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- Lavebratt, C., et al.
(författare)
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The KMO allele encoding Arg(452) is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression
- 2014
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 19:3, s. 334-341
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Tidskriftsartikel (refereegranskat)abstract
- The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P = 0.005, n = 19) or schizophrenia (P = 0.02, n = 36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P = 0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P = 0.03) and reduced lymphoblastoid and hippocampal KMO expression (P <= 0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.
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- Sellgren, C, et al.
(författare)
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Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden.
- 2011
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Ingår i: Acta psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 124:6, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Sellgren C, Landén M, Lichtenstein P, Hultman CM, Långström N. Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden. Objective: Hospital discharge registers (HDRs) are frequently used in epidemiological research. However, the validity of several important psychiatric diagnostic entities, including bipolar disorder, remains uncertain. Hence, we aimed to develop an optimal algorithm for register-based identification of DSM-IV-TR bipolar disorder. Method: We identified potential cases in the Swedish national HDR using two separate discharge diagnoses of bipolar disorder according to ICD versions 8-10 during January 1, 1973 to December 31, 2004. In a randomly selected subsample of 135 cases from the county of Sörmland, two senior psychiatrists reassessed the diagnostic status based on patients' medical records. We scrutinized false-positive cases and modified the initial algorithm to improve positive predictive value while minimizing false negatives. Finally, we externally validated resulting caseness algorithms by linking HDR diagnostic data with best-estimate clinical diagnoses from the National Quality Assurance Register for Bipolar Disorder (BipoläR), dispensed lithium prescriptions from the National Prescribed Drug Register, and the ICD-10 diagnoses from the National Outpatient Register respectively. Results: The algorithm with two discharge diagnoses of bipolar disorder yielded a positive predictive value of 0.81. Modification by excluding individuals diagnosed with ICD-8 296.20 (manic-depressive psychosis, depressed type), and/or ICD-9 296.B (unipolar affective psychosis, melancholic form), gave a positive positive predictive value of 0.92. The modified algorithm also had statistically superior external validity compared with the original algorithm. Conclusion: Our findings suggest that DSM-IV-TR bipolar disorder caseness based on two inpatient episodes with a bipolar disorder diagnosis is sufficiently sensitive and specific to be used in further epidemiological study of bipolar disorder.
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- Zetterberg, Henrik, 1973, et al.
(författare)
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Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment
- 2014
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 217:3, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. (C) 2014 Elsevier Ireland 'Ltd. All rights reserved.
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