| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Bodén, Robert, 1973-, et al.
(author)
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Suppressing visual hallucinations in an adolescent by occipital transcranial magnetic stimulation: A single-case experimental research design.
- 2021
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In: Neuropsychological rehabilitation. - : Informa UK Limited. - 1464-0694 .- 0960-2011. ; 33:2, s. 346-55
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Journal article (peer-reviewed)abstract
- Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited.
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| 9. |
- Brenner, Philip, et al.
(author)
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Substance use disorders and risk for treatment resistant depression : a population-based, nested case-control study
- 2020
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In: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 115:4, s. 768-777
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Journal article (peer-reviewed)abstract
- Background and aims: Treatment-resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD.Design: Nested case-control study.Setting: Nation-wide governmental health-care registers in Sweden.Cases and controls: Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio-demographic data with five controls with depression.Measurements: Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio-demographic covariates.Findings: Having any SUD during, or <= 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [<= 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70-2.05]. Increased risks for TRD were found <= 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88-2.99), opioids (aOR = 2.02; 1.48-2.75), alcohol (aOR = 1.77; CI = 1.59-1.98) and combined substance use (aOR = 2.31; 1.87-2.99).Conclusions: Recent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.
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| 10. |
- Cervenka, Simon, et al.
(author)
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Application of positron emission tomography in psychiatry-methodological developments and future directions
- 2022
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In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Journal article (peer-reviewed)abstract
- 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.
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| 11. |
- Clapham, Eric, et al.
(author)
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Exposure to risperidone versus other antipsychotics and risk of osteoporosis-related fractures : a population-based study
- 2020
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In: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 141:1, s. 74-83
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Journal article (peer-reviewed)abstract
- Objective Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. Methods Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. Conclusion Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.
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| 12. |
- Clapham, Eric
(author)
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Suicide in schizophrenia and adverse events during antipsychotic medication
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This thesis considers side effects and other adverse events during treatment with antipsychotic medication. All included studies use an epidemiological methodology with data from Swedish population-based health registers. The first two studies utilise a nested case-control design, whereas the third and fourth studies rely on cohort designs.The first study considers the impact of extrapyramidal symptoms on suicidality in a schizophrenia spectrum patient group in Stockholm County in Sweden. In this sample, extrapyramidal symptoms are found to be associated with a decreased risk of suicide.The second study involves suicidal communication, blindly extracted from patient records, as risk factors for suicide among patients with schizophrenia spectrum disorders. More severe forms of suicidal ideation and behaviour, such as suicide attempt, are associated with a higher risk of death by suicide, which is consistent with current clinical practice regarding suicide risk assessments.The third study considers the risk of bone fracture during treatment with antipsychotic medications. The study finds that risperidone is not associated with an increased risk of fracture compared with first-generation antipsychotics.The fourth study considers the risk of perimyocarditis and heart failure during treatment with clozapine and the chemically similar medications olanzapine and quetiapine. It finds that clozapine is associated with a substantially elevated risk of perimyocarditis in the short term and a more modest risk of heart failure in the long term, compared with no antipsychotic treatment. Treatment with at least one of olanzapine or quetiapine is not found to be associated with an increased risk of these adverse cardiac events, compared with no antipsychotic medication.
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| 13. |
- Clapham, Eric, et al.
(author)
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The association between exposure to clozapine, olanzapine, and quetiapine and the outcomes perimyocarditis and heart failure : A population-based cohort study
- 2023
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In: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 326
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Journal article (peer-reviewed)abstract
- The risk of cardiac adverse events following clozapine use is debated and is unknown for the chemically related and widely used antipsychotics olanzapine and quetiapine. National Swedish registers were used to identify all patients 16-75 years old with antipsychotic dispensations between 2005 and 2018. The short-term outcome was a diagnosis of perimyocarditis (pericarditis and/or myocarditis) within two months of first dispensation, and the long-term outcome was heart failure (including cardiomyopathy) within three years. Cox regressions with time varying exposure were used to estimate hazard rates (HR) and their 95% confidence intervals (CI). A total of 201,045 individuals were included in the cohort. The risk of developing perimyocarditis during clozapine treatment tripled compared to no antipsychotic treatment (HR 3.4, CI 1.6-7.3), although the absolute rate remained comparably low. The long-term risk of heart failure during clozapine treatment was also elevated (HR 1.3, CI 1.1-1.7). Treatment with either or both olanzapine or quetiapine was not associated with an increased relative risk of perimyocarditis, or heart failure compared to no antipsychotic treatment. Clozapine use is therefore associated with a substantially elevated short-term risk of perimyocarditis and an increased risk of heart failure within three years.
