Publications by authors named "Erik Johnsen"

92 Publications

Use of Benzodiazepines and Antipsychotic Drugs Are Inversely Associated With Acute Readmission Risk in Schizophrenia.

J Clin Psychopharmacol 2022 Jan-Feb 01;42(1):37-42

National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Purpose: Little is known about the impact of different psychotropic drugs on acute readmission risk, when used concomitantly in a real-life setting. We aimed to investigate the association between acute readmission risk and use of antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines in patients with schizophrenia.

Methods: A cohort study included all patients diagnosed with schizophrenia admitted to a psychiatric acute unit at Haukeland University Hospital in Bergen, Norway, during a 10-year period (N = 663). Patients were followed from discharge until first readmission or censoring. Cox multiple regression analyses were conducted using antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines as time-dependent variables, and periods of use and nonuse were compared within individual patients. Adjustments were made for sex, age at index admission, and excessive use of alcohol and illicit substances.

Results: A total of 410 patients (61.8%) were readmitted during follow-up, and the mean and median times in days to readmission were 709 and 575, respectively. Compared with nonuse, the use of antipsychotic drugs was associated with reduced risk of readmission (adjusted hazards ratio, 0.20; P < 0.01; confidence interval, 0.16-0.24), and the use of benzodiazepines was associated with increased risk of readmission (adjusted hazards ratio, 1.51; P < 0.01; confidence interval, 1.13-2.02). However, no relation to readmission risk was found for the use of antidepressants and mood stabilizers.

Conclusions: We found that use of benzodiazepines and antipsychotic drugs are inversely associated with acute readmission risk in schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000001497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677602PMC
December 2021

The association between cytokines and psychomotor speed in a spectrum of psychotic disorders: A longitudinal study.

Brain Behav Immun Health 2021 Dec 23;18:100392. Epub 2021 Nov 23.

NORMENT, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Background: In schizophrenia, impaired psychomotor speed is a common symptom predicting worse functional outcome. Inflammation causes changes in white matter integrity, which may lead to reduced psychomotor speed. Therefore, we wanted to investigate if peripheral inflammation assessed with cytokines affected performance on psychomotor speed in patients with a spectrum of psychotic disorders.

Methods: The current study is a prospective cohort study, including participants from a pragmatic, randomised controlled trial comparing three atypical antipsychotics in patients with a spectrum of psychotic disorders. For the purposes of this sub-study, we analysed drug treatment groups collectively. Psychomotor speed was assessed at baseline, and at weeks 6, 12, 26 and 52 of follow-up, using the neuropsychological tests trail making test (TMT) A and B, and symbol coding. Serum concentration of the following cytokines were measured: interleukin (IL)-β, IL-2, IL-4, IL-6, IL-10, IL12 p70, IL-17a, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Blood samples were collected at baseline and after 1, 3, 6, 12, 26, 39 and 52 weeks. We analysed the effect of cytokines levels on psychomotor speed over time in linear mixed effects models.

Results: In our linear mixed effects models controlling for possible confounders, IFN-γ had a significant negative effect on TMT-A and symbol coding performance. None of the other tests for psychomotor speed were significantly associated with cytokines. Overall psychomotor speed performance increased significantly across the study period while cytokine levels remained stable.

Conclusion: Our study indicates a negative association between IFN-γ and psychomotor speed, which might be of importance when understanding the mechanisms behind psychomotor deviations in psychotic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbih.2021.100392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633579PMC
December 2021

Negative valence of hallucinatory voices as predictor of cortical glutamatergic metabolite levels in schizophrenia patients.

Brain Behav 2022 Jan 7;12(1):e2446. Epub 2021 Dec 7.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Objectives: Negative emotional valence of auditory verbal hallucinations (AVHs) in schizophrenia can be a source of distress and is considered a strong predictor of illness severity. Previous studies have found glutamate to mediate AVH severity in frontal and temporal brain regions, however, they do not specifically address emotional valence of AVH. The role of glutamate for the experience of negative- versus positive emotional valence of AVH is therefore unknown and was investigated in the current study.

Methods: Using magnetic resonance spectroscopy (MRS), 37 schizophrenia patients had Glx (glutamate+glutamine) measured in the left superior temporal gyrus (STG), and additionally in the anterior cingulate cortex (ACC) and the right STG, or in the left inferior frontal gyrus (IFG). Self-reported emotional valence in AVH was measured with the Beliefs About Voices Questionnaire (BAVQ-R).

Results: Results from linear mixed models showed that negative emotional valence was associated with reduced Glx levels across all four measured brain regions in the frontal and temporal lobe. More specifically, voices that were experienced to be omnipotent (p = 0.04) and that the patients attempted to resist (p = 0.04) were related to lower Glx levels. Follow-up analysis of the latter showed that voices that evoked emotional resistance (i.e., fear, sadness, anger), rather than behavioral resistance, was a significant predictor of reduced glutamate (p = 0.02).

Conclusion: The findings could indicate aberrant glutamatergic signaling, or increased NMDA-receptor hypoactivity in patients who experience their voices to be more emotionally negative. Overall, the study provides support for the glutamate hypothesis of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.2446DOI Listing
January 2022

Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation.

