ArticlePDF AvailableLiterature Review

Circadian Misalignment and Health

June 2014
International Review of Psychiatry 26(2)

DOI:10.3109/09540261.2014.911149

Authors:

Kelly Glazer Baron

Rush University Medical Center

Kathryn J Reid

Northwestern University

Circadian rhythms are near 24-h patterns of physiology and behaviour that are present independent of external cues including hormones, body temperature, mood, and sleep propensity. The term ‘circadian misalignment’ describes a variety of circumstances, such as inappropriately timed sleep and wake, misalignment of sleep/wake with feeding rhythms, or misaligned central and peripheral rhythms. The predominance of early research focused on misalignment of sleep to the biological night. However, discovery of clock genes and the presence of peripheral circadian oscillators have expanded the definitions of misalignment. Experimental studies conducted in animal models and humans have provided evidence of potential mechanisms that link misalignment to negative outcomes. These include dysregulation of feeding behaviours, changes in appetite stimulating hormones, glucose metabolism and mood. This review has two foci: (1) to describe how circadian misalignment has been defined and evaluated in laboratory and field experiments, and (2) to describe evidence linking different types of circadian misalignment to increased risk for physical (cardiovascular disease, diabetes, obesity, cancer) and psychiatric (depression, bipolar, schizophrenia, attention deficit) disorders. This review will describe the role of circadian misalignment as a risk factor for disease in the general population and in clinical populations, including circadian rhythm sleep disorders and psychiatric disorders.

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(Received 7 March 2014 ; accepted 31 March 2014 )

Circadian misalignment and health

KELLY GLAZER BARON & KATHRYN J. REID

Feinberg School of Medicine, Northwestern University, Chicago, Illinois USA

Abstract

Circadian rhythms are near 24-h patterns of physiology and behaviour that are present independent of external cues

including hormones, body temperature, mood, and sleep propensity. The term ‘ circadian misalignment ’ describes a variety

of circumstances, such as inappropriately timed sleep and wake, misalignment of sleep/wake with feeding rhythms, or

misaligned central and peripheral rhythms. The predominance of early research focused on misalignment of sleep to the

biological night. However, discovery of clock genes and the presence of peripheral circadian oscillators have expanded the

deﬁ nitions of misalignment. Experimental studies conducted in animal models and humans have provided evidence of

potential mechanisms that link misalignment to negative outcomes. These include dysregulation of feeding behaviours,

changes in appetite stimulating hormones, glucose metabolism and mood. This review has two foci: (1) to describe how

circadian misalignment has been deﬁ ned and evaluated in laboratory and ﬁ eld experiments, and (2) to describe evidence

linking different types of circadian misalignment to increased risk for physical (cardiovascular disease, diabetes, obesity,

cancer) and psychiatric (depression, bipolar, schizophrenia, attention deﬁ cit) disorders. This review will describe the role

of circadian misalignment as a risk factor for disease in the general population and in clinical populations, including

circadian rhythm sleep disorders and psychiatric disorders.

Introduction

General

All organisms, ranging from single cell organisms,

plants, sea slugs to humans, demonstrate circadian

rhythms or near 24-h patterns which are present

independent of environmental cues. Disruption of

circadian rhythms, through extrinsic factors such

as shift work and intrinsic factors such as circadian

disorders, has been associated with both physical

and psychiatric consequences (Bass, 2012; Lam &

Levitan, 2000). The goals of this review are to

describe how circadian misalignment has been

operationalized and then describe the role of circa-

dian rhythm misalignment in the development of

chronic illnesses including cardiovascular disease,

diabetes, obesity and cancer as well as psychiatric

disorders such as mood disorders. This review has

four main sections. In the ﬁ rst part of the review,

we describe the circadian system and the ways that

circadian misalignment has been deﬁ ned. Next, we

discuss how circadian misalignment has been stud-

ied in the laboratory. The third section of the arti-

cle reviews the ﬁ eld studies of populations at risk

for circadian misalignment and related physical

and psychiatric consequences. These populations

include transient misalignment associated with

daylight saving time, chronotype and social jet lag.

The ﬁ nal section will focus on circadian misalign-

ment in clinical populations: circadian rhythm

sleep disorders, night eating syndrome (NES) and

psychiatric disorders.

Search strategy

In order to prepare this article, the authors searched

PubMed and selected articles to provide a broad over-

view of the ﬁ eld of circadian misalignment, focusing

primarily on cardiovascular disease, diabetes, obesity,

cancer, depression and bipolar disorder. Our search

included the following terms: ‘ circadian rhythm ’ , ‘ cir-

cadian misalignment ’ , ‘ chronotype ’ , ‘ social jet lag ’ ,

‘ shift -work ’ , ‘ jet lag ’ , ‘ delayed sleep phase ’ , ‘ advance

sleep phase ’ , ‘ irregular sleep ’ , ‘ non-24 h ’ , ‘ free run-

ning ’ , ‘ phase angle ’ , ‘ night eating syndrome ’ , and ‘ sea-

sonal affective disorder ’ . This article is not a systematic

review encompassing all published articles of circadian

misalignment, physical and mental health. Although

our review includes several important animal studies,

this review mostly focuses on human studies.

