Rest-Activity Cycles in Childhood and

Adolescent Depression
ROSEANNE ARMITAGE, PH.D., ROBERT HOFFMANN, PH.D., GRAHAM EMSLIE, M.D.,
JEANNE RINTELMAN, B.S., JARRETTE MOORE, M.A., AND KELLY LEWIS, B.S.

ABSTRACT
Objective: To quantify circadian rhythms in rest-activity cycles in depressed children and adolescents. Method: Rest-
activity cycles were evaluated by actigraphy over five consecutive 24-hour periods in 100 children and adolescents,
including 59 outpatients with major depressive disorder (MDD) and 41 healthy normal controls. Total activity, total light
exposure, and time spent in light at more than 1,000 lux were averaged over the recording period for each participant.
Time series analysis was used to determine the amplitude and period length of circadian rhythms in rest-activity.
Results: Overall, adolescents with MDD had lower activity levels, damped circadian amplitude, and lower light exposure
and spent less time in bright light than healthy controls. Among children, those with MDD showed lower light exposure
and spent less time in bright light, but only depressed girls showed damped circadian amplitude. The sex differences
were substantially greater in the MDD group than in the normal control group. Conclusions: These results confirm
damped circadian rhythms in children and adolescents with MDD and highlight the influence of gender and age on these
measures. J. Am. Acad. Child Adolesc. Psychiatry, 2004;43(6):761–769. Key Words: rest-activity cycles, circadian
rhythms, childhood depression, gender.

Sleep and biological rhythm abnormalities have been a
key focus of theories on major depressive disorder
(MDD) in adults for more than two decades. Begin-
ning with the work of Goodwin et al. (1982), it was
suggested that the sleep, temperature, and cortisol ab-
normalities evident in adults with MDD reflected a
phase advance in the timing of circadian rhythms. Oth-
ers have suggested that instability or irregularity of
Accepted December 19, 2003.
From the Department of Psychiatry, The University of Texas Southwestern
Medical Center at Dallas. Drs. Armitage and Hoffmann are now at the Uni-
versity of Michigan in Ann Arbor.
This research was supported by NIMH grant MH56593 (R.A.) and was
conducted at the Department of Psychiatry, University of Texas Southwestern
Medical Center at Dallas. The authors are grateful for the technical support of
the Sleep Study Unit at University of Texas Southwestern Medical Center at
Dallas, under the supervision of Darwynn D. Cole; for department support from
Eric Nestler, M.D., Ph.D. (Chair); and for the secretarial support from Doris
Benson.
Correspondence to Dr. Armitage, Director, Sleep and Chronophysiology
Laboratory, 2101 Commonwealth, Ann Arbor, MI 48105; e-mail: rosearmi@
umich.edu.
0890-8567/04/4306–0761©2004 by the American Academy of Child
and Adolescent Psychiatry.
DOI: 10.1097/01.chi.0000122731.72597.4e
sleep cycles and associated rhythms may be more char-
acteristic of MDD than either a consistent phase ad-
vance or delay in circadian timing (Healy, 1987; Schulz
and Lund, 1985; Siever and Davis, 1985). The major-
ity of more recent studies, however, have not provided
strong support for circadian abnormalities in tempera-
ture or endogenous cortisol secretion in adults with
MDD (cf. Monk, 1993). Moreover, only one study has
supported elevated cortisol at sleep onset in adolescents
with MDD (Dahl et al., 1991).
With regard to sleep laboratory findings, depressed
adults show shorter rapid eye movement latencies, re-
duced slow-wave sleep, and increased sleep fragmenta-
tion, all of which point to abnormalities in the timing
of the rapid eye movement-nonrapid eye movement
sleep cycle (Armitage, 1995; Armitage et al., 1992,
1993a,b, 1999; Kupfer et al., 1984a,b, 1990; Reynolds
and Kupfer, 1987; Reynolds et al., 1990). The findings
in children and adolescents with MDD have been more
equivocal. Although some studies have reported REM
timing problems in early-onset MDD, prolonged sleep
latency in adolescents is a more consistent finding (Bir-
maher and Heydl, 2001; Dahl, 1996).

