Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders

doi:10.4236/ijcm.2013.412098

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International Journal of Clinical Medicine, 2013, 4, 571-576

Published Online December 2013 (http://www.scirp.org/journal/ijcm)

http://dx.doi.org/10.4236/ijcm.2013.412098

Open Access IJCM

571

Dimensional Characteristics of Children and Adolescents

with Mood Disorders and Autism Spectrum Disorders

Bill J. Duke1, Dennis Staton1,2

1Child Psychopharmacology Institute, Fargo, USA; 2Lakeland Mental Health Center, Moorhead, USA.

Email: [email protected]

Received October 21st, 2013; revised November 20th, 2013; accepted December 5th, 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Objective: We sought to identify clinical discriminators between predominantly mood disordered and predominantly

autism spectrum disordered research subjects that may reflect phenotypic state and treatment response characteristics.

Method: Participants were 26 boys and 4 girls aged 2 to 18 years (Mean Age = 7.70). Subjects with DSM-IV diagnoses

of Major depression (N = 2), Bipolar Disorder (N = 4) and Mood Disorder not otherwise specified (NOS) (N = 11) rep-

resented the mo od disorder group (MD) (N = 17, Mean Age = 8.2) and those with diagnoses of Autistic Di sorder (N =

1), Asperger’ s Disorder (7) or Pervasive Develo pmental Disorder (NOS) (N = 3) comprised the autism spectru m disor-

der (ASD) group (N = 9, Mean Age = 6.8). Primary outcome measurements were continuous actigraphic measurements

collected over one to three week periods. Secondary outcomes included personality and observational measurements.

Personality characteristics reflected significant cross-group impairments related to self-control and self-discipline and

differed relative to intellectual measures. Observational measurements reflected greater general impairments among the

ASD group. Results: Predominantly mood disordered children demonstrated greater impairments related to sleep (P =

0.000) and sleep onset latency (P = 0.000) and were more active than ASD children during evening periods (P = 0.000).

ASD children had lower verbal functioning and greater deviations from the norm on measures of cognitive development

(P = 0.003) and psychosis (P = 0.047). Conclusions: Sleep disturbances, evening activity levels and phase delayed

sleep appear to differentiate predominant mood and autism spectrum disordered children suggesting future areas for

further exploration of neurological and phenotypic treatment response characteristics.

Keywords: Autism Spectrum Disorders; Mood Disorders; Children; Actigraphy; Sleep

1. Introduction

Children with mood disorders (MD) and autism spectrum

disorders (ASD) typically share co-morbid symptoms

[1-3]. The pathophysiological mechanisms which under-

lie these two broad categories of disorders are multivari-

ate and, in some cases, may overlap. The DSM-IV cate-

gorical disorders including these two broad groups have

been poor guides to effective pharmacologic treatment.

ASD and MD can be examined both clinically and

physiologically for dimensional abnormalities that reflect

dysregulated neurophysiology. Actigraphic measure-

ments give objective data regarding such dysregulation

and might identify neurophysiologic subtypes among

children with similar or overlapping symptoms. For ex-

ample, such a study might clarify whether or not the

presence of phase delayed sleep, which has been pro-

posed to be characteristic of pediatric bipolar syn-

dromes [4], is an important marker for clinical in-

tervention. A variety of childhood circadian abnor-

malities, regardless of etiology, may have pathogenic

potential, i.e., may adversely impact subsequent biologic

and psychosocial development. If so, early identification

and treatment of these markers might be extremely

important [5].

In this analysis, we evaluate measurements of sleep

and activity, personality, cognitive functioning, and ob-

served behaviors, in an attempt to better differentiate

these complex childhood clinical groups. We propose

that there is the value in sub-typing clinical pediatric

subjects as either predominantly mood disordered or pre-

dominantly autism spectrum disordered. This analysis

seeks to determine whether or not there are significant

differences between the two broad groups. We hypothe-

size that despite shared behavioral and emotional symp-

Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders

572

toms there will be significant differences be tween groups

in the nature and variation of their activity patterns and

sleep characteristics.

