Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naïve Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population

Abstract

Background: Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied. Aims: To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls. Method: Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound. Results: Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls. Conclusions: PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls.

Distinct Associations of Motor Domains in Relatives of Schizophrenia Patients—Different Pathways to Motor Abnormalities in Schizophrenia?

“…Yet, no control group was included in this latter study. In contrast, other reports ( 63 ) demonstrate an increased severity of dyskinesia ( 63 ) and Parkinsonism ( 26 , 63 ) in schizophrenia relatives compared to healthy controls. Thus, whether dyskinesia or Parkinsonism is truly associated with the genetic risk for psychosis requires further clarification in larger samples.…”

“…As for dyskinesia, from the available data, it is difficult to state whether Parkinsonism may serve as a genetic risk marker for psychosis. Some reports showed increased incidence in unaffected relatives ( 24 , 26 ) with some inconsistency ( 27 ).…”

Gamma oscillations predict pro-cognitive and clinical response to auditory-based cognitive training in schizophrenia

“…These findings underscore the utility of incorporating neurophysiologic biomarkers of gammaevoked power and synchronization in the development of pro-cognitive therapeutics and their potential application in routine clinical practice. It is conceivable that the coupling of validated behavioral 40,[70][71][72] and neurophysiologic measures of target engagement 46,47,59,60 may enhance the sensitivity and accuracy of predictive algorithms for TCT-related cognitive and clinical outcomes. These findings thus support future personalized medicine trials of pro-cognitive therapeutics, where individuals may be stratified to receive effective interventions based on their unique neurophysiologic profiles and their likelihood of response.…”

Functional Connectivity Combined With a Machine Learning Algorithm Can Classify High-Risk First-Degree Relatives of Patients With Schizophrenia and Identify Correlates of Cognitive Impairments

“…Cognitive impairments are a key component of SCZ and have been included as a diagnostic criterion for SCZ in the DSM-V classification (Bortolato et al, 2015). Previous studies have indicated that non-psychotic FDRs also exhibit similar but less severe cognitive defects (Molina et al, 2016). Study of the neurocognitive functions of non-psychotic FDRs is a widely used strategy for understanding the etiology of SCZ and is free of the confounds associated with psychosis.…”