poststroke depression ( psd ) is regarded as one the most common mental sequela of stroke 
 patients1 .
psd patients have low 
 physical and cognitive function , and low self - worth compared to those with no 
 depression2 , and they have a decreased 
 quality of life3 .
all these factors can 
 have adverse effects on the functional and mental recovery of stroke patients4 .
for this reason , various drugs are used to 
 treat psd , such as tricyclic antidepressant , monoamine oxidase inhibitors , and selective 
 serotonin reuptake inhibitors ( ssris ) . however ,
various adverse reactions to these drugs 
 have been reported , including insomnia , hyposexuality , nausea , and weight gain5 , 6 .
exercise can relieve the symptoms of depression without the adverse reactions associated 
 with drugs , by increasing the levels of chemicals related to depression , serotonin , 
 dopamine , and norepinephrine , in the hippocampus7,8,9 .
in particular , it has been shown that group exercise is more 
 effective than exercising alone10 . in 
 this respect ,
the popularity of circuit class training ( cct ) , which involves task - oriented 
 exercise in groups , is growing .
cct has been reported to have many benefits , such as 
 improving the mobility of stroke patients and shows better cost efficiency than other 
 therapies11 , 12 .
most studies of cct , however , have focused on the improvement of 
 balance , walking ability , or upper extremity functions , and few studies have investigated 
 the potential effects of group cct on depression .
accordingly , this study was conducted to 
 investigate the potential effects of cct on depression through changes in branched - chain 
 amino acids ( bcaas ) ( isoleucine , leucine , and valine ) and free - tryptophan ( f - trp ) .
the study subjects were stroke patients who were diagnosed with major depressive disorder 
 and dysthymic disorder according to dsm - iv13 guidelines following hospitalization and treatment at d hospital in 
 busan .
the degree of depression symptoms was measured with the beck depression inventory 
 ( bdi ) , which is the most widely used self - report measure of depression .
forty subjects who 
 had moderate depression , defined as a bdi score between 19 and 29 , were selected for 
 inclusion in this study14 .
additional 
 selection criteria were : absence of cognitive problems such as dementia , aphasia , or 
 dysarthria ; a score of 23 or higher on the mini - mental state examination ; absence of other 
 mental problems except depression ; absense of acute musculoskeletal problems ; and an ability 
 to walk 10  m with no physical help .
furthermore , those who had taken or were taking 
 antidepressants such as ssris prior to the onset of stroke were excluded .
the subjects were group - matched into an 
 experimental group and a control group according to sex , age , height , and weight .
the 
 experimental cct group performed gradual task - oriented cct ( 80  min per session ) and received 
 30  min of general physical therapy .
the control group performed stretching exercises and 
 weight - bearing exercises ( 80  min per session)15 .
the cct was 
 performed three times per week for eight weeks ( 24 sessions ) .
the total cct consisted of four steps : warming up ( 5  min ) , circuit 
 training ( 60  min ) , evaluation and a short break ( 10  min ) , and a group game ( 15  min ) .
the 
 control group also performed warming up for 5  min before exercise and cooling down for 
 10  min after the exercise .
two physical therapists received one day of training before this 
 program , and data on the participants attendance and adverse events ( such as falls and 
 heart problems ) were collected during the experiment16 .
preliminary training for the whole program was performed one day 
 before the start of the intervention .
bdi scores were measured before the start of the 
 experiment and again after eight weeks , at the end of the experiment .
blood sampling was performed as follows : a catheter was installed in the forearm vein of the subjects , and 5  ml was collected 
 immediately before the exercise ( 9:10 am ) and immediately after the exercise ( 10:30 am ) at 
 d1 ( the start ) , d6 ( two weeks ) , d12 ( four weeks ) , d18 ( six weeks ) , and d24 ( eight weeks ) . 