2. Methods

Descriptions of age, gender and age of onset (age at

which the parents first became concerned that their child

had a significant problem) are examined along with di-

mensional characteristics that include activity and activi-

ty patterns, sleep onset latency, sleep efficiency, sleep

time, cognitive measurements, multi-dimensional person-

ality factors and operationally defined and repeated ob-

servations. A baseline assessment included a review of a

biopsychosocial history, clinical and available educa-

tional testing and records, a mental status examination,

operationally defined symptom history and psychological

assessment. DSM IV criteria were applied and those with

major depressive disorder, bipolar disorder, mood dis-

order, NOS, autistic disorder and pervasive developmen-

tal disorder, NOS were invited to participate in th e study

as actigraphic devices were available.

Children were recruited to the study between August

2010 and August of 2011 from an out-patient child

evaluation and treatment clinic. The study had three

actigraphic devices available. The limited availability of

actigraphic devices imposed a randomization effect, with

the children meeting the selectio n criteria being recruited

when an actigraphic device was available at the time of

that determination. During the study period one acti-

watch was lost, further limiting device availability for the

duration of the study. Most children wore the watches

without difficulty or complaint and two children (one

from each group) who were invited to participate in the

study declined because they didn’t want to wear the

actiwatch. Another subject, diagnosed with autistic dis-

order was determined ineligible due to the parent’s

assessment that the child would destroy the actiwatch.

The thirty participants were two to eighteen years of

age (Mean Age = 7.7) 26 of whom were males and four

who were female.

Despite overlapping mood and behavioral sympto-

matic presentations in those with autistic characteristics

and children that are primarily mood disordered there are

clearly distinctions that separate the two broad groups.

This study sub-typed clinical pediatric subjects, as either

predominantly mood disordered or predominantly autism

spectrum disordered. Subjects with DSM-IV diagnoses

of Major depression (N = 2), Bipolar Disorder (N = 6)

and Mood Disorder not otherwise specified (NOS) (N =

11) represented the mood disorder group (MD) (N = 19,

Mean Age = 8.2) and those with diagnoses of autistic

disorder (N = 1), Asperger’s Disorder (7) or Pervasive

Developmental Disorder (NOS) (N = 3) comprised the

autism spectrum disorder (ASD) group (N = 11, Mean

Age = 6.8). The subjects categorized within the autism

spectrum group scored within a range of mild to severe

on either the Childhood Autism Rating Scale [6] or the

Asperger’s Syndrome Diagnostic Scale [7].

The primary outcome measurements of the study were

actigraphic measurements recorded every 30 seconds

during one to three-week measurement periods. Actigra-

phy has been demonstrated to be a valid method for

estimating sleep and wakefulness in a bipolar population

and has demonstrated concordance with polysomno-

graphy in the presence of sedating medication use and in

those with clinical sleep disturbances [8]. Both the refer-

enced Kaplan study and our analysis utilized a medium

threshold for sleep detection and analyzed the actigraphy

data using Actiware 5.59 (Mini Mitter Philips Respir-

onics Inc.).

The measurements were made utilizing an Actiwatch

[9] (AW-64 Phillips-Respironics, Inc.) placed on the

subject’s non-dominant wrist. Actigraphic measurements

collected at this frequency record motor activity detec-

ting mobility, immobility, sle ep states, sleep duration and

sleep disruptions.

Secondary outcome measurements included baseline

standardized personality and cognitive assessments and

episodic repeated measurements utilizing the Systematic

Observation Scale TM [10] during the measurement

periods.

Although there were no matched controls and the two

groups were not able to be gender and age matched,

standardized measures of cognition and age and gender-

normed personality inventories were incorporated in a

baseline assessment battery. This stud y did no t attempt to

differentiate these MD probands into non-polar versus

bipolar subgroups nor sub-type the ASD probands.

Statistics

Analysis was conducted utilizing the Statistical Package

for Social Sciences (SPSS 19.0). Nonparametric analysis

of group independence (Independent Samples Mann-

Whitney U Test) was applied to the actigraphic, person-

ality and observational measurements. An analysis of

variance was applied to determine significance of vari-

ance related to the standardized cognitive measure-

ments.

