Supervisor Database Search

• neuroscience and mental health
• Other

Immuno-Psychiatry, Proteomics, Predictive Biomarkers of Mental Disorder

• Child and Adolescent Psychiatry
• Neuropsychiatry

At the early stage of my career my focus was largely on the cellular/neuropathological basis of schizophrenia and affective disorders in which I published papers describing, for the first time, neuronal and glial changes in major depression and schizophrenia. The three most cited papers have been cited in total over 1250 times. Perhaps the main contribution was to show a pathological substrate to schizophrenia which previously had not been well delineated at a cellular level.

I then returned to Ireland and continued this but developed a expertise in the proteomics of psychiatric disorders, in which I have become a leader in the field. I have published the first papers showing synaptic and metabolic changes in the proteome in schizophrenia, and have undertaken pioneering work examining subproteomes and enriched samples such as those involving the postsynaptic density and utilising laser capture microdissection. This work has been published in well respected psychiatry journals Molecular Psychiatry (2008, 2012, 2014) and Archives General Psychiatry (2011).

I was then awarded a Clinician Scientist Fellowship in order to focus on understanding the pathophysiology of major mental illness and psychosis through proteomic study of plasma of subjects at risk of future disorders. This was a shift in direction and over the last two years this work has come to fruition and has demonstrated novel findings of lipid and protein changes in the blood at age 11, in apparently well children, who later go on to report psychotic experiences at age 17/18. Prominent among the protein changes are proteins involved in the complement and coagulation pathway.

My most recent publication in Biological Psychiatry for the first time integrated proteomic and lipidomic data and identified potentially important functional interrelationships lipids and proteins that may have implications not just to psychosis but to medical co-morbidity.

Based on these findings, and my established collaboration with colleagues and experts from diverse fields, we now aim to work together to improve our understanding of how/if genetic and environmental risks may lead to adult psychosis and general psychiatric outcomes though inflammatory, proteomic and lipidomic related mechanisms.

My Recent Grants
1. The identification of plasma protein markers of antipsychotic drug treatment response in first episode psychosis; a proteomic analysis of baseline plasma samples from the OPTiMiSE and PSYSCAN studies.
PI D Cotter, (2019-2022)
€380,000
Health Research Board, Health Research Award.

2. Doctoral Program in Youth Mental Health Leadership (The YouLead Program).
1.4M euro Co-PI
2018-2021.

3. Biomarker Discovery in Ultra High Risk for Psychosis: towards prediction of psychotic disorder, non-psychotic mental disorders and recovery.
PI D Cotter, (2017/18- 2021)
€380,000
Health Research Board, Health Research Award.

4. Biomarker discovery in psychosis: a longitudinal study of inflammatory cytokines and metabolome in the plasma of high risk subjects and subjects recently converted to psychosis.
PI D Cotter, (Awarded Summer 2015)
€330,000
Health Research Board, Health Research Award.

5. Biomarker discovery in psychosis: a longitudinal metabolomic study of plasma involving high risk subjects and subjects recently converted to psychosis.
PI D Cotter (2013-2016)
€330,000
Health Research Board, Health Research Award.

6. Biomarker discovery in psychosis: a longitudinal proteomic and lipidomic study of plasma involving high risk subjects and subjects recently converted to psychosis.
PI D Cotter, (2012-2016)
€1,400,000
Health Research Board, Clinician Scientist Award CSA/2012/8

My 20 most significant publications:
1. Integrated lipidomics and proteomics point to early blood-based changes in childhood preceding later development of psychotic experiences: evidence from the Avon Longitudinal Study of Parents and Children.
Madrid-Gambin F, Föcking M....Cotter DR*+, and Lorraine Brennan*
Biological Psychiatry 2019 Jul 1;86(1):25-34.
PMID: 30878195
IF 11.5
*equal senior author, + Corresponding author
This study integrated lipidomic and proteomic data for the first time in the psychiatric literature and showed early lipid and protein changes associated with future psychosis. The findings have implications with respect to the poor physical health outcomes in psychosis. See commentary based on this paper (PMID:31221245). PI and co-senior author.

2. Complement Pathway Changes at Age 12 Are Associated with the Psychotic Experiences at Age 18: Evidence from the ALSPAC Birth Cohort.
Föcking M, Sabherwal S…. Cotter DR.
Mol Psychiatry. 2019 Jan 11.
PMID: 30635638.
IF 11.9
We targeted the complement pathway in plasma using proteomic methods and showed changes in this pathway 6 years before onset of psychotic experiences. We also demonstrated a potential role of stress in leading to dysregulation of this pathway. PI and senior author.

3. Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder:
Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.
English JA, Lopez LM … Cotter DR.
Schizophr Bull. 2018 Feb 15;44(2):297-306.
PMID: 29036721
IF 7.3
We used discovery proteomic methods and for first time showed changes in many proteins, including the complement pathway, in plasma 6 years before onset of psychotic disorder. PI and senior author.