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004 761

ARMITAGE ET AL.
However, a closer examination of the EEG fre-
quency structure in sleep and ultradian rhythms
(shorter than 24 hours) has confirmed sleep abnormali-
ties in depressed adults, in children and adolescents
with MDD (Armitage et al., 2000a), and in those at
risk of, but not yet ill with, MDD (Fulton et al., 2000;
Morehouse et al., 2002). These findings provide strong
support for the dysregulation hypothesis of depression
and that a more general breakdown in biological
rhythm in rest and activity underlies depression.
Studies of motor activity rhythms have also consis-
tently reported blunted circadian amplitude in de-
pressed adults (cf. Goodwin and Jamieson, 1990) and
in children and adolescents with nonseasonal depres-
sion (Teicher et al., 1993). The data from Teicher et al.
(1993) go further to suggest that the ultradian compo-
nents of locomotor rhythms are often more pro-
nounced than circadian rhythms and that these
findings were evident in both children and adolescents
with MDD. Damped circadian amplitude was evident
in adolescents but not in children.
Interestingly, Glod et al. (1997) also reported
blunted locomotor rhythms in children and adolescents
with seasonal affective disorder, although this was not
confirmed in adults with this disorder (Teicher et al.,
1997). We have argued previously that abnormalities
in ultradian rest-activity cycles may underlie both the
sleep EEG and locomotor disturbances evident in
MDD but that the effects may be gender specific
(Armitage and Hoffmann 2001; Armitage et al.,
2000a–c, 2001, 2002; Hoffmann et al., 2000). The
sleep EEG frequency analyses do indicate a greater de-
gree of ultradian rhythm disturbance among females
with MDD, from early childhood to later adulthood
but particularly in adolescence. These findings, coupled
with the results from Teicher et al. (1993), suggest that
locomotor rhythms in those with MDD should show
both age and gender effects.
The purpose of the current study was to evaluate
rest-activity cycles and locomotor activity in 59 de-
pressed children and 41 healthy controls. Of primary
interest was an evaluation of gender differences and
age-related differences in both patients and controls.
METHOD
Subjects
Participants were recruited through campus and community ad-
vertisement, by word of mouth, or during an initial visit to the
762
Child and Adolescent Psychiatry Outpatient Clinic. Rest-activity
measurements were obtained from 100 children and adolescents, 8
to 17 years of age, including 59 outpatients diagnosed with uni-
polar, nonpsychotic MDD, single or recurrent, and 41 healthy
normal controls (NCs). There were 28 females and 31 males in the
sample of outpatients with MDD and 20 females and 21 males in
the sample of healthy NCs. All patients were symptomatic and
unmedicated at the time of the study. Independent sleep disorders
by history or polysomnography were exclusionary for all partici-
pants. Diagnostic and demographic information is shown in Table
1. Note that there were no significant differences in age or educa-
tion between groups.
Diagnostic Procedures
Patients for the study were scheduled for a full evaluation after a
telephone screening for inclusion and exclusion criteria. The study
was approved by the Institutional Review Board at the University of
Texas Southwestern Medical Center at Dallas. Before the initial
interview, the study was explained and written informed consent
was obtained from the parent(s) and assent from the patient. In
addition to a structured psychiatric interview, the initial evaluation
included a medical review of systems, a physical examination, rou-
tine laboratory tests, and neurological examination. The evaluation
was completed during a 3-week period.
At the initial visit, each patient and parent(s) were interviewed
separately using the Schedule for Affective Disorders and Schizo-
phrenia for School-Age Children–Present and Lifetime (K-SADS-
PL), a revision of the K-SADS (Kaufman et al., 1997). The
K-SADS-PL is a semistructured DSM-IV–based diagnostic inter-
view to establish that the patient met DSM-IV criteria for MDD
and to identify other concurrent and lifetime psychiatric disorders.
The final diagnoses were based on information from interviews of
the parent(s) and child. Additionally, depressive symptom severity
was assessed using the Children’s Depression Rating Scale-Revised
(Poznanski et al., 1985). While the child was being interviewed, a
separate interviewer obtained family history from the parent(s) us-
ing the Family History Diagnostic Interview. Patients completed
two self-report scales for depression and anxiety, the Weinberg
Screening Affective Scale–Short Form providing information on a
patient’s perception of his/her problems based on 10 major symp-
tom groups of depression (Weinberg and Emslie, 1988), and the
Multidimensional Anxiety Scale for Children (March et al., 1997).
The Children’s Global Assessment Scale assessed overall function-
ing (Shaffer et al., 1985). Tanner upper and lower body maturation
(1–5 scores) was self-assessed by participants using the “Typical
Progression of Pubertal Development Chart” adapted from Tanner
(1962, 1978). Breast and pubic hair development was assessed for
girls and genital and pubic hair development was assessed for boys.
Note that Duke et al. (1980) have shown that children can reliably
self-rate sexual maturation using these standard pictures. A third
interview was conducted just before the sleep study to review psy-
chiatric assessment and inventories. A Children’s Depression Rating
Scale-Revised score of 40 or more was required for entry into the
study. Further details on the clinical evaluation procedures are re-
ported elsewhere (Emslie et al., 2001).
All NC children and adolescents underwent the same initial
psychiatric and medical evaluations as those with MDD and were
scheduled for the laboratory tour after the first interview.
Procedures
All participants agreed to follow their usual school week estab-
lished by sleep history with bed- and rise-times schedules through-
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004
 REST-ACTIVITY CYCLES