3. Results

3.1. Dimensional Characteristics

Descriptive characteristics of the subjects by Gender,

Mean Age of Onset (The age at which the parent first felt

their child had a significant difficulty) and Diagnostic

Category are shown in Table 1.

Actigraphic measurements were analyzed by active,

rest and sleep intervals. The active interval represented

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Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders 573

the time from awakening to that of early evening hours.

The rest interval followed the active interval until sleep

onset was established and the sleep period began and

remained until awakening.

Table 2 presents the means of the actigraphy measures

and related tests of independence between the MD and

ASD groups . The moo d disordered an d autistic spectru m

disordered groups differed in all intervals with two ex-

ceptions. Both groups had similar periods of sleep and

immobility during the active period.

Figure 1 is a 24-hour activity graph of a six year old

mood disordered male reflecting delayed sleep onset and

disrupted sleep.

Asymptotic significances are displayed. The signifi-

cance level is .05.

Although the MD and ASD groups were similar dur-

ing active period related to wakefulness and immobility,

the ASD group had a significantly greater percentage of

immobility related to sleep time during the active inter-

val.

Total activity levels and average activity per minute

Table 1. Combined subject pool by gender, mean age of

onset* and diagnostic category.

N N ASD

Male 26 17 9

Female 4 2 2

Total 30 19 11

Table 2. Means of actigraphy measures and test of inde-

pendent samples mann-whitney U test.

Measures N MD NASD SigInterval

Total activity 699 675923.67 279 514720.63 0.000Active

Total activity 639 13213.06 346 10659.90 0.000Rest

Total activity 639 11679.53 345 9864.48 0.000Sleep

Average

activity/min 699 780.1154 279 609.7672 0.000Active

Average

activity/min 639 23.5679 346 18.3404 0.000Rest

Average

activity/min 639 22.0053 345 17.4807 0.000Sleep

Sleep onset 639 9.79 345 6.18 0.000Sleep

Sleep efficiency 639 75.07 345 80.66 0.000Sleep

Sleep time 639 489.60 346 524.75 0.000Rest

Sleep time 639 422.91 345 473.66 0.000Sleep

Immobile time 639 491.074 346 528.540 0.000Rest

Immobile time 639 469.806 345 517.701 0.000Sleep

Asymptotic s ignificances are displ ayed. The significance level is 0.05.

Figure 1. Six year old male bipolar 24-hour actigraph.

differed between the two groups across interval types.

Similarly onset latency, sleep time and sleep efficiency

were also demonstrated to be different between the

groups.

3.2. Cognitive Characteristics

Cognitive characteristics were determined utilizing the

Kaufman Brief Intelligence Test II [11]. The ASD group,

relative to the autism spectrum in general, was high func-

tioning. Statistically significant differences in verbal

functioning differentiated the two groups with statistical

significance between verbal scores (ASD = 91.3 MD =

102.33 P = 0.049) and a lack of significance between

non-verbal measures (ASD = 99.2 MD = 96.7 P = 0.763).

It was expected, given known verbal processing issues in

ASD, that those with autism spectrum disorders would

have lower verbal function. Statistically significant dif-

ferences were not seen between the groups on nonverbal

functioning, however, a trend for the mood disordered

toward lower nonverbal scores may reflect cognitive im-

pairment secondary to mood instability or other impair-

ment. The autistic spectrum group, relatively speaking,

has nonverbal strengths.

3.3. Personality Characteristics

The Personality Inventory for Children-Revised (PIC-R)

[12] is an age and gender referenced objective multi-

dimensional measurement of affect, behavior, ability and

family function. The PIC-R was administered at the time

of the initial evaluation and provided standardized age

and gender-normed values. These values are presented as

T scores whose means are 50 and standard deviations are

10. Upward deviations from the norm indicate patho-

logical associations with the measured dimension. As a

matter of practical application, scores exceeding one and

a half standard deviations i.e. >65 are frequently clini-

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Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders

574

cally significant.

