| 1. |
- Dickens, Alex M., et al.
(författare)
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Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis
- 2020
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Ingår i: NPJ schizophrenia. - : Nature Partner Journals. - 2334-265X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- There is an established, link between psychosis and metabolic abnormalities, such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by activation of specific cannabinoid targets (endocannabinoid system (ECS)). Our recent data suggest that there is a change in the circulating lipidome at the onset of first episode psychosis (FEP). With the aim of characterizing the involvement of the central and peripheral ECSs, and their mutual associations; here, we performed a combined neuroimaging and metabolomic study in patients with FEP and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n = 20 and n = 8) and HC (n = 20 and n = 10), by applying three-dimensional positron emission tomography, using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous cannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleoylethanolamide (OEA) were reduced in FEP individuals, but not in those who were predominantly medication free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, OEA, and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross talk, and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.
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| 2. |
- Goulding, Anneli, 1966, et al.
(författare)
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Person Centred Psychosis Care (PCPC) in an Inpatient Setting: The Implementation Process and Staff Experiences.
- 2016
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Ingår i: Npj Schizophrenia. - 2334-265X.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Persons with schizophrenia-spectrum disorders might benefit from increased involvement in the care process. To this end, integrated care models have been successfully implemented in outpatient settings. We wanted to develop an inpatient care model inspired by integrated care. Further, we wanted to include central components of person-centred care (asdefined by the Gothenburg Centre for Person-Centred Care) including a focus on the patient's narrative, the creation of partnership between staff and patient, and an agreement between staff and patientconcerning the care. The present research project, Person Centred Psychosis Care (PCPC), aims to develop, implement, and evaluate an inpatient care approach that utilizes aspects of integrated care as well as person-centred care. In the present study we will describe the PCPC staff educational intervention, the implementation process that followed, and staff experiences of the intervention and implementation. Methods: Emplyoing a participatory design, the PCPC staff educational intervention involved one third (n=40) of the staff working at four wards at a clinic providing inpatient care for persons with schizophrenia-spectrum disporders. Facilitators with previous experience in the implementation of person-centred care in somatic settings served as coaches. During six full day workshop, staff learned to apply theoretical concepts of both integrated care and person-centred care to their everyday ward situation and worked in groups to develop ward-level projects with the aim of stimulating patient involvement. Service users took part in the educational intervention. Staff who participated in the educational intervention transferred their new approaches to care tasks. This means that all ward staff became involved in the implementation process. Results A purposeful sample of staff memebers (both with and without course participation, n=20) were asked to praticipate in focus group interviews to relate their experiences of the PCPC staff educational intervention, the transfer to those staff memebers who did not take the course, and of recorded, transcribed verbatim, and thematically analyzed. Results regarding the implementation process will be presented, with a focus on barriers and facilitators to change. Discussion: Findings from the focus group interviews will shed light on staff members' experiences of the education intervention, as well as the experiences of staff memebers who participated in transfer activities but not in the course itself. It is our expectation that the participatory design will facilitate long lasting behaviour change in staff, resulting in patients feeling more involved in their care. Future studies will report on patient outcomes (empowerment and care satisfaction) as well as ward level outcomes. If the PCPC-intervention shows positive outcomes for patients and staff, it might be a model that other psychiatric care providers can use to enhance patient involvemebt and satisfaction with care.
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| 3. |
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| 4. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
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Antipsychotic-placebo separation on the PANSS-6 subscale as compared to the PANSS-30: a pooled participant-level analysis
- 2021
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Ingår i: Npj Schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- In order for measurement-based care to be implemented, there is a need for brief rating instruments that can be administered in a short amount of time, but that are still sufficiently informative. Here, we assessed the drug-placebo sensitivity of the six-item subscale (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) using a large collection of patient-level data (n = 6685) from randomized controlled trials of risperidone and paliperidone. When analyzing the data by study, we found no material difference in mean effect sizes (ES) between the two measures (PANSS-30 ES = 0.45, PANSS-6 ES = 0.44; p = 0.642). Stratifying the pooled population according to several putative effect moderators (e.g., age, formulation, dose, or diagnosis) generally yielded no meaningful ES differences between the two measures. Similarly, early improvement (>= 20% improvement at week 1) on the PANSS-6 predicted subsequent response (>= 40% improvement at endpoint) as well as the analog prediction using PANSS-30. Finally, cross-sectional symptom remission assessed via the PANSS-6 showed very good agreement (sensitivity = 100%, specificity = 98%) with cross-sectional symptom remission defined by the Remission in Schizophrenia Working Group.
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| 5. |
- Lee, Maria, et al.
(författare)
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No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis
- 2021
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Ingår i: NPJ SCHIZOPHRENIA. - : Springer Nature. - 2334-265X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [C-11]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (beta = 0.013-0.074, partial r= -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.
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| 6. |
- Lintunen, J, et al.
