| 1. |
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| 2. |
- Bengtsson, Johan, et al.
(author)
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A blinded validation of the Swedish version of the Clinical Assessment Interview for Negative Symptoms (CAINS)
- 2022
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In: Nordic Journal of Psychiatry. - : Taylor & Francis. - 0803-9488 .- 1502-4725. ; 76:1, s. 44-51
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Journal article (peer-reviewed)abstract
- 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 < 0.001). Self-rated measures of anhedonia correlated to CAINS-MAP with a coefficient of 0.68 (p < 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.
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| 3. |
- Bengtsson, Johan, et al.
(author)
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Ambulatory Heart Rate Variability in Schizophrenia or Depression : Impact of Anticholinergic Burden and Other Factors
- 2021
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In: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 41:2, s. 121-128
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Journal article (peer-reviewed)abstract
- BACKGROUND: Heart rate variability (HRV) has been found reduced in patients with schizophrenia and depression. However, there is a lack of knowledge on how demographic, lifestyle, and pharmacological factors contribute to the reduction in HRV in these patients.METHODS: We recruited 37 patients with schizophrenia, 43 patients with unipolar depression, and 64 healthy controls. A combined chest-worn HRV and accelerometer device was used in an ambulatory measurement. Age, sex, anticholinergic burden of medication, nicotine use, body mass index, and ongoing physical activity were assessed in multiple regression models regarding their influence on HRV, measured as the standard deviation of all the RR intervals (SDNN).RESULTS: In the fully adjusted model, schizophrenia (β = -0.23, P = 0.019), depression (β = -0.18, P = 0.028), age (β = -0.34, P < 0.000), ongoing physical activity (β = -0.23, P = 0.001), and anticholinergic burden (β = -0.19, P = 0.025) influenced SDNN negatively. Sex, nicotine use, and BMI had negligible effects on SDNN.CONCLUSIONS: We show for the first time that a quantified score of anticholinergic burden of medication has a negative relationship to HRV in patients with schizophrenia or depression, but that the diagnoses themselves still exhibit an effect on HRV.
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| 4. |
- Bengtsson, Johan, et al.
(author)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
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Journal article (peer-reviewed)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 5. |
- Bengtsson, Johan
(author)
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Negative symptoms, repetitive transcranial magnetic stimulation and heart rate variability in schizophrenia and depression
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Negative symptoms comprise anhedonia, avolition, and blunted affect. Although first described in schizophrenia, these symptoms share phenomenology with the depressive state. Pharmacological treatment has not been successful in reducing negative symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment option for moderate to severe depression. There have also been attempts to treat negative symptoms in both schizophrenia and depression with rTMS.Cardiovascular disease is common in schizophrenia and depression. Heart rate variability (HRV) is an established proxy for cardiac autonomic functioning and numerous studies have found lower HRV in patients with schizophrenia and depression. The impact of psychopharmacological treatment on HRV has been extensively studied and anticholinergic compounds have been found to decrease HRV.Lastly, since the most commonly used rTMS depression targets are also the brain regions involved in central autonomic regulation, there is reason to consider a potential effect of rTMS on HRV.The overall aim of this thesis was to investigate negative symptoms, rTMS, and HRV in schizophrenia and depression.Study I was a validation study of a Swedish translation of the Clinical Assessment Interview for Negative Symptoms (CAINS). Thirty-four patients with schizophrenia were interviewed and it was concluded that the Swedish version of the CAINS exhibited acceptable psychometric properties.Study II was a double-blind randomized controlled trial of rTMS for negative symptoms in schizophrenia and depression. There was a significant decrease of negative symptoms in the depression group, but not in the schizophrenia group. There were no effects on overall depressive symptoms in either group.Study III assessed determinants of HRV in schizophrenia, depression, and healthy controls. The results indicated lower HRV in both patient groups, even after controlling for several factors, and also that anticholinergic burden impacted HRV.In Study IV, the relationship between HRV and the functional and structural connectivity of the anterior cingulate cortex was investigated in patients with schizophrenia and compared with that in healthy controls. It was found that connectivity with the cerebellum might play a role in the autonomic modulation network in patients with schizophrenia.Lastly, in Study V, the effect of a treatment course with rTMS on HRV was investigated in patients with depression, as well as HRV’s relationship to symptom change. No effects on HRV were detected, nor any correlations between HRV and symptom change. Further, baseline HRV could not predict treatment response.
