Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities

AbstractUnderstanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study (GWAS) of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of mood disturbance (major depressive disorder, bipolar II, and self-reported symptoms of depression, mania, and psychosis) versus rarer forms of serious mental illness (bipolar I, schizoaffective disorder, and schizophrenia). Biological annotation revealed divergent genetic architectures that differentially implicated prenatal neurodevelopment and neuronal function and regulation. These findings inform psychiatric nosology and biological models of psychopathology, as they suggest the severity of mood and psychotic symptoms present in serious mental illness may reflect a difference in kind, rather than merely in degree.

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Studies of Human Twins Reveal Genetic Variation That Affects Dietary Fat Perception

Chemical Senses ◽

10.1093/chemse/bjaa036 ◽

2020 ◽

Vol 45 (6) ◽

pp. 467-481

Author(s):

Cailu Lin ◽

Lauren Colquitt ◽

Paul Wise ◽

Paul A S Breslin ◽

Nancy E Rawson ◽

...

Keyword(s):

Dietary Fat ◽

Genome Wide Association Study ◽

Corn Oil ◽

Potato Chips ◽

Hexadecanoic Acid ◽

Reliability Estimates ◽

Genome Wide ◽

A Genome ◽

Multivariate Gwas ◽

Triglyceride Content

Abstract To learn more about the mechanisms of human dietary fat perception, we asked 398 human twins to rate the fattiness and how much they liked 6 types of potato chips that differed in triglyceride content (2.5%, 5%, 10%, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (FA; hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness of and liking for the potato chips were reliable (r = 0.31–0.62, P < 0.05) and heritable (up to h2 = 0.29, P < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, P < 1 × 10–5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was 1) negatively affected by the addition of a saturated FA and 2) related to inborn genetic variants. These data suggest that liking for dietary fat is not due solely to FA content and highlight new candidate genes and proteins within this sensory pathway.

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Impact of exergames on psychiatric symptoms in older adults with serious mental illness

Aging & Mental Health ◽

10.1080/13607863.2020.1832442 ◽

2020 ◽

pp. 1-6

Author(s):

Michael Heinbach ◽

Astrid Block ◽

Erin Hubbard ◽

Janine Cataldo ◽

Bruce Cooper ◽

...

Keyword(s):

Older Adults ◽

Mental Illness ◽

Serious Mental Illness ◽

Psychiatric Symptoms

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Effects of 6-Week Use of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness

Nicotine & Tobacco Research ◽

10.1093/ntr/ntz133 ◽

2019 ◽

Vol 21 (Supplement_1) ◽

pp. S38-S45 ◽

Cited By ~ 5

Author(s):

Jennifer W Tidey ◽

Suzanne M Colby ◽

Rachel L Denlinger-Apte ◽

Christine Goodwin ◽

Patricia A Cioe ◽

...

Keyword(s):

Mental Illness ◽

Serious Mental Illness ◽

Psychiatric Symptoms ◽

High Rate ◽

Withdrawal Symptoms ◽

Treatment Seeking ◽

Nicotine Exposure ◽

Toxicant Exposure ◽

Nicotine Content ◽

The Us

Abstract Introduction The US Food and Drug Administration is considering implementing a reduced-nicotine standard for cigarettes. Given the high rate of smoking among people with serious mental illness (SMI), it is important to examine the responses of these smokers to very low nicotine content (VLNC) cigarettes. Methods This trial compared the effects of VLNC (0.4 mg nicotine/g tobacco) and normal nicotine content cigarettes (15.8 mg/g) over a 6-week period in non-treatment-seeking smokers with schizophrenia, schizoaffective disorder, or bipolar disorder (n = 58). Linear regression was used to examine the effects of cigarette condition on cigarettes per day, subjective responses, nicotine and tobacco toxicant exposure, craving, withdrawal symptoms, and psychiatric symptoms. Results At week 6, participants in the VLNC condition smoked fewer cigarettes per day, had lower breath carbon monoxide levels, lower craving scores, and rated their study cigarettes lower in satisfaction, reward, enjoyment, and craving reduction than those in the normal nicotine content condition (ps < .05). Week 6 psychiatric and extrapyramidal symptoms did not differ by condition, except for scores on a measure of parkinsonism, which were lower in the VLNC condition (p < .05). There were no differences across conditions on total nicotine exposure, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, withdrawal symptoms, or responses to abstinence. Conclusions These results suggest that a reduced-nicotine standard for cigarettes would reduce smoking among smokers with SMI. However, the lack of effect on total nicotine exposure indicates VLNC noncompliance, suggesting that smokers with SMI may respond to a reduced-nicotine standard by substituting alternative forms of nicotine. Implications Results from this trial suggest that a reduced-nicotine standard for cigarettes would reduce smoking rates and smoke exposure in smokers with SMI, without increasing psychiatric symptoms. However, noncompliance with VLNC cigarettes was observed, suggesting that these smokers might respond to a reduced-nicotine standard by substituting alternative forms of nicotine.