International Review of Psychiatry, April 2014; 26(2): 139–154

DOI: 10.3109/09540261.2014.911149

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140 K. G. Baron &. K. J. Reid

Circadian rhythms

In order to understand the consequences of mis-

alignment, it is ﬁ rst necessary to have a basic

understanding of circadian rhythms. The term

circadian is derived from Latin to mean ‘ about a

day ’ and refers to the roughly 24-h rhythm

generated by the suprachiasmatic nucleus (SCN),

located in the anterior hypothalamus (Schibler &

Sassone-Corsi, 2002). Numerous physiological

and behavioural processes demonstrate circadian

rhythms, including body temperature, hormones

such as cortisol and melatonin, as well as behav-

ioural factors such as cognition and mood. The

sleep/wake rhythm is one of the most important

and observable circadian rhythms. The circadian

clock is not exactly 24 h, and will ‘ free run ’ when

away from external cues (Czeisler et al., 1999).

Therefore, these external zeitgebers or ‘ time givers ’

such as light, endogenous melatonin and to a lesser

extent physical and social activity are important

factors for synchronizing the circadian rhythm to

the 24-h day (Baehr et al., 2003; Barger et al.,

2004; Goel, 2005). The timing of these zeitgebers

is highly important, in that they will have a differ-

ent effect on the circadian rhythm depending on

the time of exposure (Khalsa et al., 2003; Kripke

et al., 2007; Lewy, 2007). For example, morning

light will advance (move earlier) whereas evening

light will delay (move later) the circadian rhythm

(Duffy & Wright, 2005; Strogatz, 1990). Endoge-

nous melatonin, released by the pineal gland under

conditions of darkness, suppresses the signal of the

SCN (Moore, 1996). Exogenous melatonin also

shifts circadian phase, based on time of administra-

tion, but in the opposite direction to light exposure

(Burgess et al., 2010; Lewy et al., 1992).

Circadian rhythms are coordinated by the SCN

or ‘ master clock ’ ; however, the molecular mecha-

nism of the clock is present in every cell of the body.

Circadian or clock genes (in humans, e.g. CLOCK ,

CRY , PER , BMAL ) comprise an autoregulatory

transcriptional-translational feedback loop which

demonstrates a cycle every 24 h (Hardin et al.,

1990; Loros & Dunlap, 1991). In addition to indi-

vidual cells, rhythms are also generated among

organs including the heart, stomach, liver and pan-

creas (Dibner et al., 2010). Circadian patterns are

also present among physiological systems, includ-

ing the cardiovascular and renal systems (Dibner

et al., 2010; Gachon et al., 2004). These peripheral

rhythms have a unique phase relationship with the

master clock which is coordinated through neuronal

pathways, neuropeptides and hormones. Several

excellent reviews have been published on this topic

(Bass, 2012; Brown & Azzi, 2013; Zelinski et al.,

2014).

Circadian misalignment

The term ‘

circadian misalignment ’ can describe a

variety of circumstances both in the laboratory and

natural environment. In the Oxford Dictionary (2010),

‘ misalignment ’ refers to ‘ the incorrect arrangement

or position of something in relation to something

else ’ . One of the most common types of misalign-

ment studied is misalignment of the sleep/wake cycle

in relation to the biological night. Other types of mis-

alignment include misalignment of feeding rhythms

to the sleep/wake or light/dark cycle, or internal mis-

alignment of central and peripheral rhythms. Figure 1

presents a schematic depiction of the organization of

the central and peripheral circadian rhythms. This

diagram includes zeitgebers (light, melatonin and

activity) as well as the potential causes of chronic

circadian misalignment. The timing of melatonin

onset under dim light conditions (dim light mela-

tonin onset or DLMO) and the core body tempera-

ture minimum are often used as markers of circadian

timing (Benloucif et al., 2008). The timing of these

circadian markers in relation to sleep/wake behav-

iours is commonly referred to as phase angle, and

has also been used as a measure of circadian align-

ment (Figure 2). For example, the duration between

circadian markers (DLMO or core body temperature

minimum) and sleep timing (onset, midpoint or

wake time) has been evaluated. Individuals with eve-

ning chronotype (preference for later timing of sleep

and activity) have been shown in some studies to

have a shorter phase angle between circadian mark-

ers and sleep, indicating that they sleep and wake

earlier in their circadian phase (Duffy et al., 2001;

Mongrain et al., 2006). One of the most signiﬁ cant

and immediate consequences of misalignment of the

sleep/wake cycle to the biological night is sleep dis-

turbance and/or daytime sleepiness. Insomnia, difﬁ -

culty waking in the morning and sleepiness caused

by circadian misalignment are typical symptoms that

lead patients to seek care in sleep clinics for circadian

disorders. However, the physiological and psycho-

logical consequences are much broader than sleep/

wake disturbance. These include changes in feeding

patterns, metabolic function and risk for mood dis-

orders. Other types of disruption include internal

misalignment of rhythms, such as timing of central

versus peripheral clocks. For example, research in

animal models has demonstrated that altering avail-

ability of food timing shifts peripheral (e.g. hepatic)

but not central rhythms (Stokkan et al., 2001).

Mechanisms

Laboratory methods

In order to more precisely study the mechanisms

linking circadian misalignment to physiological and

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Circadian misalignment and health 141

psychiatric conditions, researchers have developed

protocols to isolate the circadian rhythm from the

sleep/wake cycle. Multiple studies have used tempo-

rary phase shifts to study the effect of misalignment

and demonstrate changes in leptin rhythm and

glucose response to meals (Hampton et al., 1996;

Schoeller et al., 1997) as well as increased depressed

mood (Surridge-David et al., 1987). However, these

approaches are limited due to the associated sleep

loss. One of the most commonly reported techniques

is forced desynchrony (Czeisler et al., 1986; Dijk

et al., 1992; Kleitman & Kleitman, 1953). In this pro-

tocol, individuals are scheduled for a ‘ day ’ that is

shorter or longer than 24 h (typically 20 or 28 h), and

then sleep and meal timing is shifted either earlier or

later around the clock. The circadian timing system

cannot adjust to this ‘ day ’ length and thus runs free

at its own endogenous period, which is slightly longer

than 24 h in humans. This technique allows research-

ers to estimate sleep, mood, and performance at var-

ious degrees of circadian misalignment. These studies

have also demonstrated that circadian misalignment

causes disruptions in appetite-regulating hormones,

glucose metabolism and mood.

