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1.
PLoS One ; 14(10): e0224127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622449

RESUMO

OBJECTIVES: Alcohol use disorders (AUD) is well known to aggregate in families and is associated with socioeconomic status (SES). The objective was to study the effect of education, income and neighborhood SES in adulthood on AUD, and to explore whether the potential associations were confounded by shared familial factors, by using a co-relative control design. METHODS: Data on AUD was drawn from the Swedish inpatient and outpatient care registers; prescription drug register; and crime data. Through national population registers we collected information on income, education and neighborhood SES at age 25, 30, 35 and 40 years in all individuals born in Sweden between 1950 and 1980. Each sex-specific stratum consisted of approximately 750,000-1,200,000 individuals, who were followed for AUD for a mean follow-up time ranging between 10 and 15 years until the end of 2013. Cox proportional hazards models were used to investigate the risk of AUD as a function of income, education and neighborhood SES in the general population and in pairs of first cousins and full siblings within the same sex, who differed in their exposure to the SES measure. RESULTS: Higher educational level, higher income and higher neighborhood SES were all associated with a reduced risk for AUD for both males and females in all ages. The potentially protective effect remained but was attenuated when comparing pairs of first cousins and full siblings. CONCLUSIONS: High educational level and income in adulthood, as well as high neighborhood socioeconomic status, may represent protective factors against alcohol use disorders, even when shared familial factors, e.g. childhood socioeconomic status and genetic factors, have been taken into account.

2.
Sci Rep ; 9(1): 12717, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481703

RESUMO

Recent studies imply that rare variants contribute to the risk of schizophrenia, however, the exact variants or genes responsible for this condition are largely unknown. In this study, we conducted whole genome sequencing (WGS) of 20 Chinese families. Each family consisted of at least two affected siblings diagnosed with schizophrenia and at least one unaffected sibling. We examined functional variants that were found in affected sibling(s) but not in unaffected sibling(s) within a family. Matching this criterion, a frameshift heterozygous deletion of CA (-/CA) at chromosome 18:24722722, also referred to as rs752084147, in the Carbohydrate Sulfotransferase 9 (CHST9) gene, was detected in two families. This deletion was confirmed by PCR-based Sanger sequencing. With the observed frequency of 0.00076 in Han Chinese population, we performed both case-control and family-based analyses to evaluate its association with schizophrenia. In the case-control analyses, Chi-square test P-value was 6.80e-12 and the P-value was 0.0008 after one million simulations. In family-based segregation analyses, segregation P-value was 7.72e-7 and simulated P-value was 5.70e-6. For both the case-control and family-based analyses, the CA deletion was significantly associated with schizophrenia in the Chinese population. Further investigation of this gene  is warranted in the development of schizophrenia by utilizing larger and more ethnically diverse samples.

3.
Epidemiol Psychiatr Sci ; : 1-9, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31441394

RESUMO

AIMS: Can drug abuse (DA) be transmitted psychologically between adult siblings consistent with a social contagion model? METHODS: We followed Swedish sibling pairs born in 1932-1990 until one of them, sibling1 (S1), had a first DA registration. We then examined, using Cox regression, the hazard rate for a first registration for DA in sibling2 (S2) within 3 years of a first DA registration in S1 as a function of their geographical proximity. We examined 153 294 informative pairs. To control for familial confounding, we repeated these analyses in sibships containing multiple pairs, comparing risk in different siblings with their proximity to S1. DA was recorded in medical, criminal or pharmacy registries. RESULTS: The best-fit model predicted risk for DA in S2 as a function of the log of kilometres between S1 and S2 with parameter estimates (±95% confidence intervals) of 0.94 (0.92; 0.95). Prediction of DA included effects of cohabitation and an interaction of proximity and time since S1 registration with stronger effects of proximity early in the follow-up period. Proximity effects were stronger for smaller S1-S2 age differences and for same- v. opposite-sex pairs. Sibship analyses confirmed sibling-pair results. CONCLUSIONS: Consistent with a social contagion model, the probability of transmission of a first registration for DA in sibling pairs is related to their geographical proximity and similarity in age and sex. Such effects for DA are time-dependent and include cohabitation effects. These results illustrate the complexity of the familial aggregation of DA and support efforts to reduce their contagious spread within families in adulthood.

