Genetic Basis of Dual Diagnosis: A Review of Genome-Wide Association Studies (GWAS) Focusing on Patients with Mood or Anxiety Disorders and Co-Occurring Alcohol-Use Disorders.
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SUBMITTER: Stoychev K
PROVIDER: S-EPMC8228390 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compared the effects of FAAH (PF-3845), MAGL (JZL184) and dual FAAH/MAGL (JZL195) inhibitors on (1) anxiety-like behaviors under non-stressed and stressed conditions, (2) locomotor activity and body temperature, (3) lipid levels in the brain and (4) cognitive functions. Behavioral analysis showed that PF-3845 or JZL184, but not JZL195, was able to prevent restraint stress-induced anxiety in the light-dark box assay when administered before stress exposure. Moreover, JZL195 treatment was not able to reverse foot shock-induced anxiety-like behavior in the elevated zero maze or light-dark box. JZL195, but not PF-3845 or JZL184, decreased body temperature and increased anxiety-like behavior in the open-field test. Overall, JZL195 did not show anxiolytic efficacy and the effects of JZL184 were more robust than that of PF-3845 in the models examined. These results showed that increasing either endogenous AEA or 2-AG separately produces anti-anxiety effects under stressful conditions but the same effects are not obtained from simultaneously increasing both AEA and 2-AG.
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Project description:ContextUnderstanding the temporal sequencing of alcohol use disorders (AUDs) and comorbid mood and anxiety disorders may help to disentangle the etiological underpinnings of comorbidity. Methodological limitations of previous studies, however, may have led to inconsistent or inconclusive findings.ObjectiveTo describe the temporal sequencing of the onset of AUDs relative to the onset of specific comorbid mood and anxiety disorders using a large, nationally representative survey.ResultsAUD onset tended to follow the onset of 2 of the 9 mood and anxiety disorders (specific and social phobia). The onset of alcohol abuse tended to precede the onset of 5 of the 9 mood and anxiety disorders (GAD, panic, panic with agoraphobia, major depression, and dysthymia), whereas the onset of alcohol dependence tended to precede the onset of only 2 of the 9 mood and anxiety disorders (GAD and panic). Lag times between primary and subsequent disorders generally ranged from 7 to 16 years. Comorbid individuals whose alcohol dependence came after panic with agoraphobia, hypomania, and GAD had increased risk of persistent alcohol dependence.ConclusionAlcohol abuse, but not dependence, precedes many mood and anxiety disorders. If the primary disorder does in fact play a causative or contributing role in the development of the subsequent disorder, this role can best be described as "temporally distal." However, in assessing the risk for persistent alcohol dependence, clinicians should not only consider the type of comorbid mood/anxiety disorder, but also the temporal ordering of these disorders.
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Project description:AimsUnder-diagnosis of mood disorders occurs worldwide. In this study, we characterized and compared Canadians with symptoms compatible with a mood disorder by diagnosis status; and described the associated health impacts, use of health services and perceived need for care.MethodsRespondents to the 2012 Canadian Community Health Survey - Mental Health, a nationally representative sample of Canadians age ≥15 years were assessed for symptoms compatible with mood disorders based on a Canadian adaptation of the World Health Organization Composite International Diagnostic Interview (n = 23 504). Descriptive and multivariate regression analyses were performed.ResultsIn 2012, an estimated 5.4% (1.5 million) Canadians aged 15 years and older reported symptoms compatible with a mood disorder, of which only half reported having been professionally diagnosed. The undiagnosed individuals were more likely to be younger (mean age: 36.2 v. 41.8), to be single (49.5 v. 32.7%), to have less than a post-secondary graduation (49.8 v. 41.1%) and to have no physical co-morbidities (56.4 v. 35.7%), and less likely to be part of the two lower income quintiles (49.6 v. 62.7%) compared with those with a previous diagnosis. Upon controlling for all socio-demographic and health characteristics, the associations with age and marital status disappeared. While those with a previous diagnosis reported significantly greater health impacts and were more likely to have consulted a health professional for their emotional and mental health problems in the previous 12 months compared with those undiagnosed (79.4 v. 31.0%), about a third of both groups reported that their health care needs were only partially met or not met at all.ConclusionsMood disorders are prevalent and can profoundly impact the life of those affected, however, their diagnosis remains suboptimal and health care use falls short of apparent needs. Improvements in mental health literacy, help-seeking behaviours and diagnosis are needed. In light of the heterogeneity of mood disorders in terms of symptoms severity, impacts and prognosis, interventions must be tailored accordingly.