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The Unified Protocol for Use with Adolescents with or at Risk for Serious Mental Illness

10.1093/med-psych/9780197527931.003.0006 ◽

2021 ◽

pp. 79-95

Author(s):

Marc J. Weintraub ◽

Jamie Zinberg

Keyword(s):

Mental Illness ◽

Emotional Disorders ◽

Skill Acquisition ◽

Serious Mental Illness ◽

Behavioral Treatment ◽

Psychiatric Symptoms ◽

Bipolar Disorders ◽

Cognitive Behavioral Treatment ◽

Transdiagnostic Treatment ◽

Unified Protocol

Youths with or at high risk for serious mental illness (SMI; i.e., psychotic or bipolar disorders) have heterogeneous psychiatric symptoms, including significant overlap with more common depressive and anxiety disorders. There are also heterogeneous illness trajectories, as some youth go on to develop chronic and debilitating SMIs while a large proportion have symptoms that remit or remain relatively milder. This chapter presents the rationale for using the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) as a first-line, transdiagnostic, cognitive-behavioral treatment for youth with early SMI symptoms. This treatment is delivered in a group format including parents in an effort to reduce stigma, increase social support, and improve skill acquisition. Preliminary feasibility and efficacy data are presented as well as a case vignette. Recommendations are offered on how to deliver this treatment and troubleshoot common difficulties.

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Exploring the Relationship Between Major Mental Illness and Sex Offending Behavior in a High-Risk Population

Criminal Justice and Behavior ◽

10.1177/0093854819887204 ◽

2019 ◽

Vol 47 (3) ◽

pp. 290-309

Author(s):

Sharon M. Kelley ◽

David Thornton ◽

Ryan Mattek ◽

Letitia Johnson ◽

Gina Ambroziak

Keyword(s):

Mental Illness ◽

High Risk ◽

Psychiatric Symptoms ◽

Sexual Offending ◽

Psychotic Symptoms ◽

High Risk Population ◽

Sex Offenses ◽

Offending Behavior ◽

Criminogenic Needs ◽

The Relationship

Empirically supported risk factors are predictive of sexual re-offense regardless of whether individuals suffer from a major mental illness. A small subgroup of individuals with major mental illness may be more likely to demonstrate acute psychotic symptoms at the time of their sexual offending behavior (Smith & Taylor, 1999). This study reviewed archival data from a high-risk sample to identify 55 individuals with major mental illness who had committed a total of 176 sex offenses. The relationship between acute psychiatric symptoms and criminogenic needs was explored. Most sex offenses were not temporally related to acute psychiatric symptoms. The apparent effect of mental health symptoms on criminogenic factors over the individual’s life was rated. Where acute symptoms were associated with worsened criminogenic factors, this most often involved Grievance Thinking, Poor Emotional Control, and Poor Problem-Solving. Typologies emerged based on the pattern of criminogenic needs along with demographic and offense characteristics. Assessment and treatment implications are discussed.

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Peer navigation for individuals with serious mental illness leaving jail: a pilot randomized trial study protocol

10.21203/rs.3.rs-20884/v3 ◽

2020 ◽

Author(s):

Maji Hailemariam ◽

Lauren M Weinstock ◽

Jennifer E. Johnson

Keyword(s):

