| 1. |
- Fazel, Seena, et al.
(författare)
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Schizophrenia, substance abuse, and violent crime
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 301:19, s. 2016-2023
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Persons with schizophrenia are thought to be at increased risk of committing violent crime 4 to 6 times the level of general population individuals without this disorder. However, risk estimates vary substantially across studies, and considerable uncertainty exists as to what mediates this elevated risk. Despite this uncertainty, current guidelines recommend that violence risk assessment should be conducted for all patients with schizophrenia. OBJECTIVE: To determine the risk of violent crime among patients diagnosed as having schizophrenia and the role of substance abuse in mediating this risk. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal designs were used to link data from nationwide Swedish registers of hospital admissions and criminal convictions in 1973-2006. Risk of violent crime in patients after diagnosis of schizophrenia (n = 8003) was compared with that among general population controls (n = 80 025). Potential confounders (age, sex, income, and marital and immigrant status) and mediators (substance abuse comorbidity) were measured at baseline. To study familial confounding, we also investigated risk of violence among unaffected siblings (n = 8123) of patients with schizophrenia. Information on treatment was not available. MAIN OUTCOME MEASURE: Violent crime (any criminal conviction for homicide, assault, robbery, arson, any sexual offense, illegal threats, or intimidation). RESULTS: In patients with schizophrenia, 1054 (13.2%) had at least 1 violent offense compared with 4276 (5.3%) of general population controls (adjusted odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2). The risk was mostly confined to patients with substance abuse comorbidity (of whom 27.6% committed an offense), yielding an increased risk of violent crime among such patients (adjusted OR, 4.4; 95% CI, 3.9-5.0), whereas the risk increase was small in schizophrenia patients without substance abuse comorbidity (8.5% of whom had at least 1 violent offense; adjusted OR, 1.2; 95% CI, 1.1-1.4; P<.001 for interaction). The risk increase among those with substance abuse comorbidity was significantly less pronounced when unaffected siblings were used as controls (28.3% of those with schizophrenia had a violent offense compared with 17.9% of their unaffected siblings; adjusted OR, 1.8; 95% CI, 1.4-2.4; P<.001 for interaction), suggesting significant familial (genetic or early environmental) confounding of the association between schizophrenia and violence. CONCLUSIONS: Schizophrenia was associated with an increased risk of violent crime in this longitudinal study. This association was attenuated by adjustment for substance abuse, suggesting a mediating effect. The role of risk assessment, management, and treatment in individuals with comorbidity needs further examination.
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| 2. |
- Goisis, Alice, et al.
(författare)
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Birth outcomes following assisted reproductive technology conception among same-sex lesbian couples vs natural conception and assisted reproductive technology conception among heterosexual couples
- 2023
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Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 329:13, s. 1117-1119
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Tidskriftsartikel (refereegranskat)abstract
- Higher rates of adverse birth outcomes have been consistently reported among children conceived via assisted reproductive technology (ART) compared with children conceived through natural conception. Higher rates of multiple births in ART pregnancies partially explain the increased risk. It remains unclear to what extent the remaining difference can be attributed to the reproductive technology or to factors related to infertility, which is associated with an elevated risk of poorer birth outcomes. Same-sex lesbian couples undergo ART treatments generally without experiencing infertility. To distinguish the effects of reproductive treatment and infertility, we compared birth outcomes in ART pregnancies among same-sex lesbian couples vs natural conceptions and ART pregnancies among heterosexual couples.Methods: In Sweden, same-sex lesbian couples have been eligible to receive publicly funded ART treatments with donated sperm since 2005. This study included all births in Sweden from 2007 to 2018. Using pseudonymized personal identifiers, the Swedish National Quality Registry for Assisted Reproduction, which includes all ART treatments (in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], and intrauterine insemination [IUI]), was linked to the medical birth register and the total population registers, which include information on birth outcomes and sociodemographic characteristics. We focused on first live births for ART and naturally conceived births because 97.3% of ART births among same-sex lesbian couples were first births. We analyzed 4 outcomes: birth weight (continuous), gestational age (continuous), low birth weight (binary, <2500 g), and preterm delivery (binary, <37 weeks of gestation). We estimated linear models on the continuous outcomes and linear probability models on the binary outcomes comparing ART-conceived births among same-sex lesbian couples (reference category) with ART births and naturally conceived births among heterosexual couples. For each outcome, we estimated unadjusted and adjusted (controlling for child sex, multiplicity, and maternal age at birth) models. We also estimated differences focusing on children conceived via IVF/ICSI because 99.4% of ART births among heterosexual couples were conceived via IVF/ICSI compared with 63.3% in same-sex couples, as same-sex couples often start treatments with IUI, which has a lower chance of success regardless of subfertility.Analyses were conducted using R version 