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| 6. |
- Bengtsson, Johan, et al.
(author)
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No effects on heart rate variability in depression after treatment with dorsomedial prefrontal intermittent theta burst stimulation
- 2023
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In: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Bengtsson, Johan, et al.
(author)
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Psychometric properties of the Clinical Assessment Interview for Negative Symptoms (CAINS) in patients with depression and its relationship to affective symptoms
- 2023
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In: Annals of General Psychiatry. - : BioMed Central (BMC). - 1744-859X. ; 22:1
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Journal article (peer-reviewed)abstract
- BackgroundThere 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.MethodsFifty-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.ResultsThe 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 < 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 < 0.001), but not with anxiety symptoms.ConclusionsNegative 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.
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| 8. |
- Bengtsson, Johan, et al.
(author)
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Theta burst transcranial magnetic stimulation of the dorsomedial prefrontal cortex in schizophrenia and depression
- 2015
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In: Brain Stimulation. - : Elsevier BV. - 1935-861X.
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Conference paper (peer-reviewed)abstract
- Negative symptoms in schizophrenia and core depressive symptoms share phenomenology and repetitive transcranial magnetic stimulation (rTMS) is a treatment modality for both conditions. The most common treatment site has been the dorsolateral prefrontal cortex (DLPFC) but there might be more optimal targets. Furthermore, the implementation of the currently approved protocols is hampered by the long duration. More intense stimulation protocols such as the theta burst stimulation (TBS) are significantly shorter and may be as effective and safe.The overall aim of this project is to evaluate the treatment effect of TBS on poor motivation and anhedonia in schizophrenia and depression and to explore the neurobiological correlates of these deficits.The dorsomedial prefrontal cortex (dmPFC) is a key cortical area in networks associated with motivation and anhedonia and it is affected in both schizophrenia and depression. The dmPFC has recently been identified as a possible site of stimulation and is now within reach by new angled coils that have deeper tissue penetration.Our study will enroll 38 patients with schizophrenia, 38 patients with depression and 38 healthy volunteers. Patients will be given daily TBS (totally 2400 pulses, 1200 on each hemisphere) over the dmPFC during 10 days. Target symptoms will be assessed with the Clinical Assessment Interview for Negative Symptoms (CAINS). We will also assess cortical excitability with paired-pulse stimulation and the pre-attentive memory function with mismatch negativity (MMN), spontaneous motor activity (assessed with 24 hours accelerometer) as well as autonomic nervous system tone (assessed by skin conductance, heart rate variability and breathing pattern). In addition, we will evaluate cognitive function (speed of processing, verbal fluency, auditory and working memory, visuospatial ability) during rest and stress.
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| 9. |
- Björkenstam, C., et al.
(author)
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Suicide in first episode psychosis : A nationwide cohort study
- 2014
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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 157:1-3, s. 1-7
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Journal article (peer-reviewed)abstract
- Background: Relatively little is known about suicide in diagnostic subtypes of first episode psychosis (FEP). Our aim was to assess suicide rates and potential risk factors for suicide in FEP. Methods: This is a national register-based cohort study of patients born in 1973-1978 in Sweden and who were hospitalized with a FEP between ages 15 and 30 years (n = 2819). The patients were followed from date of discharge until death, emigration, or 31st of December 2008. The suicide rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate ratios (IRRs) were calculated to evaluate the association between suicide and psychiatric, familial, social, and demographic factors. Results: In total 121 patients died by suicide. The overall suicide rate was 4.3 (95% confidence interval [CI] 3.5-5.0) per 1000 person-years. The highest suicide rates were found in depressive disorder with psychotic symptoms and in delusional disorder. In an adjustedmodel, the strongest risk factors for suicide were self-harm (IRR 2.7, CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2-3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk factors for suicide. Conclusions: Impulsive behavior such as self-harm as well as having a family history of severe mental disorder or substance use are important risk factors for suicide in FEP.
