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- Bohman, Hannes, 1965-, et al.
(författare)
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Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound.
- 2020
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Early-onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis.METHOD: By using 22 MHz high-frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age-matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses.RESULTS: Adolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function.CONCLUSIONS: Adolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long-term treatment of EOP and EOBP in order to reduce a future risk of CVD.
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| 2. |
- Engen, Kristine, et al.
(författare)
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Autoantibodies to the N-Methyl-D-Aspartate Receptor in Adolescents With Early Onset Psychosis and Healthy Controls
- 2020
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background Autoantibodies to theN-methyl-D-aspartate receptor (NMDAR-Abs) in autoimmune encephalitis have been associated with prominent psychiatric symptoms. The aims of the present study are to identify the prevalence of NMDAR-Abs in adolescents with early onset psychosis disorders (EOP) and healthy controls (HC) and examine its clinical significance. Method Plasma samples were acquired from 46 adolescent EOP patients and 69 age- and sex matched HC, and assessed for the presence of immunoglobulin G NMDAR-Abs. All participants underwent psychiatric evaluation, neurological examination and head magnetic resonance imaging. Results NMDAR-Abs were detected in three of 46 (6.5%) EOP patients and in two of 69 (2.9%) HC. One NMDAR-Abs EOP patient presented with unusual psychopathology and minor T1 weighted lesions of vasculopathological origin located bi-frontally and in the basal ganglia, and had a recent diagnosis of a separate autoimmune disease. One NMDAR-Ab HC displayed a T2 weighted FLAIR hyperintensity lesion in the left frontal lobe. The remaining three NMDAR-Ab participants were two EOP patients without neurological or radiological findings, and one HC without any clinical findings. Conclusions We report that a small number of EOP patients and HC have NMDAR-Abs with a similar frequency in both groups. The presence of the antibodies was not associated with any distinctive clinical or radiological features. Detection of the antibodies had no diagnostic implication, and a positive NMDAR antibody test must be carefully interpreted and reviewed within the individual clinical context.
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| 3. |
- Gurholt, Tiril P., et al.
(författare)
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Intracranial and subcortical volumes in adolescents with early‐onset psychosis : A multisite mega‐analysis from the ENIGMA consortium
- 2020
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Ingår i: Human Brain Mapping. - Stockholm : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 373-384
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Tidskriftsartikel (refereegranskat)abstract
- Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early-onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
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| 4. |
- Lundberg, Mathias, et al.
(författare)
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Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy
- 2020
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Ingår i: Bioscience Reports. - : Portland Press Ltd.. - 0144-8463 .- 1573-4935. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis, the production of newborn neurons from neural stem cells (NSCs) has been suggested to be decreased in patients with schizophrenia. A similar finding was observed in an animal model of schizophrenia, as indicated by decreased bromodeoxyuridine (BrdU) labelling cells in response to a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist. The antipsychotic drug clozapine was shown to counteract the observed decrease in BrdU-labelled cells in hippocampal dentate gyrus (DG). However, phenotypic determination by immunohistochemistry analysis could not reveal whether BrdU-positive cells were indeed NSCs. Using a previously established cell model for analysing NSC protection in vitro, we investigated a protective effect of clozapine on NSCs.Primary NSCs were isolated from the mouse subventricular zone (SVZ), we show that clozapine had a NSC protective activity alone, as evident by employing an ATP cell viability assay. In contrast, haloperidol did not show any NSC protective properties. Subsequently, cells were exposed to the non-competitive NMDA-receptor antagonist ketamine. Clozapine, but not haloperidol, had a NSC protective/anti-apoptotic activity against ketamine-induced cytotoxicity. The observed NSC protective activity of clozapine was associated with increased expression of the anti-apoptotic marker Bcl-2, decreased expression of the pro-apoptotic cleaved form of caspase-3 and associated with decreased expression of the autophagosome marker 1A/1B-light chain 3 (LC3-II).Collectively, our findings suggest that clozapine may have a protective/anti-apoptotic effect on NSCs, supporting previous in vivo observations, indicating a neurogenesis-promoting activity for clozapine. If the data are further confirmed in vivo, the results may encourage an expanded use of clozapine to restore impaired neurogenesis in schizophrenia.
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