predictors of the onset of manic symptoms and a (hypo)manic episode in patients with major depressive disorder.

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.

Effects of mood state on divided attention in patients with bipolar disorder: evidence for beneficial effects of subclinical manic symptoms.

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.

Preventive family service coordination for parents with a mental illness in the Netherlands.

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.

Relationship between clinical features and inflammation-related monocyte gene expression in bipolar disorder - towards a better understanding of psychoimmunological interactions.

OBJECTIVES: Existing and previously published datasets were examined for associations between illness and treatment characteristics and monocyte pro-inflammatory gene expression in patients with bipolar disorder (BD). We hypothesized a priori that increased monocyte pro-inflammatory gene expression would be found more frequently in patients with a lifetime history of psychotic symptoms. METHODS: Monocyte quantitative polymerase chain reaction and symptom data from 64 patients with BD were collected from three Dutch studies. Regression analyses were performed to analyze the various associations between pro-inflammatory gene expression and clinical features, from which feature-expression heat maps were drawn. RESULTS: No associations were found between pro-inflammatory gene expression and lifetime psychotic symptoms, whereas a positive association was identified between subcluster 2 genes and manic symptoms. For several subcluster 1a genes, a negative association was found with age at onset. For most subcluster 2 genes, a positive association was found with the duration of illness. Current use of antidepressants and of anti-epileptic agents was associated with subcluster 2 gene expression, and current use of lithium and antipsychotic agents with subcluster 1a gene expression. CONCLUSIONS: Our hypothesis that lifetime psychotic features would be associated with pro-inflammatory monocyte gene expression was not confirmed. In an explorative analysis we found: (i) a possible relationship between pro-inflammatory gene expression and manic symptomatology; (ii) a differential immune activation related to age at onset and duration of illness; and (iii) support for the concept of an immune suppressive action of some of the mood-regulating medications.

The Mood Disorder Questionnaire (MDQ) for detecting (hypo)manic episodes: its validity and impact of recall bias.

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 of the 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 the 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 correct recall of individual items ranged from 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 ≥ 7. 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.

Long-term cortisol in bipolar disorder: associations with age of onset and psychiatric co-morbidity.

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 1cm of scalp hair representing 1 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 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 and psychiatric co-morbidity. 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). In the subgroup of patients with age of onset ≥ 30 years, hair cortisol levels were significantly elevated compared to the subgroup with age of onset <30 years and to healthy controls (p=0.004). Psychiatric co-morbidity was associated with elevated cortisol levels (44.87 versus 31.41 pg/mg hair; p=0.021), with the exclusion of panic disorder, which was associated with decreased cortisol levels (22.13 versus 34.67 pg/mg hair; p=0.019). CONCLUSIONS: Elevated long-term cortisol levels might play a role in a subgroup of patients with BD. There may be differences in pathogenesis of younger and older onset BD suggesting two different disease entities.

Cost-effectiveness of escitalopram in major depressive disorder in the Dutch health care setting.

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.

Antipsychotics switching strategies in real life. A longitudinal study in clinical practice

Background and Objectives: Switching antipsychotics (APs) in the treatment of mental illnesses 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 year2007. 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 180episodes (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 (AU)