Mental Health ◽

Mental Illness ◽

Serious Mental Illness ◽

Suicide Attempts ◽

Psychiatric Symptoms ◽

Controlled Trial ◽

Pilot Trial ◽

Public Health Problem ◽

Training Methods ◽

Peer Navigation

Abstract Background: Serious mental illness (SMI) is a prevalent public health problem affecting 25% of individuals in jail. Re-entry to the community following incarceration is a vulnerable time for justice-involved individuals with SMI. SMI requires prompt and ongoing access to mental health and other healthcare services. Methods: The study will: 1) develop a Mentoring And Peer Support (MAPS) intervention for post-release mental health and other service connection among jailed individuals with SMI, and 2) pilot-test the MAPS intervention to determine the feasibility and acceptability of the MAPS intervention. The primary outcomes will be to evaluate the feasibility and acceptability of the proposed recruitment methods and research design, of the intervention training methods, of delivering the enhanced peer-navigator and control interventions. Study samples include (focus groups, open trial), and a randomized pilot trial in a sample of 40 individuals with SMI re-entering the community after jail release. Secondary outcomes will include post-release enrollment in mental health, medical care, and substance use services. We will also evaluate reduction in psychiatric symptoms, improvements in functioning, adherence to psychiatric medications, fewer substance using days, fewer hospitalizations and suicide attempts, nights unstably housed, and time until rearrest. Discussion: This pilot study will evaluate the feasibility and acceptability of a peer navigation intervention for individuals with serious mental illness leaving jails. The study will serve as a formative work for a larger randomized controlled trial assessing the effectiveness of peer navigator intervention for (include the primary outcome) in this population.

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The impact of psychiatric symptoms on condom self-efficacy among people with serious mental illness.

Psychiatric Rehabilitation Journal ◽

10.1037/prj0000405 ◽

2020 ◽

Vol 43 (3) ◽

pp. 205-213

Author(s):

Veronica Pinho ◽

Karen McKinnon ◽

Francine Cournos ◽

Andrea Norcini Pala ◽

Maria Cecilia Zea ◽

...

Keyword(s):

Mental Illness ◽

Serious Mental Illness ◽

Self Efficacy ◽

Psychiatric Symptoms ◽

The Impact

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P1-236: Genome-Wide Association Study for Alzheimer's Disease with Psychotic Symptoms

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.516 ◽

2011 ◽

Vol 7 ◽

pp. S186-S186

Author(s):

Paul Hollingworth ◽

Robert Sweet ◽

Rebecca Sims ◽

Denise Harold ◽

Richard Abraham ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Psychotic Symptoms ◽

Genome Wide

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Multi-Trait Genome-Wide Association Studies Reveal Loci Associated with Maize Inflorescence and Leaf Architecture

Plant and Cell Physiology ◽

10.1093/pcp/pcaa039 ◽

2020 ◽

Vol 61 (8) ◽

pp. 1427-1437 ◽

Cited By ~ 6

Author(s):

Brian R Rice ◽

Samuel B Fernandes ◽

Alexander E Lipka

Keyword(s):

Quantitative Trait ◽

Genome Wide Association Study ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Multiple Traits ◽

Leaf Architecture ◽

Genome Wide ◽

Multivariate Gwas ◽

Genomic Regions

Abstract Maize inflorescence is a complex phenotype that involves the physical and developmental interplay of multiple traits. Given the evidence that genes could pleiotropically contribute to several of these traits, we used publicly available maize data to assess the ability of multivariate genome-wide association study (GWAS) approaches to identify pleiotropic quantitative trait loci (pQTL). Our analysis of 23 publicly available inflorescence and leaf-related traits in a diversity panel of n = 281 maize lines genotyped with 376,336 markers revealed that the two multivariate GWAS approaches we tested were capable of identifying pQTL in genomic regions coinciding with similar associations found in previous studies. We then conducted a parallel simulation study on the same individuals, where it was shown that multivariate GWAS approaches yielded a higher true-positive quantitative trait nucleotide (QTN) detection rate than comparable univariate approaches for all evaluated simulation settings except for when the correlated simulated traits had a heritability of 0.9. We therefore conclude that the implementation of state-of-the-art multivariate GWAS approaches is a useful tool for dissecting pleiotropy and their more widespread implementation could facilitate the discovery of genes and other biological mechanisms underlying maize inflorescence.

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Studies of human twins reveal genetic variation that affects dietary fat perception

10.1101/2020.01.18.910448 ◽

2020 ◽

Author(s):

Cailu Lin ◽

Lauren Colquitt ◽

Paul Wise ◽

Paul A. S. Breslin ◽

Nancy E. Rawson ◽

...

Keyword(s):

Fatty Acid ◽

Dietary Fat ◽

Genome Wide Association Study ◽

Corn Oil ◽

Fatty Acid Content ◽

Potato Chips ◽

Hexadecanoic Acid ◽

Genome Wide ◽

A Genome ◽

Multivariate Gwas

AbstractTo learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1×10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

Download Full-text