Unveiling sleep mysteries: Sleep-wake cycle as a biological parameter of the circadian typology (Chronotype) / Revelando mistérios do sono: Ciclo sono-vigília como parâmetro biológico da tipologia circadiana (cronotipo)

The sleep-wake cycle that is circadian rhythm may have different patterns according to sex, environment and genetics determinants. This chronological cycle type, chronotype, may be populational expressed by the extremes, early or later going to bed and waking up, in a continuum. The first, the Morning-type individuals (the lark) and the later, the Evening types (the owl). Between the two extremes, there is the majority of these chronotypes ­ the intermediate ones. These patterns may be classified according to the questionnaires such as Horne and Ostberg Morningness/ Eveningness Questionnaire (MEQ) and the Munich Chrono Type Questionnaire (MCTQ). The rural population tends to be Morning-type, as well as children and younger women, more than men. The Morning person tends to be more healthy than the Evening ones who are more prone to diseases, as depression and metabolic syndrome. This basic knowledge may be helpful to patient's counseling and management: to avoid mismatch of circadian physiology and social duties / sleep. This circadian desynchrony can increase the risk of diseases, consequently there is a need to chrono-medicine into current treatment strategies.

O ciclo sono-vigília, que é um ritmo circadiano, pode ter padrões diferentes de acordo com os determinantes sexuais, ambientais e genéticos. Esse tipo de ciclo cronológico, cronótipo, pode ser expresso em termos populacionais pelos extremos, indo cedo ou mais tarde para a cama ou saindo dela, em um continuum. O primeiro, os indivíduos do tipo Manhã (a cotovia) e o posterior, os tipos da Tarde (a coruja). Entre os dois extremos, há a maioria desses cronotipos - os intermediários. Esses padrões podem ser classificados de acordo com questionários como o Horne e Ostberg Morningness/Eveningness Questionnaire (MEQ) e o Munich Chrono Type Questionnaire (MCTQ). A população rural tende a ser do tipo matutino, assim como crianças e mulheres mais jovens, mais que os homens.A pessoa da manhã tende a ser mais saudável do que as da noite, mais propensa a doenças, como depressão e síndrome metabólica. Esse conhecimento básico pode ser útil para o aconselhamento e tratamento dos pacientes: para evitar incompatibilidade entre a fisiologia circadiana e os deveres sociais / sono. Essa dessincronia circadiana pode aumentar o risco de doenças, consequentemente, é necessário a cronomedicina nas atuais estratégias de tratamento.

Assessment and Understanding of Chronotype / 수면정신생리

Chronotype (CT) is defined as an inter-individual difference in sleep-wake cycles and daily activities. Previous studies have suggested that this individual difference can influence our biological and psychological functioning. Literature regarding the psychometric properties and validity of CT measures are reviewed. We provide an overview of biological indicators (sleep-wake cycle, body temperature, cortisol, and melatonin) that are used for distinguishing two chronotypes: morningness (MT) and eveningness (ET). We also review the differences between CT in relation to personality traits and the occurrence of psychopathology. In addition, the methodological limitations of studies on CT are discussed. Finally, future research directions in terms of CT are proposed.

Association of the RORA Gene Polymorphism and Diurnal Preference in a Young Korean Population / 수면정신생리

OBJECTIVES: The retinoid-related orphan receptor A (RORA) gene has been reported to have an impact on circadian rhythm regulation. In this study, we analyzed the relationship between the RORA gene polymorphism and diurnal preference in Korean young adults. METHODS: A population of 504 young adults was included in the study. All subjects were given and completed a 13-item composite scale for morningness (CSM). The RORA gene rs11071547 single-nucleotide polymorphism (SNP) was genotyped by PCR-based methods. RESULTS: CSM score was not associated with genotype or allele carrier status of the RORA rs11071547 SNP. CONCLUSION: This result indicates that the RORA rs11071547 SNP does not play a role in diurnal preference.

Chronotype: a review of the advances, limits and applicability of the main instruments used in the literature to assess human phenotype / Cronotipo: uma revisão dos avanços, limites e aplicabilidade dos principais instrumentos utilizados na literatura para avaliar o fenótipo humano

The study of circadian typology differences has increased in the last few years. As a result, new instruments have been developed to estimate the individual circadian phase of temporal human behavior, also referred as chronotype. The current review was conducted to evaluate the differences among the questionnaires most frequently used to assess chronotype: the Morningness-Eveningness Questionnaire (MEQ), the Composite Scale of Morningness (CSM), and the Munich Chronotype Questionnaire (MCTQ). Each instrument evaluates a different aspect of chronotype. MEQ is considered to evaluate the phase preferences of individual behavior over a 24-hour day, while MCTQ measures the phase of sleep positions for both free and work days. CSM is similar to MEQ, but is more sensitive to measure shift work. The concept of chronotype has been used to refer to phase positions or phase preferences in the literature reviewed. Most of the time this is a consequence of different interpretations: it is not clear whether phase preferences are a direct manifestation of the individual’s internal clock or a result of external cues, e.g., social interaction (including the alarm clock). Also, phase preferences are not uniform throughout life. Therefore, a single assessment, not taking age into consideration, will not accurately describe the sample. We suggest that MCTQ is the best instrument for investigators dealing with desynchronization and as an instrument for sleep phase. Conversely, if the goal is to assess characteristics that change under specific situations - chronotype -, the MEQ should be used

