| 1. |
- Baghdassarian, Eva, et al.
(författare)
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Auditory brainstem response (ABR) profiling in schizoaffective disorder
- 2020
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:4, s. 214-217
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to assess whether the auditory brainstem response (ABR) profiling test for schizophrenia (SZ) would recognise schizoaffective disorder (SZA) patients as SZ or not.Method: Male and female SZA patients (n = 16) from the psychosis unit at Uppsala University Hospital were investigated. Coded sets of randomised ABR recordings intermingled with patients with SZ, adult attention-deficit hyperactivity disorder (ADHD) and healthy controls were analysed by an independent party blinded to clinical diagnoses.Results: The ABR profiling test for SZ was positive in 5/16 patients (31%) and negative in 11/16 patients (69%) with SZA. A surprising finding was that 4/16 (25%) SZA patients were positive for the ABR profiling test for ADHD.Conclusion: With the ABR profiling test, a minority of patients with SZA tested positive for SZ. In contrast, a majority (85%) of patients with SZ in a previous study tested positive. These preliminary results leave us ignorant whether SZA should be regarded as a SZ-like disorder or a psychotic mood disorder and add to the questions regarding the validity of this diagnostic entity. However, the ABR profiling method is still in its infancy and its exploration in a range of psychiatric disorders is warranted.
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| 2. |
- Eratne, Dhamidhu, et al.
(författare)
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Plasma neurofilament light chain is increased in Niemann-Pick Type C but glial fibrillary acidic protein remains normal
- 2024
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Ingår i: Acta Neuropsychiatrica. - 0924-2708 .- 1601-5215. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls. METHODS: Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges. RESULTS: Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1pg/mL vs 7.4pg/mL, p<0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6pg/mL vs 75.1pg/mL). DISCUSSION: The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
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| 3. |
- Hagsäter, S Melker, et al.
(författare)
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Serotonin depletion reduces both acquisition and expression of context-conditioned fear.
- 2021
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 33:3, s. 148-155
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Tidskriftsartikel (refereegranskat)abstract
- Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear.Male Sprague-Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300mg/kg daily×3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only.The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear.Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.
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| 4. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
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GOOD NEWS REGARDING SSRI SAFETY IN DANISH META-ANALYSIS.
- 2020
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 32:1, s. 54-56
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Tidskriftsartikel (refereegranskat)abstract
- In two previous letters on an SSRI meta-analysis conducted by the Copenhagen Trial Unit at Copenhagen University Hospital, we have commented on a large number of errors, almost all of which have tilted the results in an anti-drug direction, that unfortunately mar this publication. While the authors have acknowledged many of these mishaps, and may now be expected to submit an extensive errata list to the journal where their paper was once published, we regretfully note that also their latest contribution to this exchange is surprisingly inaccurate. However, its many shortcomings notwithstanding, their meta-analysis does add to the current literature by confirming that SSRIs do not seem to enhance the risk for suicide or death, and also that these drugs seem to enhance the risk of side effects categorized as serious only in the elderly.
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| 5. |
- Imbeault, S, et al.
(författare)
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Effects of IDO1 and TDO2 inhibition on cognitive deficits and anxiety following LPS-induced neuroinflammation
- 2020
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 32:1, s. 43-53
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Tidskriftsartikel (refereegranskat)abstract
- Objective:Sustained immune activation leads to cognitive dysfunctions, depression-, and anxiety-like behaviours in humans and rodents. It is modelled by administration of lipopolysaccharides (LPS) to induce expression of pro-inflammatory cytokines that then activate indoleamine 2,3 dioxygenase (IDO1), the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Here, we ask whether chronic IDO1 inhibition by 1-methyl-tryptophan (1-MT, added at 2 g/l in the drinking water) or chronic inhibition of tryptophan 2,3 dioxygenase (TDO2), another enzyme capable of converting tryptophan to kynurenine, by 680C91 (15 mg/kgper os), can rescue LPS-induced (0.83-mg/kg intraperitoneally) anxiety and cognitive deficits. We also investigate the acute effects of 680C91 on serotonergic, dopaminergic, and kynurenine pathway metabolites.Methods:We examined LPS-induced deficits in trace fear conditioning and anxiety in the light–dark box and elevated plus maze (EPM) in group-housed C57Bl6/N mice. Kynurenine pathway metabolites and monoamine levels were measured via high-performance liquid chromatography.Results:Chronic blockade of IDO1 with 1-MT did not rescue cognitive deficits or abrogate the anxiogenic behaviour caused by LPS despite a decrease in the brain kynurenine:tryptophan ratio. However, 1-MT by itself demonstrated anxiolytic properties in the EPM. Acute and chronic inhibition of TDO2 elevated brain levels of tryptophan, while chronic inhibition of TDO2 was unsuccessful in rescuing cognitive deficits and abrogating the anxiety caused by LPS.Conclusions:In line with previous studies, we show that LPS administration induces anxiety and cognitive dysfunctions in mice that however were not reversed by chronic blockade of IDO1 or TDO2 at the doses used.