Laboratory studies with misalignment of the

sleep/wake rhythm

In a forced desynchrony protocol to simulate the

experience of living on Mars, individuals were

Entraining Agents:

•

Light

• Melatonin

• Activity

Potential Causes of Chronic

Misalignment

• Chronotype

• Social Jet Lag

• Shift Work

• Circadian Rhythm

Disorders

• Disrupted Feeding

Rhythm

• Psychiatric Disorders

ANS

Behaviors

Hormones

Heart Lungs Adipose Pancreas Liver Stomach Red Blood Cells Breast Muscle

Circadian Clock

Genes (Brain and

Peripheral Cells)

Central Circadian

Pacemaker (SCN)

Peripheral

Rhythms in Cells,

Organs and

Tissues

Light/Dark Cycle

Figure 1. Representation of central and peripheral circadian rhythms. This ﬁ gure depicts the relationship between central and peripheral

circadian rhythms. Circadian genes are present in every cell in the body. The central circadian rhythm is generated by the suprachiasmatic

nucleus. The light/dark cycle is one of the main entraining agents for the central rhythm. Peripheral rhythms are present in cells, organs

and organ systems. The coordination between the central and peripheral rhythms is not fully understood but involves hormonal, neurological

and behavioural pathways. Misalignment can occur when the central rhythm is misaligned to the light/dark cycle or when central and

peripheral rhythms are misaligned.

16:00 18:00 20:00 22:00 0:00 02:00 04:00 06:00 08:00 10:00

Figure 2. Circadian phase and phase angle between melatonin and

sleep. The curved lines depict examples of the nocturnal melatonin

rhythm in individuals with normal phase (solid line) and phase

delay (dotted line). The bars below indicate the sleep periods in

normal phase (black bar) and phase delay (grey bar). Phase angles

between dim light melatonin onset (DLMO) and midpoint of

sleep are depicted with lines and arrows. Compared with the

normal alignment, the phase delayed example demonstrates a later

DLMO and a shorter duration or phase angle between DLMO

with sleep onset and midpoint of the sleep period.

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142 K. G. Baron &. K. J. Reid

assigned to a 24-h day or a 24.6-h day for 25 days.

Interestingly, some individuals were capable of

entraining their circadian rhythms and others were

not (Gronﬁ er et al., 2007; Wright et al., 2001).

Results indicated that those who were non-entrained

had poorer sleep quality, shorter sleep duration, and

had lower leptin during wakefulness. Results from a

later study also demonstrated decreased leptin and

higher glucose response to meals despite higher insu-

lin production associated with this misalignment

(Scheer et al., 2009). Most recently, a study com-

pared 3 days of phase advance to 3 days of phase

delay (21-h day versus a 27-h day), with a 4-week

wash-out period in between the two conditions

(Gonnissen et al., 2012). Results demonstrated that

in the phase delay condition, total sleep time was

related to levels of insulin and insulin resistance. In

a later analysis, it was determined that speciﬁ cally,

decreased REM in the second half of the night was

predictive of changes in cortisol, insulin and insulin

resistance (Gonnissen et al., 2013). Since REM is

modulated by the circadian clock, this suggests a role

of circadian misalignment in the metabolic changes

reported in this study.

The circadian rhythm of mood has been demon-

strated in multiple studies (Wirz-Justice, 2008).

These daily variations in mood have been studied in

forced desynchrony and have been demonstrated to

have a signiﬁ cant circadian pattern as well as an

interaction with prior wakefulness, in that the trough

of mood was lowest around the time of the core body

temperature minimum, and also deteriorated over

the wake period (Boivin et al., 1997). This relation-

ship has been demonstrated among healthy controls

as well as individuals with seasonal affective disorder

(SAD) (Koorengevel et al., 2003).

Laboratory studies of misalignment of feeding rhythms

Multiple experiments in animal models have demon-

strated the effects of mistimed feeding on sleep,

rhythms and cardiometabolic disease risk (Arble

et al., 2009; Fonken et al., 2010). Kohsaka and col-

leagues (2007) demonstrated that high-fat feeding

disrupts the circadian timing of mice, giving them a

longer circadian period (greater than 24 h) and also

increased fragmentation of their sleep and feeding

rhythms. Another study highlighted the possible del-

eterious effects of eating during the sleep period.

Mice fed during the light period (biological night)

consumed the same number of calories but gained

twice as much weight as mice fed during the dark

period (Arble et al., 2009). Further studies have

demonstrated that light and feeding period also play

a role. Fonken and colleagues (2010) demonstrated

weight gain in mice kept in constant bright light

compared with those kept in constant dim light and

standard 12-h light/dark cycle. However, the effects

of bright light were ameliorated when food was

restricted only to the dark phase (the typical feeding

time). Another study demonstrated that feeding mice

high-fat diets only during the dark phase prevented

the development of metabolic syndrome (Hatori

et al., 2012). At this point, only one study in humans

has evaluated the metabolic effects of meal timing in

an experimental design (Jakubowicz et al., 2013). In

this study, women with polysyctic ovarian syndrome

were assigned to two isocaloric weight loss diets for

12 weeks. Both diets were approximately 1400 kcal

per day. One diet contained a large breakfast (700

kcal) moderate lunch (500 kcal) and small dinner

(200 kcal). The other contained a small breakfast

(200 kcal), moderate lunch (500 kcal) and large din-

ner (700 kcal). Results indicated that participants in

the high calorie breakfast group demonstrated greater

insulin sensitivity following the intervention. This

study demonstrates that changing the timing of

caloric intake has the potential to inﬂ uence meta-

bolic processes in humans. However, this study did

not evaluate circadian alignment.

