Childhood pegboard task predicts adult-onset psychosis-spectrum disorder among a genetic high-risk sample
Introduction
Motor function deficits in individuals with psychosis-spectrum disorders are well-documented (Chan et al., 2010, Peralta and Cuesta, 2011). Common among people with psychotic disorders such as schizophrenia, motor function abnormalities show reliable impairments in performance versus healthy controls (Heinrichs and Zakzanis, 1998, Neelam et al., 2011), and are considered a key feature of illness (Tandon et al., 2009). The relation between motor abnormalities and psychosis, however, is sometimes clouded as factors such as treatment side-effects and other illness related issues can contribute to motor dysfunction in people with psychosis (Crane and Naranjo, 1971, Khot and Wyatt, 1991). Nonetheless, a large body of evidence has documented motor abnormalities prior to antipsychotic medication use or illness onset (Dickson et al., 2012, Erlenmeyer-Kimling et al., 2000, Schiffman et al., 2009, Torrey, 2002, Wolff and O'Driscoll, 1999). Motor deficits are thought to represent aspects of the underlying psychophysiology of psychosis-spectrum disorders, documented prior to clinical symptom manifestation, which may be viable candidates for illness endophenotypes. With increased recognition and precision, it has been argued that measurement of motor function deficits holds the promise of being a low cost addition to the effective screening for risk for psychosis-spectrum disorders (Burton et al., 2016). Additional research documenting the link between motor abnormalities and the premorbid stage of illness prior to the confounds of illness related issues is required to firmly identify specific types of motor abnormalities and standardized assessments associated with future psychosis-spectrum disorders (Morrens et al., 2014).
Pegboard tasks, a measure of perceptual-motor speed, have long been used to study motor function in individuals diagnosed with psychotic disorders such as schizophrenia (Collinson et al., 2004, Flyckt et al., 1999, Fuller and Jahanshahi, 1999, Green and Walker, 1985). Pegboard tasks are thought to measure underlying functioning of the frontal and parietal brain regions in the right hemisphere (Royce et al., 1976), making them particularly relevant for individuals with psychosis, as both structural and functional deficits in the right parietal and frontal regions of the brain have been implicated in psychosis-spectrum disorders (Neuhaus et al., 2011, Pettersson-Yeo et al., 2011, Yao et al., 2013, Yoon et al., 2008, Zetzsche et al., 2008). Research also suggests that abnormal striatal dopamine activity can impact pegboard performance (Bohnen et al., 2007, Mozley et al., 2001), and related deficits play an important role in etiological models of schizophrenia (Howes et al., 2012).
Despite the prominent role of pegboard tasks in psychosis research, as well as a few studies of adolescents with subclinical psychosis (Blanchard et al., 2010, Carrión et al., 2011, Lindgren et al., 2010, Roman-Urrestarazu et al., 2014), little research to date has examined the ability of pegboard tasks to predict conversion to psychosis premorbidly, prior to illness confounds (Cannon et al., 2006, Meier et al., 2014).
The aim of the current investigation was to examine performance on the Simultaneous Pegs Test premorbidly in a subgroup of the Copenhagen Perinatal Cohort known as the “OB Project,” a genetic high-risk longitudinal sample and matched controls of 244 children followed for nearly 50 years. This sample, assessed with a pegboard task in childhood prior to clinical manifestation of illness, provides an opportunity to examine genetic risk and future psychiatric outcome in relation to premorbid pegboard performance. We hypothesized that childhood deficits in performance on the Simultaneous Pegs Test would predict later development of a psychosis-spectrum disorder relative to other non-psychotic mental disorders and to no diagnosis.
Section snippets
Participants
The current study recruited from the Copenhagen Perinatal Cohort, which included 9125 births between September 1, 1959 and December 31, 1961 at Rigshospitalet, Copenhagen Denmark (Schiffman et al., 2009). In 1972, 265 participants (all between the ages of 10 and 13) were recruited from the larger cohort and underwent a more detailed evaluation. These individuals were selected based on parental psychiatric status, described below. Controls matched on race, gender, socioeconomic status, and
Results
For mean seconds needed to complete the Simultaneous Pegs Test and pass/fail score by diagnostic outcome, see Table 2. Prior to performing the main analyses, relations of time to completion on the Pegs Test with childhood IQ, gender, and handedness were estimated. As has been observed in the literature (Diaz-Asper et al., 2004), IQ was negatively correlated with seconds needed to complete the pegboard task, r = − 0.237, p < 0.001. Neither gender nor laterality were related to completion time on the
Discussion
Results suggest an association between premorbid pegboard performance and adult onset psychosis-spectrum disorders. Pass/fail and greater time to complete the Simultaneous Pegs Test in childhood was related to development of a psychosis-spectrum disorder relative to children who later developed other psychiatric disorders (trend level significance for the seconds needed analysis) or no mental illnesses. This was true while controlling for IQ and genetic risk, indicating that performance on the
Role of funding source
This work was supported in part by grant R03MH076846 to Jason Schiffman; funding from the Maryland Department of Health and Mental Hygiene, Behavioral Health Administration through the Center for Excellence on Early Intervention for Serious Mental Illness (OPASS# 14-13717G/M00B4400241); and by Sygekassernes Helsefond (Health Insurance Foundation) by grant 9700093 from the Danish Research Council. NIMH, MD HMH, and the Danish Research Council had no further role in study design; in the
Contributors
Dr. Schiffman oversaw the study design, data analysis, data interpretation, write-up, and manuscript preparation. Ms. Rakhshan contributed to data analysis, data interpretation, write-up, and manuscript preparation. Dr. Pitts contributed to the data analysis, data interpretation, and write-up. Drs. Sorensen, Mortensen, and Michelsen contributed to data-analysis consultation and write-up, and Dr. Sorensen also contributed to data collection. Drs. DeVylder and Mittal contributed to manuscript
Conflict of interest
The authors do not have any actual or potential conflicts of interest to report.
Acknowledgements
This manuscript is dedicated to the memory of Sarnoff A. Mednick, a mentor of the highest quality, and a true visionary in this, and other, fields.
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