Prognostic Factors in First-Episode Schizophrenia : Five-year Outcome of Symptoms, Function and Obesity

Our knowledge of prognostic factors and optimal treatment organisation in schizophrenia is incomplete. The disparity of outcome measures used has been a major obstacle for research. Increasing evidence has shown that schizophrenia is associated with increased cardiovascular mortality, development of obesity and autonomic nervous system imbalance. Assertive community treatment (ACT) has been suggested as a promising direction for organising treatment services for first-episode schizophrenia, but its long-term effect has not been evaluated. One aim of the present thesis was to investigate prognostic factors for 5-year symptomatic and functional outcome and obesity development. A further aim was to evaluate a recently proposed definition of remission and examine the long-term effects of introducing a modified ACT programme (mACT). Thus, we performed a follow-up study of all consecutive first-episode psychosis patients in Uppsala County, Sweden during 1995-2000 (n=144). In the first study we investigated the changes in a broad 5-year outcome of symptoms and function among patients presenting first time ever to psychiatric health care during 3 years before and during 3 years after the implementation of mACT. This change in the psychiatric service, however, was not followed by any long-term clinical benefits. In the second study, we examined the association between remission of eight core schizophrenia symptoms and functional outcome. Remission was strongly associated with having good function and having a higher self-rated satisfaction with life. In the third study, we explored a set of biochemical markers as predictors of weight gain and development of obesity. Haemoglobin, red blood cell count, hematocrit, γ-glutamyltransferase and creatinine were associated with the development of obesity in first-episode schizophrenia. In the fourth and final study, we tested electrocardiographic measures of autonomic imbalance as predictors of symptomatic remission. Higher heart rate and high ST and T-wave amplitudes were related to symptomatic remission, indicating that cardiac autonomic imbalance at baseline may have a prognostic value in first-episode schizophrenia

Habitual caffeine consumption moderates the antidepressant effect of dorsomedial intermittent theta-burst transcranial magnetic stimulation

Background: Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants. Objective: Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS). Methods: Forty patients with current depressive episodes were randomized to active iTBS (n = 19) or sham treatment (n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts. Results: Habitual caffeine consumption was associated with symptom improvement following active iTBS (r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment (r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected (p values > 0.86). Conclusion: Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets

Kunskapsdriven turismutveckling i Västernorrland : Rapport från en förstudie

Den här rapporten redovisar en förstudie som Turismforskningsinstitutet ETOUR utfört på uppdrag av Länsstyrelsen i Västernorrland. Förstudien syftar till att utreda den regionala turismorganisationen i Västernorrlands län, samt analysera tre på förhand utpekade destinationer; Sundsvall med Timrå, Höga Kusten samt en inlandsdestination. I rapporten pekas även på möjliga vägar för fortsatt kunskapsdriven turismutveckling i Västernorrland. Ser vi till de utpekade destinationerna är det idag Sundsvall som förefaller mest kommersiellt driven med flera relativt tunga kommersiella aktörer inblandade i strategiarbetet. Viss otydlighet finns kring destinationens avgränsning, med Timrå och kustområdena som något perifera i den mobilisering som skett kring konferens- och shoppingturism. Vad gäller destinationsorganisation förefaller ett av privat logik dominerat destinationsbolag ligga närmast till hands. På Höga Kusten är bilden något mer sammansatt men grunden för en organisation driven med privat logik finns genom Entré Höga Kusten. Avgränsningen är något otydligt i fråga om hur mycket inland destinationen omfattar och hur det förhåller sig med Härnösands kommun, vid sidan av de dominerande kommunerna Örnsköldsvik och Kramfors. Höga Kusten världsarvsområde ligger helt inom dessa kommuner. Här finns också statligt engagemang genom Naturvårdsverket och Länsstyrelsen i Västernorrlands län. Om det är privat mobilisering kring turism som åsyftas förefaller dock Entré Höga Kusten med sina 110 medlemmar vara den naturliga organisatoriska basen. I Inlandet, som i denna studie främst behandlar Sollefteå kommun, är organiseringen svag. Ett fåtal privata aktörer mobiliserar krafterna och efterlyser samtidigt ett tydliggörande av kommunens hållning i turismfrågorna. Destinationens avgränsningar är otydliga då kopplingarna till andra delar än Sollefteå kommun är oklara och länkarna till aktörer utanför Ångermanälvens dalgång är svaga. Det är önskvärt med ett tydliggörande av destinationens geografi samt vilka aktörer som räknas och inte. I rapportens sista kapitel finns en diskussion om fortsatt kunskapsuppbyggnad knutet till turismutvecklingsarbetet i Västernorrlands län och dess destinationer. Det är uppenbart att de olika destinationerna skiljer sig åt och då mycket väl kan göra det avseende kunskapsbehov, medan de i andra avseenden kan förmodas ha liknande behov. Detta avsnitt kan ses som en första reflektion utifrån det nu genomförda pilotprojektet. Fortsatt dialog i dessa frågor följer för att kunna konkretiseras i ett eventuellt fortsatt samarbete under hösten 2006

