Neurocognitive deficits in clinical high risk subjects: Relationship to symptoms and disease progression

Abstract

Background and Aims

Psychosis is preceded by cognitive and physiological alterations. This may be useful in the risk assessment in subjects with putatively prodromal symptoms, and could contribute to better understand the temporal unfolding of the disease.

Methods

The early recognition and intervention program of the German Research Network on schizophrenia defines early and late prodromal stages according to psychopathological criteria. For concurrent and prospective validation of these risk stages, subjects undergo neurocognitive, electrophysiological and oculomotor assessments of putative vulnerability markers. About 125 early prodromal subjects (defined by the presence of basic symptoms, Klosterkoetter et al. 2001), and 90 late prodromal subjects (defined by attenuated positive symptoms or by brief occurrences of psychotic symptoms) have been assessed at inclusion.

Results

As compared to psychiatrically healthy matched controls, late prodromals have significantly inferior verbal memory, verbal fluency, visual motor skills, and working memory. Impairments are qualitatively similar, but less pronounced in subjects in an early prodromal stage, with deficits of immediate verbal memory, verbal fluency and visuomotor performance being significant. Both groups show reduced auditory startle prepulse inhibition. Impairments are not correlated with depression and general distress scores, and are also largely independent of prodromal and attenuated positive symptoms. In early prodromals, global cognitive performance is related to the occurrence of psychotic symptoms during follow-up. Auditory P 300 is reduced in both prodromal groups, and predicts transitions to psychosis.

Conclusions

Neurocognitive and neurophysiological assessments validate and improve psychopathological risk assessment, and allow to disentangle stable vulnerability markers from indicators of imminent risk.

Funded by the German Federal Ministry for Education and Research BMBF (grant 01 GI 9934).