The results of the PIC-R indicated both similarities

and differences in symptom presentations and associated

impairments. The Personality Inventory for Children in-

cludes four broad factorial derived dimensions, scales

measuring general adjustment and informant response

style, developmental, cognitive and clinical scales. Both

the mood disordered and autism spectrum groups reflect

significant impairment related to self-control and self-

discipline. Both groups deviate from the norm by over

two standard deviations.

Difficulties in social competence between the two

groups approached but did not meet statistical signifi-

cance. Both group’s scores suggest social impairments

and deviate from the norm. The ASD group demon-

strated a statistically non-significant, but higher degree of

impairment in the domain of social competence. Differ-

ences between groups related to somatic concerns and

internalization were not significant with means of 62.89

to 66.55. Statistically significant differences existed be-

tween the mood disordered and autism spectrum disorder

groups related to general issues of cognitive develop-

ment.

Other scaled personality dimensions derived from the

Personality Inventory for Children that contributed to

characterizing and differentiating between children with

autism spectrum disorder and children with mood disor-

ders included the dimensions of intellectual screening

and psychoses. These distin ctions are noted in Table 3.

3.4. Observational Characteristics

The observational characteristics were based on the per-

centage of symptom presence observed on over 72 op-

erationally defined symptoms and the repeated meas-

urements that were collected intermittently throughout

the study period. The Systematic Observation Scale util-

izes operationally defined symptoms [13] that are pre-

sented to a primary observer (usually a self-observer or a

parent) for determination regarding the percentage of

time sy mptoms are pres ent .

These measurements are the most limited of the meas-

urements presented. Although the observations provided

meaningful individua l clinical response data, they are not

Table 3. Personality dimension T scores and test of inde-

pendent samples Mann-Whitney U test.

Description DM DSA giS

Cognitive

development 58.79 83.91 0.003*

Intellectual

screening 55.32 84.18 0.006*

Psychosis 80.32 98.45 0.047*

Asymptotic s ignificances are displ ayed. The significance level is 0.05.

standardized measurements and do not have inter-rater

reliability. And, as previously noted, various therapeutic

interventions occurred across the study period that were

not consistent across the groups. These confounding fac-

tors resulted in few items differentiating the two groups.

Nevertheless, the observational symptoms that broadly

demonstrated group differences are shown in Table 4.

4. Discussion

It is not the authors’ intention to suggest that all child

psychiatric patients can be placed into the two broad

groups we have examined. But, despite similar sympto-

matic expressions of dysregulated mood, irritability and

other impairments there is a clinically discernible differ-

ence in social relatedness among the autism spectrum

group. The fundamental neurodevelopmental nature of

autism spectrum disorders suggests neurophysiologic dif-

ferences despite elements of common symptomatic pre-

sentations. In our sample the activity patterns and sleep

characteristics differ between the included major depres-

sive disorder, bipolar disorder and unspecified mood dis-

order from our ASD sample. The ASD sample of this

study was limited by those available in a setting where a

“high functioning” bias existed. Nevertheless, there ap-

pear to be significant differences between the broad

groups of mood disorder and autism spectrum disorders

that can be further defined by applying objective meas-

ures to determine treatment response phenotypes and as a

method to support and measure specific related categori-

cal diagnoses.

The broadly defined MD and ASD groups of this study

had similar self-control and behavioral impairments, but

exhibited significant differences in circadian sleep and

motor activity characteristics. These findings are limited

but point to the potential of further characterizing these

and other differen ces. Although both groups in th is study

had sleep complaints the predominantly mood disordered

exhibited significantly different sleep characteristics than

did those with autism spectrum diagnoses. The autism

spectrum group also exhibited significantly less total

activity than the mood disordered group. Phenotypic

characteristics such as these may be associated with

Table 4. Mean percentage present of operationally defined

symptoms and test of independent samples Mann-Whitney

U test.

Observational

measure MD ASD Sig

Tics/mannerisms7.56 26.36 0.048

Picky eater 15.74 35.14 0.010

Bed wetting 6.39 32.50 0.001

Whiny 14.81 32.55 0.048

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Dimensional Characteristics of Children and Adolescents with Mood Disorders and Autism Spectrum Disorders 575

treatment response variance and may, once fully charac-

terized, reveal pathological processes that precede or

contribute to chronically established impairments.

