SCHRES-06706; No of Pages 3
Schizophrenia Research xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Schizophrenia Research
journal homepage: www.elsevier.com/locate/schres
Letter to the Editor
Aerobic exercise for cognitive deficits in
schizophrenia — The impact of frequency,
duration, and fidelity with target
training intensity
Individuals with schizophrenia display substantial deficits in cognitive
functioning (Green et al., 2004) for which available treatments offer only
limited benefits. Recent reports have indicated that aerobic exercise (AE)
leads to improvements in both aerobic fitness (AF; Vancampfort et al.,
2015; Armstrong et al., submitted for publication) and cognitive function-
ing among individual with schizophrenia (Kimhy et al., 2015; Kimhy
et al., 2014). A recent review of trials examining exercise interventions
in people with schizophrenia have suggested that clinical benefits from
such trials are related to the dose of exercise, with interventions
employing at least 90 min of moderate-to-vigorous exercise per week re-
sult in clinical improvements (i.e., Firth et al., 2015). However, the specific
AE training characteristics that contribute to cognitive improvements re-
main largely unknown.
To address this issue, we examined the impact of frequency, dura-
tion, and fidelity with target training intensity on changes in cognition
in 13 individuals with schizophrenia (average age = 36.31, SD =
11.16; 38% female) who completed an AE training program as part of
a single-blind randomized clinical trial examining the impact of AE on
cognition (Kimhy et al., 2015). Detailed descriptions of the trial and
the AE procedures have been published elsewhere (Kimhy et al.,
2015; Kimhy et al., in press). Briefly, the AE program was informed by
the American College of Sports Medicine and federal guidelines for the
frequency, intensity, time, and type of AE (US Department of Health
and Human Services, 2008). The program involved three one-hour AE
sessions/week over 12 weeks. The sessions opened with a 10-min
warm-up period, after which participants exercised individually for
45 min, ending with a 5-min cool-down period. A trainer was present
during the AE sessions for guidance and support, along with a research
assistant who collected behavioral data.
Changes in cognitive functioning from baseline to 12 weeks were
indexed by changes in the composite scores of the MATRICS Consensus
Cognitive Battery. Additionally, at baseline participants completed a
cardiopulmonary exercise test (CPET) to determine their AF (VO2
peak; ml/kg/min) and maximal heart rate (HRmax). The latter was
used to determine the in-session target AE training intensity for each
participant. Targets were set to 60% of HRmax in week 1, 65% in week
2, 70% in week 3, and 75% in weeks 4–12. The AE intensity was indexed
by the in-session heart rate recorded using Polar RS400 heart rate mon-
itors (Polar Electro Inc., Lake Success, NY) worn by participants during
sessions. The monitors were programmed to emit a soft beep if a
participant's heart rate fell below the individually-targeted AE intensity
level for a particular week of training. On such occasions, the trainer en-
couraged the participant to achieve their target goal. Following the com-
pletion of the 12-week training program, all participants completed a
second CPET to determine changes in AF.
http://dx.doi.org/10.1016/j.schres.2016.01.055
0920-9964/© 2015 Elsevier B.V. All rights reserved.
