Neurocognitive deficits in participants at clinical high-risk for psychosis: relationships to clinical symptoms and functioning

Background: Neurocognitive impairments are a core feature of schizophrenia (ScZ) contributing to ongoing psychopathology and poor psychosocial functioning. These deficits have been consistently observed before illness onset in individuals at clinical high risk for psychosis (CHR) suggesting that they may be an endophenotype of the disorder. Traditional CHR studies have recruited exclusively using clinical pathways however, it has been recently reported that the majority of individuals who present with a first episode of psychosis have not been seen by specialised prodromal services suggesting that these studies only capture a subgroup of CHR individuals (Ajnakina et al., 2017). Few studies have included CHR individuals recruited from community pathways who may differ from those recruited clinically in the degree of neurocognitive impairment and clinical trajectory. Neurocognitive functioning in CHR individuals may also be influenced by the high prevalence of comorbid non-psychotic disorders experienced by the population. So far, few studies have addressed this question which may provide valuable information to improve functional and clinical outcome in those at-risk. Aim 1: To explore the degree of neurocognitive impairment in CHR-participants recruited from the general population and identify their relationship with positive symptom severity and functioning. Aim 2: To investigate the influence of comorbid non-psychotic disorders on neurocognitive functioning in CHR-participants by identifying the degree of neurocognitive impairment in a CHR-negative group who scored below the CHR threshold but are characterised by non-psychotic disorders Aim 3: To explore the association between baseline neurocognitive functioning and clinical outcome at 12 months. Methods: The Youth Mental Health and Resilience Study (You-R) recruited CHR- and CHR-negative participants from the general population using a unique web-based screening tool. At baseline neuropsychological tests together with functioning assessments were administered to healthy controls (N = 57), CHR-negative participants (N = 43), community recruited CHR- (N = 110) and clinically recruited CHR-participants (N = 12). CHR-participants received follow-up assessments at 3 or 6 month intervals. At the 12 month assessment participants were categorised as remitters (CHR-R; N = 33), non-remitters (CHR-NR; N = 16) or converters (N = 1) depending on the change of their attenuated psychotic symptom status from the baseline to follow-up assessment. Results 1: Community recruited CHR-participants presented with small to moderate sized impairments in motor speed, processing speed, emotion recognition (response time) and attention by comparison to healthy controls. Within the community recruited CHR group emotion recognition (RT) predicted positive symptom severity while verbal memory, emotion recognition (RT) and the neurocomposite score significantly predicted functioning. Results 2: CHR-negative participants were not impaired by comparison to HC in any of the neuropsychology tests and they had a statistically significant better performance in processing speed by comparison to the CHR-positive group. Results 3: Overall, there was a high number of non-transitions and remissions at 12 months. Comparisons of baseline neurocognitive functioning revealed that non-remitters were statistically significantly more impaired in motor speed and emotion recognition (RT) than remitters. Moreover, remitters but not non-remitters performed similarly to healthy controls in a number of neuropsychological tests at baseline. Conclusions: Community recruited CHR-participants presented with neurocognitive impairments by comparison to healthy controls in domains highlighted by previous research using clinically recruited populations. These impairments were more pronounced in CHR individuals who had ongoing attenuated psychotic symptoms at 12 months compared to those who remitted. However, the high number of non-transitions and remissions questions if this was a group enriched for psychosis risk. Additionally, although the CHR-negative group presented with preserved neurocognitive functioning they had a lower prevalence of comorbid non-psychotic disorders than the CHR-positive group so the influence of comorbid non-psychotic disorders remains largely unknown.