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| 10. |
- Björkenstam, E., et al.
(author)
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A five year diagnostic follow-up of 1840 patients after a first episode non-schizophrenia and non-affective psychosis
- 2013
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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 150:1, s. 205-210
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Journal article (peer-reviewed)abstract
- ObjectiveIt is not clear which patients with a first psychotic episode will develop schizophrenia. We performed a diagnostic follow-up of patients treated for a first time non-affective, non-schizophrenia psychosis and explored potential predictors of a subsequent schizophrenia or schizoaffective diagnosis.MethodsThis register-based cohort study comprises individuals born between 1973 and 1978 in Sweden, with a first hospital-treated psychosis excluding schizophrenia, schizoaffective disorder, bipolar disorder and depressive disorder with psychotic symptoms (n = 1840). The patients were followed for five years regarding subsequent diagnoses. Psychiatric, social, family history of psychiatric illness, premorbid intellectual level, head injuries and obstetrical complications were investigated by logistic regression as predictors of schizophrenia or schizoaffective diagnosis.ResultsDuring the follow-up, 18% were diagnosed with schizophrenia or schizoaffective disorder, 5% were diagnosed with bipolar disorder, whereas 29% were not re-admitted to a psychiatric clinic. Patients with a first-degree relative hospitalized for schizophrenia and/or bipolar disorder had an increased risk of subsequent diagnosis for schizophrenia or schizoaffective disorder (odds ratio 1.9 and 95% confidence interval 1.1 to 3.0)), whereas previous severe criminality was associated with a decreased risk (odds ratio 0.5, 95% confidence interval 0.3–0.8).ConclusionDiagnostic outcome was diverse after a first non-schizophrenia and non-affective psychosis. Family history of severe mental illness and no previous conviction for severe criminality were the strongest risk factors for a future schizophrenia or schizoaffective diagnosis.
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| 11. |
- Bodén, Bo, et al.
(author)
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Kunskapsdriven turismutveckling i Västernorrland : Rapport från en förstudie
- 2006
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Reports (other academic/artistic)abstract
- 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.
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| 12. |
- Boden, Robert, et al.
(author)
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A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice
- 2013
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In: Neuropsychiatric Disease and Treatment. - 1176-6328 .- 1178-2021. ; 9, s. 371-377
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Journal article (peer-reviewed)abstract
- It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values) were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08-3.04), reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01-2.97; and OR = 2.03, 95% CI 1.32-3.13), hypertension with perphenazine (OR = 2.00, 95% CI 1.21-3.59), and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05-0.89) and positively with haloperidol (OR = 2.02, 95% CI 1.18-3.48). There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In conclusion, treatment with antipsychotic drugs is differentially associated with cardiovascular risk factors, even after adjusting for waist circumference, sex, age, and smoking.
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| 13. |
- Bodén, Robert, et al.
(author)
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Antidopaminergic drugs and acute pancreatitis : a population-based study
- 2012
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In: BMJ Open. - : BMJ. - 2044-6055. ; 2:3, s. e000914-
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the suggested association between antidopaminergic drugs and acute pancreatitis.DESIGN: A large population-based nested case-control study.SETTING: Swedish nationwide study from 2006 to 2008.PARTICIPANTS: The Patient Register was used to identify 6161 cases of acute pancreatitis. The 61 637 control subjects were randomly selected from the Register of the Total Population by frequency-based density sampling, matched for age, sex and calendar year.EXPOSURE: Exposure data were extracted from the Prescribed Drug Register. Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other antipsychotics. Current use of antidopaminergic drugs was defined as filling a prescription 1-114 days before index date, while previous use was 115 days to 3.5 years before index date.MAIN OUTCOME MEASURES: Cases were defined as being diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using unconditional logistic regression.RESULTS: The unadjusted OR indicated an increased risk of acute pancreatitis among current users of antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable model adjusting for alcohol-related comorbidity, chronic obstructive lung disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone disease, educational level, marital status and number of concomitant medications (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of antidopaminergic drugs followed a similar risk pattern as for current use.CONCLUSIONS: The lack of association between antidopaminergic drugs and acute pancreatitis after adjustment for confounding factors in this study suggests that the previously reported positive associations might be explained by confounding.