Brain Behav Immun 2022 Jan 7;99:299-306. Epub 2021 Nov 7.

Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients.

Methods: We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (n = 1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; n = 1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers.

Results: We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI.

Conclusions: Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2021.10.017DOI Listing
January 2022

Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study.

Schizophr Bull 2022 Jan;48(1):37-46

Norwegian Centre for Mental Disorders Research, NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

Background: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection.

Methods: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP.

Results: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10).

Conclusions: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbab106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781325PMC
January 2022

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder: results from the BeSt InTro study.

NPJ Schizophr 2021 Aug 18;7(1):39. Epub 2021 Aug 18.

Department of Biomedical Sciences of Cells and Systems and Department of Psychiatry, Rijksuniversiteit Groningen (RUG), University Medical Center Groningen (UMCG), Groningen, Netherlands.

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41537-021-00170-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373883PMC
August 2021

The Influence of Substance Use on Side Effects of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Psychosis.

Subst Use Misuse 2021 9;56(12):1880-1891. Epub 2021 Aug 9.

Department of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Background: Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration.

Methods: All patients ( = 226, mean age 34, females 33%) diagnosed with schizophrenia spectrum disorders (SSD; F20-F29) or other psychosis (F30-F32; F10-F19), were treated with olanzapine, quetiapine, risperidone or ziprasidone, and were assessed at baseline, 4-weeks, 14-weeks, and 27-weeks. The UKU-Side Effects Self-Rating Scale version was used to evaluate the side effect profiles, and the information on substance use was based on the Clinician Drug Use Scale.

Results: At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia.

Conclusion: Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10826084.2021.1958858DOI Listing
October 2021

Mortality and non-use of antipsychotic drugs after acute admission in schizophrenia: A prospective total-cohort study.

Schizophr Res 2021 09 21;235:29-35. Epub 2021 Jul 21.

Division of Psychiatry, Haukeland University Hospital, Postboks 1400, 5021 Bergen, Norway; Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, Postboks 1400, 5021 Bergen, Norway; NORMENT, Centre of Excellence, Haukeland University Hospital, Postboks 1400, 5021 Bergen, Norway. Electronic address:

Background: In society at large, it is debated whether use of antipsychotic drugs is associated with increased or decreased mortality among patients with schizophrenia. Large register studies have demonstrated an increased mortality risk associated with non-use of antipsychotic drugs, but prospective studies are missing.

Aims: To investigate the association between mortality and non-use of antipsychotics in patients with schizophrenia.

Method: An open cohort study included and followed all patients with a discharge-diagnosis of schizophrenia consecutively admitted to a psychiatric acute unit at Haukeland University Hospital, Bergen, Norway during a 10 year period (n = 696). Cox multiple regression analyses were conducted with use of antipsychotic drugs as a time dependent variable, and periods of use and non-use were compared within individual patients. Adjustments were made for gender, age at index admission, number of acute psychiatric hospital admissions, excessive use of alcohol and illicit substances and use of benzodiazepines and antidepressants.

Results: A total of 68 (9.8%) deaths were registered during follow-up. Of these, 40 (59%) had natural causes, whereas 26 (38%) had unnatural causes. Non-use of antipsychotics was associated with 2.15 (p = .01, CI: 1.24-3.72) times higher mortality risk compared to use of antipsychotics. The difference in mortality risk between use and non-use of antipsychotic drugs was age dependent, with the largest risk difference in young patients.

Conclusions: Non-use of antipsychotic drugs was associated with twofold increased mortality risk in patients with schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.07.009DOI Listing
September 2021

Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT.

Schizophr Res Cogn 2021 Dec 28;26:100204. Epub 2021 Jun 28.

Norment, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29;  = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scog.2021.100204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255247PMC
December 2021

STN-DBS affects language processing differentially in Parkinson's disease: Multiple-case MEG study.

Acta Neurol Scand 2021 Aug 7;144(2):132-141. Epub 2021 May 7.

Center of Functionally Integrative Neuroscience (CFIN), Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Objectives: In this study, we investigated the effects of bilateral and unilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) in PD patients on neural responses associated with two aspects of spoken language processing: semantics of action-related verbs and morphosyntactic processing.

Materials And Methods: Using a passive unattended paradigm to present spoken linguistic stimuli, we recorded magnetoencephalographic (MEG) responses in three PD patients in four DBS conditions: left unilateral STN-DBS, right unilateral STN-DBS, bilateral STN-DBS, and no STN-DBS. To ensure that any observed effects of DBS on the neuromagnetic responses could be attributed to the linguistic context per se and were not merely induced by the electrical stimulation, we assessed the effects of STN-DBS on linguistic contrasts within each stimulation condition. Hence, we contrasted the processing of action vs. abstract verbs as well as the processing of correct vs. incorrect morphosyntactic inflections within each DBS condition.

