Undergraduate Course: Genetic and Environmental Influences on Behaviour and Mental Health (BIME10022)
|School||Deanery of Biomedical Sciences
||College||College of Medicine and Veterinary Medicine
|Credit level (Normal year taken)||SCQF Level 10 (Year 4 Undergraduate)
||Availability||Available to all students
|Summary||The course will lead you through the different aspects of how genetic and environmental factors can influence behaviour and cognition, and the potential consequences for mental health and susceptibility to psychiatric disease. Importantly, it aims to give students an understanding of how these complex factors can interact with each other to impact the individual.
The information covered may vary but will cover subjects including the biology of stress: the HPA axis, glucocorticoid actions in the CNS, the sympathetic nervous system, serotonergic and noradrenergic neurotransmitter systems. The use of animal models for psychiatric disease will be discussed. The genetics of psychiatric disease and intrauterine programming mechanisms (epigenetics) that affect behavioural development in the offspring will then be introduced. We will examine how the interplay between these systems, genetics and the environment influences susceptibility psychiatric conditions including anxiety and depression, schizophrenia, addiction and Alzheimer's disease. We will also look at how cognition is affected by stress and ageing, and how genetics influences this.
There are two teaching sessions each week for 11 weeks, and each lasts for two to two and a half hours. Normally there will be a one-hour lecture or seminar. Some lectures will then be followed by student presentations or devoted to formative feedback. Others will be followed by quizzes or other student-led exercises or scheduled time to work on the group project ICA exercise.
The objectives of student presentations are to give you the opportunity to produce and deliver PowerPoint illustrated short talks on a focused topic related to the lectures, using a published research paper as the source. You will be assigned a paper and organised into pairs or threes to prepare a joint presentation to gain experience of team working. You will be expected to give a brief overview of the research, and then present the manuscript while giving reference to previous published experimental research, and giving a critical account of the work. We hope presentation of papers will stimulate discussion amongst the whole class, and other students in the class are expected to contribute by asking questions of the speakers. The oral presentations will not be formally assessed (though the lecturer/moderator may give feedback.
Each student will be required to hand in a 1000 (maximum) word summary of their critique of their assigned paper presentation in advance of the presentation which will count towards in-course assessment.
Group projects will be the other ICA exercise. You will work together in groups to design and present a research proposal to investigate a project of your choice related to the course material. You will be expected to work partly in assigned class time and partly outwith teaching time, to design the proposal. You will then be required to give a group presentation of your research plan.
Entry Requirements (not applicable to Visiting Students)
||Other requirements|| None
Information for Visiting Students
|High Demand Course?
Course Delivery Information
|Academic year 2018/19, Not available to visiting students (SS1)
|Learning and Teaching activities (Further Info)
Lecture Hours 23,
Seminar/Tutorial Hours 10,
Supervised Practical/Workshop/Studio Hours 5,
Formative Assessment Hours 4,
Summative Assessment Hours 2,
Revision Session Hours 2,
Programme Level Learning and Teaching Hours 4,
Directed Learning and Independent Learning Hours
|Assessment (Further Info)
|Additional Information (Assessment)
||In-course assessment: Students will give oral presentations in small groups; e.g. critiques of scientific papers and strategies for addressing research questions. They will be required to submit individual overviews of these presentations for assessment (30%).
Degree examination (70%).
||Feedback will be available throughout the course in several forms:
· Verbal feedback from lecturers and peers on your paper critique presentations.
· The mid-course feedback session on week 7 will cover the mock examination essay formative feedback exercise and exam techniques.
· Feedback on the written ICA paper critique exercise will be provided to all students by 15 days after the last presentation (so available at the start of week 9) in order to avoid disadvantaging those students presenting early in the course.
· A revision session has been timetabled for Week 11.
· Feedback from the exam will be made available. Please contact the course administrator for more information about how and when this will be done.