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| 14. |
- Bodén, Robert, et al.
(author)
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Antipsychotics During Pregnancy Relation to Fetal and Maternal Metabolic Effects
- 2012
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In: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 69:7, s. 715-721
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Journal article (peer-reviewed)abstract
- Context: Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. Objective: To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. Design: Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. Setting: Swedish national health registers. Participants: All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n=169), (2) other antipsychotics (n=338), or (3) no antipsychotics (n=357 696). Main Outcome Measures: Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. Results: Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). Conclusions: Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.
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| 15. |
- Bodén, Robert, et al.
(author)
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Association between symptomatic remission and functional outcome in first-episode schizophrenia
- 2009
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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 107:2-3, s. 232-237
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Journal article (peer-reviewed)abstract
- Although operational criteria for remission in schizophrenia have recently been proposed, the association of this definition with broader functional outcome has not yet been established in first-episode patients. The severity criteria for remission consist of a score of mild or less on eight core symptoms of schizophrenia. We applied the severity criteria for remission to a sample of patients with first-episode schizophrenia (n = 76) in order to explore the association with functional outcome five years after first presentation to mental healthcare. We evaluated whether other factors than those included in the remission definition predicted good function in logistic regression models. The discriminatory capacities for remission and other factors for good function were tested using C-statistics. The proportions of remitters and non-remitters having good function were 73% and 17%, respectively. Furthermore, remitters had a higher level of subjective satisfaction with life. In comparison with non-remission, symptomatic remission was strongly associated with good function: odds ratio 13.2, 95% confidence interval, 4.3 to 40.3. A duration of untreated psychosis of three months or less as compared with a longer duration was associated with having good function at a five-year follow-up independently of remission status. The discriminatory capacity for symptomatic remission between having good function vs. not was acceptable (C-statistic = 0.78), which was significantly improved to an excellent discriminatory capacity by adding duration of untreated psychosis less than three months (C-statistic = 0.83, p = 0.04). In conclusion, core symptoms of schizophrenia have an important limiting effect on functioning and subjective life satisfaction in the early course of the illness.
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| 16. |
- Bodén, Robert, et al.
(author)
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Biochemical risk factors for development of obesity in first-episode schizophrenia
- 2009
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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 115:2-3, s. 141-145
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Journal article (peer-reviewed)abstract
- Obesity is a serious health issue for many patients with schizophrenia. There is a lack of predictors for and understanding of the development of obesity in the early phase of the illness. Therefore we investigated a set of routine biochemistry variables in blood as predictors of the development of obesity and weight gain over 5 years in an observational cohort study of patients with first-episode schizophrenia (n=59). Twelve percent of the patients were obese at baseline and 37% were obese at the 5-year follow-up. The mean body mass index (BMI) change over 5 years was a 4.1 kg/m(2) increase (4.5 SD). Obesity was predicted by baseline hemoglobin levels (odds ratio per standard deviation [OR/SD] 3.3, 95% confidence interval [CI] 1.4 to 7.5), red blood cell count (OR/SD 2.6, 95% CI 1.2 to 5.5), hematocrit (OR/SD 2.8, 95% CI 1.3 to 5.9), gamma-glutamyltransferase (OR/SD 2.8, 95% CI 1.2-6.3) and creatinine (OR/SD 3.1, 95% CI 1.2 to 8.0). After adjustment for baseline BMI, the associations were attenuated for gamma-glutamyltransferase and creatinine. Low baseline BMI was associated with a greater BMI increase. The major conclusion is that easily available routine biochemistry markers can be useful in predicting the development of obesity in first-episode schizophrenia. The mechanisms underlying the observed associations are unknown, but the predictors identified in this study could signify dehydration or insulin resistance. These observations open a new window to future research on the mechanisms underlying the development of obesity in schizophrenia.