Results: The results revealed that, compared to the DBS-off state, both bilateral and right unilateral stimulation of the STN yielded significant dissociations in the processing of action and abstract verbs, with greater neuromagnetic responses for action verbs compared to abstract verbs. For morphosyntax processing, only left unilateral stimulation yielded significant dissociations (relative to the DBS-off state), with greater neuromagnetic responses to the incorrect inflections compared to the correct inflections.

Conclusion: The results reflect differential effects of unilateral and bilateral STN-DBS on neuromagnetic responses associated with the processing of spoken language. They suggest that different specific aspects of linguistic information processing in PD are affected differently by STN-DBS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13423DOI Listing
August 2021

Differential Effectiveness of Atypical Antipsychotics on Hallucinations: A Pragmatic Randomized Controlled Trial.

J Clin Psychopharmacol 2021 Jul-Aug 01;41(4):389-396

Medizinische Universität Innsbruck, Innsbruck, Austria.

Background: Most studies investigating antipsychotic effectiveness report either total psychopathology or symptom cluster findings. Studies focusing on a separate symptom, such as hallucinations, a hallmark symptom in schizophrenia, are scarce.Therefore, the current study aims to compare the antihallucinatory effectiveness of 3 pharmacologically different antipsychotics: olanzapine, amisulpride, and aripiprazole.

Methods: The present study is part of the Bergen-Stavanger-Innsbruck-Trondheim study, a 12-month prospective, randomized, pragmatic antipsychotic drug trial in active-phase schizophrenia spectrum disorders. The primary outcome of the present study was change of hallucinations as measured by item P3 (hallucinatory behavior) from the Positive and Negative Syndrome Scale in the subgroup with hallucinations at baseline. Primary analyses were intention to treat.

Results: A total of 144 participants were included in the study, where 105 (72%) had a score of 3 or more on the Positive and Negative Syndrome Scale P3 item at baseline, indicating the presence of hallucinations (HALL subgroup).In the HALL subgroup, a significantly less reduction of hallucinations was revealed for participants using olanzapine in weeks 12, 26, 39, and 52 when compared with amisulpride and in weeks 26 and 52 when compared with aripiprazole. In subanalyses for participants never exposed to antipsychotic drugs (antipsychotic-naive) and those who had used antipsychotics before entering the study, antihallucinatory differences were revealed only in the latter group.

Conclusions: A differential antihallucinatory effect of the 3 study drugs was present. The inferior effect of olanzapine seems to be driven by the subgroup of participants exposed to antipsychotic treatment before entering the study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000001403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244933PMC
December 2021

New-onset atrial arrhythmias associated with mortality in black and white patients hospitalized with COVID-19.

Pacing Clin Electrophysiol 2021 05 16;44(5):856-864. Epub 2021 Apr 16.

Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, Louisiana, USA.

Background: Specific details about cardiovascular complications, especially arrhythmias, related to the coronavirus disease of 2019 (COVID-19) are not well described.

Objective: We sought to evaluate the incidence and predictive factors of cardiovascular complications and new-onset arrhythmias in Black and White hospitalized COVID-19 patients and determine the impact of new-onset arrhythmia on outcomes.

Methods: We collected and analyzed baseline demographic and clinical data from COVID-19 patients hospitalized at the Tulane Medical Center in New Orleans, Louisiana, between March 1 and May 1, 2020.

Results: Among 310 hospitalized COVID-19 patients, the mean age was 61.4 ± 16.5 years, with 58,7% females, and 67% Black patients. Black patients were more likely to be younger, have diabetes and obesity. The incidence of cardiac complications was 20%, with 9% of patients having new-onset arrhythmia. There was no significant difference in cardiovascular outcomes between Black and White patients. A multivariate analysis determined age ≥60 years to be a predictor of new-onset arrhythmia (OR = 7.36, 95% CI [1.95;27.76], p = .003). D-dimer levels positively correlated with cardiac and new-onset arrhythmic event. New onset atrial arrhythmias predicted in-hospital mortality (OR = 2.99 95% CI [1.35;6.63], p = .007), a longer intensive care unit length of stay (mean of 6.14 days, 95% CI [2.51;9.77], p = .001) and mechanical ventilation duration(mean of 9.08 days, 95% CI [3.75;14.40], p = .001).

Conclusion: Our results indicate that new onset atrial arrhythmias are commonly encountered in COVID-19 patients and can predict in-hospital mortality. Early elevation in D-dimer in COVID-19 patients is a significant predictor of new onset arrhythmias. Our finding suggest continuous rhythm monitoring should be adopted in this patient population during hospitalization to better risk stratify hospitalized patients and prompt earlier intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pace.14226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251330PMC
May 2021

Glutamate- and GABA-Modulated Connectivity in Auditory Hallucinations-A Combined Resting State fMRI and MR Spectroscopy Study.