the blood samples were centrifuged ( 3,000  rpm  15  min ) and stored in a refrigerator ( 82c ) 
 until they were analyzed .
the f - trp , ( i.e. , not combined with albumin ) was separated from 
 the plasma using a modified version of the method of bloxam and hutson et al17 . to analyze the bcaas and f - trp , the amino acids were sampled with an acetonitrile / methanol 
 solution and diluted to another concentration by an internal standard ( norleucine and 
 d5-trp ; cambridge isotope laboratories , andover , ma ) .
the plasma concentration was then 
 analyzed by high performance liquid chromatography ( pharmacia , usa ) .
changing trends over 
 time in each group were examined using a two - way repeated measures anova .
the paired 
 t - test was used to examine intragroup variations over time , and the 
 independent t - test was used to examine intergroup variations .
the statistical significance 
 level was used 5% ( significance was accepted for values of p < 0.05 ) .
all the patients gave their written consent after receiving an explanation about the 
 experiment and had been cautioned about potential adverse effects of this experiment .
the 
 experiment was approved by the human subject s research ethics committee of the catholic 
 university of pusan ( cupirb-2013 - 019 ) .
the independent t - test for the intergroup comparison of general characteristics did not 
 show any significant differences ( table 
 1table 1 .
general characteristics of the subjects ( n=40)groupcct ( n=20)con ( n=20)sexmen 7 ( 35% ) : women 13 ( 65%)men 7 ( 35% ) : women 13 ( 65%)age57.210.858.79.7height ( cm)163.097.1165.45.2weight ( kg)66.4011.968.15.9bmi ( kg / m)24.025.725.04.2paretic sidert 11 ( 55% ) : lt 9 ( 45%)rt 12 ( 60% ) : lt 8 ( 40%)typeinfarction 14 ( 70% ) : hemorrhage 6 ( 30%)infarction 11 ( 55% ) : hemorrhage 9 ( 45%)duration ( mon)8.41.97.92.6 ) . the changes in f - trp , bcaas , and f - trp / bcaas ratios in the blood after the 
 performance of the cct or the extension / weight movement exercise for 80  min by each group 
 are shown in table 2table 2 .
responses of blood chemicals to circuit exercise test over timed1d6d12d18d24f - trp ( mol / l)precct54.52.4654.832.6254.212.2254.672.8954.061.89con53.992.8254.622.5554.992.3755.092.0755.892.03postcct60.162.2860.792.6762.663.0764.503.1965.503.29con54.461.9554.242.2754.511.7454.761.8254.371.55bcaas ( mol.l-1)precct540.8028.22538.6025.43533.3718.14534.4811.89535.3013.37con535.8119.45539.0112.49540.9812.96539.6912.26540.6811.84postcct496.5313.71488.7511.88478.1811.39471.7812.37470.5114.00con533.818.71533.8610.97538.2112.41536.3714.48539.4311.78trp / bcaas ( 102)precct1.000.061.020.071.010.051.020.061.010.04con1.000.061.010.051.010.051.020.051.010.05postcct1.210.061.240.061.310.071.370.081.390.09con1.020.031.010.041.010.041.020.041.000.03(mean sd ) different superscripts within the same rows represent 
 significant differences .
( p<0.05 ) , d1 : the first day of circuit exercise ) , d6 ( two 
 weeks of circuit exercise ) , d12 ( four weeks of circuit exercise ) , d18 ( six weeks of 
 circuit exercise ) , and d24 ( eight weeks of circuit exercise ) .
( p<0.05 ) , d1 : the first day of circuit exercise ) , d6 ( two 
 weeks of circuit exercise ) , d12 ( four weeks of circuit exercise ) , d18 ( six weeks of 
 circuit exercise ) , and d24 ( eight weeks of circuit exercise ) before the intervention , the concentrations of f - trp , bcaas , and the f - trp / bcaas ratio in 
 the blood showed no differences between the groups .
however , intergroup differences of f - trp 
 ( f = 10.457 , p = 0.00 ) , bcaas ( f= 10.847 , p = 0.00 ) , and 
 f - trp / bcaas ( f = 3.157 , p = 0.00 ) after the intervention were significant . 
 in the cct group , after cct , f - trp significantly increased from the first day of the cct 
 ( d1 ) , and it remained increased at two weeks ( d6 ) , six weeks ( d18 ) , and eight weeks ( d24 ) 
 ( f = 17.635 , p = 0.00 ) .
there were no significant differences in f - trp 
 between week one ( d1 ) and two weeks ( d6 ) and between six weeks ( d18 ) and eight weeks ( d24 ) . 

the values of the bcaas in the 
 cct group showed a significant decrease over time ( f = 10.237 , p = 0.00 ) 
 immediately after the start of the exercise , but no significant difference between six weeks 
 ( d18 ) and eight weeks ( d24)was observed .
the f - trp / bcaas ratios also showed a significant 
 increase only in the cct group ( f = 27.277 , p = 0.00 ) .
in addition , in 
 contrast to the control group , the bdi score of the cct group exhibited a significant 
 decrease in the final week ( d24 ) compared to the first day of the exercise ( d1 ) from 
 21.352.28 to 17.651.57 ( t=5.07 , p=0.00 ) ( table 3table 3 .
comparison of bdi scores between cct group and control groupgrouppre - test ( d1)post - test ( d24)bdi ( score)cct ( n=20)21.42.317.71.6con ( n=20)22.12.420.12.1(mean sd ) different superscripts represent significant differences . 