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| 14. |
- Ekman, Carl Johan, et al.
(author)
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Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression - A Swedish register-based study
- 2023
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 329, s. 50-54
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Journal article (peer-reviewed)abstract
- BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response.METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis.RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported.LIMITATIONS: Retrospective analysis of register data. No comparison group.CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.
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| 15. |
- Frick, Andreas, Docent, et al.
(author)
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Habitual caffeine consumption moderates the antidepressant effect of dorsomedial intermittent theta-burst transcranial magnetic stimulation
- 2021
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In: Journal of Psychopharmacology. - : Sage Publications. - 0269-8811 .- 1461-7285. ; 35:12, s. 1536-1541
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Journal article (peer-reviewed)abstract
- 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.
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| 16. |
- Hagg, David, et al.
(author)
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A register-based approach to identifying treatment-resistant depression : Comparison with clinical definitions
- 2020
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Journal article (peer-reviewed)abstract
- Background Several definitions of treatment-resistant depression (TRD) are used for clinical research, but no verified model for use in register data exists. We aimed to compare a novel model created for use in register data-the Karolinska Institutet Model (KIM)-to the clinical definitions regarding the proportion of patients identified with TRD, their characteristics and clinical outcomes. Methods All patients in Sweden initiating antidepressant treatment with a diagnosis of depression in specialized healthcare 2006-2014 were identified and followed in national registers. In KIM, patients who initiated a third sequential, >28-day antidepressant treatment trial were defined as having TRD. Proportion of TRD and patient characteristics were compared with register adaptations of the European Staging Model (ESM), Massachusetts General Hospital Staging Method (MGH-s), and Maudsley Staging Model (MSM). Differences in patient characteristics were assessed with Chi-square tests and one-way ANOVAs. Hazard ratios for psychiatric hospitalization and for death from external causes were estimated by Cox proportional hazard regressions. Results Out of 127,108 antidepressant initiators with depression, the highest proportion of TRD was found using the MGH-s (19.0%), followed by MSM (15.3%), KIM (12.9%), and ESM (9.5%). Clinical characteristics were similar across the models. Compared with TRD patients identified by KIM, those identified by ESM had a marginally higher risk for psychiatric hospitalization (adjusted hazard ratio [aHR] 1.03, 95%CI 1.00-1.05), whereas those identified by MGH-s (aHR 0.92; 0.90-0.94) and MSM (aHR 0.95; 0.94-0.97) had a slightly reduced risk. Patients identified by MGH-s showed a reduced mortality compared with KIM (aHR 0.84; 0.72-0.98). Conclusions This study provides insight into the differing characteristics of patients captured by various TRD models when used for register research. Models yielding lower proportions of TRD seemed to identify patients with greater morbidity. The KIM may be useful for register based research in TRD.
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| 17. |
- Kaboodvand, Neda, et al.
(author)
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Macroscopic resting state model predicts theta burst stimulation response : A randomized trial
- 2023
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In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:3
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Journal article (peer-reviewed)abstract
- Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner.Computational modelling combined with a probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil.We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony.Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.
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| 18. |
- Malm, Erika, et al.
(author)
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Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression
- 2020
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In: BMC Neurology. - : BMC. - 1471-2377. ; 20:1
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Journal article (peer-reviewed)abstract
- 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.
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| 19. |
- Maron, David J., et al.
(author)
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Initial Invasive or Conservative Strategy for Stable Coronary Disease
- 2020
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
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Journal article (peer-reviewed)abstract
- Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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| 20. |
- Novicic, Zorana Kurbalija, et al.
(author)
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Lithium influences whole-organism metabolic rate inDrosophila subobscura
- 2021
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In: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:1, s. 407-418
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Journal article (peer-reviewed)abstract
- Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito-nuclear introgression lines ofDrosophila subobscurato disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose-dependent effect on whole-organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole-organism metabolic rate across sexes. The results confirm that lithium influenced the whole-organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.
