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. Author manuscript; available in PMC: 2016 Mar 1.
Published in final edited form as: Schizophr Res. 2015 Jan 16;162(0):86–89. doi: 10.1016/j.schres.2014.12.039

Increased Postural Sway Predicts Negative Symptom Progression in Youth at Ultrahigh Risk for Psychosis

Derek J Dean a,b,*, Jerillyn S Kent c,d, Jessica A Bernard a, Joseph M Orr e, Tina Gupta a, Andrea Pelletier-Baldelli a,b, Emily E Carol a, Vijay A Mittal a,b
PMCID: PMC4339540  NIHMSID: NIHMS653640  PMID: 25601361

Abstract

Impaired ability to maintain an upright posture may reflect impairment in the cerebellum, a critical structure for the fluid coordination of neural information, thought to be disrupted in psychosis. The current study utilized an instrumental measure of posture in individuals at ultrahigh risk (UHR) for psychosis (n=43) and healthy controls (n=44). Positive and negative symptoms were assessed twice over 12-months. Results showed that increased postural sway in the UHR group predicted changes in negative symptoms. This study provides an important prospective view on the relationship between cerebellar-sensitive behavior and integral symptoms, which until now has received limited biomarker research.

Keywords: Postural sway, ultrahigh risk, cognitive dysmetria, psychosis, cerebellum

1. Introduction

A cognitive dysmetria theory of psychosis (Andreasen et al., 1998), which notes impairments in cortico-cerebellar networks, may explain, in part, the heterogeneous symptoms seen in psychosis (Andreasen and Pierson, 2008; Picard et al., 2008). Consistent with this theory, patients with schizophrenia show increased postural sway (Bernard and Mittal, 2014; Kent et al., 2012; Marvel et al., 2004), thought to largely reflect cerebellar abnormalities. While previous cross sectional research suggests that postural sway is impaired in youth at ultrahigh risk (UHR) for psychosis (Bernard et al., 2014), the potential relationship between postural dysfunction and the progression of attenuated negative and positive symptoms in UHR individuals is currently unknown.

Recent work suggests that impairment in posture may be linked to the pathophysiology of negative symptoms in schizophrenia (Docx et al., 2014). Examining behavioral markers of aberrant neurodevelopment tied to the progression of negative symptoms prior to psychosis may be helpful in understanding etiological conceptions and guide intervention efforts for symptoms that are not traditional targets of treatment (Pelletier and Mittal, 2013). In this study, participants diagnosed with an UHR syndrome, defined by moderate to severe but not psychotic levels of positive symptoms and/or a decline in global functioning accompanying the presence of schizotypal personality disorder and/or a family history of schizophrenia (Miller et al., 1999), as well as healthy controls underwent an instrumental test of postural sway and clinical assessments of negative and positive prodromal symptoms. Diagnostic status was followed for 12-months. We hypothesized that increased postural sway area (i.e. poorer postural control) would be specifically associated with elevated negative and not positive UHR symptoms, and that increased sway area at baseline would predict more severe negative symptoms after 12 months in the UHR group.

2. Materials and Methods

2.1. Participants

A total of 87 adolescent UHR and healthy control participants were recruited to the University of Colorado Boulder’s Adolescent Development and Preventive Treatment (ADAPT) research program (see Table 1). Exclusion criteria consisted of head injury, the presence of a neurological disorder, lifetime alcohol or substance dependence, and lifetime history of an Axis I psychotic disorder. The presence of a psychotic disorder in a 1st degree relative was an exclusion criterion for controls. There were 7 UHR participants who reported taking antipsychotic medication at baseline (n=4) and at follow-up (n=3). The protocol and informed consent procedures were approved by the University of Colorado Boulder Institutional Review Board.

Table 1.

Demographic characteristics and results of postural sway analysis for baseline and follow-up assessments.

