SCHRES-07069; No of Pages 2
Schizophrenia Research xxx (2016) xxx–xxx
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Schizophrenia Research
journal homepage: www.elsevier.com/locate/schres
Letter to the Editor
Yoga reduces the brain's amplitude of low-frequency fluctuations in
patients with early psychosis results of a randomized controlled trial
We present the functional MRI study from a randomized clinical trial
(RCT) investigating the effects of yoga and aerobic exercise on neuro-
cognition in female patients with early psychosis. Local spontaneous
neuronal fluctuations at rest, measured by the amplitude of low-fre-
quency fluctuations (ALFF) (Zou et al., 2008), showed alterations in
both cortical and subcortical regions in schizophrenia (Hoptman et al.,
2010). Studies in experienced meditators have suggested that medita-
tion may change brain morphology and function, particularly in areas
related to attention (Hölzel et al., 2011; Jang et al., 2011). Yoga is a
mind-body exercise with a distinctive meditative component, and is
particularly popular with women in Asian. Based on previous studies,
we initiated a RCT to examine the different effects of yoga and aerobic
exercise on neuro-cognition in early psychosis.
A total of 124 female patients diagnosed with schizophrenia spec-
trum within five years of onset completed the study. They were ran-
domized into three groups: an integrated yoga therapy group, an
aerobic exercise group, and a wait-list control group. Details of patients
recruitment and demographics were published recently (Lin et al.,
2015). Fifty-eight patients' functional MRI data (n = 23 in the yoga
group, n = 23 in the aerobic exercise group, and n = 12 in the wait-
list control group) were included in the final analyses. Both intervention
programs were held three times weekly for 12 weeks, and each session
lasted approximately 1 h. Details of all the measurements and interven-
tion programs were described in the supplementary information sheets.
Repeated-measure ANOVA and post-hoc analyses showed de-
creased ALFF in precuneus in yoga group compared to control
(p b 0.001) and aerobic exercise groups (p b 0.001) (Fig. 1); and in-
creased ALFF in visual cortex (p = 0.0018) in the wait-list control
group. All the results remained statistically significant controlling age,
education years, length of illness, and antipsychotic dose. In yoga
group, the ALFF changes in the precuneus were significantly correlated
with the changes of PANSS negative scores (r = 0.5906, p = 0.003), es-
pecially with blunted affect subscores (r = 0.551, p = 0.012).
To our knowledge, this is the first study investigating the effects of
yoga and aerobic exercise on brain functional fluctuation in early psycho-
sis. We found yoga-related ALFF changes in the precuneus, which was
positively correlated with the changes of PANSS blunted affect subscores.
Some fMRI studies have shown that experienced meditators generated
reduced neural response in regions of the default network (Pagnoni et
al., 2008), and had weaker functional connectivity between the
precuneus and inferior parietal lobule (Taylor et al., 2012). Our result of
reduced ALFF in left precuneus is in line with these findings. The
precuneus plays a pivotal role in the intrinsic activity and self-conscious-
ness during rest (Fransson and Marrelec, 2008). Reduced ALFF in left
precuneus in yoga group may indicate the potential benefit of yoga for at-
tention and self-disturbance of patients with psychosis. The correlations
between the decreased ALFF and decreased blunted affect subscores
http://dx.doi.org/10.1016/j.schres.2016.11.040
0920-9964/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Lin, J., et al., Yoga reduces the brain's amplitude of low-frequency fluctuations in patients with early psychosis results of a
randomized controlled trial, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.11.040
suggested that the neuronal fluctuations at rest in precuneus may speak
to the negative symptom severity. The increased ALFF in the visual cortex
in wait-list control group may indicate the progressing diseased-related
neuronal abnormalities in psychosis, which was consistent with the ab-
normal hyperactivity in the occipital cortex in schizophrenia reported
by Ingvar and Franzen (1974). The absence of effect of aerobic exercise
group may be due to the different mechanisms between yoga and aerobic
exercise. The mindfulness component and mind-body connection of yoga
can be a possible explanation.
The sample size actually analyzed in the wait-list control group
(n = 12) were relatively small due to the dropouts of the follow-up
MRI visits and the strict controlling for head motion during the anal-
ysis. Therefore, the results of our study should be interpreted with a
degree of caution. The neuronal activity patterns may be better con-
firmed with a larger sample. These findings should be cautiously
generalized into all participants, because only female patients were
recruited.
These findings provide possible neurobiological basis underlying the
effects of yoga, and shed light on the application of yoga in clinical prac-
tice as a safe and convenient add-on treatment for psychosis.
Contributors
All authors contributed to study design, result interpretation and writing. Drs. Lin and
Geng contributed equally. Drs Lin, Lee, Chan and Chang contributed to recruitment and
data collection. Drs Lin, and Tse contributed to interventions. Drs Lin and Geng contributed
to data analysis.
Conflicts of interest
Prof Chen sat on a scientific advisory board for Otsuka, received educational grant sup-
port from Janssen-Cilag, and research funding from AstraZeneca, Janssen-Cilag, Pfizer, Eli
Lilly, Sanofi-Aventis, and Otsuka. Prof Honer received consulting fees or participated in
paid advisory boards for In Silico Biosciences, Lundbeck/Otsuka, Eli Lilly and Roche. Dr
Lee sat on a scientific advisory board for AstraZeneca and Eli Lilly. All other authors declare
that they do not have any conflicts of interest. Other authors have no conflicts of interest.
Acknowledgments
This study was supported by the Small Research Funding of the University of Hong
Kong (201007176229), and General Research Funding (C00240/762412) by the Authority
of Research, Hong Kong. The funding agencies had no role in the design and conduct of the
study; collection, management, analysis, or interpretation of the data; preparation, review,
or approval of the manuscript; and decision to submit the manuscript for publication. We
appreciate all the clinical clusters and research assistants who were involved in this study.
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.schres.2016.11.040.
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2 Letter to the Editor

