Stabilization of Circadian Rhythm, Its Augmentation by Bright Light Treatment and Its Importance for ADHD and Depression of Adolescents

doi:10.4236/nm.2013.43024

Paper Menu >>

Journal Menu >>

Neuroscience & Medicine, 2013, 4, 150-154

http://dx.doi.org/10.4236/nm.2013.43024 Published Online September 2013 (http://www.scirp.org/journal/nm)

Stabilization of Circadian Rhythm, Its Augmentation by

Bright Light Treatment and Its Importance for ADHD and

Depression of Adole scents

Helmut Niederhofer

Department of Child and Adolescent Psychiatry and Psychotherapy, Saechsisches Krankenhaus für Psychiatrie und Neurologie

Rodewisch Bahnhofstrasse, Rodewisch, Germany.

Email: helmutnied[email protected]

Received March 11th, 2013; revised April 14th, 2013; accepted May 8th, 2013

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

ABSTRACT

Objective: ADHD is ch aracterized by the progressive development of, imp ulsiveness, attentional difficulties and some-

times also excessive hyperactivity. Main biological reason is a quantitative reduction of the neurotransmitter dopamine

in the forebrain. A lack of dopamine is also typical for depressive disorders. Methods: Bright light therapy is proven to

be effective in treating depression. Purpose of our study is to verify the therapeutic effectiveness of Bright light therapy in

subjects affected by ADHD. Results: Results show a significant improvement which lasts for at least 4 weeks, which is

superposed by regulation of the circadian rhythm. Initial decrease of especially mornin g saliva melatonin levels, due to

regular sleep under in-patient conditions, is followed by symptom improvement and a raising evening melatonin level,

due to activation during the day. This level decreases as soon as activation is ceased. Conclusion: Bright light therapy

seems to be effective as add-on therapy for ADHD, but in fact, stabilization of the circadian rhythm is the most impor-

tant therapeutic in tervention, either for ADHD or for depres si on , as demonstrated in anot her study .

Keywords: ADHD; Circadian Rhythm; Bright Light Therapy

1. Introduction

ADHD is characterized by the progressive development,

impulsiveness, attentional difficulties, which influences

also interpersonal relationships, and sometimes also of

excessive hyperactivity. Today, research has been of low

specificity and used diagnostic criterions, absent from

specific biological markers, and has been characterized

by the scarce answer to the conventional pharmacologi-

cal treatments. Recently, some researchers have under-

lined the presence of a direct correlation of the severity

of symptomatology and psychometric markers, such as a

quantitative reduction of dopamine, especially in the

right frontal lobe. Such parameters seem also to be modi-

fied by the administration, e.g. Methylphenidate [1]. A

lack of dopamine is also typical for depressive disorders.

Additional biological therapies, which elevate cerebral

dopamine levels, like repetitiv e transcranial magnetic sti-

mulation (rTMS) have been proven to be effective treat-

ing patients suffering from depression [2] and ADHD [3].

Bright light therapy also elevates cerebral dopamine lev-

els and is proven to be effective treating depression [4].

One open trial, including adults suffering from ADHD [5]

suggests that it might be also effective in wintertime and

for ADHD, at least as additional therapy. Purpose of this

placebo-controlled observation in 28 adolescents is to

verify the therapeutic effectiveness of Bright l ig ht th era py

in 28 adolescents affected by ADHD.

2. Methods

28 volunteers, aged 14 - 17 years, IQ 96 - 105, were re-

cruitred in the Dep. of Child and Adolescent Psychiatry

of the Hospital of Rodewisch from March 2011 to June

2012. Patients suffered from ADHD for more than two

years. Informed consent was obtained from each partici-

pant prior to the start of the study, in accordance with the

guidelines set forth by the Declaration of Helsinki. Pa-

tients were encouraged to continue ongoing treatment

(both received 40 mg Methylphenidate daily and Psy-

chotherapy) during the study, with the assumption that

psychotherapy and medication effects over an interval of

4 weeks were likely to be small, since there was no

change of medication/dosage and psychotherapy (2 ses-

Stabilization of Circadian Rhythm, Its Augmentation by Bright Light Treatment

and Its Importance for ADHD and Depression of Adolescents 151

sions/week) since one month before the 4 week study

period.

ADHD symptoms were assessed weekly by the Con-

ner scales [6]. This test has an excellent variation sensi-

tivity and an 81% sensitivity and 61% specificity for

ADHD. It consists of 20 items, 10 of which describe in-

attention and 10 describe hyperactivity. The items are to

be rated on a scale from 0 = never existing to 3 = always

existing. Each of the two subscales has a cut-off of 14, i.e.

that scores of >14 are typical for ADHD.