In summary, the effects of misalignment of sleep/

wake patterns as well as misalignment of feeding with

the light/dark cycles have been tested in experimental

protocols in human and animal models. Results sug-

gest potential mechanisms that may link misalign-

ment to poor health are broad and include changes

in mood, behaviour, appetite-regulating hormones

and glucose metabolism.

Circadian misalignment in naturalistic settings

Circadian misalignment occurs in many different

‘ real world ’ settings. Some types of misalignment are

transient, such as daylight saving time or time zone

travel. Other types of misalignment are chronic,

such as individuals ’ preference for sleep/wake timing

(i.e. chronotype), the change in schedule between

weekend and weekdays (social jet lag), or circadian

rhythm sleep disorders. We will ﬁ rst discuss mis-

alignment that affects the population as a whole,

including daylight saving time, chronotype and

social jet lag. The ﬁ nal section of the paper will dis-

cuss clinical populations, including circadian rhythm

sleep disorders, NES and psychiatric disorders.

Although shift work and jet lag do not always lead

to clinical disorders, they will be discussed in the

clinical disorders section.

Circadian misalignment in daylight saving time

Daylight saving time (DST) is a naturalistic experi-

ment that allows researchers to observe a transient

period of circadian misalignment as well as changes

in sleep duration at the population level (Kantermann

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Circadian misalignment and health 143

et al., 2007). Multiple studies have demonstrated a

small to modest increase in myocardial infarction risk

after the 1-h phase advance in the spring, with the

greatest increase in risk during the ﬁ rst day or two

after the shift. (Janszky et al., 2012; Janszky & Ljung,

2008). This relationship has also been documented

in stroke (Foerch et al., 2008). Fewer studies have

focused on the psychiatric effects of daylight saving

time. There is a well-established link between spring

DST, sleep loss and daytime sleepiness (Harrison,

2013; Lahti et al., 2008b). However, existing studies

have found no relationship between psychiatric

disturbance and DST. Two studies found no associa-

tion between DST transition and incidence of

manic episodes (Lahti et al., 2008a) or in psychiatric

service utilization, including outpatient visits, inpa-

tient admissions, or suicide attempts (Shapiro et al.,

1990).

Chronotype and social jet lag

Chronotype, or preference for timing of sleep and

wake behaviuors, is theorized to contribute to circa-

dian misalignment in the population. Large epide-

miological surveys demonstrate that chronotype is a

characteristic with a normal bell-shaped distribution

that varies by age and gender, in that the young and

the old demonstrate an earlier chronotype, and ado-

lescents and young adults demonstrate a later chro-

notype (Roenneberg et al., 2007). Additionally,

women report a slightly earlier chronotype than men

across their lifespan. Chronotype can be evaluated as

a continuous variable with morningness and eve-

ningness being two sides of the same dimension.

Someone can report ‘ greater eveningness ’ or ‘ less

morningness ’ depending on the perspective of the

researcher and the particular questionnaire. Addi-

tionally, individuals may be grouped at cut points

into ‘ morning types ’ , ‘ neither morning nor evening ’

and ‘ evening types ’ . Being either a late or early chro-

notype may cause misalignment because the indi-

vidual ’ s preferences for sleep and activity are at odds

with the typical workweek or social schedule. Chro-

notype is typically measured by questionnaires

including the Morning Eveningness Questionnaire

(Horne & Ostberg, 1976), the Munich Chronotype

Questionnaire (Zavada et al., 2005) or the Compos-

ite Scale of Morningness (Smith et al., 1989). The

ease of self-report questionnaires compared to the

measurement of objective circadian markers may

explain why there are so many articles published

about chronotype. However, there is evidence that

chronotype is associated with timing of melatonin

and core body temperature (Baehr et al., 2000; Fol-

kard et al., 1979; Waterhouse et al., 2001). There is

some evidence of misalignment associated with chro-

notype, in that those with an evening-type preference

(i.e. prefer to go to bed late and wake up late), sleep

earlier in their biological rhythm, and wake closer to

core body temperature minimum (Duffy et al., 2001;

Kerkhof & Lancel, 1991). Mongrain and colleagues

(2006) also reported that compared with morning

types, evening types demonstrated a phase delay as

well as a shorter phase angle between DLMO and

sleep among some but not all evening types. Being

an evening chronotype may predispose individuals to

shorter sleep duration during workdays, due to the

need to conform to typical work hours (Roenneberg

et al., 2007). However, evening chronotypes also

report longer sleep on free days, in order to compen-

sate for shorter weekday sleep duration. The majority

of studies of chronotype account for sleep duration

in statistical models. However, few studies of chro-

notype and health measure circadian markers or

phase angles.

