Cannabis involvement in individuals with bipolar disorder.
ABSTRACT: In a study of 471 bipolar disorder (BD) cases and 1761 controls, individuals with BD were 6.8 times more likely to report a lifetime history of cannabis use. Rates of DSM-IV cannabis use disorders in those with BD were 29.4% and were independently and significantly associated with increased suicide attempts, greater likelihood of mixed episodes and greater disability attributable to BD.
Project description:Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic polygenic risk score (PRS) analysis using multiple PRSs from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N?=?968) and Genetic Association Information Network (N?=?1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR?=?1.3 per S.D.; p?=?3e-5) but lower PRSs for anhedonia (OR?=?0.87; p?=?0.003) and BMI (OR?=?0.87; p?=?0.003). Rapid cycling cases had higher PRS for ADHD (OR?=?1.23; p?=?7e-5) and MDD (OR?=?1.23; p?=?4e-5) and lower BD PRS (OR?=?0.8; p?=?0.004). Cases with a suicide attempt had higher PRS for MDD (OR?=?1.26; p?=?1e-6) and anhedonia (OR?=?1.22; p?=?2e-5) as well as lower PRS for educational attainment (OR?=?0.87; p?=?0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity contributes to clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.
Project description:The complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered Cannabis use was associated with changes in circulating immune and neuroendocrine markers in schizophrenia (SCZ) and bipolar disorder (BD) patients. A screening of 13 plasma markers reflecting different inflammatory pathways was performed in SCZ (n = 401) and BD patients (n = 242) after subdividing each group into Cannabis user and non-user subgroups. We found that i) soluble gp130 (sgp130) concentrations were significantly elevated among Cannabis users in the SCZ group (p = 0.002) after multiple testing correction, but not in BD. ii) Nominally significant differences were observed in the levels of IL-1RA (p = 0.0059), YKL40 (p = 0.0069), CatS (p = 0.013), sTNFR1 (p = 0.031), and BDNF (p = 0.020), where these factors exhibited higher plasma levels in Cannabis user SCZ patients than in non-users. iii) These differences in systemic levels were not reflected by altered mRNA expression of genes encoding sgp130, IL-1RA, YKL40, CatS, sTNFR1, and BDNF in whole blood. Our results show that Cannabis self-administration is associated with markedly higher sgp130 levels in SCZ, but not in BD, and that this phenomenon is independent of the modulation of peripheral immune cells. These findings warrant further investigation into the potential IL-6 trans-signaling modulatory, anti-inflammatory, neuroimmune, and biobehavioral-cognitive effects of Cannabis use in SCZ.
Project description:Although cannabis use is common in bipolar disorder and may contribute to worse clinical outcomes, little is understood about the relationship between this drug and bipolar disorder over the course of daily life. The aim of study was to examine the effect of cannabis on affect and bipolar symptoms in a group of individuals with bipolar disorder.Twenty-four participants with bipolar disorder type I or type II completed diaries for 6 days using Experience Sampling Methodology to investigate the temporal associations between cannabis, affect and bipolar disorder symptoms.The results indicated that higher levels of positive affect increase the odds of using cannabis (OR:1.25 ,CI:1.06-1.47, P=0.008). However, neither negative affect, manic nor depressive symptoms predicted the use of cannabis. Cannabis use was associated with subsequent increases in positive affect (?=0.35, CI:0.20-0.51, P=0.000), manic symptoms (?=0.20,CI:0.05-0.34, P=0.009) and depressive symptoms (?= 0.17,CI:0.04-0.29, P=0.008).The findings indicate that cannabis use is associated with a number of subsequent psychological effects. However there was no evidence that individuals with BD were using cannabis to self-medicate minor fluctuations in negative affect or bipolar disorder symptoms over the course of daily life. The findings in relation to existing literature and clinical implications are discussed.
Project description:BACKGROUND:Using U.S. National Surveys on Drug Use and Health (NSDUH) data, researchers found that prevalence of cannabis use among adults increased in recent years, but prevalence of DSM-IV cannabis use disorder (CUD) was stable. Examining trends of all individual CUD criteria and of CUD severity may elucidate reasons for the lack of increases in CUD. METHODS:Data were from 749,500 persons aged 18 or older who participated in the 2002-2017 NSDUH. Descriptive analyses and logistic regressions were applied. RESULTS:Among adults during 2002-2017, past-year prevalence of DSM-IV CUD remained stable at 1.5% to 1.4%, but cannabis use increased from 10.4% to 15.3%, daily/near daily use increased from 1.9% to 4.2%, and mild DSM-5 CUD increased from 1.4% to 1.9%. Among adult cannabis users, past-year prevalence of DSM-IV CUD decreased from 14.8% to 9.3%, daily/near daily use increased from 18.0% to 27.2%, and DSM-5 moderate (4-5 criteria) and severe (6+ criteria) CUD decreased from 4.3% to 3.1% and from 2.4% to 1.3%, respectively. Examining trends in individual CUD criteria during 2002-2017 among adults overall revealed increases in two criteria (tolerance; spending a lot of time getting/using cannabis or getting over cannabis effects) and decreases/no changes in other criteria; among adult cannabis users, there was no change in one criterion (tolerance) and decreases in other criteria. CONCLUSIONS:DSM-5's single dimension CUD measure may be more sensitive to diagnosis prevalence changes than the separate DSM-IV cannabis dependence and abuse categories. Future diagnostic approaches to assessing CUD may benefit from quantitatively oriented criteria.