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Project description:We examined the association between regular cigarette smoking and new onset of mood and anxiety disorders.We used logistic regression analysis to detect associations between regular smoking and new-onset disorders during the 3-year follow-up among 34 653 participants in the longitudinal US National Epidemiologic Survey on Alcohol and Related Conditions (2001-2005). We used instrumental variable methods to assess the appropriateness of these models.Regular smoking was associated with an increased risk of new onset of mood and anxiety disorders in multivariable analyses (Fdf = 5,61 = 11.73; P < .001). Participants who smoked a larger number of cigarettes daily displayed a trend toward greater likelihood of new-onset disorders. Age moderated the association of smoking with most new-onset disorders. The association was mostly statistically significant and generally stronger in participants aged 18 to 49 years but was smaller and mostly nonsignificant in older adults.Our finding of a stronger association between regular cigarette smoking and increased risk of new-onset mood and anxiety disorders among younger adults suggest the need for vigorous antismoking campaigns and policy initiatives targeting this age group.
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Project description:ImportanceChildren with strabismus have poorer functional vision and decreased quality of life than those without strabismus.ObjectiveTo evaluate the association between strabismus and mental illness among children.Design, setting, and participantsThis cross-sectional study analyzed claims data from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, from 12 005 189 patients enrolled in the health plan between January 1, 2007, and December 31, 2017. Eligibility criteria included age younger than 19 years at the time of strabismus diagnosis, enrollment in the health plan between 2007 and 2018, and having at least 1 strabismus claim based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes. Controls were children in the same database with no eye disease codes other than refractive error reported. Demographic characteristics and mental illness claims were compared. Statistical analysis was conducted from December 1, 2018, to July 31, 2021.Main outcomes and measuresPresence of mental illness claims.ResultsAmong the 12 005 189 patients (6 095 523 boys [50.8%]; mean [SD] age, 8.0 [5.9] years) in the study, adjusted odds ratios for the association of mental illnesses with strabismus were 2.01 (95% CI, 1.99-2.04) for anxiety disorder, 1.83 (95% CI, 1.76-1.90) for schizophrenia, 1.64 (95% CI, 1.59-1.70) for bipolar disorder, 1.61 (95% CI, 1.59-1.63) for depressive disorder, and 0.99 (95% CI, 0.97-1.02) for substance use disorder. There was a moderate association between each strabismus type (esotropia, exotropia, and hypertropia) and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder; odds ratios ranged from 1.23 (95% CI, 1.17-1.29) for the association between esotropia and bipolar disorder to 2.70 (95% CI, 2.66-2.74) for the association between exotropia and anxiety disorder.Conclusions and relevanceThis cross-sectional study suggests that there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder. Recognizing that these associations exist should encourage mental illness screening and treatment for patients with strabismus.
| S-EPMC8914883 | biostudies-literature
Project description:BackgroundSerious and debilitating symptoms of anxiety are the most common mental health problem worldwide, accounting for around 5% of all adult years lived with disability in the developed world. Avoidance behavior-avoiding social situations for fear of embarrassment, for instance-is a core feature of such anxiety. However, as for many other psychiatric symptoms the biological mechanisms underlying avoidance remain unclear.MethodsReinforcement learning models provide formal and testable characterizations of the mechanisms of decision making; here, we examine avoidance in these terms. A total of 101 healthy participants and individuals with mood and anxiety disorders completed an approach-avoidance go/no-go task under stress induced by threat of unpredictable shock.ResultsWe show an increased reliance in the mood and anxiety group on a parameter of our reinforcement learning model that characterizes a prepotent (pavlovian) bias to withhold responding in the face of negative outcomes. This was particularly the case when the mood and anxiety group was under stress.ConclusionsThis formal description of avoidance within the reinforcement learning framework provides a new means of linking clinical symptoms with biophysically plausible models of neural circuitry and, as such, takes us closer to a mechanistic understanding of mood and anxiety disorders.
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Project description:Anxiety is characterized by altered responses under uncertain conditions, but the precise mechanism by which uncertainty changes the behaviour of anxious individuals is unclear. Here we probe the computational basis of learning under uncertainty in healthy individuals and individuals suffering from a mix of mood and anxiety disorders. Participants were asked to choose between four competing slot machines with fluctuating reward and punishment outcomes during safety and stress. We predicted that anxious individuals under stress would learn faster about punishments and exhibit choices that were more affected by those punishments, thus formalizing our predictions as parameters in reinforcement learning accounts of behaviour. Overall, the data suggest that anxious individuals are quicker to update their behaviour in response to negative outcomes (increased punishment learning rates). When treating anxiety, it may therefore be more fruitful to encourage anxious individuals to integrate information over longer horizons when bad things happen, rather than try to blunt their responses to negative outcomes.