4.
Psychol Med ; : 1-8, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31362798

RESUMO

BACKGROUND: The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed. METHODS: We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments. RESULTS: We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning. CONCLUSIONS: By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.

5.
J Nerv Ment Dis ; 207(9): 778-784, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31464988

RESUMO

The initial plans for the DSM-5 revision envisioned a paradigm shift away from traditional diagnostic categories. However, plans for a major move from descriptive to etiologic diagnoses were quickly abandoned as infeasible. Support was much broader for adding dimensional/spectrum constructs to the categorical diagnoses, although this was interpreted in various ways. Delegation of substantial autonomy to work groups with modest central coordination was seen as problematic by some work groups and positively by others. Controversies emerged around the standards for diagnostic change, and the degree to which the same standards should be used across diagnostic groups. The Summit Group was given the final task of trying to forge a consensus among the various review groups. We conclude with thoughts about the difficulty of trying to revise an entire manual all at once and the desirability of developing clear rules for change at the outset of such a diagnostic project.

6.
Nicotine Tob Res ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31294817

RESUMO

INTRODUCTION: FTND (FagerstrÓ§m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. METHODS: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. RESULTS: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. CONCLUSIONS: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. IMPLICATIONS: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

7.
J Am Coll Health ; : 1-5, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31361579

RESUMO

Objective: Alcohol-related facial flushing occurs in individuals who are unable to metabolize ethanol effectively and is associated with increased cancer risk. This study describes college students' understanding of the meaning of flushing for how much alcohol a person should drink and their use of over-the-counter medications and other strategies to reduce its visible effects. Participants: The sample includes 335 White and Asian college students who reported facial flushing after an alcoholic drink. Methods: Students completed an online survey in the spring of their junior year. Results: Most students reported that flushing had no special meaning for drinking or that they did not know what it meant. Six percent reported ever using strategies to hide facial flushing; they were mostly Asian, and those using these strategies drank more alcohol. Conclusions: Findings identify a need for targeted alcohol education with Asian college students who drink alcohol despite experiencing the flushing response.

8.
Addiction ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31313399

RESUMO

BACKGROUND AND AIMS: The non-medical use of over-the-counter or prescribed analgesics (NMUA) is a significant public health problem. Little is known about the genetic and environmental etiology of NMUA and how these risks relate to other classes of substance use and misuse. Our aims were to estimate the heritability NMUA and sources of genetic and environmental covariance with cannabis and nicotine use, cannabis and alcohol use disorders and nicotine dependence in Australian twins. DESIGN: Biometrical genetic analyses or twin methods using structural equation univariate and multivariate modeling. SETTING: Australia. PARTICIPANTS: A total of 2007 young adult twins [66% female; µage  = 25.9, standard deviation (SD) = 3.6, range = 18-38] from the Brisbane Longitudinal Twin Study retrospectively assessed between 2009 and 2016. MEASUREMENTS: Self-reported NMUA (non-opioid or opioid-based), life-time nicotine, cannabis and opioid use, DSM-V cannabis and alcohol use disorders and the Fagerström Test for Nicotine Dependence. FINDINGS: Life-time NMUA was reported by 19.4% of the sample. Univariate heritability explained 46% [95% confidence interval (CI) = 0.29-0.57] of the risks in NMUA. Multivariate analyses revealed that NMUA is moderately associated genetically with cannabis (rg  = 0.41) and nicotine (rg  = 0.45) use and nicotine dependence (rg  = 0.34). In contrast, the genetic correlations with cannabis (rg  = 0.15) and alcohol (rg  = 0.07) use disorders are weak. CONCLUSIONS: In young male and female adults in Australia, the non-medical use of over-the-counter or prescribed analgesics appears to have moderate heritability. NMUA is moderately associated with cannabis and nicotine use and nicotine dependence. Its genetic etiology is largely distinct from that of cannabis and alcohol use disorders.