(författare)
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Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
- 2021
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Ingår i: NPJ schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 7:1, s. 1-
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Tidskriftsartikel (refereegranskat)abstract
- Relapses remain common among individuals with schizophrenia indicating a need for improved treatments. Creating a completely new drug molecule is expensive and time consuming, and therefore drug repurposing should be considered. Aim of this study was to investigate the risk of psychiatric rehospitalization associated with use of adenosine modulators (AMs) and calcium channel blockers (CCBs) in schizophrenia. Individuals diagnosed with schizophrenia (N = 61,889) in inpatient care between 1972–2014 in Finland were included. The follow-up lasted from 1996 to 2017. Main exposures were use of AMs (allopurinol and dipyridamole) and CCBs (dihydropyridines, diltiazem, and verapamil). Thiazide diuretics were used as a negative control. Within-individual models in stratified Cox regression were used and adjusted hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Use of AMs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.74, 95% CI 0.65–0.84, P < 0.0001), as well as on the level of individual drugs (allopurinol HR 0.82, 95% CI 0.70–0.97, P = 0.02; dipyridamole HR 0.65, 95% CI 0.55–0.77, P < 0.0001). Use of CCBs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.81, 95% CI 0.77–0.86, P < 0.0001). From the different CCBs, only exposure to dihydropyridines was associated with a reduced risk (HR 0.79, 95% CI 0.74–0.84, P < 0.0001). No effect was observed for the negative control, thiazide diuretics (HR 0.96, 0.90–1.02, P = 0.20). The effects of dipyridamole and dihydropyridines were more pronounced among younger persons and combination of AMs, and CCBs was associated with a lower risk than either drug class as monotherapy. These results indicate a need for randomized controlled trials of these drugs.
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| 7. |
- Lorentzen, R., et al.
(författare)
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The efficacy of transcranial magnetic stimulation (TMS) for negative symptoms in schizophrenia: a systematic review and meta-analysis
- 2022
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Ingår i: Npj Schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen's d) with 95% confidence intervals (95 degrees/0C1) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.
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| 8. |
- Petty, Alice, et al.
(författare)
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Enhanced Dopamine in Prodromal Schizophrenia (EDiPS) : a new animal model of relevance to schizophrenia
- 2019
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Ingår i: npj Schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis—tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)—into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as “Enhanced Dopamine in Prodromal Schizophrenia” (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to “positive” symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an “at risk”-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.
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| 9. |
- Sabe, M, et al.
(författare)
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Antipsychotics for negative and positive symptoms of schizophrenia: dose-response meta-analysis of randomized controlled acute phase trials
- 2021
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Ingår i: NPJ schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 7:1, s. 43-
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Tidskriftsartikel (refereegranskat)abstract
- Determining the optimal antipsychotic target dose in acute phase treatment is of high clinical relevance. The effect of antipsychotics on negative symptoms should be taken into account because patients will often continue on the treatment received in the acute phase. Therefore, we conducted a formal dose-response meta-analysis of negative symptoms and positive symptoms based on a systematic review of fixed-dose randomized controlled trials (RCTs) that examined the effectiveness of antipsychotics for the acute exacerbation of schizophrenia. Forty RCTs included a total of 15,689 patients. The 95% effective doses per day for the 13 antipsychotics included and 3 long acting were mostly different for negative and positive symptoms: amisulpride (481 mg, 690.6 mg); aripiprazole (11.9 mg, 11 mg); asenapine (7.61 mg, 5.66 mg); brexpiprazole (2.1 mg, 4 mg); cariprazine (4 mg, 6.51 mg); haloperidol (6.34 mg, 7.36 mg); lurasidone (58.2 mg, 86.3 mg); olanzapine (15.5 mg, 9.52 mg); olanzapine long-acting injection (15.7 mg, 13.5 mg); paliperidone (7.2 mg, 7 mg); paliperidone long-acting injection (7.5 mg, 5.9 mg); quetiapine instant-release (264.2 mg, 316.5 mg); quetiapine extended-release (774 mg, 707.2 mg); risperidone (7.5 mg, 7.7 mg); risperidone long-acting injection (5.13 mg, 6.7 mg); sertindole (13.5 mg, 16.3 mg); and ziprasidone (71.6 mg, 152.6 mg). The shape of the dose-response curves varied across different drugs with most drugs showing a plateau at higher doses. Most dose-response curves suggested that the near-maximum effective doses could be in the lower-to-medium range of the licensed dose. Additional RCTs are necessary to establish the optimal dose.
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| 10. |
- Sommer, IE, et al.
(författare)
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The clinical course of schizophrenia in women and men-a nation-wide cohort study
- 2020
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Ingår i: NPJ schizophrenia. - : Springer Science and Business Media LLC. - 2334-265X. ; 6:1, s. 12-
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Tidskriftsartikel (refereegranskat)abstract
- Gender differences in schizophrenia have been reported in different aspect of the course of disease and may urge special clinical interventions for female patients. Current literature provides insufficient information to design guidelines for treating women with schizophrenia. We aim to quantify the clinical course of schizophrenia in men and women on premorbid hospitalizations and prescription drugs, age at diagnosis, pharmacological treatment, comorbidity, number of re-hospitalizations, and mortality. Our nationwide cohort study included all patients admitted for the first time to hospital during 2000–2014 for schizophrenia or schizo-affective disorder in Finland. Gender differences were compared with logistic regression, by calculating incidence rates, and mortality was assessed with Cox proportional hazard model. We included 7142 women and 9006 men with schizophrenia/schizo-affective disorder and found that both women (71%) and men (70%) had often been hospitalized for another psychiatric disorder in the 5 years before diagnosis. In women, the last psychiatric hospitalization before schizophrenia/schizo-affective diagnosis was often for mood disorders (62%, OR 2.56, 95% CI 2.28–2.87). Men were diagnosed earlier (mean 34.4 [SD12.6] vs. 38.2 [SD 13.8]) with peak incidence around 22, while incidence in women declining only slowly between age 18 and 65. During ten years follow-up, 69.5% of both genders needed at least one re-hospitalization, with slightly more hospitalizations in women. Women were less often prescribed clozapine or long-acting antipsychotics. Mortality was lower in women (HR = 0.54, 95% CI 0.50–0.60), with fewer suicide and cardiovascular deaths, but more cancer deaths. These results suggest a diagnostic delay for women, which might be shortened by screening women aged 20–65 participating in affective disorder programs. As number of hospitalizations is not lower for women, clinicians should take care not to undertreat women with schizophrenia.
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