An essay question will be made available to the class in Week 1, which you will complete under mock exam conditions in week 5. The essay will be timed for one hour and hand-written to emulate the course examination, but it will be open-book. Formative feedback will be given in the discussion session organised for week 7. You will get individual written feedback on your essay, and the class discussion will cover a model answer and exam technique.
||Hours & Minutes
|Main Exam Diet S1 (December)||2:00|
On completion of this course, the student will be able to:
- 1. To be able to explain and discuss: · the nature, function and control of the stress response (HPA axis, sympathetic nervous system and related neurotransmitter systems) - how exposure to extrinsic environmental factors (e.g. stress in utero, or during early or adult life), and intrinsic environmental factors (e.g. ageing), can influence subsequent behaviour and susceptibility to psychiatric disorders including depression, anxiety, addiction and impaired cognition. - how an individual's genetic profile can influence the stress response, behaviour and susceptibility to psychiatric disease - the complex manner in which genetic and environmental factors can interact with each other to influence an individual's risk of developing psychiatric disorders, including epigenetic mechanisms - the strengths and limitations of animal models for investigation of behaviour and human psychiatric disorders
- Demonstrate an ability to communicate knowledge and understanding as defined above through both written work and verbal discussion.
- Demonstrate an ability to integrate and critically evaluate information gained from different sources (lectures, paper presentations, class discussions and further research and reading) to construct arguments for individual conclusions and original ideas.
- Demonstrate effective team-working to produce presentations and arguments for debate.
|WEEK 1: |
What is stress?
McEwen, BS et al, (2015) Mechanisms of stress in the brain. Nature Neuroscience 18, 1353-1363
Sapolsky, R. M. (2015) Stress and the brain: individual variability and the inverted-U. Nature Neuroscience 18, 1344-6
Mental Disorders: a clinical overview
Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nature Reviews Disease Primers. 2015; 1:15067
Anderson IM, Haddad PM, Scott J. Bipolar disorder. BMJ. 2012 Dec 27;345.
Otte C, Gold SM, Penninx BW, et al. Major depressive disorder. Nature Reviews Disease Primers. 2016 Sep 15; 2:16065.
NICE Clinical Knowledge Summary on Dementia: https://cks.nice.org.uk/dementia#!background
For further information, this website has lots of accessible summaries of many different psychiatric problems, aimed at patients and their carers:
Animal Models of Behaviour
Crawley JN. (2008) Behavioral phenotyping strategies for mutant mice. Neuron 57(6): 809-18.
Mechanisms of glucocorticoid hormone action
Stahn C et al (2007) Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Molecular and Cellular Endocrinology 275: 71-78
Stress and anxiety-related disorders: fMRI in animals
Febo M (2011) Technical and conceptual considerations for performing and interpreting functional MRI studies in awake rats. Frontiers in Psychiatry vol 2: article 43
Brydges NM et al, (2013) Imaging Conditioned Fear Circuitry Using Awake Rodent fMRI. Plos One 8(1) e54197
Liang Z et al, (2014) Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats. Neuroimage 103: 485-491
Genetics of Common Complex Psychiatric Diseases
Szyf, M. (2013) How do environments talk to genes? Nat Neurosci 16, 2-4.
Klengel, T. et al. (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 16, 33-41
Glucocorticoids and Depression
Boyle MP, Kolber BJ, Vogt SK, Wozniak DF, Muglia LJ. (2006) Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness. Journal of Neuroscience 26(7):1971¿1978.
Harris AP, Holmes MC, de Kloet ER, Chapman KE, Seckl JR. (2013) Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and behaviour. Psychoneuroendocrinology 38(5):648-58.
Stress and Cognition
Schwabe L, Wolf OT, Oitzl MS. (2010) Memory formation under stress: quantity and quality. Neurosci Biobehav Rev. 34(4): 584-91.
de Quervain D, Schwabe L, Roozendaal B. (2017) Stress, glucocorticoids and memory: implications for treating fear-related disorders. Nature Reviews Neuroscience 18(1):7-19
Roozendaal B, McEwen BS and Chattarji S (2009) Stress, memory and the amygdala. Nature Reviews Neuroscience 10: 423-33
Hyman SE. (2005) Addiction: A Disease of Learning and Memory. 162:1414-22.
Elman I, Borsook D (2016) Common Brain Mechanisms of chronic pain and addiction. Neuron 89 (1): 11-36.
