The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model.

BACKGROUND: Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype. METHODS: Based on a dose-response study, MIA was induced in pregnant rats by injecting 4mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-α in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n=14) and weight gain (WG; n=10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections. RESULTS: Pregnant dams that lost weight following MIA showed increased levels of TNF-α compared to controls, unlike dams that gained weight following MIA. Poly I:C WL offspring showed the most severe behavioural outcome. Poly I:C WG offspring, on the other hand, did not show clear behavioural deficits. Most interestingly a reduced sucrose preference indicative of anhedonia was found in Poly I:C WL but not Poly I:C WG offspring compared to controls. Finally, there were no significant differences in microglia activation scores between any of the investigated groups. CONCLUSIONS: The individual maternal immune response to MIA is an important determinant of the behavioural outcome in offspring, including negative symptoms such as anhedonia. We failed to find any significant difference in the level of microglia activation between Poly I:C WL, Poly I:C WG and control offspring.

Validation of the Diabetes Obstacles Questionnaire (DOQ) to assess obstacles in living with type 2 diabetes in a Belgian population.

AIMS: The aim of this study was to validate the Dutch version of the Diabetes Obstacles Questionnaire (DOQ) [H. Hearnshaw, K. Wright, J. Dale, J. Sturt, E. Vermeire, P. Van Royen, Development and validation of the Diabetes Obstacles Questionnaire (DOQ) to assess obstacles in living with Type 2 diabetes, Diabetic Med. 24 (2007) 878-882] assessing people living with type 2 diabetes' obstacles to adhere to treatment recommendations. The goal is to have at one's disposal an instrument to identify obstacles to adhering to treatment recommendations for people living with type 2 diabetes in a Dutch speaking population. METHODS: Participants were recruited from a pragmatic sample of general practices in Flanders (Belgium). In accordance with the validation procedure in the UK [H. Hearnshaw, K. Wright, J. Dale, J. Sturt, E. Vermeire, P. Van Royen, Development and validation of the Diabetes Obstacles Questionnaire (DOQ) to assess obstacles in living with Type 2 diabetes, Diabetic Med. 24 (2007) 878-882], responders also completed the Dutch version of a quality of life questionnaire (ADDQoL) [C. Bradley, C. Todd, T. Gorton, E. Symonds, A. Martin, R. Plowright, The development of an individualised questionnaire measure of perceived impact of diabetes on quality of life: the ADDQoL. Qual. Life Res. 8 (1999) 79-91] and the Problem Areas in Diabetes (PAID) scale as golden standard [G. Welch, A.M. Jacobson, W.H. Polowsky, The Problem Areas in Diabetes (PAID) scale. An evaluation of its utility. Diabetes Care 20 (1997) 760-766]. Some biomedical variables such as HbA1c were collected also. RESULTS: Each scale showed sufficient reliability with Cronbach's alpha (>0.76). Each subscale had a factor structure of no more than 4, and a Kaiser-Meyer-Olkin measure of 0.75. Criterion validity was shown by significant correlation with the PAID and construct validity by a correlation with HbA1c. Construct validity has also been shown by significant correlations between ADDQoL and the DOQ Obstacles of Lifestyle changes scale. CONCLUSIONS: The Dutch version of the DOQ is a feasible and valid instrument for the assessment of obstacles to adherence to treatment recommendations in people living with type 2 diabetes.