Front Psychiatry 2021 17;12:643564. Epub 2021 Feb 17.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Auditory verbal hallucinations (AVH) have been linked to aberrant interhemispheric connectivity between the left and the right superior temporal gyrus (STG), labeled the interhemispheric miscommunication theory. The present study investigated if interhemispheric miscommunication is modulated at the neurochemical level by glutamate (Glu) and gamma-aminobutyric acid (GABA) concentrations in temporal and prefrontal lobe areas, as proposed by the theory. We combined resting-state fMRI connectivity with MR spectroscopy (MRS) in a sample of 81 psychosis patients, comparing patients with high hallucination severity (high-AVH) and low hallucination severity (low-AVH) groups. Glu and GABA concentrations were acquired from the left STG and the anterior cingulate cortex (ACC), an area of cognitive control that has been proposed to modulate STG functioning in AVH. Functional connectivity showed significant interaction effects between AVH Group and ACC-recorded Glu and GABA metabolites. Follow-up tests showed that there was a significant positive association for Glu concentration and interhemispheric STG connectivity in the high-AVH group, while there was a significant negative association for GABA concentration and interhemispheric STG connectivity in the low-AVH group. The results show neurochemical modulation of STG interhemispheric connectivity, as predicted by the interhemispheric miscommunication hypothesis. Furthermore, the findings are in line with an excitatory/inhibitory imbalance model for AVH. By combining different neuroimaging modalities, the current results provide a more comprehensive insight into the neural correlates of AVH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.643564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925618PMC
February 2021

Pragmatic antipsychotics trial-caution in interpretation - Authors' reply.

Lancet Psychiatry 2021 02;8(2):101

Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Norwegian Center for Mental Disorders Research, Centre of Excellence, Bergen, Norway.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2215-0366(20)30568-XDOI Listing
February 2021

White Matter Microstructural Differences between Hallucinating and Non-Hallucinating Schizophrenia Spectrum Patients.

Diagnostics (Basel) 2021 Jan 19;11(1). Epub 2021 Jan 19.

Mohn Medical Imaging and Visualization Center, Haukeland University Hospital, 5021 Bergen, Norway.

The relation between auditory verbal hallucinations (AVH) and white matter has been studied, but results are still inconsistent. This inconsistency may be related to having only a single time-point of AVH assessment in many studies, not capturing that AVH severity fluctuates over time. In the current study, AVH fluctuations were captured by utilizing a longitudinal design and using repeated (Positive and Negative Symptoms Scale) PANSS questionnaire interviews over a 12 month period. We used a Magnetic Resonance Diffusion Tensor Imaging (MR DTI) sequence and tract-based spatial statistics (TBSS) to explore white matter differences between two subtypes of schizophrenia patients; 44 hallucinating (AVH+) and 13 non-hallucinating (AVH-), compared to 13 AVH- matched controls and 44 AVH+ matched controls. Additionally, we tested for hemispheric fractional anisotropy (FA) asymmetry between the groups. Significant widespread FA-value reduction was found in the AVH+ group in comparison to the AVH- group. Although not significant, the extracted FA-values for the control group were in between the two patient groups, for all clusters. We also found a significant difference in FA-asymmetry between the AVH+ and AVH- groups in two clusters, with significantly higher leftward asymmetry in the AVH- group. The current findings suggest a possible qualitative difference in white matter integrity between AVH+ and AVH- patients. Strengths and limitations of the study are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11010139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832406PMC
January 2021

Roux-en-Y gastric bypass and sleeve gastrectomy for obesity-associated hypertension.

J Investig Med 2021 03 21;69(3):730-735. Epub 2020 Dec 21.

John W Deming Department of Medicine, Section of Cardiology, Tulane University School of Medicine, New Orleans, Louisiana, USA

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) reduce blood pressure (BP) in obese patients with hypertension (HTN). We compared the effect of RYGB and SG on BP in obese patients with HTN at a large-volume, private bariatric surgery center using a propensity score analysis. The measurement and management of BP were exclusively left to the patient's provider without any involvement of Tulane investigators. At month 1, RYGB and SG equally decreased: (1) mean body weight: 12.7 vs 13.2 kg (p=not significant (NS)) (2) systolic/diastolic BP: 8.5/5.3 vs 8.0/4.2 mm Hg (p=NS) and (3) average number of antihypertensive medications from 1.5 to 0.8 and from 1.6 to 0.6 per patient (p=NS). From month 1 to 12, BP remained unchanged after RYGB but tended to increase from month 6 to 12 after SG. Remission of HTN occurred in 52% and 44% of patients after RYGB and SG. In contrast to the full effect of RYGB and SG on BP at 1 month, body weight decreases steadily over 12 months after RYGB and SG. In conclusion, early after surgery, RYGB and SG equally reduce BP in obese patients with HTN. Thereafter, RYGB has a more sustained effect on BP than SG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jim-2020-001586DOI Listing
March 2021

One-Year Outcome and Adherence to Pharmacological Guidelines in First-Episode Schizophrenia: Results From a Consecutive Cohort Study.

J Clin Psychopharmacol 2020 Nov/Dec;40(6):534-540

From the TIPS-Network for Clinical Research in Psychosis, Psychiatric Department, Stavanger University Hospital, Stavanger.

Background: Remission in schizophrenia is difficult to achieve. Antipsychotic drugs are critical in the treatment of schizophrenia. International guidelines for the pharmacological treatment of schizophrenia recommend a 3-step algorithm with clozapine being the third-line antipsychotic agent. This study investigated the 1-year outcome and the application of the guidelines for the pharmacological treatment of nonremitted first-episode schizophrenia (FES) patients during the first year of follow-up.