4. O'Gorman A, Suvitaival T…. Cotter DR.
Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
Transl Psychiatry. 2017 Sep 26;7(9):
PMID: 28949339
IF 4.9 Citations 9
We used lipidomic methods and for first time showed changes in several lipids (lysophosphatidyl cholines and phosphatidyl cholines) 6 years before the development of psychotic disorder, but not at the time of psychotic disorder. PI and joint senior author.

5. Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder.
Föcking M, Dicker P, Lopez LM, Hryniewiecka M, Wynne K, English JA, Cagney G, Cotter DR
Transl Psychiatry. 2016 Nov 29;6(11):
PMID: 27898073
IF 4.9 Citations 11.

6. Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease associated changes.
Beasley CL, Pennington K, Behan A, Wait R, Dunn MJ, Cotter D.
Proteomics. 2006 Jun;6(11):3414-25.
Impact Factor: 4.0778
PMID: 16637010
IF 4.0 Citations 196.

7. Priming the brain for psychosis: maternal inflammation during fetal development and the risk of later psychiatric disorder.
Cannon M, Clarke MC, Cotter DR.
Am J Psychiatry. 2014 Sep 1;171(9):901-5.
IF 13.6. Citations 9
PMID: 25178744.

8. Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia.
Föcking M, Lopez LM, English JA, Dicker P, Wolff A, Brindley E, Wynne K, Cagney G, Cotter DR.
Mol Psychiatry. 2014 Jul 22.
PMID: 25048004
IF 11.9 Citations 53.

9. Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?
Schubert KO, Focking M, Prehn JHM, Cotter DR.
Molecular Psychiatry: 2012: 17 (7) 669-681
PMID: 21986877
IF 11.9 Citations 48
An hypothesis review which integrated our and other findings to develop a novel hypothesis concerning membrane trafficking in schizophrenia.

10. Common proteomic changes in the hippocampus in schizophrenia and bipolar disorder and particular evidence for involvement of cornu ammonis regions 2 and 3.
Föcking M, Dicker P, English JA, Schubert KO, Dunn MJ, Cotter DR.
Arch Gen Psychiatry. 2011 May;68(5):477-88.
IF 15.9 Citations 68
PMID: 21536977
Unique study used laser capture capture microdissection to focus on protein expression in hipoocampal subregions and identified synaptic and metabolic associated changes which overlapped in both schizophrenia and in bipolar disorder compared to controls.

11. The Neuroproteomics of Schizophrenia (review plus original analysis).
English JA, Pennington K, Dunn MJ, Cotter DR
Biol Psychiatry. May 1;69(9):906.
PMID: 20887976
IF 11.5 Citations 86.

12. Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression.
Behan AT, Byrne C, Dunn MJ, Cagney G, Cotter DR.
Mol Psychiatry. 2009 Jun;14(6):601-13.
PMID: 18268500
IF 11.9 Citations 112

13. Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder.
Pennington K, Beasley CL, Dicker P, Fagan A, English J, Pariante CM, Wait R, Dunn MJ, Cotter DR.
Mol Psychiatry. 2008 Dec;13(12):1102-17.
PMID: 17938637
IF 11.9 Citations 144
Highly cited. Among the very first proteomic studies to demonstrate synaptic changes in the postmortem brain in schizophrenia. We also showed metabolic changes in keeping with mitochondrial dysfunction. PI and senior author.

14. Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: Evidence for decreased neuronal somal size and increased neuronal density.
Chana G, Landau S, Everall I, Cotter D.
Biol. Psychiatry 2003 Jun 15;53(12):1086-98.
PMID: 12814860
IF 11.5 No of citations: 165
Highly cited paper among first to show neuronal somal size reductions major psychiatric disorders.

15. Stress and the progression of the developmental hypothesis of schizophrenia.
Cotter D, Pariante CM.
Br J Psychiatry. 2002 Nov;181(5):363-365.
IF 5.9 Citations 81
Among first papers to consider a shared pathology for schizophrenia and other major mental disorders and to consider the role of stress in this shared pathology. First Author.

16. The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the interior cingulated cortex in major depressive disorder, bipolar disorder, and schizophrenia.
Cotter D, Landau S, Beasley C, Stevenson R, Chana G, Macmillan L, Everall I.
Biological Psychiatry: 2002, Mar 1: 51 (5): 377-396.
IF 11.5 Citations 158.

17. Reduced Neuronal Size and Glial Cell Density in Prefrontal Cortex Area 9 of Subjects with Major Depressive Disorder.
Cotter D, Beasley C, Chana G, Landau S, Everall I.
Cerebral Cortex 2002 12(4):386-94.
PMID 11884354
IF 6.3 citations: 441.

18. Glial cell loss and reduced neuronal size in the anterior cingulate cortex in major depressive disorder.
Cotter D, Mackay D, Landau S, Kerwin R, & Everall I..
Archives of General Psychiatry 2001, 58: 545-553.
IF 15.9 Citations 532.
Highly cited. Stereological study of postmortem brain showing for the first time glial cell loss and neuronal size reduction in major depression. First author.

19. Glial Cell Abnormalities in Major Psychiatric Disorders: The Evidence and Implications.
Cotter D, Pariante C, Everall I.
Brain Research Bulletin 2001, 55(5); 585-595.
PMID 11576755
IF 3 Citations: 324.