Kunskapsdriven turismutveckling i Västernorrland : Rapport från en förstudie

Den här rapporten redovisar en förstudie som Turismforskningsinstitutet ETOUR utfört på uppdrag av Länsstyrelsen i Västernorrland. Förstudien syftar till att utreda den regionala turismorganisationen i Västernorrlands län, samt analysera tre på förhand utpekade destinationer; Sundsvall med Timrå, Höga Kusten samt en inlandsdestination. I rapporten pekas även på möjliga vägar för fortsatt kunskapsdriven turismutveckling i Västernorrland. Ser vi till de utpekade destinationerna är det idag Sundsvall som förefaller mest kommersiellt driven med flera relativt tunga kommersiella aktörer inblandade i strategiarbetet. Viss otydlighet finns kring destinationens avgränsning, med Timrå och kustområdena som något perifera i den mobilisering som skett kring konferens- och shoppingturism. Vad gäller destinationsorganisation förefaller ett av privat logik dominerat destinationsbolag ligga närmast till hands. På Höga Kusten är bilden något mer sammansatt men grunden för en organisation driven med privat logik finns genom Entré Höga Kusten. Avgränsningen är något otydligt i fråga om hur mycket inland destinationen omfattar och hur det förhåller sig med Härnösands kommun, vid sidan av de dominerande kommunerna Örnsköldsvik och Kramfors. Höga Kusten världsarvsområde ligger helt inom dessa kommuner. Här finns också statligt engagemang genom Naturvårdsverket och Länsstyrelsen i Västernorrlands län. Om det är privat mobilisering kring turism som åsyftas förefaller dock Entré Höga Kusten med sina 110 medlemmar vara den naturliga organisatoriska basen. I Inlandet, som i denna studie främst behandlar Sollefteå kommun, är organiseringen svag. Ett fåtal privata aktörer mobiliserar krafterna och efterlyser samtidigt ett tydliggörande av kommunens hållning i turismfrågorna. Destinationens avgränsningar är otydliga då kopplingarna till andra delar än Sollefteå kommun är oklara och länkarna till aktörer utanför Ångermanälvens dalgång är svaga. Det är önskvärt med ett tydliggörande av destinationens geografi samt vilka aktörer som räknas och inte. I rapportens sista kapitel finns en diskussion om fortsatt kunskapsuppbyggnad knutet till turismutvecklingsarbetet i Västernorrlands län och dess destinationer. Det är uppenbart att de olika destinationerna skiljer sig åt och då mycket väl kan göra det avseende kunskapsbehov, medan de i andra avseenden kan förmodas ha liknande behov. Detta avsnitt kan ses som en första reflektion utifrån det nu genomförda pilotprojektet. Fortsatt dialog i dessa frågor följer för att kunna konkretiseras i ett eventuellt fortsatt samarbete under hösten 2006

Psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression and its relationship to affective symptoms

Background There is a conceptual overlap between negative and depressive symptoms, requiring further exploration to advance the understanding of negative symptoms. The aim of this study was to examine psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression, and to explore the relationship between the negative and affective symptoms domains. Methods Fifty-one patients with a depressive episode were included and interviewed with the CAINS and the Brief Psychiatric Rating Scale—Expanded (BPRS-E). Self-reported depressive symptoms were collected with the Montgomery-Asberg Depression Rating Scale (MADRS-S). Inter-rater agreement, internal consistency and validity measures were examined, as were correlations between negative and affective symptoms. Results The intraclass correlation for the CAINS motivation and pleasure subscale (CAINS-MAP) was 0.98 (95% CI 0.96–0.99) and that for the expressional subscale (CAINS-EXP) was 0.81 (95% CI 0.67–0.89). Cronbach’s alpha was 0.71 (95% CI 0.57–0.82) for the CAINS-MAP and 0.86 (95% CI 0.79–0.92) for the CAINS-EXP. The correlation with the negative symptoms subscale of the BPRS-E was 0.35 (p = 0.011, blinded/different raters) or 0.55 (p &lt; 0.001, not blinded/same rater). The CAINS-MAP correlated with the affective symptoms subscale of the BPRS-E (r = 0.39, p = 0.005) and the MADRS-S total score (r = 0.50, p &lt; 0.001), but not with anxiety symptoms. Conclusions Negative symptoms in depression can be assessed with the CAINS with good inter-rater agreement and acceptable internal consistency and validity. There are associations between negative and depressive symptoms that call for further exploration.De två första författarna delar förstaförfattarskapet</p

Application of positron emission tomography in psychiatry-methodological developments and future directions.

Mental disorders represent an increasing source of disability and high costs for societies globally. Molecular imaging techniques such as positron emission tomography (PET) represent powerful tools with the potential to advance knowledge regarding disease mechanisms, allowing the development of new treatment approaches. Thus far, most PET research on pathophysiology in psychiatric disorders has focused on the monoaminergic neurotransmission systems, and although a series of discoveries have been made, the results have not led to any material changes in clinical practice. We outline areas of methodological development that can address some of the important obstacles to fruitful progress. First, we point towards new radioligands and targets that can lead to the identification of processes upstream, or parallel to disturbances in monoaminergic systems. Second, we describe the development of new methods of PET data quantification and PET systems that may facilitate research in psychiatric populations. Third, we review the application of multimodal imaging that can link molecular imaging data to other aspects of brain function, thus deepening our understanding of disease processes. Fourth, we highlight the need to develop imaging study protocols to include longitudinal and interventional paradigms, as well as frameworks to assess dimensional symptoms such that the field can move beyond cross-sectional studies within current diagnostic boundaries. Particular effort should be paid to include also the most severely ill patients. Finally, we discuss the importance of harmonizing data collection and promoting data sharing to reach the desired sample sizes needed to fully capture the phenotype of psychiatric conditions

A blinded validation of the Swedish version of the Clinical Assessment Interview for Negative Symptoms (CAINS)