Methods: A sample of 78 FES patients from the Norwegian TIPS (Early Treatment and Intervention in Psychosis) 2 study was assessed at the end of the first year of follow-up. The symptom remission criteria were those defined by the Remission in Schizophrenia Working Group. The adherence to the pharmacological guidelines was assessed by reading the medical files and by a digital search of the words "clozapine," "klozapin," and "Leponex" in the hospital electronic data system.

Results: The majority (n = 53, 67.9%) of the patients included were nonremitted at the 1-year follow-up. The majority of the nonremitted patients received either none (7.5%), one (56.6%), or 2 types (15.1%) of antipsychotic drugs during the first year of follow-up. Only 2 (3.8%) received treatment with clozapine, and 3 (5.7%) in total were offered it.

Conclusions: For our FES sample, there was a low 1-year remission rate and a poor adherence to the pharmacological guidelines. Higher adherence to treatment guidelines with a more intensified antipsychotic treatment, which in some cases will include clozapine, will enhance the quality of treatment and may enhance the rates of remission for schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCP.0000000000001303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643791PMC
July 2021

Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial.

Lancet Psychiatry 2020 11;7(11):945-954

Medizinische Universität Innsbruck, Innsbruck, Austria.

Background: Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial.

Methods: This pragmatic, rater-blind, randomised controlled trial was done in three academic centres of psychiatry in Norway, and one in Austria. Eligible patients were aged 18 years or older, met ICD-10 criteria for schizophrenia-spectrum disorders (F20-29), and had symptoms of active psychosis. Eligible patients were randomly assigned to receive oral amisulpride, aripiprazole, or olanzapine. Treatment allocation was open to patients and staff, and starting dose, treatment changes, and adjustments were left to the discretion of the treating physician. Computer-generated randomisation lists for each study centre were prepared by independent statisticians. Patients were followed up for 52 weeks after random assignment, during which assessments were done 8 times by researchers masked to treatment. The primary outcome was reduction of the Positive And Negative Syndrome Scale (PANSS) total score at 52 weeks, and primary analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01446328.

Findings: Between Oct 20, 2011, and Dec 30, 2016, we assessed 359 patients for eligibility. 215 patients were excluded (107 did not meet inclusion criteria, 82 declined to participate, 26 other reasons). 144 patients (mean baseline PANSS total estimated score 78·4 [SD 1·4]) were randomly assigned 1:1:1 to receive amisulpride (44 patients), aripiprazole (48 patients) or olanzapine (52 patients). After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025). We observed weight gain and increases of serum lipids and prolactin in all groups. 26 serious adverse events (SAEs) among 20 patients were registered (four [9%] of 44 patients allocated to amisulpride, ten [21%] of 48 patients allocated to aripiprazole, and six [12%] of 52 patients allocated to olanzapine), with no statistically significant differences between the study drugs. 17 (65%) of the 26 SAEs occurred during the use of the study drug, with readmission or protracted hospital admission accounting for 13 SAEs. One death by suicide, one unspecified death, and one life-threatening accident occurred during follow-up, after cessation of treatment.

Interpretation: Amisulpride was more efficacious than aripiprazole or olanzapine for reducing the PANSS total scores in adults with schizophrenia-spectrum disorders. Side-effect differences among the groups were generally small. This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs. Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice.

Funding: The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2215-0366(20)30341-2DOI Listing
November 2020

Mapping psychotic-like experiences: Results from an online survey.

Scand J Psychol 2021 Apr 2;62(2):237-248. Epub 2020 Oct 2.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Suggestions have been made that psychotic-like experiences (PLEs), such as hallucinatory and delusional experiences, exist on a continuum from healthy individuals to patients with a diagnosis of schizophrenia. We used the screening questions of the Questionnaire for Psychotic Experiences (QPE), an interview that captures the presence and phenomenology of various psychotic experiences separately, to assess PLEs in Norway. Based on data from an online survey in a sample of more than 1,400 participants, we demonstrated that the QPE screening questions show satisfactory psychometric properties. Participants with mental disorders reported more frequent lifetime and current hallucinatory experiences than participants without mental disorders. Childhood experiences were rather low and ranged from 0.7% to 5.2%. We further replicated findings that young age, illegal drug use, lower level of education, and having parents with a mental disorder are associated with higher endorsement rates of PLEs. Finally, a binomial regression revealed that the mere presence of PLEs does not discriminate between individuals with and without a mental disorder. Taken together, the findings of the present study support existing models that both hallucinations and delusions exist on a structural and phenomenological continuum. Moreover, we demonstrated that the QPE screening questions can be used by themselves as a complementary tool to the full QPE interview.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/sjop.12683DOI Listing
April 2021

Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 12 8;5(12):1095-1103. Epub 2020 Jul 8.

Catosenteret Rehabilitation Center, Son, Norway.

Background: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts.

Methods: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.

Results: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics.

