Digitally created image of a head and double helix

Role of genetics and stressful trauma in anxiety and depression in various participant groups from the BRID (Brain Resource International Database) (2006-)

This project include a series of independent genetic and neuroscience studies drawing on data from large healthy and clinical psychiatric samples in the BRID (Brain Resource International Database). Many of these studies included investigations of different genetic polymorphisms (SNPs) and their role in various forms of healthy or clinical brain functioning. The types of measures we investigated included neurocognitive, self-report, and neuroimaging or EEG measures. The genes of focus included genes for brain derived neurotrophic factor, serotonin receptors, monoamine oxidase A, apolipoprotein E, catechol-O-methyltransferase. For instance, we have shown that genetic polymorphisms in brain derived neurotrophic factor can impact brain function and memory and how this correlates with depressive features in a normal population (Schofield et al., 2009). We have also shown how this genetic variant (BDNF) and others such as the HTR3A variant interacts with early life trauma to accentuate depression and anxiety symptomatology in healthy samples (Gatt et al., 2009, 2010). For a review of the various SNPs involved in common and specific to 5 psychiatric disorders including major depression, anxiety disorder, bipolar disorder, schizophrenia and ADHD, please see Gatt et al., 2015.

We have also been involved in other collaborative studies focusing specifically on the role of childhood versus adult trauma in brain function in healthy and PTSD cohorts, with leads PhD student Denise Chu and Prof Richard Bryant (Chu et al., 2013, 2016, 2018); as well as treatment prediction studies in patients with major depression from the iSPOT-D trial (e.g., Day et al., 2015, Arns et al., 2016).

Team Members & Collaborators

Prof Leanne Williams (Stanford University, USA) was the lead on this project, with co-investigators including Prof Peter Schofield (NeuRA and UNSW, Australia), and Prof Robert Paul (Missouri University, USA). Dr Justine Gatt and Dr Stacey Kuan were the postdoctoral research fellows on this project. The industry partner was Brain Resource Ltd.

Grant Funding

This project was supported by an ARC Linkage Grant (Williams, Schofield, Paul; LP0455104, 2004-2007). Dr Justine Gatt and Dr Stacey Kuan were postdoctoral research fellows working on this project.

Key Outcomes & Publications

Chu DA, Bryant RA, Gatt JM, Harris AWF. (2018). Cumulative childhood interpersonal trauma is associated with reduced cortical differentiation between threat and non-threat faces in PTSD adults. Australian and New Zealand Journal of Psychiatry, Accepted 6th February 2018.

Chu D, Bryant RA, Gatt JM, Harris AWF (2016). Failure to differentiate between threat-related and positive emotion cues in healthy adults with childhood interpersonal or adult trauma. Journal of Psychiatric Research, 78, 31-41.

Arns M, Bruder G, Hegerl U, Spooner C, Palmer D, Etkin A, Fallahpour K, Gatt JM, Hirshberg L, Gordon E (2016). EEG alpha asymmetry as a gender-specific predictor of outcomes to acute treatment with different antidepressant medications in the randomized i-SPOT-D study. Clinical Neurophysiology, 127, 509-519.

Day CV, Gatt JM, Etkin A, DeBattista C, Schatzberg AF, Williams LM (2015). Cognitive and emotional biomarkers of melancholic depression: An iSPOT-D report. Journal of Affective Disorders, 176, 141-150.

Gatt JM, Burton KLO, Williams LM, Schofield PR. (2015). Specific and common genes implicated across major mental disorders: A review of meta-analysis studies. Journal of Psychiatric Research, 60, 1-13.

Myers AJ, Williams LM, Gatt JM, McAuley-Clark EZ, Dobson-Stone C, Schofield PR, Nemeroff, CB. (2014). Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. Journal of Psychiatric Research, 59, 93-100.

Korgaonkar MS, Antees C, Williams LM, Gatt JM, Bryant RA, Cohen R, Paul R, O’Hara R, Grieve SM. (2013). Early exposure to traumatic stressors impairs emotional brain circuitry. PLOS ONE, 8 (9), e75524.

Chu D, Williams LM, Harris AWF, Bryant RA, Gatt JM. (2013). Early life trauma predicts self-reported levels of depressive and anxiety symptoms in nonclinical community adults: Relative contributions of early life stressor types and adult trauma exposure. Journal of Psychiatric Research, 47 (1), 23-32.