The clinical implications of variations of activity and

sleep disruptions are numerous and include their rela-

tionship to mood, cognition and development. Sleep is

closely related to emotional regulation and cognitive

functioning. Dysphoric mood states [14]; completed sui-

cides [15] the onset of manic symptoms worsening [16]

and possible long lasting learning deficits have each been

associated with sleep disturbances [17]. Approximately

85% of bipolar children and adolescents exhibit sleep

disturbance [18] (4). And, bipolar individuals experience

sleep problems during periods of relative euthymia [19]

[16] as well as during episodic worsening of affective

illness. Bipolar children may be especially likely to ex-

hibit low sleep efficiency, frequent awakenings [20] and

phase-delayed sleep [4].

Sleep disturbances are associated with poorer acade-

mic performance among children diagnosed as having

autism and attention deficit hyperactivity (ADHD) dis-

orders, but not among normal control children [21]. Our

results suggest that predominantly mood-disordered child-

ren have significantly more severe sleep impairment than

do those with autism spectrum diagnoses. If a strong as-

sociation exists between sleep disturbance and academic

performance among predominantly mood-disordered child-

ren, as seems very likely, it would be particularly impor-

tant to address sleep symptoms during clinical treatment

of these children and adolescents.

Circadian rhythm disorders are associated with cogni-

tive impairment, mood disturbances and increased risk of

cardio-metabolic disorders and can be treated by light

management, scheduled sleep-wake time adherence, timed

low-dose melatonin and other pharmacological agents

[22]. Melatonin has demonstrated effectiveness in ad-

vancing sleep-wake rhythm and endogenous melatonin

rhythm in delayed sleep phase disorder [23].

Sleep and activity measurements are reflections of

neurophysiological states and are measureable treatment

targets. Insomnia and hypersomnia, sensitivity to shifts in

circadian rhythm, difficulties awakening, and prolonged

sleep latency may act as vulnerability factors prior to the

manifestation of manic episodes [16].

Effective reduction of sleep disturbances in children

and adolescents, particularly those with predominant

mood disorder symptoms, perhaps should be a primary

goal. Sleep disturbed adult bipolar probands treated with

ramelteon, a selective melatonin receptor agonist, were

approximately half as likely to relapse as those treated

with placebo through a 24 week treatment period [24].

Symptoms of delirium have been correlated with cir-

cadian rhythm disturbances and are reported to have been

improved by treatment with ra melteon [2 5 ]. Although the

pathophysiology of mood disorders is unknown, the dis-

ruptions in daily rhythms associated with major depres-

sive disorder and bipolar disorder have led to considera-

tion of circadian pathophysiology as a contributing cau-

sal factor [26,27].

5. Conclusion

Limitations of this study are significant and include that:

this is a small unmatched sample; subjects represented

various developmental states; the ASD subjects are heav-

ily weighted toward high functioning and are not repre-

sentative of a broad ASD group; some subjects were drug

naïve at baseline while others were not; and, subjects in

both diagnostic categories received various pharmacol-

ogical interventions during actigraphy measurement pe-

riods. Despite these limitations we propose that low

budget or no budget clinical investigations such as these

can assist in clinical management an d incrementally shed

light on phenotypic differences worthy of further inves-

tigation.

The results of this study are consistent with sleep dis-

turbances reported in studies of pediatric bipolar subjects

[18] and demonstrate the value of utilizing objective

measurements for the differentiation of complex phenol-

typic neurodevelopmental and neuropsychiatric disorders.

Phenotypic differences may be a factor in lower antide-

pressant and other variant medication efficacies seen in

the ASD population [28].

Future studies may identify phenotypic subtypes of

complex disorders that reveal dimensional aspects un-

derlying neurophysiological effects and states. Identifica-

tion of these characteristics enhances phenotypic differ-

entiation and neurodevelopmental opportunities to miti-

gate or reduce pathol ogi cal devel o pment.

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