Clozapine-induced esophagitis at therapeutic dose: a case report.

Our group has recently showed that individuals in at risk mental states for psychosis and bipolar disorder (BD) have a poorer quality of sleep, start their daily activity later, and have a fragmented circadian rhythm compared with age and gender-matched healthy controls.1,2 Another study shows that adolescents at high risk of developing psychosis are more prone to nocturnal awakening, which reduces sleep efficiency.3 Nevertheless, the relationship between circadian abnormalities and risk of transition to psychosis remains poorly explored in the literature.4 Here we present baseline data obtained at clinical assessment of sleep and circadian rhythm in three patients in at-risk states for psychosis who converted to a first episode of psychosis during follow-up.

The first case is a male patient with a strong preference for sleeping and waking up late. Polysomnography (PSG) and actigraphy showed extreme incompatibility between chronotype and social routine resulting in sleep restriction. The patient had a 93-minute sleep extension when sleep time was not restricted by routine activities.

The second case was classified as indifferent chronotype with sleep restriction (he slept 68 additional minutes during the PSG test compared to his normal routine). Furthermore, there was an increase of 100 minutes in total sleep time over the weekend compared to week days. The greatest difference in the amount of sleep was recorded on Saturdays. The data sets show chronic sleep restriction and advanced sleep phase imposed by routine.

The third case was an evening chronotype with no rigid routine, who was able to sleep and wake up late. Because he had an irregular wake-up pattern, a comparison between weekday and weekend sleep was not possible. During the active phase, 140 minutes were quantified as sleep by actigraphy, suggesting that the patient took a nap or rested at home. This finding was confirmed by the activity index, which shows 85.24% of uptime. These results indicate an active phase with rest, which was confirmed by high scores on the questionnaire on daytime sleepiness (Epworth; Table 1). The periods of rest during the awake time might be responsible for the long sleep onset latency (in both PSG and actigraphy). No sleep restriction was observed (actigraphy vs. PSG; Table 1).

Table 1

Description of baseline sleep-awake cycle in three cases of at-risk mental states who transitioned to psychosis

Variable	First case	Second case	Third case
Age	13-	19	23
HO score*	27-	46	37
Epworth score†	5	1	10
Wake-up time (actigraphy)	05:07:19-	07:48:37	10:48:02
Wake-up time (PSG)	06:31:00	06:45:00	06:25:00
Best time to wake up (HO)	12:00:00	12:00:00	08:00:00
Start time of rest (actigraphy)	01:51:00	01:29:00	3:42:00-
Start time of rest (PSG)	23:07:00	22:54:00	23:58:00
Activity index in awake time	91.35	98.63+	85.24
Sleep minutes in awake time	65.5	25.1	140.06+
Rest duration	279.8-	374.57	400.21
Total sleep time (PSG)	372.5	442.5	335
Latency min (actigraphy)	4.6	7.95	29.05++
Latency min (PSG)	20	0.1	39
Rest duration on weekdays		413
Rest duration on weekends		513.8
Wake up time on weekdays (actigraphy)		06:52:52
Wake up time on weekends (actigraphy)		09:30:20
Wake up time on Saturday (actigraphy)		10:37:40

HO = Horne-Östberg; PSG = polysomnography.

Scores may range from 16 (eveningness) to 86 (morningness).

Scores may range from 0 (low propensity to sleep) to 24 (high propensity to sleep.

Highest value compared with the groups described in Castro et al.1; ++ second highest value; - lowest value.

The results showed a pattern of circadian rhythm disturbance in the three cases, indicating the need for a personalized sleep hygiene program. Tests such as actigraphy and PSG are important to identify whether rhythm disturbances are a result of the challenge between chronotype and routine, of sleep deprivation per se, and/or of daytime sleepiness. Further studies with longer duration records and other rhythms such as temperature of the wrist and exposure to light can provide more insights into circadian rhythm disturbances and their conversion to psychosis.

The synchronization of circadian rhythms can be increased by regular routine and more exposure to light.5 Higher levels of physical activity should increase sleep rhythm amplitude and reduce sleep fragmentation. A sleep hygiene program can change the start and end times of sleep and its duration. Our results suggest that these changes to improve the circadian rhythm and sleep might help reduce conversions.

Disclosure

The authors report no conflicts of interest. BG was supported by a post-doctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grant 2015/09421-4).