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Project description:Psychiatric disorders have been widely reported to be associated with systemic inflammation upregulation and adiposity. However, there are no data that link adipose tissue inflammation to these mental disorders. The analysis of adipokines and inflammation-related markers in adipose tissue could help to elucidate the potential association between obesity and mental health. An observational study was conducted in samples of patients consisting of non-obese and obese subjects, who were diagnosed with anxiety or mood disorders. Gene expression of adiponectin (ADIPOQ), leptin (LEP) and inflammatory markers (IL6, IL1B, TNF, CCL2, CSF3, ITGAM, and PLAUR) were determined in visceral (VAT) and subcutaneous (SAT) adipose tissues. Our results showed that the gene expression of adipokines and inflammation-related markers was higher in the VAT and SAT of obese subjects compared with non-obese subjects. Regarding mental disorders, all the inflammatory genes in the VAT were significantly higher in non-obese subjects with anxiety or mood disorders than in subjects without mental disorders, except for TNF and ITGAM. Additionally, IL6 expression was significantly lower in SAT. In contrast, obese patients diagnosed with anxiety or mood disorders only showed significantly lower expression levels of IL1B in VAT and ADIPOQ in SAT when compared with obese subjects without mental disorders. These data suggest the potential involvement of VAT inflammation in anxiety and mood disorders, involving complex mechanisms which are strongly affected by obesity.
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Project description:Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have reported evidence that inflammation and release of inflammatory cytokines affect circuitry relevant to both reward and threat sensitivity to contribute to behavioral change. Of relevance to mood and anxiety-related disorders, biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of patients with major depressive disorder (MDD), bipolar disorder, anxiety disorders and post-traumatic stress disorder (PTSD).This review summarized clinical and translational work demonstrating the impact of peripheral inflammation on brain regions and neurotransmitter systems relevant to both reward and threat sensitivity, with a focus on neuroimaging studies involving administration of inflammatory stimuli. Recent translation of these findings to further understand the role of inflammation in mood and anxiety-related disorders is also discussed.Inflammation was consistently found to affect basal ganglia and cortical reward and motor circuits to drive reduced motivation and motor activity, as well as anxiety-related brain regions including amygdala, insula and anterior cingulate cortex, which may result from cytokine effects on monoamines and glutamate. Similar relationships between inflammation and altered neurocircuitry have been observed in MDD patients with increased peripheral inflammatory markers, and such work is on the horizon for anxiety disorders and PTSD.Neuroimaging effects of inflammation on reward and threat circuitry may be used as biomarkers of inflammation for future development of novel therapeutic strategies to better treat mood and anxiety-related disorders in patients with high inflammation.
| S-EPMC5997866 | biostudies-literature
Project description:Importance:It is critical to evaluate the risk of comorbid psychiatric diagnoses to meet the needs of individuals with autism spectrum disorder (ASD).Objective:To examine whether individuals with ASD are at greater risk for comorbid diagnoses of depression, anxiety, or bipolar disorder.Design, setting, and participants:This cohort study used data from a population-based birth cohort of 31 220 individuals born in Olmsted County, Minnesota, from January 1, 1976, to December 31, 2000. Patients with research-identified ASD were previously identified using a multistep process that evaluated signs and symptoms abstracted from medical and educational records. For each of the 1014 patients with ASD, 2 age- and sex-matched referents who did not meet criteria for ASD were randomly selected from the birth cohort (n?=?2028). Diagnosis codes for anxiety, depression, and bipolar disorders were electronically obtained using the Rochester Epidemiological Project records-linkage system. Data analysis was performed from July 1, 2018, to April 1, 2019.Main outcomes and measures:Cumulative incidence of clinically diagnosed depression, anxiety, and bipolar disorder through early adulthood in individuals with ASD compared with referents.Results:A total of 1014 patients with ASD (median age at last follow-up, 22.8 years [interquartile range, 18.4-28.0 years]; 747 [73.7%] male; 902 [89.0%] white) and 2028 referents (median age at last follow-up, 22.4 years [interquartile range, 18.8-26.2 years]; 1494 [73.7%] male; 1780 [87.8%] white) participated in the study. Patients with ASD were significantly more likely to have clinically diagnosed bipolar disorder (hazard ratio [HR], 9.34; 95% CI, 4.57-19.06), depression (HR, 2.81; 95% CI, 2.45-3.22), and anxiety (HR, 3.45; 95% CI, 2.96-4.01) compared with referents. Among individuals with ASD, the estimates of cumulative incidence by 30 years of age were 7.3% (95% CI, 4.8%-9.7%) for bipolar disorder, 54.1% (95% CI, 49.8%-58.0%) for depression, and 50.0% (95% CI, 46.0%-53.7%) for anxiety. Among referents, cumulative incidence estimates by 30 years of age were 0.9% (95% CI, 0.1%-1.7%) for bipolar disorder, 28.9% (95% CI, 25.7%-32.0%) for depression, and 22.2% (95% CI, 19.3%-25.0%) for anxiety.Conclusions and relevance:The findings suggest that individuals with ASD may be at increased risk for clinically diagnosed depression, anxiety, and bipolar disorder compared with age- and sex-matched referents. This study supports the importance of early, ongoing surveillance and targeted treatments to address the psychiatric needs of individuals with ASD.
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