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| 17. |
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| 18. |
- Bodén, Robert, 1973-, et al.
(author)
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Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression : a randomized controlled trial
- 2021
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 290, s. 308-315
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Journal article (peer-reviewed)abstract
- BackgroundIntermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression.MethodsIn this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS).ResultsTwenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group.LimitationsPossibly too short treatment course and few patients with schizophrenia.ConclusionIn this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.
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| 19. |
- Boden, Robert, et al.
(author)
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Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder
- 2011
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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 133:1-3, s. 36-41
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Journal article (peer-reviewed)abstract
- Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30,95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44,95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.
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| 20. |
- Bodén, Robert, 1973-, et al.
(author)
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Electrocardiographic signs of autonomic imbalance in medicated patients with first-episode schizophrenia spectrum disorders : relations to first treatment discontinuation and five-year remission status
- 2012
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In: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 27:3, s. 213-218
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Journal article (peer-reviewed)abstract
- PURPOSE:To explore measures in electrocardiograms (ECG) influenced by autonomic balance in early schizophrenia spectrum disorders and to examine their relation to subsequent first antipsychotic pharmacotherapy discontinuation and five-year remission status.SUBJECTS AND METHODS:Twelve-lead ECGs were recorded at baseline in 58 patients with first-episode schizophrenia spectrum disorders and in 47 healthy controls of similar age. Selected ECG variables included heart rate and measures of repolarization. Pharmacotherapy data were extracted from medical records. At a five-year follow-up the patients were interviewed and assessed with the Positive and Negative Syndrome Scale.RESULTS:Patients had higher heart rate and a different ST-T pattern than the controls. High T-wave amplitudes in the leads aVF and V5 and ST-elevations in V5 were associated both with higher risk of an earlier discontinuation of first antipsychotic pharmacotherapy and with non-remission five years later.DISCUSSION AND CONCLUSION:In this longitudinal cohort study, simple ECG measures influenced by autonomic balance in the early phase of schizophrenia spectrum disorders contained prognostic information. As this is the first report of this association and is based on a relatively small sample, the results should be interpreted with caution.
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| 21. |
- Bodén, Robert, et al.
(author)
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Factors associated with pregabalin dispensing at higher than the approved maximum dose
- 2014
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In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 70:2, s. 197-204
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Journal article (peer-reviewed)abstract
- Concerns have been raised about the abuse potential of pregabalin. Therefore, the aim of our study was to characterize patients dispensed pregabalin at higher than the maximum allowed dose in a cohort study based on data extracted from Swedish national registers. All patients dispensed at least three prescriptions of pregabalin between July 2006 and December 2009 were included (n = 48,550). The daily dose was defined as the amount of pregabalin dispensed divided by the number of days between the second and third dispensings. Associations between sociodemographic and clinical variables and dispensing pregabalin at a dose exceeding the maximum daily allowed dose (600 mg) were investigated in multivariate regression models. Of the patients dispensed pregabalin during the study period, 8.5 % were dispensed a dose that exceeded the maximum daily allowed dose. A previous addictive disorder drug treatment or diagnosis was present in 20 and 31 % of patients dispensed pregabalin within and exceeding the recommended dose range, respectively. Our analysis revealed that those patients at increased risk of being dispensed pregabalin at higher than the maximum allowed dose were male [adjusted odds ratio (aOR) 1.40, 95 % confidence interval (CI) 1.31-1.49], were between 18 and 29 years of age compared with those aged a parts per thousand yen65 years (aOR 1.62, 95 % CI 1.45-1.82), had a low income (aOR 1.24, 95 % CI 1.10-1.40), had epilepsy compared with no diagnosis (aOR 1.41, 95 % CI 1.10-1.81), had a previous substance use disorder treatment or diagnosis (aOR 1.41, 95 % CI 1.31-1.52) or had previously been dispensed high doses of drugs with abuse potential (aOR 1.77, 95 % CI 1.62-1.94). Based on our results we conclude that patients at a high risk of addiction and patients with epilepsy are more likely to be dispensed pregabalin at higher than the maximum approved daily dose.