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| 21. |
- Nygren, Adam, et al.
(author)
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Response to electroconvulsive therapy in treatment resistant depression : A nationwide register-based study
- 2022
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In: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 31:Suppl. 2, s. 310-310
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Journal article (other academic/artistic)abstract
- Background: Electroconvulsive therapy (ECT) is often considered for patients with treatment resistant depression (TRD), as recommended by guidelines from several countries. However, previous studies have shown inconsistent results regarding the response to ECT in patients with TRD.Objectives: To assess and compare the response rate of ECT for patients with TRD to that of other patients with depression (i.e. non-TRD) in a large and clinically representative patient sample. We hypothesized that patients with TRD would have a lower ECTresponse rate than other patients with depression.Methods: Patients ≥18 years old, treated for a unipolar, non-psychotic depressive episode with at least one ECT session as part of a first-time, index ECT series between Jan. 1 2011 and Dec. 31 2017 were identified from the Swedish National Quality Register for ECT, and individually linked with other population-based registers. Patients with any life timediagnosis of bipolar disorder, manicor hypomanic episode, psychotic disorder, or dementia as well as those lacking registration of the primary out-come measure were excluded. Using the Prescribed Drug Register, we classified patients as having TRD if they had initiated a third consecutive trial of antidepressants or add-on medications before starting ECT. Remaining patients were considered to have other depression. The main outcome measure was response to ECT according to the Clinical Global Impressions–Improvement scale (CGI-I) assessed within a week after the ECT series, defined as a CGI-I assessment of ‘much' or ‘very much improved'. Outcome measures were compared between patients with TRD and with other depression using logistic regression to calculate odds ratios of response and corresponding confidence intervals, adjusting for potential confounders including sociodemographic and clinical covariates.Results: A total of 4244 patients were included. Of these, 1121 patients were classified as TRD (61.2% female, mean age 51.4 years) and 3123 (54.3 % female, mean age 50.4 years) patients had other depression. The CGI-I response rate after ECT among patients with TRD was 65.9% compared to 75.9% in other patients with depression (adjusted odds ratio 0.64 [95% CI 0.54–0.75]).Conclusions: A clear majority of patients with TRD as well as patients with other depression responded to ECT, although the response rate was lower in TRD.
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| 22. |
- Nygren, Adam, et al.
(author)
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Response to electroconvulsive therapy in treatment-resistant depression : nationwide observational follow-up study
- 2023
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In: BJPsych Open. - : Royal College of Psychiatrists. - 2056-4724. ; 9:2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies have not investigated response rates after electroconvulsive therapy (ECT) in patients with non-psychotic treatment-resistant depression (TRD).AIMS: To assess and compare the response rate of ECT for patients with TRD and non-TRD, in a large and clinically representative patient sample.METHOD: Patients aged ≥18 years, who were treated for a unipolar, non-psychotic depressive episode with at least one ECT session as part of a first-time, index ECT series between 1 January 2011 and 31 December 2017 were included from the Swedish National Quality Register for ECT. Patients who had initiated a third consecutive trial of antidepressants or add-on medications before start of ECT were classified as having TRD. Patients not meeting criteria for TRD were classified as non-TRD. The main outcome was response to ECT according to the Clinical Global Impressions - Improvement Scale (CGI-I), scored as 1 or 2 ('very much' or 'much improved' after ECT, respectively). Logistic regression was used to compare outcome measures between TRD and non-TRD, adjusting for potential confounders.RESULTS: A total of 4244 patients were included. Of these, 1121 patients had TRD and 3123 patients had non-TRD. The CGI-I response rate was 65.9% in the TRD group compared with 75.9% in the non-TRD group (adjusted odds ratio 0.64, 95% CI 0.54-0.75). Older age and more severe depression were predictors of response in patients with TRD.CONCLUSIONS: A clear majority of patients with TRD, as well as patients with non-TRD, responded to ECT, although the response rate was somewhat lower for TRD.
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| 23. |
- Persson, Jonas, 1983-, et al.