Please cite this article as: Kimhy, D., et al., Aerobic exercise for cognitive deficits in schizophrenia — The impact of frequency, duration, and fidelity
with target training intensity, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2016.01.055
The frequency of AE was indexed by the number of sessions
attended by each participant over the 12-week program. Duration of
AE was indexed by the time individuals spent exercising using the var-
ious exercise equipment. Fidelity with target training intensity was cal-
culated using Area Under the Curve (AUC) analysis based on HR
sampled once per second during the AE training sessions. The AUC
was computed as the average volume within 5 heartbeats-per-minute
range (± 5 heartbeats) of the assigned weekly individual target HR,
over the 12-week training program (Lauriola et al., 2015).
Over the 12-week program, the participants attended on average
28.5 (SD = 2.4) of the 36 scheduled AE sessions (79%; 2.4 sessions
per week), exercising for an average of 42.7 min per session (SD =
3.51). On average, the participants increased their AF by 18% (M =
3.82 ml/kg/min, SD = 3.21), with increases in AF significantly corre-
lating with changes in cognition (r = .54, P b .01; Kimhy et al., 2015).
Examination of the training characteristics indicated frequency and
duration of AE training were not associated with changes in cognition
(r = .36, p = .21 and r = .17, p = .62, respectively) or AF (r = .24,
p = .48 and r = .43, p = .18, respectively), controlling for depression
and antipsychotic medications (indexed by chlorpromazine equivalence).
However, fidelity with target training intensity was significantly correlat-
ed with improvement in cognitive functioning, controlling for depression
and antipsychotic medications (r = .70, p = .017; n = 13; See Fig. 1).
The results highlight the importance of fidelity with target training
intensity in determining cognitive outcomes from AE interventions.
Specifically, our findings point to the importance of including sufficient-
ly high training intensity targets as part of AE interventions targeting
cognition, as well as incorporating monitoring procedures to evaluate
in-session adherence to such targets. Such information may allow for
more direct comparisons of studies and inform decisions regarding de-
sign and dissemination of AE interventions. Additionally, tracking AE in-
tensity may also have relevance to dropout rates (Vancampfort et al., in
press).
Given the relatively small sample, our results should be considered
preliminary until replicated in larger samples. However, our findings
suggest that among individuals with schizophrenia attending AE, cogni-
tive improvements are associated with a the intensity of training.
Contributors
Dr. Kimhy initiated the manuscript, conducted the data analyses, and wrote the first
draft of the manuscript. Mr. Lauriola conducted the analyses of the heart rate data. Dr.
Bartels and Ms. Armstrong conducted the aerobic fitness assessments and determined
the target exercise intensity for study participants. Dr. Vakhrusheva conducted the cogni-
tive assessments. Dr. Ballon served as a medical director of the study and assisted with
monitoring the participants' health. Dr. Sloan contributed to the design of the study and
consulted regarding its execution. All authors contributed to and approved the final ver-
sion of the manuscript.
Conflict of interest
Dr. Ballon has received investigator-initiated research funding from Novartis relating
to another project. None of the other authors had any conflict of interest relating to this
project.
2 Letter to the Editor