TABLE 1
Demographic and Clinical Features of the Sample by Diagnostic Group and Gender
MDD F MDD M NC F NC M
No. 28 31 21 20
Age overall mean 12.3 ± 2.9 12.3 ± 3.0 12.4 ± 3.1 12.4 ± 2.5
≤12 yr 9.9 ± 1.4 9.5 ± 1.3 9.9 ± 1.7 10.3 ± 1.4
≥13 yr 15.0 ± 1.4 15.5 ± 1.6 14.9 ± 1.9 14.5 ± 1.3
Tannera
A 2.9 ± 1.5 2.7 ± 1.5 3.5 ± 1.5 3.0 ± 1.6
B 2.8 ± 1.6 2.8 ± 1.7 3.3 ± 1.5 2.9 ± 1.6
FGAS 61.4 ± 10.4 64.5 ± 11.9 91.7 ± 2.6 91.5 ± 6.0
CGAS 53.0 ± 7.3 52.5 ± 6.1 90.7 ± 4.1 90.7 ± 5.4
MASC 54.2 ± 19.8 48.8 ± 16.1 33.1 ± 13.6 30.6 ± 14.7
CDRS 58.9 ± 11.1 57.1 ± 7.2 19.0 ± 2.3 18.4 ± 2.0
BPRS 33.0 ± 9.0 34.4 ± 8.4 2.4 ± 3.1 2.4 ± 2.8
No. of episodes 1.4 ± 0.7 1.4 ± 0.6 — —
Age at onset of 1st episode 11.1 ± 3.2 11.3 ± 3.3 — —
Length of current episode 18.3 ± 7.1 18.5 ± 10.2 — —
Suicide attempts 0 0 — —
Suicidal ideation 2.3 ± 0.8 2.3 ± 0.6 — —
Family history (%)
Maternal MDD 64.3 45.2
Paternal MDD 17.9 12.9
Comorbid illness, no. (%) 17 (60.2) 16 (51.6)
GAD 1 2
OCD 0 1
Dysthymia 7 4
ODD 0 1
Phobia 0 1
Enuresis 1 0
ADHD 8 7
Note: MDD F = depressed females; MDD M = depressed males; NC F = normal control females; NC M = normal control
males; FGAS = Family Global Assessment Scale; CGAS = Children’s Global Assessment Scale; MASC = Multidimensional
Anxiety Scale for Children; CDRS = Children’s Depression Rating Scale; BPRS = Brief Psychiatric Rating Scale; MDD =
major depressive disorder; GAD = general anxiety disorder; OCD = obsessive-compulsive disorder; ODD = oppositional
defiant disorder; ADHD = attention-deficit/hyperactivity disorder.
a
Tanner A is based on breast development for girls and genitalia for boys. Tanner B assesses development of pubic hair.