4.1.1 (R Foundation). Statistical significance was set at P < .05 (2-sided). This study was approved by the Regional Ethical Review Board of Stockholm. Informed consent was not required for pseudonymized data.Results: During the study period, there were 868 ART births among same-sex lesbian couples, 23 488 ART births among heterosexual couples, and 456 898 naturally conceived births. ART-conceived births from same-sex and heterosexual couples showed a higher proportion of multiplicity (5.8% and 7.5%, respectively) than naturally conceived births (2.1%) (Table 1). Couples who conceived naturally had significantly lower birth weight and gestational age and similar risk of low birth weight and preterm delivery compared with same-sex couples who conceived via ART (Table 2). For example, birth weight was 3429.5 g in naturally conceived births vs 3460.2 g in same-sex ART births (adjusted difference, −76.2 g [95% CI, −113 to −39.3 g]; P < .001; low birth weight, 4.9% vs 6.7%, adjusted difference, 0.28 [95% CI, −1.11 to 1.66] percentage points; P = .70). Heterosexual couples who conceived via ART had statistically significantly lower birth weight and gestational age than same-sex couples (eg, birth weight: 3342.9 g vs 3460.2 g; adjusted difference, −97.4 g [95% CI, −134.8 to −59.9 g]; P < .001). Percentages of low birth weight and preterm birth were higher in ART conceptions among heterosexual couples vs same-sex couples but did not reach statistical significance (eg, low birth weight: 8.9% vs 6.7%; adjusted difference, 1.23 [95% CI, −0.17 to 2.65] percentage points; P = .09). The results were qualitatively similar when only considering IVF/ICSI-conceived children (Table 2).Discussion: This study demonstrated that same-sex lesbian couples undergoing ART had more favorable or similar birth outcomes to heterosexual couples who conceived naturally or underwent ART to conceive, suggesting that infertility-related factors rather than reproductive treatments contribute to higher rates of adverse birth outcomes in ART pregnancies. Limitations of the study include that the presence of infertility factors was not directly assessed and the relatively small sample size of same-sex couples reduced the statistical power of the study, particularly in the binary outcomes analyses.
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| 3. |
- Pasche, Boris, et al.
(författare)
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Somatic acquisition and signaling of TGFBR1*6A in cancer
- 2005
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 294:13, s. 1634-1646
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Tidskriftsartikel (refereegranskat)abstract
- Context: TGFBR1*6A is a common polymorphism of the type I transforming growth factor 0 receptor (TGFBR1). Epidemiological studies suggest that TGFBR1*6A may act as a tumor susceptibility allele. How TGFBR1*6A contributes to cancer development is largely unknown.. Objectives: To determine whether TGFBR1*6A is somatically acquired by primary tumors and metastases during cancer development and whether the 3-amino acid deletion that differentiates TGFBR1*6A from TGFBR1 is part of the mature receptor or part of the signal sequence and to investigate TGFBR1*6A signaling in cancer cells. Design, Setting, and Patients: Tumor And germline tissues from 531 patients with a diagnosis of head and neck, colorectal, or breast cancer recruited from 3 centers in the United States and from 1 center in Spain from June 1, 1994, through June 30, 2004, In vitro translation assays, MCF-7 breast cancer cells stably transfected with TGFBR1*6A, TGFBR1, or the vector alone, DLD-1 colorectal cancer cells that endogenously carry TGFBR1*6A, and SW48 colorectal cancer cells that do not carry TGFBR1*6A. Main Outcome Measures: TGFBR1*6A somatic acquisition in cancer. Determination of the amino terminus of the mature TGFBR1*6A and TGFBR1 receptors. Determination of TGF-beta-dependent cell proliferation. Results: TGFBR1*6A was somatically acquired in 13 of 44 (29.5%) colorectal cancer metastases, in 4 of 157 (2.5%) of colorectal tumors, in 4 of 226 (1.8%) head and neck primary tumors, and in none of the 104 patients with breast cancer. TGFBR1*6A somatic acquisition is not associated with loss of heterozygosity, microsatellite instability, or a mutator phenotype. The signal sequences of TGFBR1 and TGFBR1*6A are cleaved at the same site resulting in identical mature receptors. TGFBR1*6A may switch TGF-beta growth inhibitory signals into growth stimulatory signals in MCF-7 breast cancer cells and in DLD-1 colorectal cancer cells. Conclusions: TGFBR1*6A is somatically acquired in 29.5% of liver metastases from colorectal cancer and may bestow cancer cells with a growth advantage in the presence of TGF-beta. The functional consequences of this conversion appear to be mediated by the TGFBR1*6A signal sequence rather than by the mature receptor. The results highlight a new facet of TGF-beta signaling in cancer and suggest that TGFBR1*6A may represent a potential therapeutic target in cancer.
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| 4. |
- Song, Huan, et al.
(författare)
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Association of Stress-Related Disorders With Subsequent Autoimmune Disease
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 319:23, s. 2388-2400
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear.Objective: To determine whether there is an association between stress-related disorders and subsequent autoimmune disease.Design, Setting, and Participants: Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients.Exposures: Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions.Main Outcomes and Measures: Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.Results: The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively; P for interaction < .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ≤179, 180-319, and ≥320 days, respectively; P for trend = .03).Conclusions and Relevance: In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.
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