There are only a handful of studies evaluating chro-

notype and risk for cardiovascular disease and diabe-

tes. This is possibly because circadian timing and

alignment has more recently become of interest to

researchers studying physical health. One of the earli-

est studies demonstrated in a cross-sectional study

that evening types were 2.5 times more likely to report

their general health was poor or fair compared with

morning types (Paine et al., 2006). The study by

Paine and colleagues did not control for sleep dura-

tion, however the majority of later studies include a

measure of self-reported sleep duration in statistical

models. In one of the only large epidemiological stud-

ies of chronotype and objectively measured health

outcomes, Merikanto and colleagues (2013b) dem-

onstrated in a cross-sectional study a 2.5-fold increase

in type II diabetes prevalence among evening types

and a 1.3-fold increase in hypertension prevalence. In

another investigation they reported greater risk for

asthma among evening types (Merikanto et al., 2014).

Reutrakul and colleagues (2013) demonstrated that

later chronotype was associated with poorer glycae-

mic control in a sample of patients with type II dia-

betes, independent of sleep duration and quality.

Longitudinal research is needed to determine whether

chronotype is related to increased incidence of car-

diovascular disease and diabetes over time.

Several studies have demonstrated greater risk for

obesity in evening chronotypes (Baron et al., 2011;

Lucassen et al., 2013). Evening chronotype was

associated with greater body fat among a sample of

participants with bipolar disorder (Soreca et al.,

2009). One study reported higher BMI associated

with later DLMO and shorter phase angle between

DLMO and sleep among depressed peri- or post-

menopausal women (Meliska et al., 2011). This is

the only study that draws a direct link between mis-

alignment and increased risk of obesity among eve-

ning chronotypes.

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144 K. G. Baron &. K. J. Reid

Lifestyle factors are also suggested to play a role

in this increased risk of obesity among evening chro-

notypes. Monk and colleagues (2004) reported that

morning types exhibit more lifestyle regularity com-

pared with evening types. Multiple studies have

reported larger dinners, poorer diet quality, and more

calories consumed in the evening (Fleig & Randler,

2009; Sato-Mito et al., 2011). Greater eveningness

was associated with higher scores on a binge eating

disorder questionnaire (Harb et al., 2012). Evening

chronotype has also been associated with smoking,

alcohol use and lower physical activity (Kabrita et al.,

2014; Urban et al., 2011).

To date, there is only one study published evalu-

ating chronotype and misalignment and cancer. In

a recent study, breast cancer survivors had a shorter

disease-free interval in metastatic breast cancer if

bedtimes were ‘ misaligned ’ (Hahm et al., 2014) as

well as in individuals with later chronotype. Both

chronotype and misalignment were independent

predictors of disease-free interval. This study deﬁ ned

misalignment as a self-reported bedtime earlier or

later than the preferred bedtime. Further research

is needed to determine the role of chronotype in

cancer incidence, disease progression and treatment

outcomes.

Social jet lag

‘ Social jet lag ’ is another proposed cause of circadian

misalignment in the general population (Wittmann

et al., 2006). It is deﬁ ned as the shift in schedule

between workdays and free days, in that most indi-

viduals use an alarm clock to rise earlier on workdays/

school days and sleep later on the weekends or days

off from work. In a sense, social jetlag is a measure

of misalignment between the individual ’ s schedule

for work and their internal schedule. Epidemiological

research has demonstrated that most individuals have

shifts in their sleep between workdays and free days

(Roenneberg et al., 2003, 2007). Evening chrono-

types are prone to larger social jet lag due to the need

to conform to a conventional work schedule. In an

analysis of a large database of 65,000 participants,

social jet lag was associated with higher BMI above

and beyond sleep duration and chronotype only for

overweight individuals (Roenneberg et al., 2012).

There was no relationship among normal weight

individuals. Social jet lag has also been associated

with smoking, alcohol consumption and caffeine con-

sumption (Wittmann et al., 2010).

Chronotype, social jet lag and psychiatric disorders

There is a large amount of literature demonstrating

a greater risk of depression and higher depressive

symptoms among evening chronotypes. Multiple

studies in high school, college and medical school

students as well as the general adult population dem-

onstrate a positive association between evening chro-

notype and depressive symptoms (Chelminski et al.,

1999; Hirata et al., 2007; Kim et al., 2010; Kitamura

et al., 2010; Merikanto et al., 2013a). Individuals

diagnosed with major depressive disorder report

greater eveningness than healthy controls (Drennan

et al., 1991) and later chronotype is an indicator of

greater depression severity among individuals diag-

nosed with major depressive disorder (Gaspar-Barba

et al., 2009). One study demonstrated that social jet

lag is associated with depressive symptoms above and

beyond chronotype and sleep duration, suggesting

that the chronic misalignment from weekdays to

weekends is an additional risk factor (Levandovski

et al., 2011).

Chronotype has also been linked to greater risk for

other psychiatric disorders or greater severity of psy-

chiatric symptoms including bipolar disorder and

attention deﬁ cit hyperactivity disorder (ADHD).

Multiple studies demonstrate greater evening-type

preference among individuals with bipolar disorder

(both I and II) compared with healthy controls or

individuals with schizophrenia or schizoaffective dis-

orders. (Ahn et al., 2008; Chung et al., 2012; Giglio

et al., 2010; Mansour et al., 2005; Wood et al., 2009).

There is one study demonstrating that sleep timing

and daytime sleepiness were signiﬁ cant predictors of

symptom severity among individuals with ADHD,

above and beyond sleep duration (Gamble et al.,

2013). A limitation of this study is that it did not

have a measure of preferred sleep timing or circadian

markers, and therefore it is unknown the degree to

which misalignment was associated with symptoms.