out the study. They were informed that a deviation of more than
one half hour would result in elimination from the study. With the
exception of two children and three adolescents, all participants
were tested Monday through Friday during the regular school year
outside of holiday and vacation schedules. Actigraphs (Actiwatch-L,
Mini-Mitter) were worn throughout the week, and sleep/wake dia-
ries were collected daily during the home recording period. Acti-
graphs were set to begin at noon and end at 9 A.M. on the last
morning of the recording. The actigraphs measured the number of
movements that exceeded 0.01g (gravitation force per minute of
recording). In addition, a photoconductive cell recorded light level
exposure, measured in lux. All actigraphs were calibrated before
recording to ensure comparability across subjects. Thresholds, sen-
sitivities, scaling, and epoch lengths were held constant across all
individual recordings. Actigraphs were not removed while shower-
ing or bathing. Subjects were asked to note in the diaries whether
the actigraphs were removed, for how long, and for what purpose
and to record any travel periods less than 15 minutes. Finally,
subjects were instructed not to wear any clothing that covered up
the watch face at any time during the recording period.
The technical reliability of the actigraph was very high, with little
loss of data. Subjects were compliant with the actigraphy proce-
dures, resulting in the loss of very few data points. Of the 100 study
participants, complete 5-day actigraphy data were available for 95
participants. For the remaining five subjects, 3 complete days of
data were available. The additional days were excluded from analy-
sis. The 24-hour blocks with missing data due to participants re-
moving the watch were excluded from the analysis.
Data Analysis
Data were downloaded from the actigraphs at the end of the
recording period. Initial data analyses were conducted with on-
board Mini-Mitter software, computing the average activity count
per epoch in the light and dark periods. Total daily light exposure
was also computed for each day of recording, along with average

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004 763

ARMITAGE ET AL.

light exposure and the amount of time in light above a 1,000-lux
level across the recording period.
The raw activity data per minute (time series) were also exported
to SAS and subjected to Fourier-based spectral analysis for each
individual subject to determine the circadian amplitude or strength
of the 24-hour rhythms. Relative circadian amplitude was also com-
puted (100 × amplitude/mean daily activity) to ensure that ampli-
tude estimates were not biased by total activity (Teicher, et al.,
1993). All data were coded for group (NC or MDD), gender, and
age, using an arbitrary cut point of 12 to contrast children and
adolescents. Average Tanner scores (upper body + lower body/2)
were also used to evaluate maturational age by gender by group
interaction. Analysis of variance (ANOVA) evaluated statistical dif-
ferences, testing the group by gender by age interactions first, and
simple interactions and main effects only if three-way interactions
were not significant. Least-squares multiple comparisons contrasted
differences between individual means only if a significant overall
ANOVA effect was obtained to protect against type I errors.
RESULTS
Using an age cut point of 12, there were 15 girls and
11 boys in the 8- to 12-year-old MDD group. There
were 10 girls and 11 boys in the 8- to 12-year-old NC
group. The adolescent group had 13 girls and 14 boys
with MDD and 10 NC girls and 10 NC boys all in the
13- to 17-year-old age range.
Activity Levels
The means and standard deviations for all the activ-
ity measures are shown in Table 2 by group and age but
collapsed across gender. The means indicate substantial
age-related differences in activity, with lower total ac-
tivity and lower activity in the light phase in the ado-
lescents but with higher activity in the dark phase.
Further, the difference in total activity between chil-
dren and adolescents was greater in the MDD group.
Statistical analyses indicated that these effects were
strongly moderated by gender. ANOVA revealed a sig-
nificant gender by diagnostic group by age interaction
for total activity (F7,92 = 2.2; p < .04) and for activity
level during the light phase (F7,92 = 2.8; p < .02) but
not during the dark phase (F7,92 = 1.1; p < .35).
The three-way interaction for total daily activity is
illustrated in Figure 1. Male children with MDD
showed more total activity than the other groups of the
same age range but differed significantly only from
MDD girls (p < .03). Moreover, the differences in total
activity between the age groups were most dramatic in
the MDD males; adolescents had significantly lower
activity than children (p < .001). By contrast, the dif-
ference between the child and adolescent groups were
not significant for NC females (p < .23), NC males (p <
.37), or MDD females (p < .22), accounting for the
three-way interaction. Results were similar for activity
in the light phase.
Activity in the dark phase did show a main effect for
age (F1,92 = 4.0; p < .05). Means indicated that activity
during the dark was higher in adolescents than in chil-
dren, in all groups, as is evident in Table 2. Note that
the minimal and maximal values were lower in the
MDD groups for all activity measures.
Light Exposure
The means and standard deviations for average daily
light level and the average time spent above a 1,000-lux
threshold are shown in Table 2. Average light levels
were lower in both children and adolescents with

