| 1. |
- Anckarsäter, Henrik, 1966
(författare)
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Beyond categorical diagnostics in psychiatry: Scientific and medicolegal implications.
- 2010
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Ingår i: International journal of law and psychiatry. - : Elsevier BV. - 1873-6386 .- 0160-2527. ; 33:2, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Conforming to a medical disease model rooted in phenomenology and natural science, psychiatry classifies mental disorders according to signs and symptoms considered to be stable and homogeneous across individuals. Scientific studies addressing the validity of this classification are scarce. Following a seminal paper by Robins and Guze in 1970, validity of categories has been sought in specific criteria referring to symptoms and prognosis, aggregation in families, and "markers", preferentially laboratory tests. There is, however, a growing misfit between the model and empirical findings from studies putting it to the test. Diagnostic categories have not been shown to represent natural groups delineated from the normal variation or from each other. Aetiological factors (genetic and/or environmental), laboratory aberrations, and treatment effects do not respect categorical boundaries. A more adequate description of mental problems may be achieved by: 1) a clear definition of the epistemological frame in which psychiatry operates, 2) a basic rating of the severity of intra- and interpersonal dysfunctions, and 3) empirical comparisons to complementary rather than exclusive dimensions of inter-individual differences in context-specific mental functions, treatment effects, and laboratory findings. Such a pluralistic understanding of mental health problems would fit empirical models in the neurosciences and postmodern notions of subjectivity alike. It would also clarify the assessment of dysfunction and background factors in relation to the requisites for penal law exemptions or insurance policies and make them empirically testable rather than dependent on expert opinion on issues such as whether a specific dysfunction is "psychiatric", "medical", or ascribable to "personality".
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| 2. |
- Anckarsäter, Henrik, 1966
(författare)
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Has biology disproved free will and moral responsibility?
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 107:28 in process
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Bjerke, Maria, 1977, et al.
(författare)
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Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.
- 2010
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Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.
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| 4. |
- Bromander, Sara, et al.
(författare)
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Cerebrospinal fluid insulin during non-neurological surgery.
- 2010
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Ingår i: J Neural Transm (Vienna, Austria:1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 20, s. 328-329
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Tidskriftsartikel (refereegranskat)abstract
- Insulin plays an important metabolic and transmitter role in the central nervous system, but few studies have investigated the relationship between central and peripheral insulin concentrations. 35 patients undergoing knee surgery had cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning following surgery. Serum insulin concentrations increased after surgery and CSF insulin concentrations changed in the same direction with far smaller amplitude. These results indicate that the blood-brain barrier protects the brain from stress-induced peripheral hormonal fluctuations.
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| 5. |
- Chaste, Pauline, et al.
(författare)
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Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.
- 2010
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.
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| 6. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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| 7. |
- Delorme, Richard, et al.
(författare)
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Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls.
- 2010
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11:1:108
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. METHODS: We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). RESULTS: Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. CONCLUSIONS: Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.
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| 8. |
- Gillberg, I Carina, 1949, et al.
(författare)
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Attention, executive functions, and mentalizing in anorexia nervosa eighteen years after onset of eating disorder
- 2010
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Ingår i: Journal of Clinical and Experimental Neuropsychology. - : Informa UK Limited. - 1380-3395 .- 1744-411X. ; 32:4, s. 358-365
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Prospective study of attention, executive functions, and mentalizing abilities in a representative sample of teenage-onset anorexia nervosa (AN). METHOD: A total of 51 AN cases recruited after community screening were contrasted with 51 matched comparison cases 18 years after AN onset. Neuropsychological tests had been done at 21, 24, and 32 years (18 years after AN onset). RESULTS: The AN-group had more attention, executive function, and mentalizing problems. Some of these problems had been present at all three follow-up occasions. CONCLUSIONS: AN is associated with a range of neuropsychological problems that are present long after the eating disorder per se is no longer an important feature.
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| 9. |
- Gustafsson, Per E, et al.
(författare)
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Does quantity have a quality all its own? Cumulative adversity and up- and down-regulation of circadian salivary cortisol levels in healthy children.
- 2010
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 35:9, s. 1410-1415
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Tidskriftsartikel (refereegranskat)abstract
- Findings have been divergent regarding the direction of basal cortisol dysregulations resulting from stressor exposure, and seem to differ between young people and adults. Accumulated stress exposure has been suggested to be a risk factor for the development of hypocortisolism. This cross-sectional study aims to examine the impact of cumulative adversity, i.e., the number of adversities, on diurnal salivary cortisol levels, including the cortisol awakening response (CAR), in children without psychiatric disorder. The sample consisted of 130 children (mean age 12.8 years), representing one in each twin pair included in the population-based Child and Adolescent Twin Study in Sweden (CATSS). Information about socioeconomic disadvantage, negative life events and potentially traumatic life events were collected by telephone interview and questionnaires, with parents as informants. Salivary cortisol sampling was performed in the home during two school days: at awakening, +30 min post-awakening, and at bedtime. Results showed that the number of adversities was related to the CAR, diurnal decline and +30 min post-awakening cortisol levels. Children with a moderate amount of cumulative adversity displayed high cortisol measures, while those with a high amount (3 or more) of adversities instead showed levels similar to the non-exposed group, yielding an inverse U-pattern of the association between cortisol and adversity. These results indicate that the accumulation of adversity might be an explanation of patterns of basal cortisol up-regulation in children and that those most severely exposed can exhibit an early stage of down-regulation, an issue which should be further examined in longitudinal studies.
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| 10. |
- Gustavson, Christina, et al.
(författare)
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Platelet Monoamine Oxidase B Activity Did Not Predict Destructive Personality Traits or Violent Recidivism: A Prospective Study in Male Forensic Psychiatric Examinees.
- 2010
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 1423-0224 .- 0302-282X. ; 61:2, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This prospective study was designed to replicate previous findings of an association between the platelet monoamine oxidase B (MAO-B) activity and factors of relevance for criminal behaviour in a well-documented clinical study population. Methods: Subjects (n = 77, aged 17-76 years, median 30 years) were recruited among consecutive perpetrators of severe interpersonal violent and/or sexual crimes referred to forensic psychiatric investigation. Participants were extensively investigated by structured psychiatric, psychological and social workups, including state-of-the-art rating instruments and official records, and with laboratory tests including venous blood sampling for determination of MAO-B activity. A subset of 36 individuals had lumbar punctures to measure cerebrospinal fluid concentrations of monoamine neurotransmitter metabolites. Results: Platelet MAO-B activity did not show any significant correlation with assessments of childhood behavioural disorders, substance abuse, or psychosocial adversity, nor with any crime-related factors, such as scores on the Life History of Aggression Scale, the Psychopathy Checklist or recidivistic violent crime. No significant correlation was found between MAO-B and any of the monoamine metabolites. Analyses in subgroups of smokers/non-smokers did not change this overall result. Conclusions: The findings of the present study did not support the use of MAO-B as a biological marker for aggression-related personality traits or as a predictor for violent recidivism among violent offenders.
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