O estudo das diferenças de tipologia circadiana tem aumentado nos últimos anos. Como resultado, novos instrumentos têm sido desenvolvidos para estimar as preferências interindividuais de fase circadiana, denominada de cronotipo, responsável pela organização temporal do processo de regulação do organismo. O objetivo desta revisão foi avaliar as diferenças dos principais questionários utilizados para avaliar cronotipos: o Questionário de Matutinidade e Vespertinidade (Morningness-Eveningness Questionnaire, MEQ), o Composite Scale of Morningness (CSM) e o Questionário de Cronotipo de Munique (Munich Chronotype Questionnaire, MCTQ). Cada instrumento avalia um aspecto diferente dos cronotipos. Considera-se que o MEQ avalia as preferências de fase do comportamento individual ao longo de um dia de 24 horas, ao passo que o MCTQ mede a posição da fase de sono tanto em dias livres como em dias de trabalho. O CSM é semelhante ao MEQ, mas é mais sensível para ser utilizado em indivíduos que realizam trabalho em turnos. O conceito de cronotipo tem sido utilizado para se referir a posições de fase ou preferências de fase na literatura revisada. Na maioria das vezes, isso é consequência de diferentes interpretações: não está claro se as preferências de fase são uma manifestação direta do relógio interno do indivíduo ou um resultado de sinais externos, como por exemplo, interação social (incluindo o uso de despertador). Além disso, as preferências de fase não são uniformes ao longo da vida. Sendo assim, uma única avaliação, sem levar em consideração a idade do indivíduo nos escores utilizados nessas escalas, não descreverá a amostra com precisão. Sugerimos, através desta revisão, que o MCTQ deve ser considerado como instrumento para investigações que lidam com dessincronização e como instrumento de medida de fase de sono. Por outro lado, se o objetivo é avaliar características que mudam em determinadas situações - cronotipo -, o MEQ deve ser utilizado

Sleep Wake Patterns and Nocturnal Sleep Parameters in the Morning and Evening Types / 신경정신의학

OBJECTIVES: The aim of our study was to compare sleep wake patterns and nocturnal sleep parameters between the morning type (MT) and evening type (ET). METHODS: The Morningness-Eveningness Questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Korean version of the Epworth Sleepiness Scale (KESS) were administered to subjects recruited among visitors to the Chuncheon National Museum from 2010 to 2011. Actigraphy data (Actiwatch-2, Philips-Respironics Co.) were collected from eight MT (Age 38.0+/-3.8, M : F=2 : 6), 12 neither type (NT) (Age 34.2+/-5.1, M : F=2 : 10), and nine ET (Age 30.3+/-6.8, M : F=2 : 7) subjects. RESULTS: Scores for PSQI and KESS did not differ significantly among the MT, NT, and ET groups. No differences in time in bed, total sleep time, sleep efficiency, wake after sleep onset, sleep latency, and fragmentation index were observed among the three groups. In the ET group, the mean wake time on free days was significantly later, and the mean sleep duration on free days was significantly longer, compared with those of the MT group (p<0.01). CONCLUSION: No differences in sleep quality, daytime sleepiness, and nocturnal sleep parameters were observed among the MT, NT, and ET groups. Compared to MT subjects, ET subjects showed later wake time and longer sleep duration on free days.

Association Study between Per3 Gene Polymorphism and Diurnal Preference / 수면정신생리

OBJECTIVE: Diurnal preference is an attribute reflecting whether people are alert and preferring to be active either early or late in the day. It also referred to as chronotype or morningness-eveningness trait. The PER3 genes have been known to influence diurnal preference. In this study, we have investigated the associations between the PER3 gene polymorphisms and diurnal preference in a healthy young population, controlling for the social and environmental confounding factors. METHODS: The participants in this experiment included 299 unrelated medical college students (M=191, F=108), with a mean age of 22.9 years. Diurnal preference was measured by a single administration of the 13-item Composite Scale for Morningness (CSM). Genotyping of the PER3 VNTR (rs57875989) was performed using polymerase chain reaction. A two-tailed alpha of 0.05 was chosen. RESULTS: The mean+/-SD score on the CSM scale for all subjects was 31.90+/-6.39. There was no significant difference in total CSM score between gender groups, although females showed a trend towards higher morningness score. Although PER3 5R/5R showed the tendency towards high CSM scores, there were no significant differences on CSM scores among genotypes and allele status of PER3 VNTR (rs57875989). CONCLUSIONS: We could not confirm that the PER3 VNTR is associated with diurnal preference in a Korean healthy young population. The future studies need to investigate the association between diurnal preference and other polymorphisms of PER3 gene in larger sample of Korean young healthy population.