TABLE 2
Means (and Standard Deviations) of Actigraphy Measures by Diagnostic Group (NC Versus MDD) and Age Group
NC MDD
Children Adolescents Children Adolescents
a
Activity total 18,313.6 (9,378.2) 14,461.4 (8,464.7) 18,888.2 (9,936.4) 11,626.7 (7,380.8)
Avg. no. in light 386.0 (191.9) 288.2 (169.1) 389.9 (212.9) 236.7 (153.7)
Avg. no. in dark 25.2 (27.5) 38.2 (28.5) 28.5 (30.9) 40.6 (33.3)
Light avg.b (lux) 847.9 (758.6) 832.7 (1,162.9) 597.9 (647.1) 408.1 (586.1)
Timec (min) 99.6 (90.4) 81.4 (67.5) 64.0 (44.6) 50.3 (50.1)
Circadian period (h) 24.30 (0.30) 24.09 (0.36) 23.98 (0.38) 24.18 (0.32)
Amplituded 2,865.3 (2,784.6) 1,467.8 (1,335.9) 3,311.5 (3,038.5) 987.1 (1,757.1)
a
Total number of events more than criterion × 103.
b
Average time at more than 1,000 lux.
c
Average daily time spent at 1,000 or more lux.
d
Power (area under the curve) × 104.