Step 1 (Baseline): 28 Volunteers were admitted and

began with the initial baseline week of the study. The

purpose of the baseline week of the study was to be able

to differentiate change s of the Conner score between out-

and in-patient treatment and to that of placebo and BLT

treatment. Conner scores were measured at the day of

admission and one week after admission (Prae-trial).

Step 2 (Verum): In the second week of the study, the

28 patients were asked to sit alone in front of the bright

light box (2500 lux) from 09:00 to 10:00 a.m. In this time,

patients played or listened to a story. Conner scores were

measured after the second week.

Step 3 (Placebo): In the third week of the study, the 28

volunteers were asked to sit alone in front of the placebo

light box for (50 lux) 60 minutes in the morning, from

09:00 to 10:00 a.m, In this time, patients played or lis-

tened to a story. This aspect of the design followed the

general principle of clinical trial design that better con-

trasts between active and placebo. As reviewed by East-

man [7], the issue of placebo responses has been a seri-

ous problem in clinical bright light studies, though the

placebo problem has been negligible in studies of the

physiologic effects of light. Conner scores were meas-

ured after the third week.

Step 4 (Post): In the fourth week of the study, the 28

patients received neither placebo nor BLT. The purpose

of this week of the study was again to be able to differ-

entiate changes of the Conner score related to ADHD to

that of placebo and BLT treatment. Conner scores were

measured after the fourth week.

Saliva samples were collected one week before (Base-

line) and one day be fore placebo treatment (Prae), on the

day between verum and placebo treatment (Verum), on

the day after placebo treatment (Placebo) and one week

after placebo treatment (Post), at each time at 08:00 a.m.

and 08:00 p.m., and assayed for melatonin to characterize

the circadian phase of the subject’s melatonin rhythms

(ELISA, Immuno Biological Laqboratories, Hamburg,

Germany). Saliva samples were used because of the con-

venience for the patients.

The subjects completed a weekly Assess ment for Treat-

ment Emergent Events (SAFTEE) symptom scale. Four

weeks of treatment were carried out with weekly symp-

tom assessments. The investigators visited su bjects weekly

to assure their safety and their compliance with the study,

and to administer and collect rating forms.

3. Results

Subjects’ moods and salivary melatonin levels improved

under both treatments (Table 1). With respect to inatten-

tion, Conner scores were stable in the pre-treatment pe-

riod (Score 16.3, cut-off 14), improved during treatment

with bright light therapy to the score of 12.7. In the pla-

cebo and post-treatment period, the score rose again up

to 15.8 (Figure 1).

Regarding hyperactivity, Conner scores dropped in the

pre-treatment period from 17.4 to 16, improved during

treatment with bright light therapy to the score of 13.6. In

the placebo and post-treatment period, the score rose

again up to 16.9 (Figure 1).

Salivary melatonin, measured in the morning, showed

a remarkable decrease from the pre-treatment period (13

pg/ml-range < 10 pg/ml) to the BLT, placebo-, and the

post-treatment period (4pg/ml). Salivary melatonin,

measured in the evening, also decreased slightly in the

pre-treatment period from 8 pg/ml to 5 pg/ml (range > 10

pg/ml), and increased after placebo to again 8pg/ml, after

BLT even to 9 pg/ml, and to 12 pg/ml in the post-treat-

ment week (Figure 2).

Significant differences of Conner scores and melatonin

levels are depicted in Table 1.

Participants experienced no suicide attempts. There

were no incidents of mania or hypomania during the light

treatment.

The weekly SAFTEE physical symptom inventory

(range: severe-moderate-mild-minimal-not existing) was

examined for adverse reactions. The symptom Headache

improved with bright light in one patient from mild to

minimal, and with dim light, nausea and vomiting im-

proved in the other patient also from mild to minimal.

This improvement lasted until th e end of the study. With

respec t to the other symptoms, patient did not repo rt any

change, i.e. they were always scored as “minimal” or

“not existing”, without any changes in the four weeks.

4. Discussion

BLT led to a significant reduction of the Con ner Inatten-

tion score and also showed an improvement in the Con-

ner Hyperacivity Score. In addition, the social structure

and regularized sleep might be beneficial. Interestingly,

there was a more significant decrease in the Hyperactiv-

ity than in the Inattention Score, which suggested that

BLT was more effective in case of Hyperactivity than of

Inattention. This corresponds to recent findings which

suggest biological therapies (such as sleep regulation and

Stabilization of Circadian Rhythm, Its Augmentation by Bright Light Treatment

and Its Importance for ADHD and Depression of Adolescents

152

Figure 1. Changes of ADHD Scores before, during and after Bright light Therapy.