this study investigated the effects of cct on the amelioration of depression in chronic 
 stroke patients who had moderate depression symptoms .
in particular , changes in the 
 f - trp / bcaas ratio , which can indirectly determine the level of brain serotonin , an indicator 
 of depression , was measured over eight weeks .
bcaas ( isoleucine , leucine , and valine ) are essential amino acids , which can not be 
 synthesized by the body . theoretically , they increase in response to the decomposition of 
 proteins in the body , and they are decomposed again and oxidized to energy sources through 
 the same metabolic process used for carbohydrates and fatty acids18 .
in contrast to most general amino acids , which are 
 oxidized in the liver , the amino acids derived from bcaas are oxidized mainly in the 
 skeletal muscles19 .
therefore , the use of 
 bcaas increases in the muscles during recovery after exercise .
this decreases the 
 concentration of bcaas in plasma and thereby increases the f - trp / bcaas ratio . for the cct 
 group in this study , the plasma concentration of bcaas after cct was significantly lower 
 than prior to the exercise , and the concentration of bcaas after exercise decreased over 
 time .
this finding is likely due to increased use of bcaas to improve the recovery rate of 
 fatigued muscles in the recovery process over time .
however , as 
 the percentage of f - trp under stable conditions is only 10% of the total trp , it is 
 difficult to convert it into brain serotonin .
it has been reported , however , that long - term 
 exercise could help to increase the level of serotonin in the brain by increasing the 
 concentration of f - trp20 .
the results of 
 the cct group in the present study provide evidence in support of this hypothesis .
long - term 
 cct is believed to increase the concentration of f - trp , which then increases the 
 catecholamine level in the blood while decreasing insulin and glucose levels .
this causes an 
 increase in lipocyte - induced free fatty acids in plasma . as a result , trp , which strongly 
 combines with albumin ,
the latter then combines loosely with 
 albumin , and the level of f - trp in plasma increases . due to increase in f - trp and
decrease 
 in bcaas over time , the concentration of f - trp in plasma is expected to rise and aid the 
 competitive passage of f - trp through the cerebrovascular barrier with the help of the amino 
 acid carrier ( system l)21 .
consequently , we believed that the ratio of f - trp / bcaas increased over time in the cct 
 group in this study , and that this increase enhanced the concentrations of trp and serotonin 
 in the brains of the subjects in the cct group , likely contributing to the improvement in 
 depression as shown by their bdi scores
. limitations of this study were that the subjects were limited to those with moderate 
 depression , and dietary adjustments that could have affected the plasma amino acids were not 
 taken into account .
furthermore , although it has been reported that the f - trp / bcaas ratio 
 affects central fatigue , this was not considered .
future studies on central fatigue and psd could contribute to the clarification of the 
 effects of the f - trp / bcaas ratio on psd . in conclusion
, this study found that cct exercise 
 for eight weeks increased the f - trp / bcaas ratio and might help improve psd .
   [ purpose ] the purpose of the present study was to investigate the potential effects of 
 circuit class training ( cct ) on poststroke depression through changes in branched - chain 
 amino acids ( bcaas ) ( isoleucine , leucine , and valine ) and free - tryptophan ( f - trp ) . 
 
 [ subjects ] the study subjects were 40 stroke patients with major depressive disorder . 
 the 
 subjects were group - matched into an experimental and a control group according to sex , 
 age , height , and weight . 
 [ methods ] the experimental cct group performed gradual 
 task - oriented cct ( 80  min per session ) . 
 the control group performed stretching exercises 
 and weight bearing exercises ( 80  min per session ) . 
 both groups performed the exercises 
 three times per week for eight weeks ( 24 sessions ) . 
 blood samples were collected 
 immediately before the exercise ( 9:10 a.m. ) and after the exercise ( 10:30 a.m. ) , every two 
 weeks for eight weeks . [ results ] the f - trp / bcaas ratio in the cct group showed a 
 significant increase compared to the control group over time . 
 [ conclusion ] the results 
 show that the cct may help to improve depression in people with poststroke depression 
 ( psd ) . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION