Working under daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder?

A 47-yr-old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep-wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part-time position 7 yrs ago, because he was unable to maintain a regular full-time job schedule. A 10-day actigraphic record revealed an irregular sleep-wake pattern with extensive day-to-day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep-wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond-grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep-wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10-day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep-wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep-wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep-wake cycle and melancholy.

Role of the orbital cortex and of the serotonergic system in a rat model of obsessive compulsive disorder.

The serotonergic system and the orbitofrontal cortex have been consistently implicated in the pathophysiology of obsessive compulsive disorder. Yet, the relations between these two systems and the ways they interact in producing obsessions and compulsions are poorly understood. The present study tested the hypothesis that pathology of the orbitofrontal cortex leads to a dysregulation of the serotonergic system which is manifested in compulsive behavior, using a new rat model of this disorder. In the model, 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. We found that lesion to the rat orbital cortex led to a selective increase in compulsive lever-pressing that was prevented by the serotonin re-uptake inhibitor, paroxetine, and was paralleled by an increase in the density of the striatal serotonin transporter, assessed using high affinity [3H]imipramine binding. These results suggest that the serotonergic system is involved in orbital lesion-induced compulsivity, and provide a possible account for the observed association between obsessions and compulsions and dysfunction of the orbitofrontal cortex and of the serotonergic system in obsessive compulsive disorder.

'Compulsive' lever-pressing in rats is attenuated by the serotonin re-uptake inhibitors paroxetine and fluvoxamine but not by the tricyclic antidepressant desipramine or the anxiolytic diazepam.

Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior, exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward, which may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder (OCD). Given that one of the most salient features of OCD is its selective response to treatment with serotonin re-uptake inhibitors (SRIs), the present study compared the effects of the SRIs paroxetine and fluvoxamine on compulsive lever-pressing, with those of the tricyclic antidepressant, desipramine, and the benzodiazepine, diazepam, which are not effective in the treatment of OCD. Paroxetine (1-15 mg/kg) and fluvoxamine (10-20 mg/kg) dose-dependently reduced the number of compulsive lever-presses and the number of lever-presses followed by an attempt to collect a reward; desipramine (5-15 mg/kg) dose-dependently reduced only the number of lever-presses followed by an attempt to collect a reward; diazepam (2-10 mg/kg) did not affect either type of lever-pressing, except for the highest dose (10 mg/kg), which almost completely abolished lever-press responding. When administered in an extinction session not preceded by signal attenuation, paroxetine, fluvoxamine and desipramine affected only the number of lever-presses followed by an attempt to collect a reward, whereas diazepam (4-8 mg/kg) decreased both types of lever-presses. The present findings strengthen the suggestion that compulsive lever-pressing may serve to model compulsive behavior in OCD, and lends the model predictive validity.

Enhancement of excessive lever-pressing after post-training signal attenuation in rats by repeated administration of the D1 antagonist SCH 23390 or the D2 agonist quinpirole, but not the D1 agonist SKF 38393 or the D2 antagonist haloperidol.

The authors have recently shown that attenuation of an external response feedback leads to excessive lever-pressing that is not associated with attempts to collect reward, and they have suggested that this may be an analogue to "unreasonable" excessive behavior characteristic of obsessive-compulsive disorder. The present study shows that repeated administration of SCH 23390 or quinpirole, but not SKF 38393 or haloperidol, enhances this behavioral pattern. On the basis of data regarding the enduring effects of chronic treatment with dopaminergic agents, these results suggest that overstimulation of striatal D1 receptors underlies enhanced response to signal attenuation. These results may link the hypothesis that obsessions and compulsions result from a deficient response feedback mechanism with findings implicating dopaminergic abnormalities in the production of obsessions and compulsions.