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• neuroscience and mental health

• Medicine
• Psychiatry
• Pathology

• Immunology
• Neurology
• Neuropsychiatry
• Pharmacology
• Psychiatry

The research group is focused on elucidation of mechanisms and biomarkers related to neuro-endocrine-immune axis dysregulation, inflammation and brain glia-neuron interactions in psychiatric disorders and age associated pathologies.

Currently the group collaborates within EU funded networks that gather experts on molecular mechanisms of age-associated pathologies including neurodegeneration and depression. The goal is to identify stress-regulated molecules provoking neuronal atrophy and to monitor the consequences of these processes in human brain. At the cellular level, neuronal atrophy contributes to cognitive decline and increased depressive and anxiety disorders that are associated with ageing. A further current objective is the development of a biomarker test for mood disorder patients based on an activated inflammatory response system and inflammation-mediated disturbances in tryptophan metabolism.

A broad range of techniques spanning molecular and cellular approaches incorporating animal and clinical investigations are employed including imaging (MRI), histopathology/immunohistochemistry, molecular neuroscience, neuropharmacology and patient studies.

Recent relevant publications:
[1] Hughes MM, Connor TJ, Harkin A. (2016) Stress-Related Immune Markers in Depression: Implications for Treatment. Int J Neuropsychopharmacol. Review. PMID: 26775294
[2] O'Farrell K, Harkin A. (2015) Stress-related regulation of the kynurenine pathway: Relevance to neuropsychiatric and degenerative disorders. Neuropharmacology. Review. PMID: 26690895

The kynurenine pathway is a major route through which the essential amino acid tryptophan is metabolised and is activated in times of stress and immune activation. The generation of pathway metabolites can influence neurotransmission in the brain implicated in both neurodegenerative and neuropsychiatric disorders where imbalances in tryptophan and pathway metabolites have been reported. In the brain the pathway is compartmentalised as a consequence of differential expression of pathway enzymes which ultimately confer neurotoxic and neuroprotective properties to microglia and astrocytic glia respectively.

The focus of the proposed project is to elucidate the impact of pathway activation and regulation within glial compartments on neuronal integrity and plasticity. The approach will lead from in vitro cell culture systems to animal studies which allow for the inclusion of behavioural and brain imaging measures and which take account of peripheral pathway metabolism in mediating brain effects. The investigation bridges to existing clinical cohorts including a large population sample with longitudinal measures of general and psychological health and cohorts of younger and older adults with depressive illness where pathway indices in tandem with brain imaging are evaluated as biomarkers relating to brain health.

This research project will be conducted in Trinity College Institute of Neuroscience (www.tcd.ie/Neuroscience). The research fellow will be trained in a variety of molecular, cellular, imaging and analytical techniques and gain experience in managing and analysing large datasets. The principle outcomes of the project will be to show that the kynurenine pathway plays a key role in regulating neuronal integrity and plasticity, capable of influencing synaptic connections and connectivity in the brain that relate to behavioural resilience. The project will link to the identification of biochemical measures of kynurenine pathway activity and brain imaging in relevant clinical cohorts that allow us to validate these measures as biomarkers relating to stress, the ageing brain and neuropsychiatric disorders.