Conclusions: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2020.06.014DOI Listing
December 2020

Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 12 8;5(12):1095-1103. Epub 2020 Jul 8.

Catosenteret Rehabilitation Center, Son, Norway.

Background: Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts.

Methods: We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18-94 years of age) and applied the models to the test sets including 648 patients with SZ (18-66 years of age), 185 patients with BD (18-64 years of age), and 990 HC subjects (17-68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.

Results: Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen's d = -0.29) and patients with BD (Cohen's d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy-based models showed larger group differences than the models based on other DTI-derived metrics.

Conclusions: Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bpsc.2020.06.014DOI Listing
December 2020

Prednisolone versus placebo addition in the treatment of patients with recent-onset psychotic disorder: a trial design.

Trials 2020 Jun 8;21(1):492. Epub 2020 Jun 8.

Norment, Division of Psychiatry, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.

Background: The symptom severity of a substantial group of schizophrenia patients (30-40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials, and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients. Corticosteroids are effective in various chronic inflammatory and autoimmune disorders. Prednisolone, a potent glucocorticosteroid, has minor mineral-corticosteroid potencies and can adequately pass the blood-brain barrier and its side effects and safety profile are well known. Therefore, the effect of prednisolone can be studied as a proof of concept for immune modulation as a treatment for schizophrenia.

Methods/design: In total, 90 subjects aged 18-70 years and diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) 295.x) or psychosis not otherwise specified (NOS; 298.9) will be included. The time interval between the onset of psychosis and study entry should not exceed 7 years. Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks in addition to a stable dose of antipsychotic medication. Study medication will be initiated at 40 mg for 3 days, after which it will be tapered down within 6 weeks after initiation, following inflammatory bowel diseases treatment guidelines. Primary outcome is change in symptom severity, expressed as change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of treatment. Cognitive functioning (measured through the Brief Assessment of Cognition in Schizophrenia (BACS)) and change in Global Assessment Functioning (GAF) and depressive symptoms as measured with the Calgary Depression Scale for Schizophrenia (CDS) will be assessed, in addition to various immunological biomarkers. Secondary outcomes are a 4- and 6-month follow-up assessment of PANSS, BACS, and GAF scores and immunological biomarkers. Additionally, a subgroup of patients will be included in the magnetic resonance imaging (MRI) part of the study where MR spectroscopy and structural, functional, and diffusion MRI will be conducted.

Discussion: It is expected that prednisolone addition to current antipsychotic medication use will reduce symptom severity and will improve cognition when compared to placebo.

Trial Registration: ClinicalTrials.gov, NCT02949232 and NCT03340909. Registered 31 October 2016 and 14 November 2017. EudraCT-number 2014-000520-14 and 2017-000163-32.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04365-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278136PMC
June 2020

Hallucinating schizophrenia patients have longer left arcuate fasciculus fiber tracks: a DTI tractography study.

Psychiatry Res Neuroimaging 2020 08 22;302:111088. Epub 2020 May 22.

Division of Psychiatry and NORMENT Center of Excellence, Haukeland University Hospital, Bergen, Norway; Department of Biological and Medical Psychology, University of Bergen, Norway; Department of Radiology, Haukeland University Hospital, Bergen, Norway. Electronic address:

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on the constrains for interaction between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer reconstructed tracks along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer tracks in the left compared to the right side. In addition, there were significant positive correlations between PANSS scores and track length, track volume, and number of track streamlines for the posterior AF segment on the left side. It is concluded that the present DTI results may have implications for interpretations of functional imaging results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pscychresns.2020.111088DOI Listing
August 2020

Dynamic Functional Connectivity Patterns in Schizophrenia and the Relationship With Hallucinations.

Front Psychiatry 2020 31;11:227. Epub 2020 Mar 31.

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

There is a wealth of evidence showing aberrant functional connectivity (FC) in schizophrenia but with considerable variability in findings across studies. Dynamic FC is an extension of traditional static FC, in that such analyses allow for explorations of temporal changes in connectivity. Thereby they also provide more detailed information on connectivity abnormalities in psychiatric disorders such as schizophrenia. The current study investigated dynamic FC in a sample of 80 schizophrenia patients and 80 matched healthy control subjects, replicating previous findings of aberrant dwell times in specific FC states, and further supporting a role for default mode network (DMN) dysfunction. Furthermore, relationships with hallucinations, a core symptom of schizophrenia, were explored. Two measures of hallucinations were used, one measure of current hallucination severity assessed on the day of scanning, and one trait-measure where hallucinations were assessed repeatedly over the course of 1 year. Current hallucination severity did not show a significant relationship with dynamic FC. However, the trait-measure of hallucination proneness over 1 year showed a significant relationship with dynamic FC. Patients with high hallucination proneness spent less time in connectivity states characterized by strong anti-correlation between the DMN and task-positive networks. The findings support theoretical models of hallucinations which have proposed an instability of the DMN and impaired cognitive control in patients with hallucinations. Furthermore, the results point to hallucination proneness as a potential marker for identifying distinct subgroups of schizophrenia patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.00227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145395PMC
March 2020

Different response patterns in hallucinations and delusions to antipsychotic treatment.

