2011

Daskalakis, N.P., Claessens, S.E., Laboyrie, J.J., Enthoven, L., Oitzl, M.S., Champagne, D.L., de Kloet, E.R. , The newborn rat's stress system readily habituates to repeated and prolonged maternal separation, while continuing to respond to stressors in context dependent fashion, Horm Behav, vol. 60, no. 2, pp. 165-176.

Daskalakis, N.P., Martens, G.J., Cools, A.R., de Kloet, E.R. , Schizophrenia endophenotypes and stress hyper-reactivity co-precipitate following adverse life events in genetically susceptible rats, European Neuropsychopharmacology, vol. 21, pp. S85-S86.

Claessens, S.E., Daskalakis, N.P., van der Veen, R., Oitzl, M.S., de Kloet, E.R., Champagne, D.L. , Development of individual differences in stress responsiveness: an overview of factors mediating the outcome of early life experiences, Psychopharmacology, vol. 214, no. 1, pp. 141-154.

Richter, S., Schulz, A., Zech, C.M., Oitzl, M.S., Daskalakis, N.P., Blumenthal, T.D., Schachinger, H. , Cortisol rapidly disrupts prepulse inhibition in healthy men, Psychoneuroendocrinology, vol. 36, no. 1, pp. 109-114.

2010

Daskalakis, N.P., Fung, W.L., Schnorr, S., Meelis, W., Oitzl, M.S., de Kloet, E.R. , The three hit hypothesis of schizophrenia tested in genetically selected rats exposed to early life experience and adolescent psycho-social stressor, Int J Dev Neurosci, vol. 28, no. 8, pp. 698-698.

2009

Daskalakis, N.P., Kaperoni, M., Koros, C., de Kloet, E.R., Kitraki, E. , Environmental and tactile stimulation modulates the neonatal handling effect on adult rat spatial memory, Int J Dev Neurosci, vol. 27, no. 8, pp. 747-755.

Novel susceptibility pathways and drug targets for psychosis

Schizophrenia is a complex mental disorder often characterised by social dysfunction, breakdown of thinking, and a loss of contact with reality. It usually begins in early adulthood and is associated with disturbed neurodevelopment.  Genetic risk-factors are clearly involved and the role of non-genetic factors is debated (van Os & McGuffin, 2003). The perinatal period, as a time of rapid development, plasticity and vulnerability to environmental influences, as well as additional cumulative exposure to psychosocial stressors are of special interest (McDonald & Murray, 2000; van Winkel, Stefanis, & Myin-Germeys, 2008).

This so-called “three-hit model” of psychopathology is defined as the interaction between [1] predisposing genes, and [2] early-life experience and [3] later-life cognitive/emotional inputs. It is thought that this interaction may produce a vulnerability or resilience to psychopathology.

Objectives

-       To show the importance of early-life adversity on the neonate’s stress response, dam’s care and pre-adult/adult behaviour in outbred rat populations.

-       To observe the naturally occurring maternal environment in rat families genetically predisposed for behavioural features of psychosis. The phenotype of the offspring will be correlated with the dam’s behaviour and genotype.

-       To manipulate in such families the early- and later-life environment in order to attenuate or to enhance the behavioural features of psychosis.

In the final stage of the project, we will have a nature-nurture rat model for schizophrenia valid for pathway identification and investigation of epigenetic influence on psychopathology.