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1.
  • Baghdassarian, Eva, et al. (författare)
  • Auditory brainstem response (ABR) profiling in schizoaffective disorder
  • 2020
  • Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 32:4, s. 214-217
  • 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.
  • 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.
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4.
  • Björkman, Sven, et al. (författare)
  • Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.
  • 1981
  • Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 33:9, s. 580-585
  • Tidskriftsartikel (refereegranskat)abstract
    • Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.
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5.
  • Comasco, Erika, 1982-, et al. (författare)
  • Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
  • 2017
  • Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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6.
  • Edvinsson, Dan, et al. (författare)
  • ADHD-related symptoms among adults in out-patient psychiatry and female prison inmates as compared with the general population
  • 2010
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:1, s. 30-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the prevalence of symptoms consistent with attention deficit hyperactivity disorder (ADHD) and related problems in adults in the general population, out-patient psychiatry (where females are in majority), and female convicts. Method. A questionnaire based on the DSM-IV criteria of ADHD, reported childhood symptoms, reading and spelling problems, difficulties and suffering, and general assessment of functioning (GAF) was distributed to samples of the general population, open care psychiatry, and female prison inmates. Completed questionnaires were received from 517/1000, 349/400, and 50/65 of the three samples, respectively. Results. Symptoms consistent with ADHD were more than three times higher in out-patient psychiatry than in the general population (6.6% versus 2.1%), with a male-to-female ratio of 1.6-1.7. The severity of symptoms and frequencies of associated disabilities were similar in men and women. ADHD symptoms and related problems occurred in 50% of the female prisoners, which is similar to male prisoners according to the literature. Conclusion. The high prevalence of symptoms and disabilities of ADHD in women should lead to awareness of the disorder in both sexes and be addressed in terms of diagnostic work-up, treatment, and rehabilitation.
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7.
  • Edvinsson, Dan (författare)
  • Attention Deficit/Hyperactivity Disorder in Adults : Prevalence, Psychiatric Comorbidities and Long-term Outcome
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Attention Deficit/Hyperactivity Disorder (ADHD) was originally thought to occur only in children, but is increasingly recognised as causing functional impairment also in adulthood. The overall aim of this thesis was to achieve a comprehensive understanding of ADHD in adulthood.A questionnaire based on the DSM-IV criteria of ADHD, reported childhood symptoms, reading and spelling problems, difficulties and suffering and general assessment of functioning (GAF) was distributed to three samples: the general population (GP), outpatient psychiatry (OPP) and female prison inmates. Symptoms consistent with ADHD were more than three times higher in the OPP sample than in the GP sample (6.6 versus 2.1%). ADHD symptoms and related problems occurred in 50% of the prison inmates.A cohort of 168 patients diagnosed with ADHD in adulthood was interviewed about current ADHD symptoms and psychiatric comorbidity on axis I and II. The lifetime prevalence of psychiatric comorbidity on axis I was 92% and current comorbidity, including autism spectrum disorders and Tourette’s syndrome, was 47%. The sex-specific pattern of the comorbid disor-ders was similar to that in the general population. Forty-six per cent of the patients endorsed the specific criteria for at least one personality disorder.After a mean follow-up of six years, there was remission of adult ADHD in about 30% of the patients, regardless of whether there was ongoing medication or not. There were no differences in function and quality of life, except for global general improvement, which was better in patients currently on medication.The most prevalent long-term side effects of pharmacological treatment with mainly stimulants were decreased appetite, dry mouth, anxiousness/restlessness and an increase in pulse frequency. The discontinuation rate was about 50%: 29% discontinued because of a perceived lack of effect, followed by elevated mood or hypomania (11%). No detectable evidence of tolerance and increased need for dosage over time was observed.To conclude, Symptoms of ADHD is highly overrepresented in OPP and in female inmates compared with the GP. Furthermore, adults diagnosed with ADHD have a high lifetime prevalence of psychiatric comorbidity. Long-term pharmacological treatment with stimulants is safe with relatively mild and tolerable adverse effects. Continued medication, however, is not related to remission.
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8.