Fig. 1. Association of fidelity with target training intensity and changes in Cognitive functioning in individuals with schizophrenia n = 13; Change in Cognitive Functioning — indexed by
change from baseline to 12 weeks in MATRICS Consensus Cognitive Battery composite score; Fidelity with Aerobic Exercise Training Target Intensity — indexed by Area Under the Curve
(AUC) analysis computed as the average volume within 5 heartbeats-per-minute (±5 heartbeats) of the assigned target heart-rate over the 12-week training program (controlling for
depression and antipsychotic medications).

Acknowledgment Vancampfort, D., Rosenbaum, S., Schuch, F.B., Ward, P.B., Probst, M., Stubbs, B., 2016. Prev-
This work was supported by grant 1R21MH096132 from the National Institute of alence and predictors of treatment dropout from physical activity interventions in
Mental Health, Bethesda, MD to Dr. Kimhy. schizophrenia: a meta-analysis. Gen. Hosp. Psychiatry http://dx.doi.org/10.1016/j.
genhosppsych.2015.11.008 (In Press).

References
David Kimhy
Armstrong, H.F., Bartels, M.N., Paslavski, O., Cain, D., Shoval, H.A., Ballon, J.S., Department of Psychiatry, Columbia University, New York, NY, United
Sloan, R.P., Kimhy, D., 2016. The Impact of Aerobic Exercise Training on Car- States
diopulmonary Functioning in Individuals with Schizophrenia (submitted for
New York State Psychiatric Institute, New York, NY, United States
publication).
Firth, J., Cotter, J., Elliott, R., French, P., Yung, A.R., 2015. A systematic review and meta- Corresponding author at: Department of Psychiatry, Box #55, Columbia
analysis of exercise interventions in schizophrenia patients. Psychol. Med. 45, University, 1051 Riverside Drive, New York, NY 10032, United States.
1343–1361.
E-mail address: kimhyda@nyspi.columbia.edu.
Green, M.F., Nuechterlein, K.H., Gold, J.M., Barch, D.M., Cohen, J., Essock, S., Fenton,
W.S., Frese, F., Goldberg, T.E., Heaton, R.K., Keefe, R.S., Kern, R.S., Kraemer, H.,
Stover, E., Weinberger, D.R., Zalcman, S., Marder, S.R., 2004. Approaching a con- Vincenzo Lauriola
sensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS Department of Psychiatry, Columbia University, New York, NY, United
conference to select cognitive domains and test criteria. Biol. Psychiatry 56,
301–307. States
Kimhy, D., Vakhrusheva, J., Bartels, M.N., Armstrong, H.F., Ballon, J.S., Khan, S., Chang, R.W.,
Hansen, M.C., Ayanruoh, L., Smith, E.E., Sloan, R.P., 2014. Aerobic fitness and body Matthew N. Bartels
mass index in individuals with schizophrenia: implications for neurocognition and
daily functioning. Psychiatry Res. 220, 784–791. Department of Rehabilitation Medicine, Albert Einstein College of Medicine,
Kimhy, D., Vakhrusheva, J., Bartels, M.N., Armstrong, H.F., Ballon, J.S., Khan, S., Chang, R.W., Bronx, NY, United States
Hansen, M.C., Ayanruoh, L., Lister, A., Castren, E., Smith, E.E., Sloan, R.P., 2015. The im-
pact of aerobic exercise on brain-derived neurotrophic factor and neurocognition in
individuals with schizophrenia: a single-blind, randomized clinical trial. Schizophr.
Hilary F. Armstrong
Bull. 41, 859–868. Department of Rehabilitation & Regenerative Medicine, Columbia
Kimhy, D., Khan, S., Ayanrouh, L., Chang, R.W., Hansen, M.C., Lister, A., Ballon, J.S., University, New York, NY, United States
Vakhrusheva, J., Armstrong, H.F., Bartels, M.N., Sloan, R.P., 2016. Use of active-play
video games to enhance aerobic fitness in schizophrenia: feasibility, safety, and ad-
herence. Psychiatr. Serv. http://dx.doi.org/10.1176/appi.ps.201400523 (in press). Julia Vakhrusheva
Lauriola, V., MCKinley, P.S., McIntyre, K.M., Choo, T.J., Choi, J.C., Lee, S., Sloan, R.P., 2015. Department of Psychiatry, Weill Cornell Medical College, New York, NY,
Health benefits of exercise: is performance what really matters? 2015. Med. & Exer.
United States
Spor. & Sci. 47 (5S), 378.
US Department of Health and Human Services, 2008. physical activity guidelines for
Americans. (2008. http://www.health.gov/PAGuidelines. Accessed January 15, Jacob S. Ballon
2015). Department of Psychiatry and Behavioral Sciences, Stanford University,
Vancampfort, D., Rosenbaum, S., Ward, P.B., Stubbs, B., 2015. Exercise improves cardiore-
spiratory fitness in people with schizophrenia: a systematic review and meta- Stanford, CA, United States
analysis. Schizophr. Res. 169, 453–457.

Please cite this article as: Kimhy, D., et al., Aerobic exercise for cognitive deficits in schizophrenia — The impact of frequency, duration, and fidelity
with target training intensity, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2016.01.055
 Letter to the Editor 3

Richard P. Sloan
Department of Psychiatry, Columbia University, New York, NY, United
States
New York State Psychiatric Institute, New York, NY, United States

23 December 2015
Available online xxxx

Please cite this article as: Kimhy, D., et al., Aerobic exercise for cognitive deficits in schizophrenia — The impact of frequency, duration, and fidelity
with target training intensity, Schizophr. Res. (2015), http://dx.doi.org/10.1016/j.schres.2016.01.055