Interactions of polymorphisms in different clock genes associated with circadian phenotypes in humans

Several studies have shown that mutations and polymorphisms in clock genes are associated with abnormal circadian parameters in humans and also with more subtle non-pathological phenotypes like chronotypes. However, there have been conflicting results, and none of these studies analyzed the combined effects of more than one clock gene. Up to date, association studies in humans have focused on the analysis of only one clock gene per study. Since these genes encode proteins that physically interact with each other, combinations of polymorphisms in different clock genes could have a synergistic or an inhibitory effect upon circadian phenotypes. In the present study, we analyzed the combined effects of four polymorphisms in four clock genes (Per2, Per3, Clock and Bmal1) in people with extreme diurnal preferences (morning or evening). We found that a specific combination of polymorphisms in these genes is more frequent in people who have a morning preference for activity and there is a different combination in individuals with an evening preference for activity. Taken together, these results show that it is possible to detect clock gene interactions associated with human circadian phenotypes and bring an innovative idea of building a clock gene variation map that may be applied to human circadian biology.

The search for circadian clock components in humans: new perspectives for association studies

Individual circadian clocks entrain differently to environmental cycles (zeitgebers, e.g., light and darkness), earlier or later within the day, leading to different chronotypes. In human populations, the distribution of chronotypes forms a bell-shaped curve, with the extreme early and late types _ larks and owls, respectively _ at its ends. Human chronotype, which can be assessed by the timing of an individual's sleep-wake cycle, is partly influenced by genetic factors - known from animal experimentation. Here, we review population genetic studies which have used a questionnaire probing individual daily timing preference for associations with polymorphisms in clock genes. We discuss their inherent limitations and suggest an alternative approach combining a short questionnaire (Munich ChronoType Questionnaire, MCTQ), which assesses chronotype in a quantitative manner, with a genome-wide analysis (GWA). The advantages of these methods in comparison to assessing time-of-day preferences and single nucleotide polymorphism genotyping are discussed. In the future, global studies of chronotype using the MCTQ and GWA may also contribute to understanding the influence of seasons, latitude (e.g., different photoperiods), and climate on allele frequencies and chronotype distribution in different populations.

Caracterização e distribuição de cronotipos no sul do Brasil: diferenças de gênero e estação de nascimento / Characterization and distribution of chronotypes in southern Brazil: gender and season of birth differences

OBJETIVO: Investigar a tipologia circadiana e as diferenças de gênero em universitários do sul do Brasil. MÉTODOS: Voluntários (736) de 17 a 49 anos preencheram a versão brasileira do Questionário de Cronotipo (QC), tradução do Morningness-eveningness Questionnaire (MEQ) de Horne e Õstberg. Medidas de tendência central e dispersão e curva de distribuição dos escores do QC (Kolmogorov-Smirnov) foram calculadas de acordo com gênero (teste t de Student), idade, estação de nascimento e desconforto com o horário de verão (qui-quadrado). RESULTADOS: Foram incluídos 648 indivíduos (36 por cento homens, 64 por cento mulheres), com perdas de 12 por cento por questionários incorretos. A distribuição dos escores do QC evidenciou uma curva normal (amplitude = 18-77; média = 46,6; desvio-padrão = 10,8). Nesta amostra, 32 por cento foram vespertinos, 54 por cento intermediários e 14 por cento matutinos. As médias do QC foram significativamente diferentes (p = 0,003): homens (44,9 ± 10,8) comparados com mulheres (47,5 ± 10,7) e 70 por cento dos que nasceram na primavera e no verão foram vespertinos (p = 0,015), sem associação gênero-estação do ano. CONCLUSÃO: Homens e nascidos na primavera-verão evidenciaram preferência pela vespertinidade, não havendo diferença de gênero com relação à estação de nascimento. Nossos resultados estão de acordo com estudos realizados no hemisfério norte que mostraram, também, uma associação entre a estação de nascimento e o cronotipo.

OBJECTIVE: To analyze circadian typology (diurnal preference) and gender differences in a university student population from Southern Brazil. METHODS: Seven hundred and thirty six university student volunteers, with an age range 17-49 years, filled the Brazilian version of the Chronotype Questionnaire (CQ), the portuguese translation of the Horne and Õstberg's Morningness-Eveningness Questionnaire (MEQ). Central and dispersion tendencies measures and CQ scores distribution curve (Kolmogorov-Smirnov) were calculated according to gender (Student t), age, birth season, and daylight-saving time discomfort (qui-square). RESULTS: Six hundred and fourty eight individuals (36 percent men; 64 percent women) were included in this study, with 12 percent of losses due to incorrect questionnaires. CQ score distribution was correlated to the normal curve (range=18-77; mean=46.6; s.d.=10.8). In this sample, 32 percent were evening-types; 54 percent were intermediate-types, and 14 percent were morning-types. CQ means were significatively different (p=0.003) when males (44.9±10.8) were compared to females (47.5±10.7), and 70 percent of those born during spring and summer were evening-types (p=0.015).There was no gender-by-season association. CONCLUSIONS: Men, and Individuals born in spring and summer, presented eveningness preference, without gender-birth season interaction. Our results are also in agreement with studies performed in the Northern Hemisphere, which showed an association between birth season and diurnal preference.