Neurological soft signs (NSS) are subtle, non-localizable neurological abnormalities in motor and sensory performance.^1,2 Professor Raymond Chan, Institute of Psychology, Chinese Academy of Sciences, argued that NSS, such as sequential thumb-to-finger tapping, used to investigate motor co-ordination together with other hand-focused exercises, are promising endophenotypes for schizophrenia.

NSS – not so soft in schizophrenia

This is because NSS are not ‘soft’ in brain structural and functional networks.³ He suggests that NSS are more or less equivalent to the conventional construct of cognitive functioning.⁴ Together with the short time taken to assess NSS and the development of sensory gloves, which can assess hand co-ordination speed and strength, he believes these subtle hand movement deficiencies offer a feasible and efficient method for mental disorder community screening.

Subtle hand movement deficiencies offer a feasible and efficient method for mental disorder community screening

Data supporting his contention include a study which demonstrates the sensitivity and specificity of NSS to schizophrenia spectrum, but no other neuropsychiatric disorders, that those at ultra-high risk of psychosis can be discriminated from healthy controls with 85.9% accuracy and the impressive heritability of NSS both at the behavioral and neural levels.^5-7

Together, Professor Chan suggested, these data suggest that NSS offer promising endophenotypes for the early detection of schizophrenia spectrum disorders and are suitable candidate biomarkers in precision medicine.

Longer pauses in schizophrenic speech patterns

Professor Vijay Mittal, Northwestern University, IL, described several novel types of biomarker potentially suitable for the prodromal assessment of patients at high risk (HR) of psychosis, including speech analysis and blunted facial expressivity.

When speaking, turn-taking anomalies are tied to social deficits in schizophrenia. Those at HR pause longer before responding to a question - on average 102 mseconds longer – than normal controls.⁸ Even after response complexity and question type are taken into consideration, the deficit remains and appears to scale-up with positive symptom severity. Thus, this deficit is an ideal candidate for further investigation as a non-invasive biomarker for HR and one suited to automation.

Those at high risk psychosis pause on average 102 mseconds longer – than normal controls when answering questions

Joy and anger expression blunted in schizophrenia

So, too, is automation of the assessment of blunted facial expression in those at HR. The Facial Action Coding System, the current gold standard used for this task, is complicated and time-consuming to administer. A small study comparing 42 HR patients with 42 controls has assessed the validity of automating the assessment process.⁹ Automated coding developed parameters for 7 basic emotions. Of these ‘joy’ and ‘anger’ were statistically significantly different in the HR group compared to controls (p<0.05) and could be valuable future prodromal biomarkers of HR individuals.

‘Joy’ and ‘anger’ were statistically significantly different in the high risk psychosis group compared to controls and could be valuable future prodromal biomarkers of high risk individuals

Motivational issues in schizophrenia due to poor assessment valuation

Motivation and reward deficits may also be potential non-invasive biomarkers of psychosis.

Professor James Waltz, Maryland Psychiatric Research Centre, BL, showed data to suggest that those at HR seem unable to gauge the values of the choices they are making when solving problems, albeit disguised as games.¹⁰ Such deficits can be recognized and assessed in those at HR through a series of ‘fixed’ probability reward card sets and could form the basis of a testing regime more suitable for general usage.

Motivation and reward deficits may also be potential non-invasive biomarkers of psychosis

Motivational clusters

Professor Kathryn Eve Lewandowski, Harvard Medical School, MA, took a different approach to identifying motivational deficits. Her group has taken advantage of the heterogeneity in the multi-dimensional constructs describing motivation and reward in psychosis to undertake a cluster analysis based on methodology previously used in a study on cognition.¹¹

Four distinct clusters were identified when patients with a variety of conditions associated with psychosis were assessed. However, while it may be possible to tailor interventions based on the motivational profiles uncovered, it was suggested that further analyses are required.