In summary, having an evening chronotype is asso-

ciated with misalignment of the preferred sleep tim-

ing to external demands. Some studies have linked

evening chronotype to misalignment of the sleep/

wake period relative to circadian markers but few

studies of disease risk measure objective circadian

markers. Chronotype has been linked to greater

psychiatric symptoms (particularly depression) and

poorer health behaviours in many studies. More

recent studies are beginning to reveal the relationship

between chronotype and risk for cardiovascular dis-

ease and diabetes. At this time, mechanisms by which

chronotype affects health outcomes are poorly under-

stood. Misalignment is hypothesized to play a role,

but few studies include subjective or objective mea-

sures of circadian misalignment. Studies have dem-

onstrated that clock genes, most notably PER3

polymorphisms, may contribute to the determination

of chronotype through affecting sleep/wake regula-

tion and intrinsic circadian period (Dijk & Archer,

2010). There has also been a relationship reported

between some of the clock genes and psychiatric

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Circadian misalignment and health 145

disorders (Bersani et al., 2012; Etain et al., 2011;

Mansour et al., 2009; McCarthy & Welsh, 2012;

Takahashi et al., 2008). For example, alteration in

circadian clock proteins in the circadian pacemaker

is associated with mania-like behaviour in mice

(Roybal et al., 2007). In addition, in a few human

genetic studies, there is evidence for weak associa-

tions between circadian gene polymorphisms and

mood disorders (Takahashi et al., 2008). For exam-

ple, a polymorphism in NPAS2 has been associated

with SAD (Johansson et al., 2003), and PER3 ,

BMAL1 , and CLOCK have been associated with

bipolar disorder (Benedetti et al., 2003, 2008; Desan

et al., 2000; Nievergelt et al., 2006). However,

other circadian clock genes such as CLOCK and

PER2 have shown no link with affective disorders, or

CRY1 with bipolar disorders (Bailer et al., 2005;

Desan et al., 2000; Nievergelt et al., 2005). Examina-

tion of molecular changes in evening types with and

without psychiatric diagnosis may be extremely use-

ful in elucidating the role of the circadian clock in

mental health. These data suggest a shared genetic

vulnerability for evening chronotypes to experience

circadian phase delay, chronic misalignment, and

increased risk of psychiatric and medical disorders.

Misalignment in clinical populations

Circadian rhythm sleep disorders

Circadian rhythm disturbances (CRSDs) are catego-

rized by the International Classiﬁ cation of Sleep Disor-

ders (ICSD), second edition (AASM, 2005) into

extrinsic and intrinsic disorders. Extrinsic CRSDs

include disorders where the internal rhythm is dis-

rupted due to changes in the external environment,

such as shift work and jet lag. Intrinsic CRSDs are

deﬁ ned as disruption in sleep and/or daytime func-

tion due to alteration in the internal circadian timing

system, and include delayed sleep phase disorder,

advanced sleep phase disorder, non-24-h sleep/wake

disorder, and irregular circadian rhythm sleep disor-

der. The following section will describe associations

between circadian rhythm sleep disorders with phys-

ical and psychiatric disorders.

Shift work and shift work sleep disorder

Shift work has become more common in the last

century with at least 20% of the work force employed

in a position requiring a shift work schedule.

Although most shift workers experience circadian

disruption and sleep curtailment, not all shift work-

ers have the circadian rhythm sleep disorder, shift

work sleep disorder (SWD). SWD is characterized

by complaints of insomnia and excessive sleepiness

that are temporarily associated with a work schedule

that occurs during the usual sleep period. Shift work

is typically deﬁ ned as work outside the hours of

about 7 a.m. to 6 p.m., or in the case of the CRSD

shift work sleep disorder, a work schedule that over-

laps with the timing of the usual primary sleep

period (i.e. at least 50% of the work period is between

10 p.m. to 6 a.m.). Both night work and early morn-

ing start times (before 6 a.m.) are associated with

the most sleep curtailment, typically anywhere

between 1 – 4 h less sleep per day compared to non-

shift workers (Akerstedt, 1995; Knauth et al., 1980).

It is estimated that 10% of night and rotating shift

workers and 1% of the population meet criteria for

SWD (Drake et al., 2004). Those with SWD have

shorter sleep duration, worse sleep quality and per-

formance on memory tasks, and greater prevalence

of gastric ulcers and depressive symptoms than shift

workers without SWD (Drake et al., 2004; Gume-

nyuk et al., 2010, 2014).

Much of the research on shift work and health has

focused on the effects of shift work itself, rather than

SWD. There is evidence to suggest that shift work is

associated with a greater incidence of cardiovascular

disease and risk factors, diabetes, obesity, cancer,

triglycerides (Esquirol et al., 2011) and poor repro-

ductive health (Labyak et al., 2002; Nurminen,

1998). The cause of these poor health outcomes in

shift workers is thought to be due to a complex com-

bination of circadian misalignment, chronic sleep

loss, increased light exposure at night, altered feeding

patterns, restricted access to healthy foods, increases

in smoking, and other poor health behaviours.

The role of shift work as a risk factor for cardio-

vascular disease is controversial (Esquirol et al.,

2011); some studies suggest an association but others

do not. There is a similar case with diabetes risk.

Further studies are required to deﬁ nitively determine

the role of shift work in these disorders, although the

overall consensus is that there is likely to be a nega-

tive impact of repeated circadian misalignment and

sleep loss on health.

Shift work has been identiﬁ ed as a risk factor for

cancer, particularly among women, although there is

a clear need for further research using objective pro-

spective exposure measures (Ijaz et al., 2013). Sev-

eral studies, including the Nurses ’ Health Study,

report increased risk of cancer among shift workers

including breast cancer (Schernhammer et al., 2001)

and colorectal cancer (Schernhammer et al., 2003).