  • Edvinsson, Dan, et al. (författare)
  • Gender differences of axis I and II comorbidity in subjects diagnosed with attention-deficit hyperactivity disorder as adults
  • 2013
  • Ingår i: Acta Neuropsychiatrica. - 0924-2708 .- 1601-5215. ; 25:3, s. 165-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate gender differences in psychiatric comorbidity patients diagnosed with attention-deficit hyperactivity disorder (ADHD) as adults. Methods: Interviews about current ADHD symptoms and psychiatric comorbidity on axis I and II (Structured Clinical Interview for DSM-IV axis I and axis II) were conducted in a clinical cohort of 168 patients (78 women, 90 men). Independent information on childhood and current symptoms was collected from parents, partners and patient files. Results: The lifetime prevalence of psychiatric comorbidity on axis I reached 92%, and current comorbidity, including autism spectrum disorders and Tourette's syndrome, was 47%. Women had a higher lifetime prevalence of mood and eating disorders compared with men, where substance-use disorders were more frequent. Ten per cent of patients fulfilled diagnostic criteria for a personality disorder. When excluding the general diagnostic criteria, 46% of the patients endorsed the specific criteria for at least one personality disorder. Gender differences were identified with predominance of histrionic personality traits in women and conduct disorder in men. Conclusion: Patients diagnosed with ADHD as adults display an extremely high lifetime axis I comorbidity with a gender-specific pattern similar to the general population. No gender differences were identified with regard to personality disorders; however, an increased prevalence of deviant personality traits was confirmed. This study stresses the importance of evaluating comorbidity among patients diagnosed with ADHD as adults to secure optimal treatment.
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9.
  • Färdig, Rickard, et al. (författare)
  • A randomized controlled trial of the illness management and recovery program for persons with schizophrenia.
  • 2011
  • Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 62:6, s. 606-12
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of the study was to evaluate the effects of the illness management and recovery (IMR) program on symptoms and psychosocial functioning of individuals with schizophrenia or schizoaffective disorder in an outpatient setting in Sweden.METHODS: A total of 41 persons with schizophrenia or schizoaffective disorder who were receiving treatment at six psychiatric outpatient rehabilitation centers were randomly assigned to either an IMR group for nine months or to treatment as usual (control condition). Assessments were conducted at baseline, posttreatment (nine months), and follow-up (21 months) and included self-reports and ratings by clinicians (both blind and nonblind to treatment assignment) of illness management, psychiatric symptoms, recovery, coping, quality of life, hospitalization, insight, and suicidal ideation.RESULTS: As measured by self-report and ratings of nonblinded clinicians, IMR program participants demonstrated significantly greater improvement in illness management than participants in the control condition. Ratings of psychiatric symptoms by blinded clinicians using the Psychosis Evaluation Tool for Common Use by Caregivers and self-reported ratings of psychosocial functioning on the Ways of Coping Questionnaire also showed better outcomes than for participants in treatment as usual. A statistically significant decrease in suicidal ideation between baseline and follow-up was found for IMR program participants.CONCLUSIONS: The study supports previous findings and suggests that the IMR program is effective in improving the ability of individuals with schizophrenia to better manage their illness.
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10.
  • Färdig, Rickard, et al. (författare)
  • A Randomized Controlled Trial of the Illness Management and Recovery Program for Persons With Schizophrenia
  • 2011
  • Ingår i: Psychiatric Services. - 1075-2730 .- 1557-9700. ; 62:6, s. 606-612
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of the study was to evaluate the effects of the illness management and recovery (IMR) program on symptoms and psychosocial functioning of individuals with schizophrenia or schizoaffective disorder in an outpatient setting in Sweden. Methods: A total of 41 persons with schizophrenia or schizoaffective disorder who were receiving treatment at six psychiatric outpatient rehabilitation centers were randomly assigned to either an IMR group for nine months or to treatment as usual (control condition). Assessments were conducted at baseline, posttreatment (nine months), and follow-up (21 months) and included self-reports and ratings by clinicians (both blind and nonblind to treatment assignment) of illness management, psychiatric symptoms, recovery, coping, quality of life, hospitalization, insight, and suicidal ideation. Results: As measured by self-report and ratings of nonblinded clinicians, IMR program participants demonstrated significantly greater improvement in illness management than participants in the control condition. Ratings of psychiatric symptoms by blinded clinicians using the Psychosis Evaluation Tool for Common Use by Caregivers and self-reported ratings of psychosocial functioning on the Ways of Coping Questionnaire also showed better outcomes than for participants in treatment as usual. A statistically significant decrease in suicidal ideation between baseline and follow-up was found for IMR program participants. Conclusions: The study supports previous findings and suggests that the IMR program is effective in improving the ability of individuals with schizophrenia to better manage their illness.
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11.