Baseline Follow-Up
UHR Control Total p≤ UHR Control Total p≤
Age
 Mean (SD) 18.49 (1.86) 17.98 (2.63) 18.23 (2.29) NS 19.43 (1.95) 19.09 (2.93) 19.27 (2.45) NS
Gender
 Male 24 23 47 14 7 17
 Female 19 21 40 9 15 23
 Total 43 44 87 NS 23 22 45 NS
Education (years)
 Mean (SD) 12.41 (1.94) 12.06 (2.45) 12.23 (2.21) NS 12.57 (1.72) 11.82 (2.50) 12.20 (2.15) NS
Parent Education
 Mean (SD) 15.96 (2.00) 15.72 (2.84) 15.84 (2.45) NS 16.33 (2.09) 15.93 (2.37) 16.13 (2.21) NS
Positive Symptoms
 Mean (SD) 12.12 (3.99) .43 (1.17) 6.14 (6.55) .001 9.43 (6.96) .23 (.61) 4.93 (6.79) .001
Negative Symptoms
 Mean (SD) 10.44 (.38) .38 (.81) 5.36 (6.95) .001 7.43 (.38) .82 (1.82) 4.20 (5.92) .001
BMI
 Mean (SD) 21.65 (3.44) 23.25 (4.97) 22.43 (4.30) NS - - - -
Postural Sway
 Mean (SD) 42.16 (49.77) 27.49 (19.83) 34.74 (38.22) .05 - - - -
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NS indicates not significant.

The ADAPT study is ongoing, and to date, 12 months have passed for 67 individuals who have completed a baseline assessment. Each of these individuals was invited back, and 45 participants agreed to return to complete clinical interviews. There were no baseline differences in age, gender, education or parent education between those who did and did not return for follow-up. A subset of the current participants in this study also took part in a previous study examining cortico-cerebellar functional connectivity and postural sway (Bernard et al., 2014). This study focused on the neural correlates of postural dysfunction and did not include a longitudinal component.

2.2. Clinical Interviews

The Structured Interview for Prodromal Syndromes (SIPS) (McGlashan et al., 2010) was administered to diagnose an UHR syndrome and track negative and positive symptom progression over time for the subgroup who returned for the 12-month clinical assessment. A total sum score for each domain is used as an indicator of the respective dimensions of symptomatology. The Structured Clinical Interview for Axis-I DSM-IV Disorders (First et al., 1995) was administered to rule out a psychotic disorder diagnosis at baseline. Interviews were conducted by trained advanced doctoral students, and inter-rater reliabilities exceeded the minimum study criterion of Kappa≥.80.

2.3. Postural Sway Area

Postural sway was assessed using an Advanced Mechanical Technology Incorporated Accusway force platform (Watertown, MA). Participants stood still while keeping their arms by their sides, their feet shoulder width apart, and their eyes focused on a fixed point on the wall directly across from them. Height and weight was recorded for calculations of participant’s body mass index (BMI), which was used to assess group differences in body composition, and by proxy, physical fitness. The center of pressure (COP) was recorded for two minutes with a sample rate of 50 Hz. To isolate the low-frequency postural sway process in the recorded data, we applied a 9th order Butterworth filter with a 20 Hz cutoff frequency. COP and the 95% confidence interval of COP area were measured using principle component analysis (Oliveira et al., 1996).

2.4. Data Analysis

Independent t-tests and chi-square tests were employed to examine group differences in continuous and categorical demographic variables, respectively. Based on previous work suggesting that UHR and schizophrenia patients show increased postural sway (Bernard et al., 2014), and studies linking cerebellar or posture dysfunction to negative symptoms (Mittal et al., 2014; Morrens et al., 2014) one-tailed independent t-tests were used to assess group differences in postural sway and one-tailed bivariate correlations were used to examine predicted relationships between larger sway area and increased negative symptoms within the UHR group. A series of 2 hierarchical regression analyses were conducted within the UHR group alone. Negative and positive symptoms at the follow-up assessment were used as the dependent variables. The respective symptom variable for the baseline assessment was entered in the first block (i.e., time 1 negative and positive symptom total). In the second block, COP area was entered as the predictor variable. With each analysis, the magnitude of R2 change (ΔR2) was tested for significance. This analytic approach tests the hypotheses that, while controlling for the variance explained by symptoms at baseline, increased COP area will predict significant changes in respective symptoms 12 months later.

3. Results

3.1. Participants

There were no significant differences between groups on demographic characteristics at baseline assessments including age t(77.32)=1.05, education t(85)=.74, gender χ2(1, N=87)=.11, parental education t(85)=.47 or BMI t(69.02)=-1.70 and at follow-up including age t(43)=1.03, education t(43)=1.71, gender χ2(1, N=45)=3.81, or parental education t(43)=.59. UHR participants were rated significantly higher than controls on both SIPS symptom domains at baseline and follow-up (see Table 1).