The mechanism proposed in these studies is increased

exposure to light at night, resulting in reduced levels

of endogenous melatonin. More recently, a study

from Canada with a diverse population of shift work-

ers supports the increased risk of breast cancer in

shift workers (Grundy et al., 2013). The data in this

area is sufﬁ cient enough such that in 2007 the Inter-

national Agency for Research on Cancer (the cancer

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146 K. G. Baron &. K. J. Reid

arm of the World Health Organization) listed shift

work as a possible carcinogen.

In addition to the impact on physical health out-

comes, there is also evidence that shift work affects

emotional well-being, such as increased divorce rates,

social isolation (Barnes, 2011; Drake et al., 2004)

and poor mood (Perry-Jenkins et al., 2007).

Jet lag and jet lag disorder

Jet lag results from a misalignment between the inter-

nal circadian clock and the external environment as

a result of rapid travel across multiple time zones.

Similar to shift work, not all travellers will experience

jet lag or meet the criteria for the CRSD, jet lag

disorder. Symptoms of this transitory CRSD range

from difﬁ culty sleeping, excessive daytime sleepiness,

general malaise, impaired daytime function, and

gastrointestinal upset (Boulos et al., 1995). Speciﬁ c

ICSD criteria include a complaint of insomnia or

excessive daytime sleepiness associated with jet

travel across at least two time zones and associated

impairment in daytime function, general malaise, or

somatic symptoms such as gastrointestinal distur-

bance occurring within 1 – 2 days after travel (AASM,

2005). The ICSD criteria do not require a minimum

number of jet lag occasions or a speciﬁ c duration of

symptoms; rather, individuals who suffer from jet lag

disorder will seek medical advice for the condition,

if it is problematic. This is likely to be the case for

individuals who travel across multiple time zones on

a consistent basis, although no prevalence data for

jet lag disorder are available. The degree of sleep dis-

ruption and sleepiness associated with travel is vari-

able, depending for example on the number of time

zones crossed, direction of travel (east or west), and

age. The functional impairment associated with jet

lag disorder results from a combination of circadian

misalignment and the associated sleep loss (for a

review, see Reid, 2011). Currently, there are no pub-

lished studies of the long-term impact of frequent or

chronic jet lag for cardiovascular disease, diabetes,

obesity or mental health disorders.

Delayed sleep phase disorder

Delayed sleep phase disorder (DSPD) is an intrinsic

CRSD characterized by sleep onset insomnia and/or

morning sleepiness due to a 3 – 6 h delay in the sleep/

wake cycle. Individuals with DSPD typically report

an evening chronotype, but the main distinction is

that DSPD is characterized by sleep/wake dysfunc-

tion and signiﬁ cant distress as a result of these con-

sequences (ICSD-2). It is estimated to be one of

the most prevalent circadian rhythm disorders. Prev-

alence of DSPD has been reported between 0.2%

and 10% depending on the population surveyed and

criteria used for diagnosis (Regestein & Monk, 1995;

Schrader et al., 1993; Weitzman et al., 1981). Mis-

alignment between the biological timing and sleep/

wake timing has been proposed as one of the mech-

anisms that causes the sleep/wake dysfunction in

DSPD. Many studies have documented that sleep/

wake timing and circadian markers are delayed in

this population relative to healthy controls (Chang

et al., 2009; Ozaki et al., 1996; Shibui et al., 1999;

Uchiyama et al., 2000a). Some but not all studies

have documented misalignment between core body

temperature minimum and sleep compared with

healthy controls (Uchiyama et al., 2000a; Uchiyama

et al., 2000b). However, Chang and colleagues from

our laboratory (2009) did not observe a difference

in DLMO or core body temperature minimum and

sleep timing among DSPD compared to healthy con-

trols. Therefore, the extent to which misalignment is

present and explains the health risks in DSPD is not

completely understood at this time.

There have been only a few investigations of the

effects of having DSPD on health, and the majority

have focused on obesity and health behaviours. There

are no studies of cardiovascular disease diabetes or

cancer. There is one case control study that reported

higher BMI among DSPD versus control partici-

pants (33 versus 30 kg/m

; Kripke et al., 2008). This

study also reported the DSPD participants had

greater medication use, particularly antacids and

hypnotics. Several studies have observed poorer

health behaviours among individuals with DSPD

compared to controls. Among Norwegian high school

students, a probable diagnosis of DSPD (difﬁ culty

falling asleep before 2 a.m.) was associated with

smoking and alcohol use (Saxvig et al., 2012).

Another study conducted in Australia used more

stringent criteria to evaluate DSPD (objective rest/

activity pattern monitoring via wrist actigraphy and

clinical interview) and found that half of the sample

of high school students met one of the criteria for

DSPD but only 1.1% met the full ICSD-2 criteria

(Lovato et al., 2013). In this study there was higher

caffeine and alcohol use and less sports participation

among adolescents who met criteria for DSPD.

Multiple studies demonstrate higher depressive

symptoms and greater prevalence of depressive dis-

orders among individuals with DSPD. Even among

those who meet criteria for DSPD, there is a rela-

tionship between later chronotype and depression

scores (Abe et al., 2011). Among those diagnosed

with DSPD, 64% had clinically signiﬁ cant depres-

sive symptoms (Abe et al., 2011). SAD is also

reported to be higher among individuals with DSPD

compared to controls (Lee et al., 2011). A study

from our group compared prevalence of DSM-IV

axis I disorders among individuals with evening

chronotype and DSPD (Reid et al., 2012). Results

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Circadian misalignment and health 147

demonstrated no difference in rates of depressive

disorders, either current or lifetime, between evening

chronotype and DSPD. The diagnosis of DSPD did

not increase risk for depression above and beyond

evening chronotype.