  • Färdig, Rickard, et al. (författare)
  • Evaluation of the Illness Management and Recovery Scale in schizophrenia and schizoaffective disorder
  • 2011
  • Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 132:2-3, s. 157-164
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to evaluate the psychometric properties of the parallel client and clinician versions of the Illness Management and Recovery Scale (IMRS) developed to monitor the clients' progress in the Illness Management and Recovery (IMR) program in schizophrenia. A total of 107 study participants completed assessments of the IMRS, interview-based ratings of psychiatric symptoms, self-ratings of psychiatric symptoms, perception of recovery, and quality of life. Case managers completed the clinician version of the IMRS. Both versions of the scale demonstrated satisfactory internal reliability and strong test-retest reliability. The results also indicated convergent validity with interview-based ratings of psychiatric symptoms, self-rated symptoms, perception of recovery, and quality of life for both versions of the IMRS. These findings support the utility of the IMRS as a measure of illness self-management and recovery in clients with schizophrenia.
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12.
  • Färdig, Rickard, 1975- (författare)
  • Illness Management and Recovery : Implementation and evaluation of a psychosocial program for schizophrenia and schizoaffective disorder
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of the present thesis was to examine the effectiveness of the Illness Management and Recovery (IMR) program for teaching clients with schizophrenia or schizoaffective disorder to better manage their illness and to promote recovery. This was accomplished through an examination of the program’s effects on psychosocial functioning and psychopathology, the evaluation of general and specific impact of neurocognition on learning the fundamentals of illness self-management, and the impact of symptom severity on outcome of the IMR program. The utility of the illness management and recovery scale to evaluate illness self-management of clients with schizophrenia and schizoaffective disorder was also investigated.The effects of the IMR program were evaluated in a randomized controlled trial that compared participants in the program to participants receiving treatment as usual. 41 participants were recruited at six psychiatric outpatient rehabilitation centers in Uppsala, Sweden, and were randomly assigned to IMR groups for approximately 40 sessions or to a treatment as usual control condition. The IMR program participants demonstrated greater improvement compared to participants in treatment as usual in illness self-management, reduced psychiatric symptoms, improved coping skills, and decreases in suicidal ideation. The findings suggest that the IMR program is effective in improving the ability of individuals with schizophrenia and schizoaffective disorder to better manage their illness.Possible association between neurocognitive functioning and the acquisition of illness self-management skills was investigated in a total of 53 participants who completed the IMR program. Speed of processing was related to client reported illness self-management skills acquisition, before and after controlling for psychiatric symptoms and medication, but neurocognitive functioning did not predict improvement in clinician ratings of client illness self-management skills. The findings suggest that compromised neurocognitive functioning does not reduce response to training in illness self-management.The impact of symptom severity on outcome of the IMR program was explored in 52 participants who completed the program. The results suggest that significantly more participants met the severity criterion of remission at post-treatment, and it appears that participants not reaching the severity criterion at post-treatment, also benefited from the IMR program, as indicated by the similar effect sizes of the two subgroups (meeting versus not meeting the severity criterion at post-treatment).The psychometric properties of the Illness Management and Recovery Scale (IMRS) were evaluated in 107 participants with a diagnosis of schizophrenia or schizoaffective disorder. And an item-by-item investigation was conducted in order to establish their utility in monitoring the clients' progress in the IMR program. Both the client and clinician version of the IMRS demonstrated satisfactory internal consistency, large test-retest reliability, and convergent validity with conceptually related measures of psychiatric symptoms, quality of life, and perception of recovery. The findings support the utility of the IMRS as a measure of illness self-management and recovery in clients with schizophrenia and schizoaffective disorder.The general findings of this thesis support the IMR program to be effective in improving the ability of the participants to manage their disorder. The impact of neurocognitive dysfunction on the participants’ ability to learn the fundamentals of illness self-management seems to be limited, and symptom severity did not limit the benefits of the IMR program. Support for the utility of the IMRS to monitor the participants’ progress in the program was also found, providing a brief and economical method for assessing outcome of the IMR program.
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13.
