Sunday, January 12, 2014

Can Neuropsychology Detect Psychosis Before it Ever Occurs?

Over the last several years, interest in detecting schizophrenia (and other psychotic disorders) in its prodromal phase (before the appearance of any psychotic symptoms have manifested) has been rapidly increasing. Detecting one’s vulnerability to acute psychosis before suffering a first event has many theoretical and practical advantages. Evidence suggests that the length and severity of untreated psychosis is directly related to an individual’s long-term outcome. If psychosis can be delayed, reduced, or ideally, altogether prevented by targeted interventions, the morbidity of the illness should be greatly improved (Eastvold, Heaton, & Cadenhead, 2007; Hawkins et al., 2004).
In the past, attempts at diagnosing prodromal psychosis have relied upon criteria that included transient psychotic symptoms, and/or a family history of psychosis combined with a marked decline in functioning; however, this method is marred by a 50% or higher false positive rating in most studies, and most people identified as at risk do not go on to develop psychosis, at least not over the duration of the studies that are monitoring them (Haroun, Dunn, Haroun, & Cadenhead, 2006). This high rate of false positives and low rate of conversions to psychotic states raises ethical concerns about if and how to treat those identified as having a high risk of developing a psychotic illness (Haroun, Dunn, Haroun, & Cadenhead, 2006).
The above has led to a desire to develop a more accurate way of identifying those most at risk of having a psychotic episode. The neurodevelopmental model provides strong evidence that cognitive abnormalities related to abnormal brain maturation is a core feature of psychotic illnesses (Lencz et al., 2006; Eastvold, Heaton, & Cadenhead, 2007). These neurocognitive deficits are well established in schizophrenia, span multiple domains, and include motor abilities, executive functions, language, general intelligence, learning/memory, and spatial abilities (Eastvold, Heaton, & Cadenhead, 2007).
Similar neurocognitive dysfunction, especially those related to visuospatial processing impairment and working memory deficits, has been detected in first degree relatives of family members of psychotic patients and those with schizotypal disorder who are known to be at greater risk of developing psychosis (Brewer et al, 2005). Because these neurocognitive features are present prior to the onset of any psychotic symptoms, they may be a trait marker for schizophrenia. This has raised the very interesting possibility of identifying those at high risk of developing psychosis by using neuropsychological assessments such as the Wechsler Memory Scales-R (WMS-R), the Wisconsin Card Sorting Test, the Vocabulary and Block Design subtests of the WAIS IV, and others (Brewer et al, 2005; Eastvold, Heaton, & Cadenhead, 2007; Lencz et al., 2006).
These findings represent very exciting developments in the field of psychological assessment. While the current research is very promising, most studies call for continued research with larger cohorts to further define and validate the neurocognitive profile that best indicates future psychotic symptoms, as well as to validate the cognitive deficits as a true trait marker for psychotic vulnerability.
Another problem to be addressed is the high degree of variability presently found within the composition of the neuropsychological batteries being tested for detecting prodromal psychosis by various researchers. This is part of the process of developing a standardized test battery, but presently we are without any general consensus about which tests to use and what results to look for, causing the utility of neuropsychological assessments as an identifier for those at risk of psychosis to remain quite limited.
I find the prospect of being able to assess for prodromal psychosis to be tantalizing. As a student of clinical psychology, this could potentially be an important part of my future. I think that being able to reliability detect psychotic disorders before they strike would be a wonderful development for clients, their families, and the field of clinical psychology. It could potentially prevent much personal and economic devastation; it is noninvasive, relatively brief to administer (at least in regard to the enormity of possibly preventing disorders as severe as these from manifesting), and is potentially much more reliable than what is presently available.
Of course, even with all of the obvious benefits, that are certainly potential problems to address. Aside from further validating the neurocognitive trait marker and assessment batteries, I can see ethical concerns looming as perhaps the largest potential challenge. Determining who should be screened, when they should be screened, and who pays for said screening are among the first concerns. What will the threshold be for a positive screening, and what, if anything, should be done for those deemed at only moderate risk for developing a psychotic state are all questions in need of answers.
Perhaps the biggest ethical dilemma will be reserved for those that are deemed to be highly likely to develop a psychotic illness. Presently, most interventions for psychosis involve antipsychotic medications, which come with a host of unpleasant and potentially dangerous side effects (although in this regard they are little different from other pharmaceuticals). Would it be ethical to recommend a client be prescribed these drugs in perpetuity if one was not 100% sure they were needed? The line between pragmatic risk prevention and unnecessary risk is a thin one indeed, and our accuracy in detecting prodromal psychosis will need to improve before we are informed enough to make such profound decisions.
It also seems likely that psychologists will face issues informing client’s that they have been found likely to develop psychosis. This knowledge, like the genetic knowledge that one will almost certainly develop cancer, could be very beneficial in reducing morbidity, but it is not without considerable stress. Knowing one’s vulnerability to psychosis could have both long and short term negative effects on one’s psychological health. It is even possible that the sheer anxiety caused by this information could increase the chances of a vulnerable person having a first psychotic event, and/or increase the chances of them developing other mental illnesses. This problem is magnified if we do not have any palatable and efficacious interventions to offer them at the time the prognosis is delivered.
Ultimately, I think that using neuropsychological assessments to detect prodromal psychotic disorders will become a valued part of what clinical neuropsychologists provide. Before that can happen, it is paramount that the neurocognitive deficits being assessed are validated and then quantified in such a way that they can very reliably predict the future onset of psychotic illness. The ethical concerns described above will also need to be addressed before any widespread adoption of a neuropsychological battery used for the detection of potential psychotic illnesses should occur. Finally, while I feel that the development of these test batteries should proceed as rapidly as possible, the benefits of detection will be blunted by our present lack of quality preventative interventions. In some cases, early detection could cause potentially damaging anxiety, precisely because of our present dearth of safe and proven options for preventing psychosis from developing. This downside is likely outweighed by the fact that at the very least, those identified as at high risk could be carefully monitored and provided with proper medications at the very first signs of an initial psychotic break, greatly improving their long-term outcomes.  


Brewer, W. J., Francey, S. M., Wood, S. J., Jackson, H. J., Pantelis, C., Phillips, L. J., ... & McGorry, P. D. (2005). Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis.American Journal of Psychiatry, 162, 71-78.

Eastvold, A. D., Heaton, R. K., & Cadenhead, K. S. (2007). Neurocognitive deficits in the (putative) prodrome and first episode of psychosis. Schizophrenia research, 93, 266-277.

Haroun, N., Dunn, L., Haroun, A., & Cadenhead, K. S. (2006). Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophrenia bulletin, 32, 166-178.

Hawkins, K. A., Addington, J., Keefe, R. S. E., Christensen, B., Perkins, D. O., Zipurksy, R., ... & McGlashan, T. H. (2004). Neuropsychological status of subjects at high risk for a first episode of psychosis. Schizophrenia research,67, 115-122.

Lencz, T., Smith, C. W., McLaughlin, D., Auther, A., Nakayama, E., Hovey, L., & Cornblatt, B. A. (2006). Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biological psychiatry, 59, 863-871.

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