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Psychotic disorders – from dawn ‘til dusk

‘From dusk ‘til dawn’ was the title of a symposium at SIRS 2018 that brought together current findings on cognitive functioning in patients at all stages of the psychosis life-cycle. However, it possibly should have been retitled ‘From dawn ‘til dusk’ as the trajectories, key-predictors and functional consequences of cognitive impairments in schizophrenia and related psychotic disorders described in this fascinating symposium were drawn from developmental epidemiological, prodromal, and clinical research stretching from birth to death.

Dawn – cognition deficits emerge in psychosis

Josephine Mollon, Yale, New Haven, USA presented data that investigated the origin of cognitive impairment across the psychosis spectrum. Her investigations used the Avalon Long Study of Parents/Children population-based cohort that had been followed prospectively from birth.

Her group’s findings demonstrate that individuals who go on to develop a psychotic disorder exhibit a dynamic course of cognitive deficits, emerging early and in certain functions (e.g. processing speed and working memory) and continuing to increase throughout adolescence.

It appears that cognitive deficits are associated only with psychosis. Furthermore, a dynamic course of increasing deficits across domains is specific to psychotic disorders and is not seen in those with psychotic experiences who do not transition to the full disorder or even in individuals with comorbid psychosis and depression.

Cognitive deficits are seen only in the psychosis spectrum and not in depression

Considering specific domains of cognition, verbal intelligence quotient (IQ) declines early and then stabilizes, while non-verbal IQ continues to decline throughout adolescence. Language and visuospatial deficits emerge early and stabilize, while processing speed, working memory and attention deficits increase into adulthood. However, the decline in IQ between childhood and adulthood does not reflect an absolute deterioration in cognitive function because raw subtest scores increased across all groups.  However, it implies that some individuals’ developmental growth lags behind their peers.

Verbal deficits emerge early and remain relatively stable thereafter, while deficits in non-verbal IQ and executive functions continue to increase throughout adolescence. This implies that verbal abilities may be more amenable to interventions during childhood while interventions during adolescence may be most effective for executive function.

Dr Mollon then described how some individuals who developed psychotic disorders (with and without co-morbid depression) showed abnormal connectivity and organization of cognitive networks in childhood, while those with depression and psychotic experiences showed only subtle deviations in cognitive network structure.

These findings suggest it’s important to look beyond cognitive performance to cognitive networks. This was exemplified by a group of patients with psychotic disorders who showed abnormal connectivity and organization of cognitive processes despite having only a small IQ deficit.

Cognition in the afternoon

Eva Velthorst, New York, USA, explained how most studies of neurocognitive functioning in patients with clinical high-risk of developing psychosis have reported results in terms of group averages, thereby likely concealing heterogeneity between subjects. Dr. Velthorst described how her group used two independent methods - one using a statistical and one a clinical approach - to identify neurocognitive subgroups in the large North American Prodrome Longitudinal Study (NAPLS-I) population at clinical high-risk CHR for developing psychosis.

Heterogeneity between subjects became apparent because, as Dr Velthorst stated, cognitive impairment was not mild for everyone. While the clinical rather than the statistical approach was more conservative in determining cognitive impairment, overall, neurocognitive profiles varied greatly in severity using both approaches and were associated with diagnostic and functional outcome, underscoring neurocognition as a predictor of illness outcomes.

Cognitive impairment was not mild for everyone

Anne-Kathrin Fett described cognitive functioning in a large group of patients enrolled in the Suffolk County Mental Health Project who have been followed for 20-years post-first admission for a psychotic disorder. Her group’s findings indicate that cognitive functioning in psychotic disorders continues to decline after illness onset, and is most apparent in schizophrenia. The rate of decline is in line with that expected with age i.e. processing and executive functioning decline after the age of 30.  However, relative to never-psychotic individuals, impairments on some key cognitive domains worsen with age. Currently, cognitive decline cannot reliably be predicted by patient characteristics at baseline.

Cognitive functioning in psychotic disorders continues to decline after illness onset, and is most apparent in schizophrenia

Cognition at dusk

The course of cognitive functioning in middle aged and older patients with schizophrenia was the subject of a presentation by Philip Harvey, Miami, Florida, US. He reported that the variability in outcome in schizophrenia seen in early life is apparently exaggerated in late-life patients – varying from patients being symptom-free, to having cyclical exacerbations or to running a continuous course of illness.

Cognitive performance, everyday functioning and communication disorders worsen over time in older patients with schizophrenia.  Importantly, communication disorders contribute to cognitive impairments in everyday outcomes. Verbal under-productivity and disconnected speech had different functional correlates; under-productivity impacting clinician-rated social outcomes and performance on measures of interpersonal social competence.

Cognitive performance, everyday functioning and communication disorders worsen over time in older patients with schizophrenia

Side-effects of second-generation antipsychotics on functioning

Daily functioning in patients with schizophrenia was also considered in a poster presentation by Tandon et al., Florida, USA. Here, understanding the impact of side-effects associated with use of second-generation antipsychotic medications on daily functioning was examined using a web-based, patient-reported survey.

Included in the survey were a quality of life measure (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form, Q-LES-Q-SF), questions on treatment satisfaction, the side-effects experienced (Glasgow Antipsychotic Side-Effect Scale, GASS) and their effects on functioning and emotions. Patients were self-reported, aged 18 to 65 years, stable for ≥ 1 month when screened, had been prescribed a second-generation antipsychotic medication for 1-12 months.

Overall, the minimum impact from side-effects on daily functioning was 53.2 on a 0-100 Visual Analogue Scale (0 = no impact; 100 = very highly impacted).  The survey found that side-effects directly impacted e.g. patients’ ability to work, enjoy sex and their ability to concentrate. 

In the 180 patients who experienced at least one side-effect, those most commonly reported were ‘difficulty sleeping’ (81.1%), ‘feeling sleepy during the day’ (77.2%), ‘dry mouth’ (70.6%), and ‘feeling restless (60.6%). Distressing side-effects included difficulty passing urine (23.3%), and feeling drugged/like a zombie (19.4%).

These findings suggest that both activating and sedating side-effects can have a negative impact on patients’ daily functioning and underscores the importance of understanding the perspectives of patients during clinical care, especially when assessing any side-effects associated with use of second generation antipsychotic medications.

Activating and sedating side-effects negatively impact on patients’ functioning

The poster denoted in this article was supported by Lundbeck.

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