Psychiatric Disorders PDF

Psychiatric Disorders 04 December 2023 15:47 Main Ideas Notes What have behavioural genetic studies taught us about psychiatric disorders a. Genetic risk for psychiatric disorders is the norm – not the exception ▪ Individual differences in degree of symptoms are partly heritable ▪ Genetic architectu...

Psychiatric Disorders 04 December 2023 15:47 Main Ideas Notes What have behavioural genetic studies taught us about psychiatric disorders a. Genetic risk for psychiatric disorders is the norm – not the exception ▪ Individual differences in degree of symptoms are partly heritable ▪ Genetic architecture of psychiatric risk is complex b. Current diagnostic categories don't match up with reality ▪ Pleiotropy is common ▪ A single diagnostic category usually contains individuals with different aetiology for their disorder c. Understanding of development within a genetically sensitive framework can help us understand disorder progression ▪ what is driving stability? ▪ What drives change? d. Environmental risk for psychiatric disorders is complex ▪ Non-shared environmental influences are important ▪ Many environmental risk factors for psychiatric disorders partly reflect genetic endowments ▪ need genetically informative designs to understand how environmental risk operates e. Response to intervention may be conditional on genetic make-up ▪ Are good interventions those that take into account genetic differences? f. Can we begin to synthesise current finding to inform new approaches to prevention and treatment Genetic risk for psychiatric disorders is the norm – not the exception ○ Most psychiatric traits are heritable ○ Despite the moderate to strong heritability findings, finding the specific genes has been slow ▪ Notes Understanding of development within a genetically sensitive framework can help us understand disorder progression ○ Early longitudinal study in individuals from 8 to 13 years by Larsson et al. found that in ADHD , both stability and change influenced by genetic factors. ▪ Non-shared environmental factors also important for change ▪ Conclusions □ Genetic influences important for stability of ADHD □ New genetic influences come to play at the second measurement point ® Genes that affect the maturation of prefrontal cortex? □ Non-shared environmental influences also important for change ® Environmental influences that affect the maturation of prefrontal cortex? ○ Genetically informative, longitudinal study designs can also help us understand what contributes to individual differences in initial risk for symptomatology and risk trajectories. ○ Such studies can help constrain subsequent research and provide clues that may be clinically relevant ○ can compare the findings from genetically informative studies with findings from research using other methodologies (e.g. neuroimaging) ○ can compare the findings from genetically informative studies with findings from research using other methodologies, e.g. neuroimaging - e.g. study found that children with ADHD had different levels cortical thickness compared to neurotypical children for areas important for attentional control (Shaw et al., 2006) ○ Summary ▪ Genetically informative study designs can help us understand what drives risk (or resilience) at different points of development ▪ This can help us identify optimal windows for intervention ▪ This can also guide the nature of interventions (e.g. do we need multiple interventions at different developmental points) Environmental risk for psychiatric disorders is complex ○ need twin and adoption designs to evaluate whether there is a main effect of a proposed environmental risk factor ▪ Or whether the environmental risk factor is genetic confounding ○ Risk factors of psychiatric disorders and heritability ○ Rare variants can explain the missing variance for risk in traits such as autism and schizophrenia ○ Summary ▪ Psychiatric disorders are polygenic □ Multiple genes probabilistically increase risk of developing a disorder □ Common genetic variants ® Can be detected using GWAS ® Polygenic risk scores ▪ Rare variants □ Only affect a small proportion of the population □ Can have a larger impact than common SNPs Current diagnostic categories are not rooted in biological reality ○ Pleiotropy : one gene influence more than one gene ○ --> multiple genes influencing psychiatric risk - shown by polygenic risk scores ○ Multivariate twin and family studies have conclusively demonstrated pleiotropy in relation to different psychiatric disorders ○ Molecular genetic findings also support pleiotropy ○ Summary ▪ Genetic ‘diagnoses’ do not mirror symptom based ‘diagnoses’ ▪ Pleiotropy common □ Implications for understanding psychiatric risk, e.g. what leads to differentiated behavioural manifestations of overlapping genetic risk Summary Behavioural genetic studies of psychiatric disorders can help frame our understanding of psychiatric disorders in ways that help inform interventions Information from these studies is more nuanced than what can be gained from phenotypic investigations alone PSYC0036 Genes and Behaviour Page 1 ○ Non-shared E: Psychopathology ▪ can use e.g. MZ twin differences design to investigate non-shared environment (e.g. Caspi et al., 2004; Viding et al., 2009) ▪ Most studies that have investigated the impact of an environmental risk factor in a genetically informative design have demonstrated smaller effects than anticipated based on phenotypic studies □ This is likely to reflect genetic confounding and multi-factorial nature of disorder origin ○ Gene-environment correlation ▪ Assumed environmental variance may actually be partly genetically driven ○ People shape their own environments ▪ Parents and children in biological families share genetic vulnerabilities ▪ Some ‘parenting child psychiatric risk associations an ‘epiphenomenon’ of genetic risk in the family ▪ People also evoke responses in their social environment that are in line with their genotypic vulnerabilities (and strengths) ▪ People actively seek out different environments, in line with their genotypic propensities □ This manifests more robustly as people increase in independence Notes Gene-environment interaction ○ Environmental risk factors do not impact everyone the same way ▪ Environmental risk effects can be conditional on genetic make-up Response to intervention may be conditional on genetic make-up There is evidence from genetically informative study designs that genetic factors can constrain response to pharmacological and behavioural interventions for psychiatric disorders These findings need replication, but are in line with the notion of gene-environment interaction Gene-environment correlation and success in interventions ○ DNA in clinical psychology means ‘did not attend’ ○ Is not attending random? ○ Intervention cannot be successful if it is not administered consistently – this applies also to taking medications as instructed Summary: Environmental risk and response to intervention Genetically informative study designs have robustly shown that there are environmental risk factors for psychiatric disorders Genetic endowments drive selection of and response to environments ○ This has implications for how we understand development of psychiatric disorders and think about their treatment Can we begin to synthesize current findings to inform new approaches to prevention and treatment? Pleiotropic findings indicate that there is generic psychiatric liability that may manifest in different ways ○ Challenge to better understand why the liability manifests in different ways ▪ Conditional on other genetic effects? Environmental risk factors? Timing of these? ○ Common treatment approaches may be useful for symptoms across a variety of disorders Approach intervention like we approach vaccination ○ Genetic research suggests that for many disorders, we may need multiple, developmentally appropriate interventions for those who are most vulnerable Gene-environment interplay also introduces challenges for interventions that cannot be ignored Interventions manifestly do not have the same effect for everybody ○ Personalised intervention informed by gene-environment interaction Gene-environment correlation presents additional challenges to the treatment setting ○ What reactions does an individual with a psychiatric disorder evoke? ○ How does this impact the ability to deliver the intervention? ○ Is the uptake of the intervention equally likely for everyone? Summary ○ Behavioural genetic studies of psychiatric disorders can help frame our understanding of psychiatric disorders in ways that help inform interventions ○ Information from these studies is more nuanced than what can be gained from phenotypic investigations alone PSYC0036 Genes and Behaviour Page 2