Nord J Psychiatry 2020 Oct 3;74(7):497-504. Epub 2020 Apr 3.

Division of Psychiatry and Centre of Excellence NORMENT, Haukeland University Hospital, Bergen, Norway.

Psychosis is a multifaceted clinical phenomenon in which the various symptoms may show a differential response to treatment. Important information may be lost when heterogeneous symptoms are grouped together in global sum scores when studying treatment effects. The aim of this study was to compare the level and rate of change in the two separate symptoms hallucinations and delusions during the acute psychotic phase, and to explore whether potential temporal differences depend on diagnosis or patients being previously medicated with antipsychotics or not. Patients admitted with active symptoms of schizophrenia or related psychotic disorders were included in the Bergen Psychosis Project (BPP) (=226), a prospective, pragmatic, study of four second-generation antipsychotics. The Positive and Negative Syndrome Scale were assessed at baseline, one, three and six months. Over the total follow-up period, latent growth curve models showed greater reductions in delusions than in hallucinations. However, the percentage of the total reduction was found to be larger in hallucinations than that of delusions in the first interval (91% vs. 64%). The levels and changes in these variables were dependent on diagnosis and whether or not patients had a life-time history of antipsychotic use. Focusing on separate symptoms rather than general symptom clusters could offer clinicians a useful approach when evaluating the early response of antipsychotics. NCT00932529; URL: http://www.clinicaltrials.gov/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08039488.2020.1745273DOI Listing
October 2020

Cognitive Profile in Ultra High Risk for Psychosis and Schizophrenia: A Comparison Using Coordinated Norms.

Front Psychiatry 2019 1;10:695. Epub 2019 Oct 1.

Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Cognitive impairment is not only a core aspect of schizophrenia but also commonly observed in help-seeking youth at ultra high risk for psychosis (UHR), with potential implications for prognosis and individualized treatment. However, there is no consensus on the cognitive profile in the UHR state, partly due to lack of valid comparisons of performance in established schizophrenia and UHR. To compare the cognitive functioning and profile of UHR subjects to a sample with schizophrenia, they were split into two groups based on duration of illness. Comparisons were made using coordinated norms based on healthy controls reflecting the younger UHR age spectrum. Participants for UHR ( = 51) and schizophrenia groups ( = 19 and = 22) were included from the Prevention of Psychosis and Bergen Psychosis 2 projects. All subjects completed a comprehensive neurocognitive test battery aiming to measure speed of processing, working memory, verbal learning, reasoning, and problem solving, as well as visual problem solving. Cognitive functioning was compared between groups based on coordinated norms using -scores derived by regression modeling from an age-matched healthy control group ( = 61). UHR subjects showed significantly impaired speed of processing ( < 0.001) working memory ( = 0.042) and verbal learning, reasoning, and problem solving ( = 0.007) as compared to the control group. Visual problem-solving skills appeared unimpaired. UHR subjects significantly outperformed the schizophrenia group with duration of illness >3 years for speed of processing and working memory (both < 0.001). There were no significant differences in performance between the UHR group and the group with duration of schizophrenia <3 years. Cognitive performance is impaired in UHR subjects as compared to healthy controls and should thus be monitored when a person is deemed at high risk of psychotic illness. Spatial skills, as measured by tests using physical objects, appear less affected than other domains. The pattern of impairment is similar to that of a group with recent onset schizophrenia but is less severe than in a group with duration of illness <3 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2019.00695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779770PMC
October 2019

Intra-Regional Glu-GABA vs Inter-Regional Glu-Glu Imbalance: A 1H-MRS Study of the Neurochemistry of Auditory Verbal Hallucinations in Schizophrenia.

Schizophr Bull 2020 04;46(3):633-642

Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.

Glutamate (Glu), gamma amino-butyric acid (GABA), and excitatory/inhibitory (E/I) imbalance have inconsistently been implicated in the etiology of schizophrenia. Elevated Glu levels in language regions have been suggested to mediate auditory verbal hallucinations (AVH), the same regions previously associated with neuronal hyperactivity during AVHs. It is, however, not known whether alterations in Glu levels are accompanied by corresponding GABA alterations, nor is it known if Glu levels are affected in brain regions with known neuronal hypo-activity. Using magnetic resonance spectroscopy (MRS), we measured Glx (Glu+glutamine) and GABA+ levels in the anterior cingulate cortex (ACC), left and right superior temporal gyrus (STG), and left inferior frontal gyrus (IFG), in a sample of 77 schizophrenia patients and 77 healthy controls. Two MRS-protocols were used. Results showed a marginally significant positive correlation in the left STG between Glx and AVHs, whereas a significant negative correlation was found in the ACC. In addition, high-hallucinating patients as a group showed decreased ACC and increased left STG Glx levels compared to low-hallucinating patients, with the healthy controls in between the 2 hallucinating groups. No significant differences were found for GABA+ levels. It is discussed that reduced ACC Glx levels reflect an inability of AVH patients to cognitively inhibit their "voices" through neuronal hypo-activity, which in turn originates from increased left STG Glu levels and neuronal hyperactivity. A revised E/I-imbalance model is proposed where Glu-Glu imbalance between brain regions is emphasized rather than Glu-GABA imbalance within regions, for the understanding of the underlying neurochemistry of AVHs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147588PMC
April 2020

A study of the discriminative properties of the Six-Spot Step Test in people with Parkinson's disease at risk of falling.