Project description:BACKGROUND:We explore the factor structure of DSM-5 cannabis use disorders, examine its prevalence across European- and African-American respondents as well as its genetic underpinnings, utilizing data from a genome-wide study of single nucleotide polymorphisms (SNPs). We also estimate the heritability of DSM-5 cannabis use disorders explained by these common SNPs. METHODS:Data on 3053 subjects reporting a lifetime history of cannabis use were utilized. Exploratory and confirmatory factor analyses were conducted to create a factor score, which was used in a genome-wide association analysis. p-values from the single SNP analysis were examined for evidence of gene-based association. The aggregate effect of all SNPs was also estimated using Genome-Wide Complex Traits Analysis. RESULTS:The unidimensionality of DSM-5 cannabis use disorder criteria was demonstrated. Comparing DSM-IV to DSM-5, a decrease in prevalence of cannabis use disorders was only noted in European-American respondents and was exceedingly modest. For the DSM-5 cannabis use disorders factor score, no SNP surpassed the genome-wide significance testing threshold. However, in the European-American subsample, gene-based association testing resulted in significant associations in 3 genes (C17orf58, BPTF and PPM1D) on chromosome 17q24. In aggregate, 21% of the variance in DSM-5 cannabis use disorders was explained by the genome-wide SNPs; however, this estimate was not statistically significant. CONCLUSIONS:DSM-5 cannabis use disorder represents a unidimensional construct, the prevalence of which is only modestly elevated above the DSM-IV version. Considerably larger sample sizes will be required to identify individual SNPs associated with cannabis use disorders and unequivocally establish its polygenic underpinnings.
Project description:Despite twin studies showing that 50-70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genome-wide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis-dependent cases with 2346 cannabis-exposed non-dependent controls was conducted using logistic regression in PLINK. None of the 948?142 single nucleotide polymorphisms met genome-wide significance (P at E-8). The lowest P values were obtained for polymorphisms on chromosome 17 (rs1019238 and rs1431318, P values at E-7) in the ANKFN1 gene. While replication is required, this study represents an important first step toward clarifying the biological underpinnings of cannabis dependence.
Project description:BACKGROUND:Bipolar disorder (BD) is a common severe mental disorder among homeless people and is associated with an increased risk of disability and mortality from suicide, medical causes (including HIV/AIDS, hepatitis infection, hypertension, and tuberculosis), as well as substance use disorders. However, a systematic synthesis of the existing evidence on the subject is lacking. To fill this gap in the literature, this study aimed to carry out systematic review and meta-analysis to determine the consolidated prevalence of BD among homeless people. METHODS:In this systematic review and meta-analysis, we searched Embase, PubMed, and Scopus to identify pertinent studies that reported the prevalence of BD among homeless people in March 2019. Random effect meta-analysis was employed to pool data from the eligible studies. Subgroup and sensitivity analysis was conducted and Cochran's Q- and the I2 test were utilized to quantify heterogeneity. Publication bias was assessed by using Egger's test and visual inspection of the symmetry in funnel plots. RESULTS:Of 3236 studies identified, 10 studies with 4300 homeless individuals were included in the final analysis. Among the 10 studies, five studies used the Diagnostic Statistical Manual of Mental disorders (DSM), three studies used Mini-International Neuropsychiatric Interview (MINI), one study used Schedule for Clinical Assessment of Neuropsychiatry (SCAN), and one study used Composite International Neuropsychiatric Interview (CIDI) to assess BD among homeless individuals. Based on the results of the random effect model, the prevalence of BD among homeless people was 11.4% (95% CI; 7.5-16.9). The prevalence of BD was 10.0% (95% CI; 3.1-27.9) in Europe and it was 13.2% (95% CI; 8.9-19.3) in other countries. Moreover, the prevalence of BD was 11.5% (95% CI; 5.5-22.3) for studies that used DSM to assess BD and it was 11.0% (95% CI; 6.1-19.2) for studies that used other instruments (MINI, SCAN, and CIDI). CONCLUSION:Our meta-analysis demonstrated that BD is highly prevalent among homeless individuals, underlying the importance of early screening and targeted interventions for BD among homeless individuals.