(author)
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Inhibitory and excitatory neurotransmitter systems in depressed and healthy : A positron emission tomography and magnetic resonance spectroscopy study
- 2021
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In: Psychiatry Research. - : Elsevier. - 0925-4927 .- 1872-7506. ; 315
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Journal article (peer-reviewed)abstract
- The Gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems are implicated in depression. While previous studies found reduced GABA levels, and a tendency towards reduced Glu, using proton (H-1) magnetic resonance spectroscopy (H-1-MRS), little is known about GABA(A) receptor availability in depression. Here, the aim was to characterize GABA and Glu-levels in dorsal anterior cingulate cortex (dACC), whole-brain GABA(A) availability, and their relationship in patients with depression compared to healthy controls. Forty-two patients and 45 controls underwent H-1-MRS using a MEGA-PRESS sequence to quantify dACC GABA+ and Glu (contrasted against creatine [Cr]). Immediately preceding the H-1-MRS, a subsample of 28 patients and 15 controls underwent positron emission tomography (PET) with [C-11]Flumazenil to assess whole-brain GABA(A) receptor availability. There were no differences in dACC GABA+/Cr or Glu/Cr ratios between patients and controls. The same was true for whole-brain GABA(A) receptor availability. However, there was a significant negative relationship between GABA+/Cr ratio and receptor availability in ACC, in a whole-brain voxel-wise analysis across patients and controls, controlling for group or depressive symptoms. This relatively large study did not support the GABA-deficit hypothesis in depression, but shed light on GABA-system functioning, suggesting a balance between neurotransmitter concentration and receptor availability in dACC.
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| 24. |
- Persson, Jonas, 1983-, et al.
(author)
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Intermittent theta burst stimulation over the dorsomedial prefrontal cortex modulates resting-state connectivity in depressive patients : A sham-controlled study
- 2020
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 394
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Journal article (peer-reviewed)abstract
- The mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) treatment are largely unknown. Although there is a general lack of sham controlled studies, findings show altered functional connectivity to the stimulated region following treatment. When targeting the dorsolateral prefrontal cortex (dlPFC), connectivity with the subgenual anterior cingulate cortex (sgACC) is predictive of response, but less is known about the effects on functional connectivity of targeting the dorsomedial PFC (dmPFC). Here, 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta burst stimulation (iTBS) over dmPFC. Those receiving sham were offered active treatment in a subsequent open phase. A seven minute resting-state scan and depressive symptom assessment was performed before and after treatment. After exclusions due to attrition and excessive head movements 23 patients remained for analysis. Seed-based resting-state connectivity was calculated using two seeds for the dmPFC target as well as the sgACC. A symptom related increase in dmPFC connectivity after active treatment, compared to sham treatment, was found. The effect was observed in a region overlapping the precuneus and the posterior cingulate cortex (PCC), suggesting an increase in the connectivity between the targeted salience network and the default mode network mediating improvement in depressive symptoms. Connectivity between the precuneus and both the sgACC and the treatment target was predictive of symptom improvement following active treatment. The findings have implications for understanding the mechanisms behind iTBS and may inform future efforts to individualize the treatment.
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| 25. |
- Persson, Jonas, 1983-, et al.
(author)
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Phosphodiesterase 10A levels are related to striatal function in schizophrenia : a combined positron emission tomography and functional magnetic resonance imaging study
- 2020
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In: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:4, s. 451-459
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Journal article (peer-reviewed)abstract
- Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.
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| 26. |
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| 27. |
- Reynolds, Harmony R., et al.
(author)
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Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease : Insights From the ISCHEMIA Trial
- 2024
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In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:5
-
Journal article (peer-reviewed)abstract
- BackgroundWomen with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.Methods and ResultsThe ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions.ConclusionsWomen had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.
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| 28. |
- Steinholtz, Linda, et al.
(author)
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GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy : A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.
- 2024
-
In: Neuropsychobiology. - : S. Karger. - 0302-282X .- 1423-0224. ; 83:1, s. 17-27
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.
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| 29. |
- Steinholtz, Linda, et al.
(author)
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Response rate and subjective memory after electroconvulsive therapy in depressive disorders with psychiatric comorbidity
- 2021
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 292, s. 276-283
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Journal article (peer-reviewed)abstract
- Background: Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain.Methods: Data on patients with a depressive episode and a first course of ECT were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3497 patients.Results: In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34-0.55, and aOR 0.61, 95% CI 0.51-0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57-1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity.Limitations: Observational non-validated clinical data.Conclusions: The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT.
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| 30. |
- Stenmark, Linnea, et al.
