Genome-wide association studies (GWAS) have identified multiple disease-associated genetic variations across different psychiatric disorders raising the question of how these genetic variants relate to the corresponding pharmacological treatments. In this talk, I will outline our work investigating whether functional information from a range of open bioinformatics datasets such as protein interaction network (PPI), brain eQTL, and gene expression pattern across the brain can uncover the relationship between GWAS-identified genetic variation and the genes targeted by current drugs for psychiatric disorders. Focusing on four psychiatric disorders---ADHD, bipolar disorder, schizophrenia, and major depressive disorder---we assess relationships between the gene targets of drug treatments and GWAS hits and show that while incorporating information derived from functional bioinformatics data, such as the PPI network and spatial gene expression, can reveal links for bipolar disorder, the overall correspondence between treatment targets and GWAS-implicated genes in psychiatric disorders rarely exceeds null expectations. This relatively low degree of correspondence across modalities suggests that the genetic mechanisms driving the risk for psychiatric disorders may be distinct from the pathophysiological mechanisms used for targeting symptom manifestations through pharmacological treatments and that novel approaches for understanding and treating psychiatric disorders may be required.

How inclusive and diverse is non-invasive brain stimulation in the treatment of psychiatric disorders?Indira Tendolkar, Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry. Mental illness is associated with a huge socioeconomic burden worldwide, with annual costs only in the Netherlands of €22 billion. Over two decades of cognitive and affective neuroscience research with modern tools of neuroimaging and neurophysiology in humans have given us a wealth of information about neural circuits underlying the main symptom domains of psychiatric disorders and their remediation. Neuromodulation entails the alteration of these neural circuits through invasive (e.g., DBS) or non-invasive (e.g., TMS) techniques with the aim of improving symptoms and/or functions and enhancing neuroplasticity. In my talk, I will focus on neuromodulation studies using repetitive transcranial magnetic stimulation (rTMS) as a relatively safe, noninvasive method, which can be performed simultaneously with neurocognitive interventions. Using the examples of two chronifying mental illnesses, namely obsessive compulsive disorders and major depressive disorder (MDD), I will review the concept of "state dependent" effects of rTMS and highlight how simultaneous or sequential cognitive interventions could help optimize rTMS therapy by providing further control of ongoing neural activity in targeted neural networks. Hardly any attention has been paid to diversity aspects in the studies. By including studies from low- and middle income countries, I will discuss the potential of non-invasive brain stimulation from a transcultural perspective.

Are the immune system, brain, mind and mood related? Could this explain why chronic low-grade peripheral inflammation is also noted in approximately 1/3 of those with major depressive disorder (MDD)? The field recognized today as immunopsychiatry was founded on scientific evidence that germinated over 30 years ago. Since, it has been understood that (i) there could be a causal link between inflammation and depression, (ii) select blood immune markers show robust potential as biomarkers for inflammation-linked depression, and more generally, (iii) Descartes' theories on mind-body dualism were biologically erroneous. Nonetheless, the mechanistic brain-immune axis in the trinity formulating inflammation-linked depression i.e. psycho-neuro-immunology, still remains unclear. This talk will discuss findings from our recent investigation endeavored to unpack this by linking functional connectivity abnormalities with peripheral immune markers.

Major depressive disorder (MDD) is a sexually dimorphic disease. This sexual dimorphism is believed to result from sex-specific molecular alterations affecting functional pathways regulating the capacity of men and women to cope with daily life stress differently. Transcriptional changes associated with epigenetic alterations have been observed in the brain of men and women with depression and similar changes have been reported in different animal models of stress-induced depressive-like behaviors. In fact, most of our knowledge of the biological basis of MDD is derived from studies of chronic stress models in rodents. However, while these models capture certain aspects of the features of MDD, the extent to which they reproduce the molecular pathology of the human syndrome remains unknown and the functional consequences of these changes on the neuronal networks controlling stress responses are poorly understood. During this presentation, we will first address the extent by which transcriptional signatures associated with MDD compares in men and women. We will then transition to the capacity of different mouse models of chronic stress to recapitulate some of the transcriptional alterations associated with the expression of MDD in both sexes. Finally, we will briefly elaborate on the functional consequences of these changes at the neuronal level and conclude with an integrative perspective on the contribution of sex-specific transcriptional profiles on the expression of stress responses and MDD in men and women.