Fig. 1. Significant main effect of interventions on the longitudinal changes of ALFF (a), and results of post hoc analyses (b). (a) Top row showed a cluster of visual cortex and bottom showed
a cluster of left precuneus. Results are corrected after FWE correction with uncorrected p b 0.005 and cluster size N48 voxels. Regions are colored by F statistics. (b) Top scatter plot shows
results of post hoc analyses in the cluster of visual cortex: significant within-subject difference in waitlist control group (paired t-test between baseline and follow-up), significant
differences (follow-up minus baseline ALFF) between yoga and aerobic exercise groups, and between yoga and control groups. Bottom scatter plot shows results of post hoc analyses
in the precuneus cluster: significant within-subject difference in yoga group, significant differences in the ALFF changes between yoga and aerobic exercise groups, and between yoga
and control groups. All post-hoc results reported were corrected for multiple comparison corrections.

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Jingxia Lin1 PL Khong

Department of Psychiatry, University of Hong Kong, Hong Kong Department of Diagnostic Radiology, University of Hong Kong, Hong Kong

William G Honer
Xiujuan Geng1
Department of Psychiatry, University of British Columbia, Vancouver,
Laboratory of Neuropsychology and Laboratory of Social Cognitive Affective
Canada
Neuroscience, Department of Psychology, University of Hong Kong, Hong
Kong
Eric YH Chen
The State Key Laboratory of brain and Cognitive Sciences, University of
Department of Psychiatry, University of Hong Kong, Hong Kong
Hong Kong, Hong Kong
The State Key Laboratory of brain and Cognitive Sciences, University of
Hong Kong, Hong Kong
Edwin HM Lee
Department of Psychiatry, University of Hong Kong, Hong Kong 7 June 2016
Corresponding author at: Department of Psychiatry, University of Hong Available online xxxx
Kong, 2/F, New Clinical Building, Queen Mary Hospital, 102 Pokfulam
Road, Hong Kong.
E-mail address: Edwinlhm@hku.hk.

1
These authors contribute equally.

Please cite this article as: Lin, J., et al., Yoga reduces the brain's amplitude of low-frequency fluctuations in patients with early psychosis results of a
randomized controlled trial, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.11.040