  • Färdig, Rickard, et al. (författare)
  • Neurocognitive functioning and outcome of the Illness Management and Recovery Program for clients with schizophrenia and schizoaffective disorder
  • 2016
  • Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 70:6, s. 430-435
  • Tidskriftsartikel (refereegranskat)abstract
    • The relationship between psychosocial programming and neurocognition has been established in previous research, but has not been explored in the context of the Illness Management and Recovery Program (IMR). This study examined associations between neurocognition and illness self-management skills acquisition, based on two previous trials of IMR. Neurocognitive functioning was assessed at baseline and post-treatment in 53 participants with schizophrenia or schizoaffective disorder who completed the IMR. Illness self-management was measured by the client and clinician versions of the Illness Management and Recovery Scale. Statistical analyses investigated improvements in neurocognitive functioning and possible association between illness self-management skills acquisition and neurocognitive functioning. Speed of processing as measured by the Trail Making Test A, was related to client-reported acquisition of illness self-management skills, before and after controlling for psychiatric symptoms and medication, but did not predict improvement in clinician ratings of client illness self-management skills. However, when controlling for client session attendance rates, the association between speed of processing and client-reported illness self-management skills acquisition ceased to be statistically significant, which suggests that compromised neurocognitive functioning does not reduce response to training in illness self-management in itself. The association between the frequency of attended IMR sessions and outcome of the IMR seems to decrease the negative impact of compromised neurocognition on illness self-management skills acquisition. Also, clients with slower speed of processing may experience less benefit from the IMR and may attend fewer sessions.
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14.
  • Färdig, Rickard, et al. (författare)
  • Symptom severity and outcome of the Illness Management and Recovery (IMR) program for schizophrenia and schizoaffective disorder
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The present study explored the effects of the Illness Management and Recovery program on the severity criterion of symptomatic remission in schizophrenia and schizoaffective disorder, and whether participants meeting the severity criterion experienced greater improvement in the outcomes of the IMR program. The results suggest that significantly more participants met the severity criterion at post-treatment. Improvements in general psychopathology, self-rated and clinician rated illness self-management, and subjective satisfaction with life, were found for the total sample. Although demonstrating significantly higher levels of general psychopathology, compared to participants meeting the severity criterion, it appears that participants not meeting the severity criterion also benefited from the IMR program, as indicated by the similar effect sizes of the two subgroups (meeting versus not meeting the severity criterion at post-treatment).
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15.
  • Hedelin, M., et al. (författare)
  • Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population
  • 2010
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Methods: Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic- like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic- like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. Results: 18 411 women were classified as having a low level of psychotic- like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic- like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic- like symptoms. Conclusion: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic- like symptoms.
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17.
  • Häubner, Norbert, et al. (författare)
  • The analysis of vitamin E in phyto- and zooplankton samples
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Vitamin E (a-tocopherol in particular) is one of the major and most potent lipid-soluble antioxidants in vivo. It is produced by autotrophs and is essential in the diet of heterotrophs. In the last decades deficiencies of essential substances such as astaxanthin and vitamin B1 (thiamine) were discovered in aquatic top predators and underlying causes seem to be food-web related. In the case of vitamin E, there is a lack of studies on the mechanisms of production and transport in aquatic food webs, which is partly related to complicated extraction procedures and high detection limits. This paper presents an improved method for the extraction and detection of a-, g- and d-tocopherol in low-biomass plankton samples. The method uses N,N-dimethylformamide (DMF) and n-hexane as extraction solvents  with sodium dodecyl sulphate (SDS) as  additive. This improves extraction yield and simplifies the extraction procedure because elaborate homogenization and saponification steps are unnecessary and extraction time is  decreased to 1 min. Quantification of vitamin E is performed with high performance liquid chromatography (HPLC) using electrochemical detection (ECD). Detection limits of the new method are 18.5, 16.3 and 8.0 pg injected and 0.74, 0.65 and 0.32 ng mL-1 extract for a-, g- and d-tocopherol, respectively. Altogether, this is a reliable, fast and sensitive method which will allow more detailed investigations of vitamin E dynamics in aquatic food webs.  
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18.
  • Johansson, Jessica, 1977-, et al. (författare)
  • Decreased binding capacity (Bmax) of muscarinic acetylcholine receptors in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD)
  • 2013
  • Ingår i: ADHD Attention Deficit and Hyperactivity Disorders. - Berlin, Germany : Springer Berlin/Heidelberg. - 1866-6116 .- 1866-6647. ; 5:3, s. 267-271
  • Tidskriftsartikel (refereegranskat)abstract
    • Monoaminergic dysregulation is implicated in attention-deficit/hyperactivity disorder (ADHD), and methylphenidate and amphetamines are the most frequently prescribed pharmacological agents for treating ADHD. However, it has recently been proposed that the core symptoms of the disorder might be due to an imbalance between monoaminergic and cholinergic systems. In this study, we used fibroblast cell homogenates from boys with and without ADHD as an extraneural cell model to examine the cholinergic receptor density, that is, muscarinic acetylcholine receptors (mAChRs). We found that the binding capacity (Bmax) of [³H] Quinuclidinyl benzilate (³H-QNB) to mAChRs was decreased by almost 50 % in the children with ADHD (mean = 30.6 fmol/mg protein, SD = 25.6) in comparison with controls [mean = 63.1 fmol/mg protein, SD = 20.5, p ≤ 0.01 (Student's unpaired t test)]. The decreased Bmax indicates a reduced cholinergic receptor density, which might constitute a biomarker for ADHD. However, these preliminary findings need to be replicated in larger ADHD and comparison cohorts
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20.