Williams LM, Cooper NJ, Wisniewski S, Gatt JM, Koslow SH, Kulkarni J, Gordon E, Rush AJ. (2012). Sensitivity, specificity and predictive power of the “Brief Risk-resilience Index for Screening,” a brief pan-diagnostic web screen for emotional health. Brain and Behavior, 2 (5): 576-589.

Gatt JM, Nemeroff CB, Schofield PR, Paul RH, Clark CR, Gordon E & Williams LM. (2010). Early life stress combined with HTR3A and BDNF Val66Met genotypes impacts emotional brain and arousal correlates of risk for depression. Biological Psychiatry, 68, 818-824.

Williams LM, Gatt JM, Grieve SM, Dobson-Stone C, Paul RH, Gordon E & Schofield PR. (2010). COMT Val108/158Met polymorphism effects on emotional brain function are modulated by level of awareness and associated with negativity biases. NeuroImage, 53, 918-925.

Gatt JM, Williams LM, Schofield PR, Dobson-Stone C, Paul RH, Grieve S, Clark CR, Gordon E & Nemeroff CB. (2010). Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood. Depression and Anxiety, 27: 752-759.

Wacker J, Gatt JM. (2010). Resting posterior versus frontal delta/theta EEG activity is associated with extraversion and the COMT Val158Met polymorphism.  Neuroscience Letters, 478: 88-92.

Williams LM, Gatt JM, Schofield PR, Olivieri G, Peduto A, Gordon E. (2009). ‘Negativity bias’ in risk for depression and anxiety: Brain-body fear circuitry correlates, 5-HTT-LPR and early life stress. NeuroImage, 47: 804-814.

Gatt JM, Nemeroff CB, Dobson-Stone C, Kuan SA, Paul RH, Bryant RA, Schofield PR, Gordon E & Williams LM. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14(7): 681-695.

Joffe RT, Gatt JM, Kemp AH, Grieve S, Dobson-Stone C, Kuan S, Schofield PR, Gordon E & Williams LM. (2009). Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness. Human Brain Mapping, 30(4): 1246-1256.

Schofield PR, Williams LM, Paul RH, Gatt JM, Brown K, Luty A, Cooper N, Grieve S, Dobson-Stone C, Kuan SA & Gordon E. (2009). Disturbances in selective information processing associated with the BDNFVal66Met polymorphism: Evidence from cognition, the P300 and fronto-hippocampal systems. Biological Psychology, 80: 176-188.

Williams LM, Gatt JM, Kuan SA, Dobson-Stone C, Palmer DM, Paul RH, Song L, Costa PT, Schofield PR, Gordon E. (2009). A polymorphism of the MAOA gene is associated with emotional brain markers and personality traits on an antisocial index. Neuropsychopharmacology, 34: 1797-1809.

Gatt JM, Kuan S, Dobson-Stone C, Paul RH, Joffe RT, Kemp A, Gordon E, Schofield PR & Williams LM. (2008). Association between BDNF Val66Met polymorphism and trait depression is mediated via resting EEG alpha band activity. Biological Psychology, 79 (2): 275-284.

Williams LM, Gatt JM, Kuan SA, Dobson-Stone C, Cooper N, Grieve S, Gur R, Paul RH, Gordon E, Schofield PR. (2008). The INTEGRATE model of emotion, thinking and self regulation: An application to the “paradox of aging”. J Integrative Neuroscience, 7: 367-404.

Alexander DM, Williams LM, Gatt JM, Dobson-Stone C, Kuan S, Todd EG, Schofield PR, Cooper N, & Gordon E. (2007). The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades. Biological Psychology, 75: 229-238.

Dobson-Stone C, Gatt JM, Kuan SA, Grieve SM, Gordon E, Williams LM & Schofield PR. (2007). Investigation of MCPH1 and ASPM polymorphisms and brain size in a healthy cohort. NeuroImage, 37: 394-400.

Gatt JM, Clark CR, Kemp AH, Liddell BJ, Dobson-Stone C, Kuan S, Schofield PR & Williams LM. (2007). A genotype-endophenotype-phenotype path model of depressed mood: Integrating cognitive and emotional markers. Journal of Integrative Neuroscience, 6 (1), 75-104.

Gordon E., Liddell BJ, Brown KJ, Bryant R, Das P, Dobson-Stone C, Falconer E, Felmingham K, Flynn G, Gatt JM, Harris, A, Hermens DF, Hopkinson P, Kemp AH, Kuan S, Moyle J, Paul RH, Rennie C, Whitford T, Williams LM. (2007). Integrating objective gene-brain-behavior markers of psychiatric disorders. Journal of Integrative Neuroscience, 6 (1), 1-34.