NeuroRehabilitation 2019 ;45(2):265-272

Department of Public Health - Section of Sport Science, Aarhus University, Aarhus, Denmark.

Background: Clinical tests that can discriminate between people at risk of falling and those not at risk are warranted. The discriminative properties of the Six-Spot Step Test was investigated in people with Parkinson's disease at risk of falling.

Methods: Eighty-one participants with a median age of 69 years (Q1-Q3:63-74) and a median Hoehn and Yahr score of 2.5 (Q1-Q3:2-3) completed the Six-Spot Step Test and the Timed "Up and Go" test. A mini-BESTest score of 19 or below was used as a cut-off for defining risk of falling, and a receiver operating characteristics curve was generated to determine clinical relevant cut-off scores.

Results: A cut-off score of 7.0 and 6.8 seconds identified people not at risk of falling, while 11.1 and 9.4 seconds identified people at risk of falling for the Six-Spot Step Test and the Timed "Up and Go" test, respectively. When maximizing the sensitivity and specificity a cut-off score of 9.2 (accuracy of 84%) and 8.1 seconds (accuracy of 70%) was found for the Six-Spot Step Test and the Timed "Up and Go" test, respectively.

Conclusion: The Six-Spot Step Test discriminates accurately between people with Parkinson's disease at risk of falling and people not at risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/NRE-192801DOI Listing
January 2020

Predictors of treatment satisfaction in antipsychotic-naïve and previously medicated patients with acute-phase psychosis.

Nord J Psychiatry 2019 Aug 4;73(6):349-356. Epub 2019 Jul 4.

a Division of Psychiatry and Centre of Excellence NORMENT, Haukeland University Hospital , Bergen , Norway.

Treatment satisfaction predicts treatment adherence and long-term outcome for patients with psychosis. It is therefore important to understand the underpinnings of patient satisfaction in psychosis treatment for optimal treatment delivery. To examine the associations between satisfaction and level and change in positive symptoms, insight, depression and side effects of antipsychotics in previously medicated and antipsychotic-naïve patients. Data derive from a randomised trial, with 226 respondents at baseline and 104 at follow-up. The measures were the positive subscale and insight item from the Positive and Negative Syndrome Scale, Calgary Depression Scale, the UKU Consumer Satisfaction Rating Scale, and the UKU side effects scale. Structural equation modelling was used to test the model. The full information maximum likelihood estimator used all available data. In the sample of 226 patients, 67.3% were male and 44.2% were antipsychotic-naïve. The mean age was 34.1 years. For previously medicated patients, satisfaction was predicted by level of insight ( = -2.21, β = -0.42) and reduction in positive symptoms ( = -0.56, β = -0.39). For antipsychotic-naïve patients, satisfaction was predicted by level and change of insight ( = -2.21, β = -0.46), change in depression ( = -0.37, β = -0.26) and side effects ( = -0.15, β = -0.30). All predictors were significant at the 0.05 level. Reducing positive symptoms and side effects are important to enhance patient satisfaction. However, improving insight and reducing depression are more important in antipsychotic-naïve patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08039488.2019.1636134DOI Listing
August 2019

The influence of substance use on the effectiveness of antipsychotic medication: a prospective, pragmatic study.

Nord J Psychiatry 2019 May - Jul;73(4-5):281-287. Epub 2019 May 29.

a Division of Psychiatry , Haukeland University Hospital , Bergen , Norway.

Psychosis is associated with a high prevalence of substance use, leading to worsened prognosis. Less is known about how comorbid substance abuse may influence the effectiveness of antipsychotic medications. The aim of this study was to compare the effectiveness of second generation antipsychotics in patients with psychosis with and without substance use. All patients ( = 226) were aged >18 years old had symptom level scores of ≥4 on selected psychosis items on the Positive and Negative Syndrome Scale and met ICD-10 diagnostic criteria for psychosis. Information on substance use was collected based on the Clinician Drug Use Scale. Patients were grouped at baseline according to the presence of substance use, medication history and diagnosis group. Clinical symptoms at baseline and changes at follow-up were assessed with the PANSS. At baseline about 30% of the patients used substances, most frequently cannabis followed by methamphetamine. About half (47%) of the patients had no prior exposure to antipsychotic medication at inclusion. Patients who had consumed substances showed no substantial differences in the PANSS score reduction as a result of antipsychotic medication compared to patients without substance. There were, however, some group differences in relation to pattern of change that were influenced by medication history. Substance use was found to be related to stronger reduction of positive symptoms from week 4 to week 27. Substance use alone did not influence antipsychotic effectiveness in this sample of patients with psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08039488.2019.1622152DOI Listing
August 2019
-->