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| 22. |
- Bodén, Robert, et al.
(author)
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Five-year outcome of first-episode psychosis before and after the implementation of a modified assertive community treatment programme
- 2010
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In: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 45:6, s. 665-674
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Assertive community treatment programmes are increasingly common worldwide but without much knowledge of their long-term effect. We investigated whether the implementation of such a programme would improve symptomatic and functional outcome 5 years later. METHODS: Naturalistic cohort study between 1995 and 2000 of all first-episode psychosis patients (n = 144) in Uppsala County, Sweden. We compared a 3-year period before (non-mACT) and after the introduction of a modified assertive community treatment (mACT) programme in 1998. Five-year outcome was assessed for symptoms and functioning and the two co-primary outcome measures were positive and negative symptoms. Regression models were adjusted for a propensity score based on multiple baseline variables and use of antipsychotics at 5-year follow-up. RESULTS: Contrary to our hypothesis, patients in the mACT group, compared to those in the non-mACT group, had a borderline significant increased risk of having a poor 5-year outcome regarding positive psychotic symptoms [adjusted odds ratio (OR) 3.21, 95% confidence interval (CI) 0.97-10.63]. There was no difference at the 5-year follow-up between the mACT and non-mACT group regarding negative symptoms (adjusted OR 1.65, 95% CI 0.48-5.66), or any of the secondary outcome measures: global assessment of functioning, hazardous alcohol use, use of illicit drugs, working or being in education, independent living, subjective satisfaction with life or suicide. Results were similar in subgroup analyses. CONCLUSIONS: The implementation of a modified assertive community treatment was not followed by subsequent improvements of 5-year outcome on a group level for patients with first-episode psychosis.
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| 23. |
- Boden, Robert, et al.
(author)
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Higher mortality after myocardial infarction in patients with severe mental illness : a nationwide cohort study
- 2015
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 277:6, s. 727-736
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Journal article (peer-reviewed)abstract
- ObjectivesThe aim of this study was to explore the impact of severe mental illness (SMI) on myocardial infarction survival and determine the influence of risk factor burden, myocardial infarction severity and different treatments. Design, setting and participantsThis population-based cohort study, conducted in Sweden during the period 1997-2010, included all patients with a first diagnosis of myocardial infarction in the Swedish nationwide myocardial infarction register SWEDEHEART (n=209592). Exposure was defined as a diagnosis of SMI (i.e. bipolar disorder or schizophrenia) in the national patient register prior to infarction. Bias-minimized logistic regression models were identified using directed acyclic graphs and included covariates age, gender, smoking, diabetes, previous cardiovascular disease, myocardial infarction characteristics and treatment. Main outcome measuresThe outcomes were 30-day and 1-year mortality, obtained through linkage with national population registers. ResultsPatients with bipolar disorder (n=442) and schizophrenia (n=541) were younger (mean age 68 and 63years, respectively) than those without SMI (n=208609; mean age 71years). The overall 30-day and 1-year mortality rates were 10% and 18%, respectively. Compared with patients without SMI, patients with SMI had higher 30-day [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.55-2.56] and 1-year mortality (OR 2.11, 95% CI 1.74-2.56) in the fully adjusted model. The highest mortality was observed amongst patients with schizophrenia (30-day mortality: OR 2.58, 95% CI 1.88-3.54; 1-year mortality: OR 2.55, 95% CI 1.98-3.29). ConclusionSMI is associated with a markedly higher mortality after myocardial infarction, also after accounting for contributing factors. It is imperative to identify the reasons for this higher mortality.
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| 24. |
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| 25. |
- Bodén, Robert, 1973-
(author)
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Prognostic Factors in First-Episode Schizophrenia : Five-year Outcome of Symptoms, Function and Obesity
- 2010
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Doctoral thesis (other academic/artistic)abstract
- 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.
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