  • Kallstrand, Johan, et al. (författare)
  • A new method for analyzing auditory brain-stem response waveforms using a moving-minimum subtraction procedure of digitized analog recordings
  • 2014
  • Ingår i: Neuropsychiatric Disease and Treatment. - 1176-6328 .- 1178-2021. ; 10, s. 1011-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • The auditory brain-stem response (ABR) waveform comprises a set of waves (labeled I-VII) recorded with scalp electrodes over 10 ms after an auditory stimulation with a brief click sound. Quite often, the waves are fused (confluent) and baseline-irregular and sloped, making wave latencies and wave amplitudes difficult to establish. In the present paper, we describe a method, labeled moving-minimum subtraction, based on digitization of the analog ABR waveform (154 data points/ms) in order to achieve alignment of the ABR response to a straight baseline, often with clear baseline separation of waves and resolution of fused waves. Application of the new method to groups of patients showed marked differences in ABR waveforms between patients with schizophrenia versus patients with adult attention deficit/hyperactivity disorder versus healthy controls. The findings show promise regarding the possibility to identify ABR markers to be used as biomarkers as support for clinical diagnoses of these and other neuropsychiatric disorders.
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24.
  • Nyholm, Dag, et al. (författare)
  • Enteral Levodopa/Carbidopa infusion in advanced Parkinson disease : Long-term exposure
  • 2008
  • Ingår i: Clinical neuropharmacology. - 0362-5664 .- 1537-162X. ; 31:2, s. 63-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In patients with advanced Parkinson disease, levodopa/carbidopa formulated as a gel suspension (Duodopa) permits continuous delivery into the small intestine using a portable pump, resulting in less variability in levodopa concentrations and fewer motor fluctuations and dyskinesias than with oral levodopa administration. This is a retrospective analysis of the long-term clinical experience with this agent. Methods: All but 1 of the patients who had received enteral levodopa infusion treatment between January 1, 1991, and June 30, 2002, consented to a review of their hospital charts. Results: Of the 65 patients with initial testing of the treatment, 86% opted for continued treatment via percutaneous endoscopic gastrostomy or gastrojejunostomy. Total exposure to levodopa infusion was 216 patient-years (mean, 3.7 years). Maximum treatment duration was 10.7 years. Fifty-two patients were treated for 1 year or longer. The adverse effect profile of levodopa/carbidopa infusion was similar to that observed with oral administration of levodopa. Seven deaths occurred, all considered unrelated to the treatment. Intestinal tube problems, including dislocation of the intestinal tube to the stomach, were the most common technical problem, occurring in 69% of the patients during the first year. The optimal daily dose of levodopa decreased by an average of 5% during follow-up. Conclusions: The safety of enteral infusion of levodopa/ carbidopa formulated as a gel suspension was found acceptable. For most patients, the technical challenges posed by the enteral infusion system were offset by the improvement in motor fluctuations and dyskinesias offered by this technique.
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25.
  • Nyholm, Dag, et al. (författare)
  • Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers
  • 2013
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 127:2, s. 124-132
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).MATERIALS AND METHODS:A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.RESULTS:Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.CONCLUSIONS:Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.
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26.
  • Nyholm, Dag, et al. (författare)
  • Pharmacokinetics of levodopa/carbidopa microtablets versus levodopa/benserazide and levodopa/carbidopa in healthy volunteers
  • 2012
  • Ingår i: Clinical neuropharmacology. - 0362-5664 .- 1537-162X. ; 35:3, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration. METHODS: A single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation. RESULTS: The LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence. CONCLUSIONS: The new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.
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27.
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28.
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29.
  • Vumma, Ravi, et al. (författare)
  • Tryptophan transport in human fibroblast cells : a functional characterization
  • 2011
  • Ingår i: International Journal of Tryptophan Research. - : Libertas Academica Ltd.. - 1178-6469. ; :4, s. 19-27
  • Tidskriftsartikel (refereegranskat)abstract
    • There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.Tryptophan kinetic parameters (Vmax and Km) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of 3H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high Vmax and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower Vmax and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na+) dependent, while uptake at high substrate concentration was mainly Na+ independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.
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