Horvath S, Raj K. (2018) DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genetic Jun;19(6):371-384
Epigenetics and Psychiatric Illness
Relton CL, Hartwig FP, Davey Smith G. (2015) From stem cells to the law courts: DNA methylation, the forensic epigenome and the possibility of a biosocial archive. Int J Epidemiol. 44(4):1083-93. PMID: 26424516
Mill J, Heijmans BT. (2013) From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet. 2013 14(8):585-94. PMID: 23817309
Genetic and Environmental Influences on Substance Use
Kreek MJ, Nielsen DA, Butelman ER, LaForge KS (2005). Genetic ifluences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nature Neuroscience 8, 1450-1457
Olfson E, Edenberg HJ, Nurnberger J et al. (2014) An ADH1B variant and peer drinking in progression to adolescent drinking milestones: Evidence of a gene-by-environment interaction. Alcohol Clin Exp Res. 2014 Oct; 38(10): 2541¿2549.
Rose, R. J., Dick, D. M., Viken, R. J., & Kaprio, J. (2001). Gene¿environment interaction in patterns of adolescent drinking: Regional residency moderates longitudinal influences on alcohol use. Alcoholism: Clinical and Experimental Research, 25, 637¿643.
Emmanuel Darcq & Brigitte Lina Kieffer (2018) Opioid receptors: drivers to addiction? Nature Reviews Neuroscience 19, 499¿514
Maccari S, Krugers HJ, Morley-Fletcher S, Szyf M, Brunton PJ. (2014) The consequences of early life adversity: neurobiological, behavioural and epigenetic adaptations. J Neuroendocrinol. EPub Jul15.
Bale TL. (2015) Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci. 16, 332-344.
McGowan PO, Matthews SG. (2018) Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response. Endocrinology. 2018 Jan 1;159(1):69-82.
Environmental risk factors and dementia
Underwood E. (2017) The polluted brain. Science 355(6323): 342-345.
Cacciottolo M, Wang X, Driscoll I et al. (2017) Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry 7(1): e1022.
Killin LO, Starr JM, Shiue IJ, Russ TC. (2016) Environmental risk factors for dementia: a systematic review. BMC Geriatr 16(1): 175.
Mokry LE, Ross S, Morris JA, Manousaki D, Forgetta V, Richards JB. (2016) Genetically decreased vitamin D and risk of Alzheimer disease. Neurology 87(24): 2567-2574.
Genetics of Cognitive Ageing
Plomin R, Deary IJ. (2015) Genetics and intelligence differences: five special findings. Mol Psychiatry 20, 98-108. (Essential)
Davies G, et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nat Commun 9(1):2098. (Recommended)
Hagenaars et al. (2016) Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia. Mol Psychiatry. 21, 1624-1632. (Further).
Davies G, et al. (2014). A genome-wide association study implicates the APOE locus in non-pathological cognitive ageing. Mol Psychiatry. 19, 76-87. (Further).
Stress and the Ageing Brain
McEwen BS, de Leon MJ, Lupien SJ et al (1999) Corticosteroids, the aging brain and cognition. Trends Endocrin Met 10, 92-96.
Sapolsky RM. (1999) Glucocorticoids, stress and their adverse neurological effects: relevance to ageing. Exp. Gerontology 34, 721-732.
Rothman SM and Mattson MR (2010) Adverse stress, hippocampal networks, and Alzheimer¿s disease. Neuromolecular Med 12(1): 56-70
DISC1, environment and schizophrenia
Kim JY et al. (2012) Interplay between DISC1 and GABA signalling regulates neurogenesis in mice and risk for schizophrenia. Cell 148: 1051-1064
Niwa M et al. (2013) Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids. Science 339: 335-339
Brandon NJ & Sawa A. (2011) Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nat Rev Neurosci 12: 707-722 2011
Sims R, Williams J. (2016) Defining the Genetic Architecture of Alzheimer's Disease: Where Next. Neurodegener Dis 16, 6-11. (Essential)
Karch CM, Cruchaga C, Goate AM. (2014) Alzheimer's Disease Genetics: From the Bench to the Clinic. Neuron. 83,11-26. (Recommended)
Lambert et al. (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature Genetics 45, 1452-1458. (Further)
Marioni RE, et al (2018) GWAS on family history of Alzheimer's disease. Transl Psychiatry. 8(1):99. (Further)
|Graduate Attributes and Skills
||1. The ability to communicate knowledge and understanding through written work and verbal discussion.
2. The ability to integrate and critically evaluate information gained from different sources including personal research and reading to construct arguments for individual conclusions and to synthesise original ideas.
3. The ability to participate in effective team-working to deliver completed projects.
|Course organiser||Dr Joyce Yau
Tel: (0131) 242 6760
|Course secretary||Ms Deborah Walker
Tel: (0131 6)51 1513