Neurocognitive Functioning in Subjects at Risk for a First Episode of Psychosis Compared with First- and Multiple-episode Schizophrenia

Abstract

Evidence from neurobiological studies suggests that schizophrenia arises from an early abnormality in brain development and possibly further progressive developmental mechanisms. Despite a delay between the acquisition of neuropathology and the triggering of psychosis, neurobiological susceptibility is likely to be expressed subclinically by biobehavioral markers in the premorbid stage. The exploratory study aims at identifying potential neurocognitive risk factors and investigating the unfolding of the illness within a cross-sectional design by comparing neurocognitive profiles in 179 healthy controls, 38 clinically identified subjects in an early initial prodromal state (EIPS) for psychosis, 90 subjects in a late initial prodromal state (LIPS), 86 first-episode patients with schizophrenia, and 88 multiple-episode patients. Subjects at risk were substantially impaired in verbal executive and verbal memory functions. Compared to EIPS subjects, LIPS subjects demonstrated additional attentional deficits. Both EIPS and LIPS subjects were superior to first-episode patients who presented a generalized neuropsychological deficit profile, and to multiple-episode patients who showed evidence for further decline. Although results were influenced by general intellectual abilities and demographic and clinical characteristics, they could not account for total group differences. Results support a neurodevelopmental model of psychosis with further progressive mechanisms and are consistent with a primary involvement of left frontotemporal networks in the prodromal phase.

The role of cognitive functioning in the outcome of those at clinical high risk for developing psychosis

“…Interestingly, the majority of studies do not support a difference in visual memory (Niendam et al 2006(Niendam et al , 2007Pukrop et al 2006;Becker et al 2010b;Lindgren et al 2010). Both verbal and visuo-spatial workingmemory deficits have frequently been reported in the CHR population (Brewer et al 2006); however, recent results are inconsistent with four to five studies demonstrating working-memory deficits and the same number reporting no differences.…”

Predicting Risk and the Emergence of Schizophrenia

“…Several groups have demonstrated executive function deficits in UHR patients. [130][131][132] Pukrop and colleagues 139 showed deficits on the WCST in a German sample of 90 UHR patients. Pflueger and colleagues, 129 using both the WCST and Tower of Hanoi tasks, also found executive functioning deficits in a sample of 60 UHR patients in Basel, Switzerland.…”

“…Verbal learning tasks regularly show some of the greatest levels of impairment relative to other neurocognitive domains. [137][138][139][140][141][142] Niendam and colleagues, 142 for example, showed pronounced verbal learning deficits in a sample of 45 12-year-old to 29-year-old UHR patients attending a prodromal clinic in California. Similarly, Jhashan and colleagues 143,144 demonstrated marked deficits in verbal learning in a sample of 48 12-year-old to 30-year-old patients with prodromal syndromes.…”

Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis

“…10 Neuropsychological studies indicate that the ARMS is associated with cognitive impairments that are qualitatively similar to, but less severe than those seen in schizophrenia, with consistent evidence of deficits on tasks that engage executive functions. 11,12 The impairment in verbal fluency performance is particularly marked, with performance about one s.d. below the normative level.…”