9.
Drug Alcohol Depend ; 201: 94-100, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31203149

RESUMO

BACKGROUND: Can we validate a contagion model for drug abuse (DA) in Propinquity-of-Rearing Defined Acquaintances (PRDAs)? METHODS: PRDAs were defined as pairs of same-age males born 1975-1990 who grew up within 2 km of each other, one of whom (PRDA1) being first registered for DA in national registries. Using adult residential location, we predicted, using regression splines, proximity-dependent risk for DA first registration in a second PRDA (PRDA2) within 3 years of PRDA1's registration. RESULTS: In 181,743 PRDA pairs, the best-fit model, controlling for age and PRDA2 community risk, included 2 slopes of proximity-risk relationships in childhood and three in adulthood. Risk for DA in PRDA2 was strongly predicted by childhood proximity to PRDA1: 0 to 0.5 km - Hazard ratio (HR) per kilometer 0.52 and 0.6-2 km 0.78. HRs for PRDA2 as a function of adult proximity to PRDA1 were: 0-1 km 0.887, 1-75 km 0.996 and >75 km 0.9997. Proximity-dependent PRDA2 risk was moderated by age, familial risk and educational attainment, attenuated by increasing PRDA1-PRDA2 age differences and stronger for older to younger versus younger to older pairs. CONCLUSIONS: Transmission of DA risk between acquaintances growing up together was attenuated by increasing distance in adulthood. Strength of the acquaintance, indexed by childhood propinquity and age difference, modified transmission strength. The impact of adult proximity on transmission was reduced in acquaintances with higher resistance to DA due to older age, higher educational attainment or lower familial risk. Our results support the validity of DA contagion models.

10.
Schizophr Bull ; 45(5): 971-990, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31206162

RESUMO

IMPORTANCE: First-rank symptoms (FRS), proposed by Kurt Schneider in 1939, subsequently became influential in schizophrenia diagnosis. We know little of their prehistory. How often were FRS described before 1939 and in which countries and time periods? Which FRS was most frequently noted? OBSERVATIONS: Forty psychiatric texts from 37 authors, published 1810-1932, were identified that described FRS. In a systematic subsample, half of the textbooks examined contained such descriptions with little differences between countries or over time. Somatic passivity was most commonly noted, followed by thought insertion, thought withdrawal, and made actions. This pattern resembled that reported in recent studies of schizophrenia. A novel term-delusions of unseen agency-was seen in psychiatric texts and then found, from 1842 to 1905, in a range of official reports, and psychiatric, medical, and general audience publications. The Early Heidelberg School (Gruhle, Mayer-Gross, Beringer) first systematically described "self-disturbances" (Ichstörungen), many of which Schneider incorporated into FRS. CONCLUSIONS AND RELEVANCE: From the beginning of Western descriptive psychopathology in the early 19th century, symptoms have been observed later described as first-rank by Schneider. A term "delusion of unseen agency"-closely related to Schneider's first-rank concept-was popular in the second half of the 19th century and described in publications as prominent as the Encyclopedia Britannica and New England Journal of Medicine. The descriptions of these specific symptoms, with substantial continuity, over more than 2 centuries and many countries, suggest that an understanding of their etiology would teach us something foundational about the psychotic illness.

11.
JAMA Psychiatry ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215968

RESUMO

The search for the causes of medical and psychiatric disorders has gone through 3 historical phases. First, up until the mid-19th century, causes of illness were anecdotally recorded from individual cases, resulting in long and diverse lists for all disorders. Second, in the latter half of the 19th century, with the use of microbiological methods, single causes were found for many infectious diseases that led to specific diagnostic tests, effective preventions, and, in some cases, treatments. Causal thinking in medicine shifted from the earlier multicausal approaches to monocausal theories of etiology. Indeed, proving monocausal etiology became a way to establish the legitimacy of a disorder. Through the writings of Kahlbaum and Hecker, psychiatry was deeply influenced by this monocausal perspective, the importance of which was substantially amplified by a twist of fate: the increasing clinical importance of general paresis of the insane throughout the 19th century and the eventual proof that it too was a monocausal condition. However, in the mid-20th century, the third phase began. With decreasing deaths from infectious diseases, epidemiology and clinical medicine shifted to a chronic disease model in which paradigmatic disorders, such as cancer and cardiovascular disease, were shown to be highly multicausal. Biostatistics evolved from deterministic to probabilistic models of disease risk factors. Paradoxically, at this time, biological psychiatry, then rising to dominance in American psychiatry, vigorously pursued monocausal theories, first of neurochemical origin and then of genetic origin. We were trying to establish the legitimacy of our field by pursuing an outmoded model-that "real" diseases are monocausal. Despite ample evidence to the contrary, monocausal thinking continues to influence our field, for example, in the popular but improbable view that we can, with a few key advances, move easily from descriptive to etiologically based diagnoses.

