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- Jonsson, Lina, 1982, et al.
(författare)
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Association of Occupational Dysfunction and Hospital Admissions With Different Polygenic Profiles in Bipolar Disorder.
- 2024
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Ingår i: American Journal of Psychiatry. - 0002-953X .- 1535-7228. ; 181:7, s. 620-629
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Tidskriftsartikel (refereegranskat)abstract
- Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric disorders and educational attainment were assessed for associations with occupational functioning and psychiatric hospital admissions in bipolar disorder.A total of 4,782 patients with bipolar disorder and 2,963 control subjects were genotyped and linked to Swedish national registers. Longitudinal measures from at least 10 years of registry data were used to derive percentage of years without employment, percentage of years with long-term sick leave, and mean number of psychiatric hospital admissions per year. Ordinal regression was used to test associations between outcomes and PGSs for bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and educational attainment. Replication analyses of hospital admissions were conducted with data from the Bipolar Disorder Research Network cohort (N=4,219).Long-term sick leave and unemployment in bipolar disorder were significantly associated with PGSs for schizophrenia, ADHD, major depressive disorder, and educational attainment, but not with the PGS for bipolar disorder. By contrast, the number of hospital admissions per year was associated with higher PGSs for bipolar disorder and schizophrenia, but not with the other PGSs.Bipolar disorder severity (indexed by hospital admissions) was associated with a different polygenic profile than long-term occupational dysfunction. These findings have clinical implications, suggesting that mitigating occupational dysfunction requires interventions other than those deployed to prevent mood episodes.
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- Kakko, Johan, et al.
(författare)
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A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence : A randomized controlled trial
- 2007
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Ingår i: American Journal of Psychiatry. - 0002-953X .- 1535-7228. ; 164:5, s. 797-803
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. METHOD: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. RESULTS: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. CONCLUSIONS: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.
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- Kauppi, Karolina, et al.
(författare)
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Revisiting Antipsychotic Drug Actions Through Gene Networks Associated With Schizophrenia
- 2018
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Ingår i: American Journal of Psychiatry. - : AMER PSYCHIATRIC PUBLISHING, INC. - 0002-953X .- 1535-7228. ; 175:7, s. 674-682
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel "druggable" pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated, but specific genes and pathways constituting this overlap are undetermined. Risk genes of polygenic disorders do not operate in isolation but in combination with other genes through protein-protein interactions among gene product.Method: The protein interactome was used to map antipsychotic drug targets (N=88) to networks of schizophrenia risk genes (N=328).Results: Schizophrenia risk genes were significantly localized in the interactome, forming a distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH, and HCN families were not connected to existing antipsychotics but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia, such as cognitive or negative symptoms.Conclusions: The network medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multitarget antischizophrenia drugs. This approach is transferable to other diseases.
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