PURPOSE: The Clinical Assessment Interview for Negative Symptoms (CAINS) was developed in order to advance the assessment of negative symptoms. The aim of this study was to validate the Swedish version of the CAINS. MATERIALS AND METHODS: Thirty-four out-patients with a schizophrenia spectrum disorder were recruited. All patients were videotaped while interviewed with the CAINS and the Brief Psychiatric Rating Scale (BPRS). Another rater watched the video recordings in the reverse order, enabling a blinded design. The patients also filled in self-reported measures of depression, quality of life, and social and vocational functioning. We calculated inter-rater agreement and internal consistency for the CAINS. We also calculated validity measures by correlating the subscales Motivation and Pleasure (CAINS-MAP) and Expression (CAINS-EXP) to subscales of the BPRS. RESULTS: The blinded inter-rater agreement for the CAINS total score was high (ICC = 0.92) but slightly lower for the expression subscale (ICC = 0.76). Cronbach's alpha was 0.84 for the total score. Convergent validity with the negative symptoms subscale of BPRS was different for the blinded and the unblinded data, with a CAINS-MAP correlation of 0.10 (p = 0.580) and a CAINS-EXP correlation of 0.48 (p = 0.004) in the blinded data. The unblinded data had a CAINS-MAP correlation of 0.38 (p = 0.026) and a CAINS-EXP correlation of 0.87 (p &lt; 0.001). Self-rated measures of anhedonia correlated to CAINS-MAP with a coefficient of 0.68 (p &lt; 0.001), while the CAINS-EXP only had a correlation of 0.16 (p = 0.366) to these measures. CONCLUSION: The Swedish version of the CAINS displays adequate psychometric properties in line with earlier validation studies

Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression

Background: Prefrontal repetitive transcranial magnetic stimulation is an established add-on treatment for major depressive disorder and is increasingly feasible with protocols of short duration, such as intermittent theta burst stimulation (iTBS). The most common and limiting side effect is pain at the site of application. Our objective was to investigate how pain develops over time in patients with depression receiving iTBS compared to sham stimulation. Methods: This is a subsample from a randomized clinical trial. Patients received daily sessions of 2400 pulses of dorsomedial prefrontal iTBS or sham stimulation with transcutaneous electric stimulation during 2 to 3 weeks. After unmasking of treatment allocation, patients receiving sham treatment were offered active iTBS in an open phase. Patients rated pain on a scale from 0 to 10 after the last train of stimulation on the first, fifth and final treatment day. A Mann-Whitney U-test was conducted to test for group differences and related-samples Friedman's tests to analyze changes in pain ratings over time. Results: The scalp pain in the group receiving iTBS was rated higher than sham treatment on the first (U = 263.5,p = 0.035) and fifth day (U = 271.0,p = 0.020) but not on the final day (U = 210.5,p = 0.121). The pain decreased mainly during the first 5 days of treatment (chi(2) = 0.875,p = 0.040). In the open phase the pain decreased from the first day to the final day (chi(2) = 1.194,p = 0.001). Conclusions: The subjective pain perception of active dorsomedial iTBS was higher than sham treatment but decreased over time, indicating an analgesic effect, or habituation. The result from this study can be used to inform patients about what to expect regarding pain during an iTBS treatment course. Trial registration: Clinicaltrials.gov, NCT02905604. Registered 19 September 2016

No effects on heart rate variability in depression after treatment with dorsomedial prefrontal intermittent theta burst stimulation

Background: The purpose of this study was to investigate whether treatment of a depressive episode with intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) had any effects on heart rate variability (HRV). We also investigated if changes in HRV covaried with symptom change after iTBS and if HRV could predict symptom change. Methods: We included 49 patients with a current depressive episode. All were randomized to receive a double-blind treatment course with active or sham iTBS over the DMPFC. HRV data were obtained from 1 h of night data before and after the iTBS. The standard deviation of the RR interval (SDNN) was chosen as primary outcome measure. Depressive, negative, and anxiety symptoms as well as self-rated health were assessed by clinicians or by self-report. Results: The group×time linear mixed model revealed no effect of iTBS on SDNN (estimate = −1.8, 95% confidence interval [CI]: −19.9 to 16.2). There were neither correlations between HRV and depressive, negative, or anxiety symptom change after iTBS nor with self-assessed health. No predictive value of HRV was found. Conclusions: Treatment for depression with dorsomedial iTBS had neither negative nor positive effects on the cardiac autonomic nervous system.Title in thesis list of papers: No effects on heart rate variability after a treatment course of dorsomedial prefrontal intermittent theta burst stimulation in depression</p