764 J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004


Fig. 1 Total daytime activity counts over 5 days in children (filled bars)
and adolescents (open bars) by gender and group. NC F = normal control
females; MDD F = depressed females; NC M = normal control males;
MDD M = depressed males.
MDD compared with controls. The between-group
differences are illustrated in Figure 2. Young girls with
MDD had lower light exposure than the other groups
of children, whereas adolescent males in the NC group
had the highest level of exposure, confirmed by mul-
tiple comparisons (p < .05). The NC males were also
the only group to show more light exposure in the
adolescents than in the children, accounting for the
nearly significant three-way interaction (p < .06). In-
terestingly, adolescent NC girls and girls and boys with
MDD were exposed mostly to indoor light levels. Only
the adolescent NC males had sustained outdoor light
exposure. However, no significant gender by diagnostic
Fig. 2 Day light level (lux) averaged over 5 days in children (filled bars)
and adolescents (open bars) by group and gender. NC F = normal control
females; MDD F = depressed females; NC M = normal control males;
MDD M = depressed males.
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004
REST-ACTIVITY CYCLES
group by age interaction was obtained for this measure
(F7,92 = 2.04; p < .06).
The average time spent in bright light showed simi-
lar results. Also seen in Table 2, the MDD group spent
roughly 30 minutes less on average in bright light than
NCs, regardless of age. ANOVA indicated significant
age by diagnostic group and gender by diagnostic
group interactions (F3,96 = 3.1, 2.7; p < .05, respec-
tively) but no significant three-way interaction (F7,92 =
1.6; p < .17). As seen with the average light level, NC
adolescent males showed slightly more (4 minutes)
time spent in bright light compared with children in
this group. Although the means in Table 2 suggest
equivalent age-related differences in the daily time
spent in bright light in the MDD and NC groups, the
greatest difference between children and adolescents
was observed in the NC females. Girls in the NC group
had an average of 90 minutes of bright light exposure,
whereas adolescents in this group spent only 67 min-
utes in bright light (data not shown). Nevertheless,
both male and female adolescents in the NC group still
had more light exposure than their MDD counterparts
(p < .05). Once again, the minimal and maximal values
were lower in those with MDD than in the NCs for
both light variable groups.
Circadian Rhythm Measures
The means and standard deviations for the period
length and the amplitude of circadian rest-activity
rhythms are also shown in Table 2. Although children
with MDD had a circadian rhythm that was 21 min-
utes shorter than that of NC children (23 hours 59
minutes versus 24 hours 20 minutes), this difference
was not significant. The circadian period length did not
appear to differ by age or diagnostic group. Further,
ANOVA did not indicate significant main effects or
interactions for this variable (p > .23).
Collapsed across gender, the amplitude of circadian
rhythms was lower in adolescents with MDD com-
pared with NCs, as seen in Table 2. Children with
MDD had higher amplitude rhythms than controls;
however, a significant three-way interaction was ob-
tained for this measure (F7,91 = 3.0; p < .006). Relative
circadian amplitude adjusted for total activity also
showed a three-way interaction (F7,91 = 3.8; p < .002)
and is depicted in Figure 3. The means indicated that
both female children and adolescents with MDD had
lower relative amplitude circadian rhythms than all
765
ARMITAGE ET AL.
Fig. 3 Relative amplitude (power) of circadian (24-hour) rhythms in total
activity in children (filled bars) and adolescents (open bars) averaged by
group and gender. Amplitude determined by time series analysis (based on
a fast Fourier transform) of activity count per minute throughout five
consecutive 24-hour recording periods for each individual. NC F = normal
control females; MDD F = depressed females; NC M = normal control
males; MDD M = depressed males.
other groups, whereas MDD boys showed higher cir-
cadian amplitude than any other group. Multiple com-
parisons confirmed these differences (p < .05), except
when comparing NC boys with MDD boys. In addi-
tion, Figure 3 also illustrates the dramatic age differ-
ences in circadian amplitude, evident in all groups. The
difference between children and adolescents was, how-
ever, most pronounced in the MDD males, with more
than 70% lower amplitude in the adolescents (p <
.002), further contributing to the significant three-way
interaction.
Thus, circadian rhythms and light exposure were
most abnormal in girls with MDD and evident even in
preteens.
Chronological Versus Maturational Age
To ensure that our arbitrary age cut point of 12 years
did not produce an artificial distinction between
groups, we also conducted an analysis of age using
average upper and lower body Tanner scores. The
three-way interactions (group by gender by develop-
mental age) were evaluated for relative circadian am-
plitude, light exposure, and total activity. The outcome
was strikingly similar to that obtained with chronolog-
ical age (F7,69 = 3.1, 2.8, 2.4; p < .01, .02, .03, respec-
tively), significantly lower circadian amplitude, light
exposure, and total activity in prepubertal (Tanner 1 or
2) girls with MDD (p < .05). Pubertal (Tanner 4 or 5)
but not prepubertal boys with MDD also showed
766
damped circadian amplitude compared with NCs (p <
.05).
Attention-Deficit/Hyperactivity Disorder Comorbidity
One further concern was the higher incidence of
comorbid attention-deficit/hyperactivity disorder
(ADHD) in the children with MDD, particularly with
regard to the failure to find lower activity or damped
circadian amplitude in young boys with MDD. We
recomputed the analyses of the rest-activity measures
excluding the three adolescents and 12 children who
had morbid ADHD. Removing these subjects had only
a small effect on results, reducing the overall probabil-
ity due to the loss of degrees of freedom, but did not
alter the effect size. For relative circadian amplitude,
light exposure and activity levels, the resulting three-
way interactions were (F7,85 = 2.7, 2.4; p < .03, 1.93;
p < .07, respectively). Even excluding the outpatients
with comorbid MDD, circadian amplitude was
damped in preteen and teenage girls and in teenage
boys with MDD. Thus, the failure to find damped
amplitude rhythms in preteen depressed boys was not
due to comorbid ADHD.
DISCUSSION
To summarize the overall findings, adolescents with
MDD had lower activity levels, damped circadian am-
plitude, and lower light exposure and spent less time in
bright light than healthy controls. Among preteens,
girls with MDD had lower light exposure, spent less
time in bright light than controls, and showed lower
circadian amplitude. By contrast, preteen boys with
MDD had robust circadian amplitude. Most impor-
tantly, the same results were obtained with relative cir-
cadian amplitude, adjusted for mean activity levels.
Thus, it is not just reduced activity that is evident in
those with MDD. The results of the current study
conform to those of Teicher et al. (1993), indicating
that circadian amplitude was damped in adolescents
with MDD. The Teicher et al. sample of control sub-
jects was substantially smaller, patients were 2.5 to 3.4
years older than controls, and neither potential gender
effects nor light levels were evaluated. Nevertheless, the
rest-activity cycle data in the current study are remark-
ably similar to those shown in the Teicher et al. report.
Damped circadian amplitude is likely to reflect weak
entrainment to a 24-hour day and/or reduced
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004
 REST-ACTIVITY CYCLES