Project description:OBJECTIVE:Given changes in U.S. marijuana laws, attitudes, and use patterns, individuals with pain may be an emerging group at risk for nonmedical cannabis use and cannabis use disorder. The authors examined differences in the prevalence of nonmedical cannabis use and cannabis use disorder among U.S. adults with and without pain, as well as whether these differences widened over time. METHODS:Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309) were analyzed using logistic regression. Risk differences of past-year nonmedical cannabis use, frequent (at least three times a week) nonmedical use, and DSM-IV cannabis use disorder were estimated for groups with and without moderate to severe pain, and these risk differences were tested for change over time. RESULTS:Any nonmedical cannabis use was more prevalent in respondents with than without pain (2001-2002: 5.15% compared with 3.74%; 2012-2013: 12.42% compared with 9.02%), a risk difference significantly greater in the 2012-2013 data than in the 2001-2002 data. The prevalence of frequent nonmedical cannabis use did not differ by pain status in the 2001-2002 survey, but was significantly more prevalent in those with than without pain in the 2012-2013 survey (5.03% compared with 3.45%). Cannabis use disorder was more prevalent in respondents with than without pain (2001-2002: 1.77% compared with 1.35%; 2012-2013: 4.18% compared with 2.74%), a significantly greater risk difference in the data from 2012-2013 than from 2001-2002. CONCLUSIONS:The results suggest that adults with pain are a group increasingly vulnerable to adverse cannabis use outcomes, warranting clinical and public health attention to this risk. Psychiatrists and other health care providers treating patients with pain should monitor such patients for signs and symptoms of cannabis use disorder.
Project description:In the present study, we examined the relationship between cannabis involvement and suicidal ideation (SI), plan and attempt, differentiating the latter into planned and unplanned attempt, taking into account other substance involvement and psychopathology.We used two community-based twin samples from the Australian Twin Registry, including 9583 individuals (58.5% female, aged between 27 and 40). The Semi-Structured Assessment of the Genetics of Alcoholism (SSAGA) was used to assess cannabis involvement which was categorized into: (0) no cannabis use (reference category); (1) cannabis use only; (2) 1-2 cannabis use disorder symptoms; (3) 3 or more symptoms. Separate multinomial logistic regression analyses were conducted for SI and suicide attempt with or without a plan. Twin analyses examined the genetic overlap between cannabis involvement and SI.All levels of cannabis involvement were related to SI, regardless of duration (odds ratios [ORs]=1.28-2.00, p<0.01). Cannabis use and endorsing ?3 symptoms were associated with unplanned (SANP; ORs=1.95 and 2.51 respectively, p<0.05), but not planned suicide attempts (p>0.10). Associations persisted even after controlling for other psychiatric disorders and substance involvement. Overlapping genetic (rG=0.45) and environmental (rE=0.21) factors were responsible for the covariance between cannabis involvement and SI.Cannabis involvement is associated, albeit modestly, with SI and unplanned suicide attempts. Such attempts are difficult to prevent and their association with cannabis use and cannabis use disorder symptoms requires further study, including in different samples and with additional attention to confounders.
Project description:Background:Climate and weather are known to affect multiple areas of human life, including mental health. In bipolar disorder (BD), seasonality represents an environmental trigger for mood switches, and climatic variables may contribute to recurrences. Several studies reported seasonal and climatic-related variations in the rate of suicide attempts. Suicide risk is relevant in BD, with approximately 25% of patients attempting suicide. Therefore, this study aimed to assess sensitivity to weather and climatic variations in BD subjects and its relationship with lifetime suicide attempts. Methods:Three hundred fifty-two euthymic BD and 352 healthy control subjects, homogeneous with respect to socio-demographic characteristics, were enrolled. All participants were administered the METEO-Questionnaire (METEO-Q) to evaluate susceptibility to weather and climatic changes. We also investigated the potential relationship between sensitivity to climate and weather and lifetime suicide attempts in BD patients. Results:METEO-Q scores and the number of subjects reaching the cut-off for meteorosensitivity/meteoropathy were significantly higher in BD patients. Within the clinical group, BD subjects with lifetime suicide attempts obtained higher METEO-Q scores, with no differences between BD-I and BD-II. The number of suicide attempts directly correlated with METEO-Q scores. The presence of suicide attempts was associated with the physical and psychological symptoms related to weather variations. Discussion:Our findings support the relevance of sensitivity to weather and climate variations in a large sample of BD subjects and point out the association of this feature with lifetime suicide attempts.