| 1. |
- Angelucci, F, et al.
(författare)
-
CGRP in a gene-environment interaction model for depression: effects of antidepressant treatment
- 2019
-
Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 31:2, s. 93-99
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveGenetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored.MethodsWe therefore superimposed maternal separation (MS) onto a genetic rat model (Flinders-sensitive and -resistant lines, FSL/FRL) of depression, treated these rats with antidepressants (escitalopram and nortriptyline) and measured CGRP-LI in selected brain regions.ResultsCGRP was elevated in the frontal cortex, hippocampus and amygdala (but not in the hypothalamus) of FSL rats. However, MS did not significantly alter levels of this peptide. Likewise, there were no significant interactions between the genetic and environmental factors. Most importantly, neither escitalopram nor nortriptyline significantly altered brain CGRP levels.ConclusionOur data demonstrate that increased brain levels of CGRP are present in a well-established rat model of depression. Given that antidepressants have virtually no effect on the brain level of this peptide, our study indicates that further research is needed to evaluate the functional role of CGRP in the FSL model for depression.
|
|
| 2. |
- Baghdassarian, Eva, et al.
(författare)
-
Auditory brainstem response (ABR) profiling tests as diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD)
- 2018
-
Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 30:3, s. 137-147
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the performances of two auditory brainstem response (ABR) profiling tests as potential biomarkers and diagnostic support for schizophrenia and adult attention-deficit hyperactivity disorder (ADHD), respectively, in an investigator-initiated blinded study design.Method: Male and female patients with schizophrenia (n=26) and adult ADHD (n=24) meeting Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) diagnostic criteria and healthy controls (n=58) comprised the analysis set (n=108) of the total number of study participants (n=119). Coded sets of randomized ABR recordings were analysed by an independent party blinded to clinical diagnoses before a joint code-breaking session.Results: The ABR profiling test for schizophrenia identified schizophrenia patients versus controls with a sensitivity of 84.6% and a specificity of 93.1%. The ADHD test identified patients with adult ADHD versus controls with a sensitivity of 87.5% and a specificity of 91.4%.Conclusion: The ABR profiling tests discriminated schizophrenia and ADHD versus healthy controls with high sensitivity and specificity. The methods deserve to be further explored in larger clinical studies including a broad range of psychiatric disorders to determine their utility as potential diagnostic biomarkers.
|
|
| 3. |
- Cleland, N, et al.
(författare)
-
A 16-year-old girl with anti-NMDA-receptor encephalitis and family history of psychotic disorders
- 2015
-
Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 27:6, s. 375-379
-
Tidskriftsartikel (refereegranskat)abstract
- Autoimmune NMDA-R encephalitis (ANRE) shares clinical features with schizophrenia. Recent research also indicates that both disorders are associated with dysfunction of the N-Methyl-D-Aspartate glutamate receptors (NMDA-R) subunit 1.MethodsWe present the case of Ms A, 16 years old. Ms A presented with acute personality change, bizarre behaviour, delusional ideas and atypical seizures. She had a family history of psychotic disorders, and autistic traits diagnosed in childhood. She was initially diagnosed with a psychotic disorder. Delayed testing of CSF indicated ANRE. As the patient was a Jehovah's witness the treating team was unable to use gammaglobulin therapy; they instead relied on combined plasmapheresis and rituximab. To exclude the possibility that the affected members of this family shared a gene coding for an abnormal configuration of the NMDA receptor subunit 1 we sequenced the region of the GRIN1 gene in DNA extracted from blood in both Ms A and her grandmother.ResultsMs A’s condition improved dramatically, though her long-term memory is still demonstrably impaired. No genetic abnormality was detected.ConclusionsThis case emphasizes how important it is, for a first episode psychosis, to exclude ANRE and other autoimmune synaptic encephalitides, even in the face of significant family history, and if seronegative, the importance of testing for CSF autoantibodies.
|
|
| 4. |
- Ekemohn, Maria, et al.
(författare)
-
Systematic evaluation of skeletal fractures caused by induction of electroconvulsive seizures in rat state a need for attention and refinement of the procedure
- 2017
-
Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 29:6, s. 363-373
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Electroconvulsive therapy (ECT) is one of the most efficient treatments for major depression. Electroconvulsive seizures (ECS), the animal model of ECT, is widely used to study both mechanisms of action and adverse effects of ECT. As the treatment itself serves as an instant anaesthetic and anaesthetic agents may affect memory functions and behaviour, ECS is traditionally administered without muscle relaxation and anaesthesia. A major problem of unmodified ECS, which has only been addressed peripherally in the literature, is that some animals sustain spinal fractures and subsequent hind leg paralysis (paraplegia). This phenomenon leads to a higher degree of suffering and these animals need to be excluded from the studies. To reach sufficient statistical power, the group sizes are therefore often increased and this may lead to a pre-selected study group in risk of skewing the results. Moreover, the study design of the experiments do not comply with the 3R principles, which advocate for both refinement and reduction of animal experiments. The objective of this study is to systematically evaluate injuries caused by ECS. Methods: We summarise the incidence of spinal fractures from 24 studies conducted during 2009–2015 in six different rat strains and report preliminary findings on scapular fractures following auricular ECS. Results: In total, 12.8% of all tested animals suffered from spinal fractures and we find an increase in spinal fracture incidence over time. Furthermore, X-ray analyses revealed that some animals displayed scapular fractures. Conclusion: We discuss consequences of and possible explanations for ECS-induced fractures. Modifications of the method are highly warranted and we furthermore suggest that all animals are thoroughly examined for discrete fractures.
