| 31. |
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| 32. |
- Castensson, Anja, et al.
(författare)
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Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis
- 2003
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 54:11, s. 1212-1221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains. METHODS: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type. RESULTS: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p =.001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p =.001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis. CONCLUSIONS:The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.
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| 33. |
- Castensson, Anja, et al.
(författare)
-
Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis
- 2003
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 54:11, s. 1212-1221
-
Tidskriftsartikel (refereegranskat)abstract
- Background: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains.Methods: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type.Results: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p = .001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p = .001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis.Conclusions: The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.
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| 34. |
- Chang, Zheng, et al.
(författare)
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Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Depression : A Nationwide Longitudinal Cohort Study
- 2016
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Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 80:12, s. 916-922
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with high rates of psychiatric comorbidity, including depression. However, it is unclear whether ADHD medication increases or decreases the risk for depression.Methods: We studied all individuals with a diagnosis of ADHD born between 1960 and 1998 in Sweden (N = 38,752). We obtained data for prescription of ADHD medication, diagnosis of depression and other psychiatric disorders, and sociodemographic factors from population-based registers. The association between ADHD medication and depression was estimated with Cox proportional hazards regression.Results: After adjustment for sociodemographic and clinical confounders, ADHD medication was associated with a reduced long-term risk (i.e., 3 years later) for depression (hazard ratio = 0.58; 95% confidence interval, 0.51-0.67). The risk was lower for longer duration of ADHD medication. Also, ADHD medication was associated with reduced rates of concurrent depression; within-individual analysis suggested that occurrence of depression was 20% less common during periods when patients received ADHD medication compared with periods when they did not (hazard ratio = 0.80; 95% confidence interval, 0.70-0.92).Conclusions Our study suggests that ADHD medication does not increase the risk of later depression; rather, medication was associated with a reduced risk for subsequent and concurrent depression.
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| 35. |
- Chang, Zheng, et al.
(författare)
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Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Suicide Attempts
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 88:6, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for suicidal behavior, but the effect of ADHD medication on suicidal behavior remains unclear. This study aimed to examine the associations between medication treatment for ADHD and risk of suicide attempts.METHODS: We identified a large cohort of patients with ADHD (N = 3,874,728, 47.8% female patients) using data from commercial health care claims from 2005 to 2014 in the United States. We used population-level and within-individual analyses to compare risk of suicide attempts during months when individuals received prescribed stimulant or nonstimulant medication relative to months when they did not receive medication.RESULTS: In both population-level and within-individual analyses, ADHD medication was associated with lower odds of suicide attempts (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.73; and OR, 0.61; 95% CI, 0.57-0.66, respectively). Similar reductions were found in children to middle-aged adults and in clinically relevant subgroups, including patients with ADHD with preexisting depression or substance use disorder. The reduction was mainly seen for stimulant medication (OR, 0.72; 95% CI, 0.66-0.77); nonstimulant medication was not associated with statistically significant changes in risk of suicide attempts (OR, 0.94; 95% CI, 0.74-1.19). Sensitivity analyses assessing the influence of different exposure definitions, different outcome definitions, subsets of the cohort, and different analytic approaches provided comparable results.CONCLUSIONS: Stimulant medication was associated with a reduced risk of suicide attempts in patients with ADHD, and nonstimulant medication is unlikely to increase the risk of suicide attempts.
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| 36. |
- Chang, Zheng, et al.
(författare)
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Risks and Benefits of Attention-Deficit/Hyperactivity Disorder Medication on Behavioral and Neuropsychiatric Outcomes : A Qualitative Review of Pharmacoepidemiology Studies Using Linked Prescription Databases
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:5, s. 335-343
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Forskningsöversikt (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) medication is one of the most commonly prescribed medication classes in child and adolescent psychiatry, and its use is increasing rapidly in adult psychiatry. However, major questions and concerns remain regarding the benefits and risks of ADHD medication, especially in real-world settings. We conducted a qualitative systematic review of studies that investigated the effects of ADHD medication on behavioral and neuropsychiatric outcomes using linked prescription databases from the last 10 years and identified 40 studies from Europe, North America, and Asia. Among them, 18 used within-individual designs to account for confounding by indication. These studies suggested short-term beneficial effects of ADHD medication on several behavioral or neuropsychiatric outcomes (i.e., injuries, motor vehicle accidents, education, substance use disorder), with estimates suggesting relative risk reduction of 9% to 58% for these outcomes. The within-individual studies found no evidence of increased risks for suicidality and seizures. Replication studies are needed for several other important outcomes (i.e., criminality, depression, mania, psychosis). The available evidence from pharmacoepidemiology studies on long-term effects of ADHD medication was less clear. We discuss time-varying confounding and other limitations that should be considered when interpreting results from pharmacoepidemiology studies. Furthermore, we highlight several knowledge gaps to be addressed in future research and implications for research on mechanisms of outcomes of ADHD medications.
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| 37. |
- Charney, Alexander W, et al.
(författare)
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Contribution of Rare Copy Number Variants toBipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p= .001), BD I (p= .0003), and BD II (p= .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p= .0007, PRS p= .004), and BD I without psychosis (CNV p= .0004, PRS p= 3.9× 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p= .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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| 38. |
- Cippitelli, Andrea, et al.
(författare)
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Alcohol-induced neurodegeneration, suppression of transforming growth factor-beta, and cognitive impairment in rats : prevention by group II metabotropic glutamate receptor activation
- 2010
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 67:9, s. 823-830
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown. Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol.METHODS: Following 4-day binge alcohol exposure concurrent with LY379268 or vehicle treatment, Fluoro-Jade B and transforming growth factor-beta (TGF-beta) staining were carried out, and reversal learning in the Morris water maze was assessed.RESULTS: Fluoro-Jade B staining indicating neurodegeneration was most extensive in the ventral hippocampus and the entorhinal cortex (EC). LY379268 was potently neuroprotective in the EC but not in the dentate gyrus of the hippocampus. In parallel, binge alcohol exposure suppressed TGF-beta expression in both the EC and dentate gyrus, whereas LY379268 increased TGF-beta in the EC only. Finally, neuroprotective effects of LY379268 were accompanied by prevention of deficits in spatial reversal learning.CONCLUSIONS: Our data support a neuroprotective role for group II metabotropic glutamate receptor agonists and TGF-beta in alcohol-induced neurodegeneration.
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| 40. |
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