exposure to zeitgebers (time cues and entrainment) are more dramatic in those with MDD (Armitage,
(Teicher et al., 1993). Because the master circadian 1995; Armitage and Hoffmann, 2001; Armitage et al.,
clock is strongly driven by light (Czeisler et al., 1989) 1999, 2000b,c).
and given the low light levels that appear to accompany
damped amplitude, it suggests that increasing light ex- Limitations
posure will enhance circadian amplitude. Additional
There are limitations to this study that need to be
clinical implications of these results are discussed below.
considered when interpreting data, most notably
Our findings are also in agreement with those of
sample size. Splitting the groups by age and gender left
Glod et al. (1997) who reported blunted circadian am-
only 10 to 17 subjects per cell. There is some concern
plitude but no phase disruption in children with sea-
that the findings may not generalize to a larger sample.
sonal affective disorder, although their study did not
Thus, it will be necessary to replicate our findings.
assess gender. Consistent with the dysregulation hy-
Such efforts are currently underway.
pothesis of depression (Siever and Davis, 1985), we did
In addition, it is also necessary to determine whether
not find evidence of a phase advance in circadian timing.
the rest-activity abnormalities obtained in this study
The strong influence of gender obtained in the cur-
correlate with the amplitude and phase of other circa-
rent study is also consistent with our previous reports
dian measures such as temperature and cortisol. A con-
on sleep data. The gender differences in the MDD
stant routine or forced desynchrony paradigm would
group were substantially larger than those obtained in
allow an assessment of the interaction of circadian and
healthy controls overall. We have previously reported
wake-dependent processes, including mood. Because
larger gender differences in adults with MDD com-
recent work has demonstrated that circadian phase also
pared with controls on several quantitative EEG mea-
affects mood regulation (Boivin et al., 1997), it would
sures during sleep (Armitage and Hoffmann, 2001;
be of significance to include repeated mood assessments
Armitage et al., 1999, 2000b,c). Further, we have also
in further studies of circadian rhythms in depression. It
reported a greater degree of ultradian rhythm distur-
will undoubtedly be necessary to manipulate light ex-
bance in females with MDD, in line with increased risk
posure and rest-activity cycles, including sleep-wake
of MDD among women (Armitage and Hoffmann,
cycles to evaluate the clinical impact directly of these
2001) and with studies of continuing biological vul-
measures in depression and to further elucidate the
nerability to recurrence that is greater in women. The
mechanisms responsible for damped amplitude rest-
data from the current study extend these gender dif-
activity cycles.
ferences to circadian rest-activity cycles. Even 8- to
An additional limitation to this study is our inability
12-year-old girls with MDD show damped circadian
to fully assess the influence of comorbidity on rest-
amplitude, whereas damped circadian rhythms were
activity cycles. Although we reanalyzed our data ex-
only evident in the adolescent boys with MDD.
cluding those with comorbid ADHD and found very
Interestingly, it is believed that the increased risk of
similar results to full analysis, it is still possible that this
MDD in females does not occur until after puberty,
and other comorbid illness could contribute to rest-
with equivalent risk of MDD in prepubertal boys and
activity cycle parameters. Nonetheless, comorbid illness
girls (Frank and Young, 2000; Kessler, 2000; Parry,
was not found to differentiate between the genders.
2000). Our data suggest that the developmental time
Thus, comorbidity cannot account for the significant
course of biological rhythm abnormalities is different in
group by gender effects obtained in this study.
boys and girls with MDD. Damped circadian rest-
activity cycles are evident earlier in females than in
males with MDD. It is not clear, however, how (or Clinical Implications
whether) these biological abnormalities relate to the The current study indicates that damped circadian
risk of MDD or to the clinical course of illness. A study amplitude is characteristic of teenagers with MDD and
of children at risk of MDD and longitudinal evalua- of preteen depressed girls. Because relative circadian
tions of those already ill are necessary to address these amplitude was also found to be damped, it appears
issues. Regardless of the outcome, the current study unlikely that increasing total activity alone would nor-
supports our previous findings that gender differences malize circadian amplitude. The regularity of daytime

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 43:6, JUNE 2004 767

ARMITAGE ET AL.
and nighttime schedules, of the amount of light expo-
sure, and of the timing of these events is more likely
to have an impact on the strength of rhythms. The
outcome of this study suggests that behavioral and
chronobiological intervention may be of benefit in
early-onset depression. Regularized sleep-wake sched-
ules, structured daytime activity, and increased light
exposure may serve to strengthen entrainment and to
stabilize sleep-wake cycles. Ultimately, improving sleep
and circadian rhythm regulation should the biological
risk of depression, although any direct clinical benefit
remains to be established.
Disclosure: Dr. Armitage currently has two RO1 (MH54593 and
MH061515). She currently serves on advisory boards for Pfizer and
Takeda Pharmaceuticals.
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