(author)
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Predictors of Treatment Response to Electroconvulsive Therapy in Schizophrenia : A Nationwide Registry-Based Study
- 2020
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In: Schizophrenia Bulletin Open. - : Oxford University Press. - 2632-7899. ; 1:1
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Journal article (peer-reviewed)abstract
- Up to 30% of patients with schizophrenia respond insufficiently to antipsychotic drugs. Electroconvulsive therapy (ECT) has been reported to effectively augment the effects of antipsychotics in some of these patients. To date, there are few established predictors of treatment response to ECT in patients with schizophrenia. The primary aim was to determine the response rate to ECT in patients with schizophrenia. The secondary aim was to investigate predictors of treatment response. All patients admitted to any Swedish hospital for schizophrenia from 2011 to 2017, who were treated with ECT while in inpatient care, were included in the Swedish National Quality Registry for ECT (Q-ECT), and were assessed using the Clinical Global Impression – Improvement (CGI-I) scale after treatment were included. CGI-I scores of 1 or 2 were considered a response to treatment. Multiple national registries were used to obtain information on demographics and clinical variables. The study included 285 patients who were concurrently treated with antipsychotic drugs. The response rate to ECT was 73.0%. Among those patients with outcome data, treatment with long-acting injectable antipsychotics was predictive of a better response, whereas comorbid substance use disorders were predictive of a worse response. This study provides new evidence on predictors of who might respond among patients with schizophrenia treated by ECT. Additional studies of ECT in schizophrenia are needed.
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| 31. |
- Strandberg, Pontus, et al.
(author)
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Electroconvulsive Therapy Versus Repetitive Transcranial Magnetic Stimulation in Patients With a Depressive Episode : A Register-Based Study
- 2024
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In: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 40:2, s. 88-95
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions.METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively.RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression.CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.
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| 32. |
- Struckmann, Wiebke, et al.
(author)
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Modulation of dorsolateral prefrontal cortex functional connectivity after intermittent theta-burst stimulation in depression : combining findings from fNIRS and fMRI
- 2022
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In: NeuroImage. - : Elsevier. - 2213-1582. ; 34
-
Journal article (peer-reviewed)abstract
- Background: Resting-state functional magnetic resonance imaging (fMRI) can assess modulation of functional connectivity networks following repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Functional near-infrared spectroscopy (fNIRS) is well suited for the concurrent application during rTMS treatment sessions to capture immediate blood oxygenation (oxy-Hb) effects, however limited in spatial resolution.Objective: To understand the network effects behind such a prefrontal fNIRS response during rTMS, and to test whether the fNIRS signal may be predictive of treatment response, we linked data from fNIRS and fMRI within a clinical intervention study.Methods: 42 patients with ongoing depression were recruited and randomized to receive active or sham intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex (dmPFC) twice daily for ten days at target intensity. Oxy-Hb was recorded with fNIRS during the first, fifth, and final day of iTBS, with the probe holders located laterally to the TMS coil over regions corresponding to the left and right dorsolateral prefrontal cortex (dlPFC). Resting-state fMRI scanning was performed before and after the whole iTBS treatment course. Functional connectivity analyses were then performed using dlPFC seeds from parcels of a brain atlas showing most overlap with the fNIRS probe locations during treatment.Results: After active iTBS, left dlPFC-connectivity to the right insula/operculum was reduced compared to sham. The left insula showed a connectivity reduction to the left dlPFC that correlated with an improvement in symptoms. In addition, the posterior parietal cortex showed a connectivity reduction to the left dlPFC that correlated with the fNIRS signal following active iTBS. Finally, the fNIRS oxy-Hb signal from the left dlPFC-seed during the first treatment day was predictive of dlPFC-connectivity change to precentral and temporal cortex regions.Conclusion: By linking findings from these two different methods, this study suggests that changes within both the salience network and the central executive network affect the fNIRS response to iTBS.
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| 33. |
- Struckmann, Wiebke, et al.