3.2. Postural Sway and Symptoms at Baseline

The UHR group exhibited a significantly larger postural sway area than healthy controls t(54.75)=1.80, p≤.05. Within the UHR group, increased COP area was significantly related to more severe negative r(41)=.43, p≤.01 symptoms and was related to more severe positive symptoms at trend level r(41)=.27, p=.08.

3.3. Postural Sway and Progression of Symptoms

Regression analyses were conducted within the UHR group only because the control group reported a limited range in symptoms. COP area accounted for 11% of the variance for negative symptoms one year later, indicating that a larger sway area was associated with an increase in symptoms (β=.38, p≤.05). Greater COP area did not predict changes in positive symptoms (p≥.5).

4. Discussion

The findings of the current study add to the growing body of literature suggesting that impaired behavior related to cerebellar function may be related to core features of psychosis (Bernard et al., 2014; Bernard and Mittal, 2014; Dean et al., 2014; Forsyth et al., 2012; Mittal et al., 2014). Furthermore, the present results represent the first evidence to suggest that impaired posture may also be specifically related to the longitudinal course of negative symptoms in UHR individuals. This is consistent with the cognitive dysmetria theory of psychosis that suggests that impairment in cerebellar networks may contribute to symptom and motor impairment (Andreasen et al., 1998; Andreasen and Pierson, 2008).

The current findings bolster recent work suggesting that a range of movement abnormalities, including postural instability, psychomotor slowing, Parkinsonism, and catatonia may hold predictive value for negative symptoms in psychosis (Docx et al., 2012; Morrens et al., 2014). Indeed, relevant research in UHR and first episode psychosis patients also shows that motor function associated with neurologic soft sign exams and spontaneous Parkinsonisms predict cognitive impairment and worsening negative symptoms (Cuesta et al., 2014; Dean and Mittal, 2014; Mittal et al., 2014). In contrast to the current results, hyperkinetic movements (e.g., dyskinesias) appear to be more closely linked to aberrant dopaminergic processes and predict exacerbation of positive symptoms (Callaway et al., 2014; Mittal et al., 2010; Mittal et al., 2008; Mittal et al., 2007).

The current postural sway analysis benefits from using an instrumental measure, which has been shown to offer a reliable and more sensitive measure of movement abnormalities in psychosis than tradition observer based methods (Docx et al., 2012). The present sample included several UHR participants taking antipsychotic medication, and while exclusion of these participants did not change the direction or magnitude of the findings, future work should seek to examine postural sway in neuroleptic free UHR participants. Previous research has shown that postural sway area increases with decreased visual input and closer feet placement (Kent et al., 2012; Marvel et al., 2004). While it may be helpful for future work to examine interactions of symptom changes and postural sway conditions, the current study showed that impairment in a basic condition could give a robust picture of impaired postural stability.

Table 2.

Linear regression results. Separate linear regression was used to evaluate if postural sway area at baseline predicted worsening negative and positive symptoms in the UHR group alone. Symptom totals at follow-up were entered as the predicted variable. Baseline symptom totals were entered in the first block and center of pressure (COP) area was entered in the second block.

Block I- Baseline Symptoms Block II- Postural Sway Area
R2 df F β P ΔR2 df F β P
Negative Symptoms .34 1, 21 10.73 .58 .004 .11 1, 20 4.01 .38* .03
Positive Symptoms .39 1, 21 13.53 .63 .001 .006 1, 20 .20 .08 .66
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*

indicates p ≤ .05.

Acknowledgments

Role of the Funding Source

This work was supported by National Institutes of Health Grants R01MH094650 and R21/R33MH103231 to V.A.M. J.A.B. is currently supported by F32MH102989-01. J.M.O. is supported by F32DA034412-01A1. A.P.B is supported by F31MH100821-01A1.

Footnotes

Conflict of Interest

None.

Contributors

Authors D.J.D, J.S.K, J.A.B, and V.A.M developed the study concept. V.A.M. obtained funding for the study. All authors contributed to the study design. Testing and data collection were performed by D.J.D, J.A.B, J.M.O., A.L.P., T.G., and E.E.C. D.J.D performed the data analysis and interpretation under the supervision of V.A.M. D.J.D drafted the paper, and J.S.K, J.A.B, J.M.O, A.L.P, T.G, E.E.C, and V.A.M provided the critical revisions. All authors approved the final version of the paper for submission.

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