12.
Am J Psychiatry ; 176(9): 711-719, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31055966

RESUMO

OBJECTIVE: The objective of this study was to clarify the etiology of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. METHODS: Individuals with a registration of substance-induced psychotic disorder between 1997 and 2015 in national medical registries (N=7,606) were followed up for a mean of 84 months. Data from medical, criminal, and pharmacy registries on first-degree through third-degree relatives were used to calculate familial risk scores for nonaffective psychosis, drug abuse, and alcohol use disorder. RESULTS: Individuals with substance-induced psychotic disorder had large elevations in standardized familial risk scores for drug abuse (+1.09, 95% CI=1.02, 1.15) and alcohol use disorder (+0.98, 95% CI=0.93, 1.03) and modest elevations for nonaffective psychosis (+0.35, 95% CI=0.30, 0.41). The cumulative risk for progression to schizophrenia was 11.3%; it was lowest for alcohol-induced and highest for cannabis-induced psychotic disorder, and it was predicted by early age at diagnosis of substance-induced psychotic disorder, male sex, and further registrations for episodes of drug abuse, alcohol use disorder, and substance-induced psychotic disorder. A risk prediction model found that 47% of individuals who converted to schizophrenia were in the upper 20% of risk. Familial risk scores for drug abuse and alcohol use disorder did not significantly discriminate those who converted to schizophrenia from those who did not, while familial risk score for nonaffective psychosis did (0.67, 95% CI=0.40, 0.95, versus 0.33, 95% CI=0.28, 0.39). Familial risk scores for nonaffective psychosis were indistinguishable between individuals with schizophrenia with and without prior substance-induced psychosis. Assignment of early retirement by the Swedish Social Insurance Agency strongly discriminated between individuals with substance-induced psychotic disorder with and without later schizophrenia. CONCLUSIONS: Substance-induced psychotic disorder appears to result from substantial drug exposure in individuals at high familial risk for substance abuse and moderately elevated familial risk for psychosis. Familial risk for psychosis, but not substance abuse, predicts progression from substance-induced psychosis to schizophrenia. Schizophrenia following substance-induced psychosis is likely a drug-precipitated disorder in highly vulnerable individuals, not a syndrome predominantly caused by drug exposure.

13.
J Interpers Violence ; : 886260519849680, 2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31130049

RESUMO

This study examined the prevalence rates of sexual violence revictimization during each year of college. In addition, the impact of key mental health concerns on these rates was investigated. Incoming first-year students at a large, urban university completed a survey about their exposure to incidences of sexual assault before college and about their mental health symptoms. During each subsequent spring semester, experiences of sexual assault and mental health symptoms were reassessed. The sample was limited to individuals who reported sexual assault for at least one time period ( N = 3,294). More than 60% of individuals who endorsed an initial incident of sexual assault reported no subsequent incidences, leading to an overall revictimization rate of 39.5%. Rates of revictimization were higher for those identifying as women, as compared to men, and those identifying as White, as compared to those identifying as Asian or "other." Trauma-related distress and increased symptoms of alcohol use disorder (AUD) and depression were all related to a greater risk of experiencing revictimization. Given that experiencing an initial sexual assault greatly increases the risk of experiencing revictimization, and considering the notable prevalence rates of sexual assault on college campuses, it is imperative to examine trends in revictimization throughout the course of college. Examining factors that increase risk for experiencing revictimization is crucial to developing university-wide effective prevention and intervention efforts. In addition to the efforts to increase the reporting of incidences of sexual assault, universal programming efforts should also focus on factors that promote resilience in the face of sexual assault, such as reducing risky drinking behavior, increasing social support, and reducing stigma around the reporting of mental health symptoms.

