Predictors of conversion to psychosis

The prodromal phase of psychosis represents an opportunity to understand how psychosis develops, and research in this area has the potential to generate strategies for treatment and prevention. This chapter reviews findings from clinical high risk (CHR) and general population sampling research related to prediction of psychosis, discussing what has been learned from these two approaches as well as theoretical and practical pitfalls of each. Work conducted in the CHR paradigm has yielded practical tools for psychosis prediction as well as evidence that progressive loss of neuronal connectivity may underlie onset of full psychosis, but cases meeting criteria for a CHR syndrome represent a small fraction of new onsets of psychosis in the population. Population-based studies benefit from a broader ascertainment scheme but are limited in feasibility of in-depth or frequent assessments and follow-ups. The chapter concludes with a discussion of how to reconcile different approaches under a transdiagnostic framework.

Exposure to Pesticides and Welding Hastens the Age-at-Onset of Parkinson’s Disease

ABSTRACT:Background:The age-at-onset (AAO) of Parkinson’s disease (PD) is thought to be influenced by environmental factors and polygenic predispositions. Professional exposures to pesticides and toxic metals were shown to be associated with an earlier onset in small sample studies.Aim of Study:The aim of this study was to confirm the association between professional exposures to pesticides and toxic metals and the AAO of PD, on a larger cohort of patients, defined with a clinic-based ascertainment scheme.Methods:We used an incident cohort of 290 patients recruited through three designated movement disorder clinics in the province of Quebec, Canada. Patients completed a detailed questionnaire regarding professional exposures to pesticides and toxic metals. We compared the AAO in patients without prior professional exposure (N = 170) and those with exposure to pesticides (N = 53) or toxic metals through welding (N = 30). We further subdivided patients exposed to pesticides according to the frequency and proximity of their contacts.Results:Patients with prior exposure to pesticides (AAO = 54.74 years) or toxic metals (54.27 years) had a significantly earlier AAO compared to the control group (59.26 years) (p = 0.003). In those exposed to pesticides, closer (p = 0.03) and more frequent (p = 0.02) contacts were negatively correlated with AAO.Conclusion:Exposure to pesticides and toxic metals were both associated with an earlier onset of PD, an effect that was greater with higher levels of exposure, both in terms of frequency and proximity.

The Essence of Single Ascertainment

We propose a fundamental new definition of single ascertainment, namely, that single ascertainment is any ascertainment scheme in whichP[pedigree is ascertained∣true structure of pedigree]∝p(θ)where p(θ) is some function of genetic parameters θ but is not a function of pedigree structure. Stated in words: Under single ascertainment, all pedigrees have equal (or proportional with respect to genetic parameters) probabilities of being ascertained, independent of pedigree size or structure. This new definition of single ascertainment allows us to show several results: (1 ) The correct likelihood consists of the probability of the data conditioned on the observed pedigree, divided by the function p(θ), whether sampling is “proband-independent” or “proband-dependent.” ( 2 ) More-familiar definitions of single ascertainment all represent special cases of our definition. ( 3 ) When p(θ) represents the prevalence of the trait being studied, our definition corresponds to “classical” single ascertainment, i.e., ascertainment through a single “proband.” However, the concept of p(θ) can also be generalized to represent the population frequency of configurations of affected relatives (such as affected sib pairs); we call this “generalized single ascertainment.”