Figure 2. Changes of Morning and Evening Melatonin Saliva levels before, during and after Bright light Therapy.

BLT in our trial) to be more effective for Hyperactivity

than for Inattention.

It was also evident that both scores did not change sig-

nificantly in the pre-treatment period, i.e. in the first

week after admission. The morning melatonin level de-

creased significantly in the first week after admission, the

evening melatonin level in a non-signif icant way. During

BLT, the morning melatonin level remained stable within

Stabilization of Circadian Rhythm, Its Augmentation by Bright Light Treatment

and Its Importance for ADHD and Depression of Adolescents 153

Table 1. Differences of ADHD Scores and Melatonin saliva levels before, during and after Bright light Therapy.

Wilks Lambda 1 Factor Analyasis of Variance, corrected by Bonferoni

Differences between

BLT and

Differences between

Placebo light and Differences Baseline to…

Baseline Prae Placebo Post BaselinePrae Post Prae Post Prae to Post

F p p p p p p p p p p p

Attention 3.96 0.011 0.013 0.005 0.001 0.007 n.s. n.s. n.s. n.s. n.s. n.s.

Hyperactivity 4.11 0.025 0.006 0.003 0.001 0.005 n.s. n.s. n.s. n.s. n.s. n.s.

Melatonin

morning 5.62 0.012 0.006 0.004 0.004 0.002 n.s. n.s. n.s. n.s. n.s. n.s.

Melatonin

evening 3.34 0.039 0.017 0.014 n.s. 0.008 n.s. 0.012 0.003 n.s. n.s. 0.002

the normal range, whereas the evening melatonin level

rose step by step, also under placebo and in the post-

treatment period, up to the normal range. These facts

suggest, that the regulated circadian rhythm under in-

patient condition seems to be more important than BLT.

In the first seven days after admission patients, regular

sleep is compensated by excitement which leads to a de-

crease of both melatonin morning and also for evening

levels. Morning melatonin levels remain then stable (in-

dependently of BLT, due to continued regular sleep con-

ditions), whereas evening melatonin levels raise step by

step, also independently of BLT, which might be due to

physical activation during the day. Altogether, BLT im-

proves clinical ADHD symptoms, Hyperactivity more

than Inattention, but with respect to both morning and

evening melatonin levels, a regular circadian rhythm

seems to be more important than BLT. Furthermore, a

normalization of the morning melatonin level also seems

to improve ADHD symptoms, followed by the normali-

zation of the evening melatonin level. The fact that espe-

cially the Hyperactivity score does not reach the pre-

treatment value suggests that physical activation during

the day under in-patient conditions itself improves Hy-

peractivity. BLT has only an additional effect. Anyway,

our data suggest that the circadian rhythm, objectivated

by salivary melatonin levels, is also deranged in case of

ADHD. It can be concluded, that the normalization of the

morning melatonin level induces improvement of clinical

symptoms, which itself induces normalization of the

evening melatonin level. According to our results, there

seems to be a causal association between melatonin lev-

els and clinical symptoms, which may be caused by im-

portant confunding variables (sleep regulation, physical

activation, etc.) affecting the melatonin levels and clini-

cal symptoms at least as much as BLT itself. It can be

concluded that regular sleep (objectivated by morning

melatonin level) induces improvement of clinical symp-

toms which enables the patient to be more active during

the day (objectivated by evening melatonin level). Mela-

tonin levels must decrease rapidly i.e. melatonin storages

must be depleted rapidly first. Then, clinical symptoms

will improve and the circadian clock (suprachiasmatic

nucleus) will work properly and refill the melatonin

storage at night.

Sleep deprivation augments this procedure: first, de-

pleting the melatonin storage and then refilling it by

means of a properly working circadian clock. One night

without sleep fills the melatonin storage in the morning

and further until the following day’s ev ening (the patient

does not feel better that day, only more tired) and it’s then

depleted rapidly the next night, when the patient sleeps,

which improves clinical symptoms in the following day

and enables the patient to be more active that day and,

based on this, reorganizes the circadian clock, filling the

melatonin storage correctly during the day. The reason,

why sleep deprivation must not last for more than one

night is that the melatonin stor age is completed after that

time and refilled in the following night. It is an adjunc-

tive strategy to support rapid depletion of the melatonin

storage indirectly by filling it previously—with the aim

to reorganize the circadian clock which fills the melato-

nin storage agai n.