14.
Twin Res Hum Genet ; 22(2): 108-113, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31006403

RESUMO

While snus has been the focus of increasing public health interest, twin studies have examined neither sources of individual variation for its use nor the sources of resemblance between snus and cigarette use. Twins from the Norwegian Institute of Public Health Panel were assessed by self-report questionnaire for the initiation of regular use and maximal quantity used for snus and cigarettes. Twin modeling was performed using OpenMx on data from 2767 twins including 856 complete pairs. Fitting univariate twin models produced similar results for cigarette initiation and quantity with estimates of additive genetic, shared environmental and unique environmental effects of approximately 77%, 0% and 23%, respectively. Estimates of snus initiation and quantity were, respectively, approximately 53%, 26% and 21%. Joint analyses suggested that the genetic, shared environmental and unique environmental correlations between cigarette and snus initiation and quantity were +.82, 0 and +.42, respectively. However, these results could not be statistically distinguished from a model which postulated that resemblance between cigarette initiation and quantity resulted from genetic and unique environmental correlations of +.47 and +.43. Compared with cigarette initiation and quantity of use in Norwegian twins, the role of genes was less prominent and shared environment more prominent for initiation and quantity of use of snus. Joint analyses of both tobacco phenotypes suggested, but did not confirm definitively, that genetic risk factors for cigarette and snus use were similar but not identical, while shared environmental factors existed that were specific to snus use.

15.
Psychol Med ; 49(7): 1218-1226, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30929657

RESUMO

BACKGROUND: Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS: Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS: Positive genetic correlation was observed between MD and AD (rgMD-AD = + 0.47, P = 6.6 × 10-10). AC-quantity showed positive genetic correlation with both AD (rgAD-AC quantity = + 0.75, P = 1.8 × 10-14) and MD (rgMD-AC quantity = + 0.14, P = 2.9 × 10-7), while there was negative correlation of AC-frequency with MD (rgMD-AC frequency = -0.17, P = 1.5 × 10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10-6). There was no evidence for reverse causation. CONCLUSION: This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.

16.
Psychol Med ; : 1-6, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30935430

RESUMO

BACKGROUND: The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets. METHODS: Using a large case-control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status. RESULTS: Over and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD. CONCLUSIONS: Results indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.

17.
Psychol Med ; : 1-8, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30992087

RESUMO

BACKGROUND: We introduce and apply an elegant, contrastive genetic-epidemiological design - Maternal Half-Sibling Families with Discordant Fathers - to clarify cross-generational transmission of genetic risk to alcohol use disorder (AUD), drug abuse (DA) and major depression (MD). METHOD: Using Swedish national registries, we identified 73 108 eligible pairs of reared together maternal half-siblings and selected those whose biological fathers were discordant for AUD, DA and MD, and had minimal contact with the affected father. We examined differences in outcome in half-siblings with an affected v. unaffected father. RESULTS: For AUD, DA and MD, the HR (95% confidence intervals) for the offspring of affected v. unaffected fathers were, respectively, 1.72 (1.61; 1.84), 1.55 (1.41; 1.70) and 1.51 (1.40; 1.64). Paternal DA and AUD, but not MD, predicted risk in offspring for attention deficit hyperactivity disorder, conduct disorder, and poor educational performance and attainment. Offspring of affected v. unaffected fathers had poorer pregnancy outcomes, with the effect strongest for DA and weakest for MD. A range of potential biases and confounders were examined and were not found to alter these findings substantially. CONCLUSION: Reared together maternal half-siblings differ in their paternal genetic endowment, sharing the same mother, family, school and community. They can help clarify the nature of paternal genetic effects and produce results consistent with other designs. Paternal genetic risk for DA and AUD have effects on offspring educational achievement, child and adult psychopathology, and possibly prenatal development. The impact of paternal genetic risk for MD is narrower in scope.