(author)
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Modulation of the prefrontal blood oxygenation response to intermittent theta-burst stimulation in depression : A sham-controlled study with functional near-infrared spectroscopy
- 2021
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In: World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 22:4, s. 247-256
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To better understand the neural mechanisms behind the effect of intermittent theta-burst stimulation (iTBS), we investigated how the prefrontal blood oxygenation response measured by changes in oxygenated haemoglobin (oxy-Hb) was modulated during a sham-controlled iTBS treatment course, and whether this was related to depressive symptom change.METHODS: In this randomised, double-blind study, patients with ongoing treatment-resistant depression received either active (n = 18) or sham (n = 21) iTBS over the dorsomedial prefrontal cortex for ten to fifteen days with two sessions daily. Event-related functional near-infrared spectroscopy (fNIRS) was measured during each iTBS train, and resting-state oxy-Hb was compared before and after each iTBS session at the first, fifth, and last treatment day.RESULTS: Patients receiving active iTBS had an increase of the event-related oxy-Hb response compared to the sham group on the fifth (bilateral prefrontal cortices p < .001) and last (left prefrontal p = .007, right prefrontal p = .025) treatment day. Resting-state analysis showed suppressed oxy-Hb change in active iTBS compared to sham iTBS on the last treatment day (p = .024). Oxy-Hb change was unrelated to depressive symptom change (p = .474).CONCLUSIONS: This study describes a modulation of the blood oxygenation response over the prefrontal cortex that was built up during the course of active iTBS treatment in depression.
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| 34. |
- Struckmann, Wiebke, 1991-
(author)
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The effect of intermittent theta-burst stimulation over the dorsomedial prefrontal cortext on brain activity in depression
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- Repetitive transcranial magnetic stimulation is an emerging alternative for treatment-resistant depression, with ongoing developments in stimulation protocols and treatment targets. As such, intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (dmPFC) has shown promise, however establishing a need for neuroimaging studies to further understand the treatment mechanisms. This thesis aims to explore the effects of dmPFC-iTBS on brain activity in depression, using data from a randomized controlled trial and two add-on brain imaging studies with shared methodology. Study I investigated the prefrontal blood oxygenation (oxy-Hb) response during, as well as before and after iTBS sessions at the first, fifth, and final day of treatment. Oxy-Hb was assessed using functional near-infrared spectroscopy (fNIRS). Study II examined patients’ cognitive performance and concurrent prefrontal oxy-Hb before and after a full iTBS treatment course, again using fNIRS. The patient data were also compared to a sample of healthy controls. Study III assessed whether iTBS modulates functional brain activity during an emotional picture anticipation paradigm, using functional magnetic resonance imaging (fMRI). Study IV investigated the functional connectivity of the brain network behind the oxy-Hb response observed in study I. This was done by using the fNIRS optode locations as seeds in a resting-state fMRI analysis before and after a full iTBS treatment course. In summary, brain activity was modulated by iTBS both in an acute and delayed matter. Patients receiving active iTBS had increased prefrontal oxy-Hb levels during the fifth and final iTBS session, suggesting that this modulation was being built up during the treatment course (study I). Resting-state functional connectivity of this prefrontal cortex region to the insula or, when adding oxy-Hb change as a regressor, the posterior parietal cortex was modulated after active, but not sham, iTBS (study IV). Likewise, amygdala activation during exposure to picture stimuli of negative valence was reduced after active, but not sham, iTBS (study III). While patients displayed cognitive deficits compared to healthy controls before treatment start, active iTBS did not alter their cognitive performance or concurrent prefrontal oxy-Hb (study II).
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| 35. |
- Struckmann, Wiebke, et al.
(author)
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Unchanged cognitive performance and concurrent prefrontal blood oxygenation after accelerated intermittent theta-burst stimulation in depression : a sham-controlled study
- 2021
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In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
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Journal article (peer-reviewed)abstract
- Aim: Intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (DMPFC) has shown promise as a treatment for anhedonia and amotivation in patients with depression. Here, we investigated whether this protocol modulates cognitive performance and concurrent prefrontal blood oxygenation. We also examined whether depressed patients exhibit cognitive dysfunction and prefrontal hypoactivity at baseline compared to healthy controls.Methods: This sham-controlled study comprises 52 patients randomized to either active or sham accelerated iTBS over the DMPFC (applied twice daily) for 10 consecutive treatment days, and 55 healthy controls. Cognitive performance was assessed at baseline and once again 4 weeks later using a cognitive test battery targeting attention, inhibitory control, and numerical, verbal, and visual working memory. Concurrent prefrontal oxygenated hemoglobin (oxy-Hb) was captured with functional near-infrared spectroscopy.Results: Active iTBS over DMPFC did not affect cognitive performance or concurrent oxy-Hb change compared to sham iTBS in patients with depression. Compared to controls, patients at baseline showed impaired performance in the Trail Making Test,the Rey Auditory Verbal Learning Test, the Animal Naming Test, and the Digit Symbol Substitution Test, however no difference in prefrontal oxy-Hb was observed.Conclusion: Patients with treatment-resistant depression displayed cognitive deficits, however without prefrontal hypoactivity, compared to healthy controls at baseline. iTBS treatment did not alter cognitive performance, nor concurrent prefrontal blood oxygenation, in patients. Taken together, iTBS can likely be considered a cognitively safe treatment option in this sample of patients.
