Neurocognition in Prodromal Psychosis

JAMA Psychiatry recently published new results from the North American Prodrome Longitudinal Study (NAPLS), a multi-site longitudinal study of the early warning signs of schizophrenia and other psychotic disorders. NAPLS tested and followed 689 clinical high risk (CHR) subjects (398 male and 281 female) and 264 healthy control (HCs) subjects (137 male and 127 female). In this latest analysis, the authors found that neurocognitive dysfunction is related to later conversion to full-blown psychotic disorders in clinical high-risk subjects (CHRs). Patients were initially identified as high-risk by factors such as unusual thoughts, family history, and functional deficits. In particular, CHRs who later converted to psychosis (CHR-Cs) showed high premorbid verbal abilities but deficits in attention, working memory, and declarative memory when compared to either healthy controls (HCs) or CHRs who did not convert to psychosis (CHR-NCs).

napls

The long-term goal of this study is to improve early detection and treatment of psychosis. As far as early detection goes, the results they report appear to be confirmation that the combination of cognitive signs they identified, especially declarative memory, are a sensitive marker for conversion from prodromal to active psychosis. In terms of treatment, there did not seem to be a large difference in cognitive deficits between medicated and unmedicated CHR-Cs. Medicated subjects showed somewhat greater attention and working memory abilities but were overall comparable to unmedicated subjects. The authors of the study emphasize that more research should be done to determine what early interventions might be more protective of cognition specifically.

One intervention that might be promising is cognitive training. One small pilot study from 2009 found that prodromal patients benefited from 10 sessions of computer-based cognitive training, showing improvements in long-term memory and attention. Patients who already had schizophrenia, on the other hand, showed no benefit from the same intervention. According to the authors of the study,

The existence of such a higher potential in comparison to patients with schizophrenia is supported by the findings that persons at ultra-high-risk mental state show smaller gray matter volumes than controls but still larger gray matter volumes than patients who already underwent transition to psychosis. […] In terms of the improved performance of the persons at risk mental state in this study, it is conceivable that cognitive training may facilitate neuroplastic phenomena and may thus have a neuroprotective functioning. Thus, the application of cognitive training has to be provided as early as possible in the prodromal phases of schizophrenia.

They added that additional research with larger sample sizes would be needed to confirm these results.

A 2014 review of cognitive training and mental illness in the American Journal of Psychiatry suggests that training seems to be of modest benefit overall, but that the best results so far have come from studies that combine cognitive training with other forms of rehabilitation, such as medication, and strategy training. Initial results from neuroimaging studies show that  positive results correspond with structural and functional changes in the prefrontal regions of the brain. The review also suggests that factors like therapeutic alliance, age, motivation, and clinician expertise could play a large role in successful cognitive training, and suggests that future research should focus on teasing out the different mechanisms involved.

 

Sources:

Keshavan, M. S., Vinogradov, S., Rumsey, J., Sherrill, J., & Wagner, A. (2014). Cognitive training in mental disorders: update and future directions. American Journal of Psychiatry.

Rauchensteiner, S. S. (2011-02). Test-performance after cognitive training in persons at risk mental state of schizophrenia and patients with schizophrenia.. Psychiatry research, 185(3), 334-339.doi:10.1016/j.psychres.2009.09.003

Seidman LJ, Shapiro DI, Stone WS, Woodberry KA, Ronzio A, Cornblatt BA, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Mathalon DH, McGlashan TH, Perkins DO, Tsuang MT, Walker EF, Woods SW. Association of Neurocognition With Transition to PsychosisBaseline Functioning in the Second Phase of the North American Prodrome Longitudinal Study. JAMA Psychiatry. Published online November 02, 2016. doi:10.1001/jamapsychiatry.2016.2479