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| 6. |
- Kang, Matthew J.Y., et al.
(författare)
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Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders
- 2023
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Ingår i: Acta Neuropsychiatrica. - 0924-2708. ; 36:1, s. 17-28
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Tidskriftsartikel (refereegranskat)abstract
- Objective People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. Methods We collected longitudinal diagnostic information (mean=36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other), and PSY. We pre-specified NfL>582pg/mL as indicative of ND/MCI/other. Results Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. Conclusions CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
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| 7. |
- Nilsson, Marie, 1968, et al.
(författare)
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Effect of the monoaminergic stabiliser (-)-OSU6162 on mental fatigue following stroke or traumatic brain injury
- 2020
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:6, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- Objective:The purpose of the present study was to evaluate the efficacy and safety of (-)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI).Methods:This 4+4 weeks double blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least twelve months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes (CPRS), the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events.Results:There were significant differences on the patients' total FAI scores (p=0.0097), the subscale FAI outdoor scores (p=0.0243), and on the trail making test (TMT-B) (p=0.0325) in favour of (-)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported adverse events were mild or moderate in severity and did not differ between the (-)-OSU6162 and the placebo period.Conclusion:The most obvious beneficial effects of (-)-OSU6162 was on the patients' activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the Mental Fatigue Scale. Based on these observed therapeutic effects, in conjunction with the good tolerability of (-)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke-or TBI-induced mental fatigue. © Scandinavian College of Neuropsychopharmacology 2020.
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| 8. |
- Näslund, Jakob, et al.
(författare)
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Expression of 22 serotonin-related genes in rat brain after sub-acute serotonin depletion or reuptake inhibition
- 2020
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:3, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent the manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas. Methods: Male Wistar rats were administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, for 3 days and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex was investigated using real-time quantitative PCR (rt-qPCR). Results: While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust downregulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, that is, the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum and a marked reduction in the expression of Htr6 in prefrontal cortex; it also enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus. Conclusion: With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin.
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| 9. |
- Puolakka, Hanna, et al.
(författare)
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Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients
- 2024
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press. - 0924-2708 .- 1601-5215.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes.Methods: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients.Results: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p=0.013) and use of other antipsychotics (p=0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p=0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p=0.029).Conclusion: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.
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| 10. |
- Salminen, Simo-Pekko, et al.
(författare)
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Genetic risk scores associated with temperament clusters in finnish depression patients
- 2023
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press. - 0924-2708 .- 1601-5215.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cloninger's temperament dimensions have been studied widely in relation to genetics. In this study, we examined Cloninger's temperament dimensions grouped with cluster analyses and their association with single nucleotide polymorphisms (SNPs). This study included 212 genotyped Finnish patients from the Ostrobothnia Depression Study.Methods: The temperament clusters were analysed at baseline and at six weeks from the beginning of the depression intervention study. We selected depression related catecholamine and serotonin genes based on a literature search, and 59 SNPs from ten different genes were analysed. The associations of single SNPs with temperament clusters were studied. Using the selected genes, genetic risk score (GRS) analyses were conducted considering appropriate confounding factors.Results: No single SNP had a significant association with the temperament clusters. Associations between GRSs and temperament clusters were observed in multivariate models that were significant after permutation analyses. Two SNPs from the DRD3 gene, two SNPs from the SLC6A2 gene, one SNP from the SLC6A4 gene, and one SNP from the HTR2A gene associated with the HHA/LRD/LP (high harm avoidance, low reward dependence, low persistence) cluster at baseline. Two SNPs from the HTR2A gene associated with the HHA/LRD/LP cluster at six weeks. Two SNPs from the HTR2A gene and two SNPs from the COMT gene associated with the HP (high persistence) cluster at six weeks.Conclusion: GRSs seem to associate with an individual's temperament profile, which can be observed in the clusters used. Further research needs to be conducted on these types of clusters, and their clinical applicability.
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