|
|
| 5. |
- Hagsäter, S Melker, et al.
(författare)
-
Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing.
- 2019
-
Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 31:1, s. 46-51
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.Male Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.Noise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.The data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.
|
|
| 6. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
-
Katakam and co-workers have not shown SSRIs to be harmful and ineffective and should stop claiming that they have.
- 2018
-
Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 30:5, s. 266-274
-
Tidskriftsartikel (refereegranskat)abstract
- Funded by the Danish state to provide guidance in health-related matters, the Copenhagen Trial Unit (CTU) at Rigshospitalet may cause considerable societal harm if allowing their analyses to be influenced by bias and prejudice rather than rigor and impartiality. This is why we found it worthwhile to comment on a report from the CTU in which the authors invoked analyses marred by numerous errors and methodological mistakes to claim that selective serotonin reuptake inhibitors (SSRIs) are harmful and ineffective. The CTU group has now produced a response to our comment which is on par with their original contribution in terms of bias, misconceptions and mistakes. Our conclusion is that the reputation of the CTU would be best served by the authors asking for retraction of their SSRI paper.
|
|
| 7. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
-
Multiple possible inaccuracies cast doubt on a recent report suggesting selective serotonin reuptake inhibitors to be toxic and ineffective.
- 2018
-
Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 30:5, s. 244-250
-
Tidskriftsartikel (refereegranskat)abstract
- According to a systematic review on the use of selective serotonin reuptake inhibitors (SSRIs) in adult depression that was recently published in BMC Psychiatry, the results of which have been widely disseminated in lay media, these drugs increase the risk for serious adverse events (SAEs) while exerting poor antidepressant efficacy. A cursory analysis, however, suggests the analysis of SAEs conducted by the authors to be marred by both methodological inaccuracies and blatant errors. After having corrected for these apparent mistakes, we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age; while this suggests SSRIs to be safe drugs in the non-elderly, they do confirm what is already known, that is, that they may enhance the risk for SAEs in the old. Given the loose definition of SAE, including also innocuous phenomena, the possible clinical significance of the latter observation, however, remains unclear until the nature and actual impact of the SAEs in question have been clarified. Moreover, with respect to efficacy, we find the paper in BMC Psychiatry misleading: first, the authors seem unaware of the well-established shortcomings associated with the conventional efficacy parameter on which their analysis is based, second, they have included suboptimal SSRI doses and third, they have missed some pivotal trials. Unless there are explanations for the many peculiarities in this paper that have escaped us, and which may be satisfactorily clarified by the authors, it seems important that the conclusions presented in this paper be publicly rectified.
|
|
| 8. |
- Liu, XC, et al.
(författare)
-
Decreased levels of kynurenic acid in prefrontal cortex in a genetic animal model of depression
- 2017
-
Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 29:1, s. 54-58
-
Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest in the role of kynurenine pathway and tryptophan metabolites in the pathophysiology of depression. In the present study, the metabolism of tryptophan along the kynurenine pathway was analysed in a rat model of depression.MethodsKynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were measured by high-performance liquid chromatography (HPLC) in prefrontal cortex (PFC) and frontal cortex (FC) in a rat model of depression, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL) rats. In addition, KYNA was also measured in hippocampus, striatum and cerebellum.ResultsKYNA levels were reduced in the PFC of FSL rats compared with FRL rats, but did not differ with regard to the FC, hippocampus, striatum or cerebellum. 3-HK levels in PFC and FC, representing the activity of the microglial branch of the kynurenine pathway, did not differ between the FSL and FRL strains.ConclusionOur results suggest an imbalanced metabolism of the kynurenine pathway in the PFC of FSL rats.
|
|
| 9. |
|
|
| 10. |
- Nilsson, Marie, 1968, et al.
(författare)
-
A randomised controlled trial of the monoaminergic stabiliser (−)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome
- 2018
-
Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 30:3, s. 148-57
-
Tidskriftsartikel (refereegranskat)abstract
- © Scandinavian College of Neuropsychopharmacology 2017 Objective: The monoaminergic stabiliser (−)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (−)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Methods: A total of 62 patients were randomly assigned to placebo or (−)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks. Results: MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (−)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1–0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (−)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment. Conclusion: (−)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (−)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.
|
|
