scholarly journals A NewT. gondiiMouse Model of Gene-Environment Interaction Relevant to Psychiatric Disease

Scientifica ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Geetha Kannan ◽  
Emese Prandovszky ◽  
Emily Severance ◽  
Robert H. Yolken ◽  
Mikhail V. Pletnikov
Keyword(s):  
Psychiatric Disorders ◽  
Acoustic Startle ◽  
Experimental System ◽  
Dominant Negative ◽  
Psychiatric Disease ◽  
Environment Interaction ◽  
Dependent Manner ◽  
Mechanistic Studies ◽  
Gene Environment Interaction ◽  
Gene Environment

Infection with the protozoan parasite,Toxoplasma gondii(T. gondii), was linked to several psychiatric disorders. The exact mechanisms of a hypothesized contribution ofT. gondiiinfection are poorly understood, and it appears that only a subset of seropositive individuals go on to develop a mental illness, suggesting genetic vulnerability. In order to stimulate mechanistic studies of how exposure toT. gondiicould interact with genetic predisposition to psychiatric disorders, we have generated and characterized a mouse model of chronicT. gondiiinfection in BALB/c mice with inducible forebrain neuronal expression of a C-terminus truncated dominant-negative form of disrupted-in-schizophrenia 1 (DN-DISC1). In this gene-environment interaction (GxE) model, exposing control and DN-DISC1 male and female mice toT. gondiiproduced sex-dependent abnormalities in locomotor activity and prepulse inhibition of the acoustic startle. No genotype- or sex-dependent effects were found on levels of anti-Toxoplasma IgG antibodies or anti-NMDAR or C1q antibodies. Our work demonstrates that a psychiatric genetic risk factor, DN-DISC1, modulates the neurobehavioral effects of chronicT. gondiiinfection in a sex-dependent manner. The presentT. gondiimodel of GxE provides a valuable experimental system for future mechanistic studies and evaluation of new treatments.

scholarly journals The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank

2019 ◽  
Author(s):  
Judit García-González ◽  
Julia Ramírez ◽  
David M. Howard ◽  
Caroline H Brennan ◽  
Patricia B. Munroe ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Smoking Behaviour ◽  
Environment Interaction ◽  
Uk Biobank ◽  
Psychotic Experiences ◽  
Gene Environment Interaction ◽  
Gene Environment

ABSTRACTWhile psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n=2067), hallucinations (n=6689), and any psychotic experience (delusions or hallucinations; n=7803) in 144818 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in the UK Biobank participants to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were significantly associated with psychotic experiences (p<1.77×10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p<1.99×10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD(but not PRSSCZ) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p<0.0028). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

Genetic and environmental pathways to suicidal behavior: Reflections of a genetic epidemiologist

2010 ◽  
Vol 25 (5) ◽  
pp. 300-303 ◽  
Author(s):  
K.S. Kendler
Keyword(s):  
Psychiatric Disorders ◽  
Suicidal Behavior ◽  
Indirect Effects ◽  
Genetic Risk ◽  
Developmental Pathways ◽  
Early Adversity ◽  
Environment Interaction ◽  
Direct Effects ◽  
Gene Environment Interaction ◽  
Gene Environment

AbstractThis paper presents a tentative typology of genetic and environmental pathways to suicidal behavior. Ten pathways are proposed and briefly illustrated: (i) direct effects from psychiatric disorders; (ii) direct effects from personality; (iii) direct effects of early adversity; (iv) direct effects of current adversity; (v) indirect effects of genes on selection into adversity (gene–environment correlation); (vi) interactions between genetic risk and current adversity: gene–environment interaction; (vii) interactions between early and current adversity: environment–environment interaction; (viii) interactions between culture and genes; (ix) dynamic developmental pathways involving causal loops from genes to environment and back again; and (x) gene × environment × development interaction.

scholarly journals The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Judit García-González ◽  
Julia Ramírez ◽  
David M. Howard ◽  
Caroline H. Brennan ◽  
Patricia B. Munroe ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Risk ◽  
Maternal Smoking ◽  
Smoking Status ◽  
Smoking Behaviour ◽  
Environment Interaction ◽  
Uk Biobank ◽  
Psychotic Experiences ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5–10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144,818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p < 1.77 × 10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p < 1.99 × 10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p < 0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

Sign in / Sign up

Export Citation Format

Share Document