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- Thörnblom, Elin, et al.
(author)
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Intercorrelation of physiological seizure parameters and hormonal changes in electroconvulsive therapy
- 2023
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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 77:3, s. 312-318
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Journal article (peer-reviewed)abstract
- Objective Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak heart rate. As a proxy for peripheral endocrine stress response, we examined the correlation to postictal cortisol increase. Methods Participants were consecutively recruited from clinical ECT patients (n = 131, age 18-85 years). The first ECT session in a series was examined. For each participant, blood serum concentrations of prolactin and cortisol were measured immediately before and within 30 min after the seizure. Physiological parameters were extracted from clinical records: peak heart rate (HR) during seizure, electroencephalography (EEG) seizure duration, and motor seizure duration. Correlations were calculated using non-parametric tests. Results Serum prolactin increased after ECT and correlated with peak HR, EEG seizure duration, and motor seizure duration. Peak HR during seizure also correlated positively with both EEG seizure duration and motor seizure duration. Correlations were unaffected by age, sex, baseline prolactin levels, antipsychotics, or beta-blocking agents. Serum cortisol increased after ECT but did not correlate with the seizure evaluation parameters, nor with prolactin concentrations. Conclusions Our findings of a positive correlation between peak HR and prolactin that was independent from the peripheral endocrine stress response might be in line with the idea that tachycardia during ECT seizures reflects seizure propagation to the diencephalon. This supports the practice of monitoring cardiovascular response for ECT seizure evaluation.
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- Trolle Lagerros, Ylva, et al.
(author)
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Risk of Delayed Discharge and Reoperation of Gastric Bypass Patients with Psychiatric Comorbidity : a Nationwide Cohort Study
- 2020
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In: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 30:7, s. 2511-2518
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Journal article (peer-reviewed)abstract
- BackgroundGastric bypass (GBP) surgery is considered a safe and effective treatment for obesity. However, there is uncertainty regarding the impact of preexisting psychiatric comorbidity on GBP complications. We have investigated whether a psychiatric diagnosis before GBP surgery is associated with delayed discharge (the odds of being in the 90th percentile of length of stay) and rate of reoperation in a nationwide Swedish cohort.MethodsPatients undergoing GBP surgery during 2008–2012 were identified and followed up through the National Patient Register and the Prescribed Drug Register. Logistic regression models were fitted to the studied outcomes.ResultsAmong the 22,539 patients identified, a prior diagnosis of bipolar disorder, schizophrenia, depression, neurotic disorders, ADHD (attention deficit hyperactivity disorder), substance use disorder, eating disorder, personality disorder, or self-harm since 1997 (n = 9480) was found to be associated with delayed discharge after GBP surgery (odds ratio [OR] = 1.47, confidence interval [CI] 1.34–1.62), especially in patients with psychiatric hospitalization exceeding 1 week in the 2 years preceding GBP surgery (OR = 2.06, CI 1.30–3.28), compared with those not hospitalized within psychiatry. Likewise, patients with a prior psychiatric diagnosis were more likely to be reoperated within 30 days (OR = 1.25, CI 1.11–1.41), with twice the likelihood OR 2.23 (CI 1.26–3.92) for patients with psychiatric hospitalization of up to a week in the 2 years preceding GBP surgery, compared with patients who had not been hospitalized within psychiatry.ConclusionsA psychiatric diagnosis before GBP surgery was associated with delayed discharge and increased likelihood of reoperation within 30 days. Patients with a prior psychiatric diagnosis may, therefore, need additional attention and support.
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