18.
Mol Psychiatry ; 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967680

RESUMO

In developing his mature concept of hebephrenic dementia praecox (DP) in his 4th (1893) through 6th textbook editions (1899), Kraepelin worked from the hebephrenic syndrome first described by Hecker (1871) and then carefully studied by his student Daraszkiewicz (1892). Working under Kraepelin's supervision, Daraszkiewicz followed Hecker in emphasizing several key features of hebephrenia (distinctive deteriorative course, importance of silliness and minimal positive psychotic symptoms) but expanded the syndrome to include cases developing severe dementia, rejected the link to prodromal depressive and manic phases, and reduced the emphasis on thought disorder. Daraszkiewicz proposed a soft subtyping of hebephrenia based on level of deterioration, which Kraepelin adopted in his 4th edition with an additional emphasis on severe positive psychotic symptoms. In his 5th edition, Kraepelin created a third subform with even more pronounced and bizarre delusions and hallucinations. In his 6th edition, which contained his first articulation of DP, Kraepelin eliminated his hebephrenia subforms presenting a single syndrome, which, compared to Hecker, included more emphasis on positive psychotic and catatonic symptoms and severe dementia. Kraepelin's paths to hebephrenic and paranoid DP differed in important ways. Paranoid DP was a de novo syndrome created by differentiation from paranoia. Hebephrenia, by contrast, evolved from a disorder created in the Kahlbaum/Hecker paradigm of the iterative study of clinical features, course and outcome. Kraepelin further implemented this approach in substantially reworking, over several drafts, the hebephrenic syndrome to fit into his emerging construct of dementia praecox.

19.
Depress Anxiety ; 36(6): 522-532, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30838764

RESUMO

BACKGROUND: It is unknown whether social anxiety disorder (SAD) has a unique association with alcohol use disorder (AUD) over and beyond that of other anxiety disorders, how the associations develop over time, and whether the associations are likely to be causal. METHODS: Diagnoses of AUD, SAD, generalized anxiety disorder, panic disorder, agoraphobia, and specific phobias were assessed twice using the Composite International Diagnostic Interview among 2,801 adult Norwegian twins. The data were analyzed using logistic regression analyses and multivariate biometric structural equation modeling. RESULTS: SAD had the strongest association with AUD, and SAD predicted AUD over and above the effect of other anxiety disorders. In addition, SAD was prospectively associated with AUD, whereas other anxiety disorders were not. AUD was associated with a slightly elevated risk of later anxiety disorders other than SAD. Biometric modeling favored a model where SAD influenced AUD compared to models where the relationship was reversed or due to correlated risk factors. Positive associations between AUD and other anxiety disorders were fully explained by shared genetic risk factors. CONCLUSIONS: Unlike other anxiety disorders, SAD plausibly has a direct effect on AUD. Interventions aimed at prevention or treatment of SAD may have an additional beneficial effect of preventing AUD, whereas interventions aimed at other anxiety disorders are unlikely to have a similar sequential effect on AUD.


Assuntos
Alcoolismo/complicações , Alcoolismo/psicologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/psicologia , Fobia Social/complicações , Fobia Social/psicologia , Adulto , Agorafobia/complicações , Agorafobia/psicologia , Feminino , Humanos , Masculino , Noruega , Transtorno de Pânico/complicações , Transtorno de Pânico/psicologia , Transtornos Fóbicos/complicações , Transtornos Fóbicos/psicologia , Fatores de Risco , Gêmeos/psicologia , Adulto Jovem
20.
Am J Psychiatry ; 176(3): 239-248, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818984

RESUMO

OBJECTIVE:: The purpose of this study was to determine whether, controlling for genetic effects, drug abuse was transmitted within families as predicted by a contagion model. METHODS:: The authors examined 65,006 parent-offspring, sibling, and cousin pairs ascertained from Swedish population registries in which the primary case subject had a drug abuse registration. The rate of drug abuse registration among at-risk secondary case subjects ages 19-23 was studied. Utilizing matched control pairs, a difference-in-difference approach was used to infer causal effects. RESULTS:: In offspring, risk for drug abuse registration in the 3 years after an index registration of a parent residing in the same household, neighborhood, or municipality increased 5.9%, 3.4%, and 1.8%, respectively. For siblings of sibling index case subjects, parallel results were 5.9%, 3.9%, and 1.2%. For cousins of cousin index case subjects, excess risk for those in the same neighborhood or municipality was 2.9% and 0.9%, respectively. In all sets of relatives, drug abuse transmission was strongest in male-male pairs and in pairs closest in age. In sibling pairs, stronger transmission was observed in older to younger siblings compared with younger to older siblings. Transmission was stronger within than across the two drug classes with sufficient data (opiates and cannabis). CONCLUSIONS:: These results suggest that drug abuse can be transmitted within families by an environmentally mediated temporally defined model of contagion. The most important methodological limitation is that drug abuse registration is an inaccurate measure of the onset of drug abuse. Indeed, as predicted, drug abuse risk increased among potential secondary case subjects in the year before drug abuse registration of the index case subject.

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