Involvement of psychotropic medications in the development of visceral pain and obesity

Dr. Siobhain O' Mahony

Psychotropic medications modify behaviour and are useful in the treatment of a host of psychiatric, functional gastrointestinal and pain disorders. Although these disorders manifest due to perturbations of the central nervous system a growing body of evidence suggests that they are influenced by bi-directional brain-gut interactions.  Recent studies have hi-lighted the involvement of an altered gut microbiota in obese patients and those suffering from visceral hypersensitivity.  Drug -induced obesity is one of the most common reasons for non-compliance in psychiatric patients. Hence we aim to study the impact of anti-psychotic medication on the microbiota and development of obesity, metabolic syndrome and altered pain responses in rats.

Seisures and Pain

Dr Deniz Yilmazer - Hanke

Limbic brain regions, and especially the amygdala play an important role in the regulation of emotional responses. Moreover, they are frequently involved in a variety of conditions including stress, epilepsy and neurodegenerative disorders like Alzheimer's and Parkinson's disease. Hence there is some evidence that a dysfunction in prefrontal-limbic circuits and amygdala pathology contributes to comorbid emotional disturbances like anxiety or depression in these disorders.

The current projects therefore focus on the molecular and structural changes and signal transduction mechanisms leading to neurodegeneration and neural plasticity in limbic brain regions including the human amygdala, as well as in in-vivo (psychogenetically selected inbred mouse strains, disease models) and in-vitro (neuronal cell cultures) experimental models. These include the analysis of candidate peptides and molecules, which are involved in the modulation of anxiety-related behaviour.

Seisures and Pain

Dr Colm Ó Tuathaigh

Research interests to date have focused on the study of gene-gene and gene-environment interactions in genetic models of neuropsychiatric disorders and, in particular, elucidation of the involvement of candidate genes in social and cognitive endophenotypes relevant to psychosis.

Human genetic disease gene mapping.

Dr Collette Hand

Research focus is the genetic investigation of a variety of conditions and focuses on the mapping and identification of human disease genes through the study of families affected by disease. Linkage analysis remains one of the most robust and reliable methods of identification of disease gene loci. It is independent of gene function or disease pathogenesis and has clearly outlined and developed statistical parameters. The significant advantage of linkage analysis is its application to all type of genetic disease regardless of clinical manifestations. One of the main challenges of this approach is the collection of suitably large families with affected individuals for study. Strong collaborations with clinical colleagues are vital.

Identification of novel genes

Involved in the identification of the causative genes for a number of disorders. Described the gene responsible for a juvenile form of familial amyotrophic lateral sclerosis (ALS) which is a devastating neurodegenerative disorder. Involved in the studies to establish the gene responsible for hidrotic ectodermal dysplasia (HED), an autosomal dominant skin disorder characterised by palmoplantar hyperkeratosis, hair defects (from partial to total alopecia), nail hypoplasia and nail deformities. HED occurs worldwide with a very low frequency, but is more common in French- Canadians and so the known founder effect was exploited to identify the causative gene in this and other populations.

Identification of novel loci

Involved in the identification of novel loci for a number of conditions including congenital hereditary endothelial dystrophy (CHED2) which is a rare corneal disorder, a familial ALS locus (ALS3) and a spastic ataxia locus (SAX1). We have recently identified a novel locus of autosomal dominant restless legs syndrome (RLS) using an Irish family.

Identification of novel mutations

Screening genes for mutations allows the identification of novel mutations which expand the understanding of the disease mechanism and may allow for genotype- phenotype correlations to be developed. This approach has been applied to a number of conditions including familial migraine (ATP1A2 gene), retinitis pigmentosa (RPGR gene), amyotrophic lateral sclerosis (SOD1, ALS2 genes) and hereditary spastic paraparesis (ALS2, PLP, SPG4 genes).

New Disorders

Involved in studies of the genetic basis of pain response in individuals. In the last year we have established new studies on the genetics of the ion channel disorders periodic paralyses and sudden cardiac death through strong clinical collaborations.