Altogether, it seems to be more important to deplete

the melatonin storage rapidly first than to fill it, e.g. ad-

ministering melatonergic drugs such as melatonin or ago-

melatine. These drugs should only be given if regular

sleep with an immediate effect and physical activation

during the day with a delayed effect as first steps did not

show a sufficient improvement for some weeks.

Interestingly, we saw similar effects, investigating

BLT for adolescents suffering from depression: initially

morning melatonin levels decreased (due to regular sleep

under in-patient conditions and evening melatonin levels

remained stable due to physical activation during the

day), followed by an improvement of clinical symptoms

and a normalization of evening melatonin levels (due to

physical activation), amplified by BLT [8]. Ceasing the

physical activation led to a new decrease of evening me-

Stabilization of Circadian Rhythm, Its Augmentation by Bright Light Treatment

and Its Importance for ADHD and Depression of Adolescents

154

latonin levels. It can be assumed that a new dysregulation

of sleep conditions might also lead to a new gain of

morning melatonin levels.

Altogether, regular sleep (morning melatonin levels

react immediately) and physical activation during the day

(evening melatonin levels react with a delay) seem to be

more important than BLT itself, which amplifies this

effect. This effect can be seen in patients suffering either

from depression or from ADHD.

Apart from an advantage on one scale (Head) of the

SAFTEE side effects inventory, bright light treatment

was superior to dim placebo light. The beneficial effects

found in the study might be attributed to several factors

that were common to the treatment and control groups.

The “placebo” effect, chiefly positive expectations, and

positive staff contacts may have contributed to positive

responses. An hour a day engaging in a treatment, which is

thought to be helpful, may have induced a reduction in

ADHD symptoms. A longer period may be needed for

this population with ADHD symptoms.

Rhythms of melatonin, sleep, and activity all peak la-

ter in ADHD patients as compared to healthy controls.

However, since increased light exposure is generally as-

sociated with more advanced rhythms (as was observed

comparing the bright light and placebo period in this

study), the results are consistent with the possibility that

these patients are subsensitive to circadian effects of

light.

REFERENCES

[1] G. H. Moll, H. Heinrich, G. Trott, S. Wirth and A. Roth-

enberger, “Deficit Intracortical Inhibition in Drug-Naive

Children with Attention Deficit Hyperactivity Disorder Is

Enhanced by Methylphenidate,” Neuroscience Letters,

Vol. 21, 2000, pp. 121-125.

doi:10.1016/S0304-3940(00)00980-0

[2] J. Hoeppner, F. Padberg, G. Domes, A. Zinke, S. C. Her-

pertz, N. Grossheinrich and U. Herwig, “Influence of Re-

petitive Transcranial Magnetic Stimulation on Psycho-

motor Symptoms in Major Depression,” European Ar-

chives of Psychiatry and Clinical Neuroscience, Vol. 260,

No. 3, 2010, pp. 197-202.

doi:10.1007/s00406-009-0039-8

[3] H. Niederhofer, “Effectiveness of the Repetitive Tran-

scranical Magnetic Stimulation (rTMS) of 1 Hz for Atten-

tion-Deficit Hyperactivity Disorder (ADHD),” Psychia-

tria Danubia, Vol. 20, No. 1, 2008, pp. 91-92.

[4] C. Even, C. M. Schroeder, S. Friedman and F. Rouillon,

“Efficacy of Light Therapy in Nonseasonal Depression: A

Systematic Review,” Journal of Affective Disorders, Vol.

108, No. 1, 2008, pp. 11-23.

doi:10.1016/j.jad.2007.09.008

[5] Y. E. Rybak, H. E. McNeely, B. E. Mackenzie, U. R. Jain

and R. D. Levitan, “An Open Trial of Light Therapy in

Adult Attention-Deficit/Hyperactivity Disorder,” Journal

of Clinical Psychiatry, Vol. 67, 2006, pp. 1527-1535.

doi:10.4088/JCP.v67n1006

[6] C. H. Goyette, C. K. Conners and R. F. Ulrich, “Norma-

tive Data on Revised Conners Parent and Teacher Rating

Scales,” Journal of Abnormal Child Psychology, Vol. 6,

No. 2, 1978, pp. 221-236. doi:10.1007/BF00919127

[7] C. I. Eastman, “What the Placebo Literature Can Tell Us

about Light Therapy for SAD,” Psychopharmacol Bul-

letin, Vol. 26, No. 4, 1990, pp. 495-504.

[8] H. Niederhofer and K. Klitzing, “Bright Light Treatment

as Add-On Therapy for Depression in 28 Adolescents: A

Randomized Trial,” Primary Care Companion CNS Dis-

orders, Vol. 13, No. 6, 2011.