DSPD is also reported to be more prevalent among

individuals with bipolar disorder, compared to uni-

polar depression and healthy controls (Robillard

et al., 2013). There is one study that evaluated the

sleep and circadian parameters of individuals with

ADHD co-morbid with DSPD. Compared with

controls, individuals with DSPD demonstrated a

more variable bedtime, shorter sleep duration on

week days and a longer duration between dim light

melatonin onset and sleep onset than control par-

ticipants, suggesting they tended to sleep later in

their circadian phase (Bijlenga et al., 2013).

Advanced sleep phase disorder

There is much less known about the physical and

emotional consequences of advanced sleep phase

disorder (ASPD). This is likely due in part to lower

prevalence of ASPD. It is estimated that the preva-

lence of ASPD is 1% of the general population (Ando

et al, 2002). However, this number is likely to be an

underestimation because individuals with ASPD may

adapt their work and social schedules to accommo-

date early wake times. ASPD is an intrinsic CRSD

where the individual ’ s sleep/wake timing is signiﬁ -

cantly earlier than desired (ICSD-2). Individuals

often experience sleepiness in the early evening as

well as early morning awakenings. Individuals with

ASPD have demonstrated earlier timing of biological

markers including melatonin (Reid et al., 2001).

There are no published studies comparing the phys-

ical or psychiatric health of individuals with ASPD

to healthy controls or other sleep disorders, therefore

it is unknown whether ASPD predisposes individuals

to health risk beyond that of sleep loss alone.

Non-24-h sleep/wake disorder

Non-24-h sleep/wake disorder (N24HSWD) is an

intrinsic CRSD in which the individual ’ s sleep/wake

cycle progressively delays each day, rather than

entraining to a stable time (AASM, 2005). This leads

to periods of insomnia and daytime sleepiness depend-

ing on where the individual is in their sleep/wake pat-

tern as well as fragmented sleep if the individual is

attempting to sleep when night-time is misaligned

with internal timing. In the case of N24SWD, the

individual is in a constant and changing degree of

misalignment. N24HSWD is more commonly seen

among blind people, and is the most common among

totally blind, due to the role of the visual system in

circadian phase entrainment (Lockley et al., 1997).

However, it has been reported among sighted indi-

viduals as well (Hayakawa et al., 2005). Although

N24HSWD is clearly disruptive to an individual ’ s

social, emotional and occupational functioning, there

are few reports of how this disorder affects risk for

physical or psychiatric disease. Lockley and colleagues

(2008) published a study of 52 blind free-running

type participants and demonstrated no differences

overall in mood, but non-entrained individuals rated

their mood as worse when their melatonin peak

occurred during their waking hours. Data from a

large case series of sighted N24HSWD from Japan

(57 participants) reported that psychiatric disorders

preceded the onset of N24HSWD among 28% of the

sample, and 34% of the sample developed major

depressive disorder after the onset of N24HSWD

(Hayakawa et al., 2005).

Irregular sleep/wake type

Irregular sleep/wake type is an intrinsic CRSD in

which the individual does not demonstrate a clear

sleep/wake rhythm (ICSD-2) and has three or more

sleep periods per 24-h day. Individuals with this dis-

order report insomnia, daytime sleepiness and frag-

mented sleep. Much of the literature about irregular

sleep/wake type focuses on sleep in the elderly. This

sleep disorder is more common among institutional-

ized elderly and those with dementia (Hoogendijk

et al., 1996; Witting et al., 1990). Decreased circa-

dian rhythmicity is associated with incidence of

dementia and mild cognitive impairment (Tranah

et al., 2010). Circadian rhythmicity has been dem-

onstrated to be strongly associated with all-cause

mortality (Gehrman et al., 2004; Paudel et al., 2010;

Tranah et al., 2011) and mortality from cardiovas-

cular disease (Paudel et al., 2011).

Meal timing and pattern

One of the largest literatures on misalignment of

eating in humans comes from NES, a disorder char-

acterized by evening hyperphagia and nocturnal

awakenings in which individuals wake and are unable

to return to sleep without eating (Stunkard et al.,

1955). Individuals with NES demonstrate greater

calorie intake at night, as well as delayed sleep pat-

terns and delayed melatonin onset, leptin and insu-

lin rhythms (Goel et al., 2009; O ’ Reardon et al.,

2004). The prevalence of NES is higher amongst

individuals who are overweight or obese (Calugi,

2009), bariatric surgery candidates (Adami et al.,

1999; Allison et al., 2008; Rand et al., 1997), and

individuals with psychiatric disorders (Lundgren

et al., 2006). NES is associated with weight gain over

time (Marshall et al., 2004) and depression, par-

ticularly depressed mood in the evening (Birketvedt

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148 K. G. Baron &. K. J. Reid

et al., 1999; Lundgren et al., 2008). Several, but not

all studies have reported poorer weight loss out-

comes in individuals with NES participating in

behavioural weight loss programmes (Gluck et al.,

2001; Stunkard et al., 1955). However, one recent

study reported similar weight loss outcomes in indi-

viduals with NES compared to control participants

without NES (Dalle Grave et al., 2011).

There are several studies linking the timing of eat-

ing to weight regulation among participants without

NES. Our group reported in a sample of healthy,

non-depressed adults a correlation between calories

consumed after 8:00 p.m. and BMI, which was inde-

pendent of sleep timing and duration (Baron et al.,

2011). Lucassen and colleagues (2013) reported that

in a sample of overweight individuals with short

sleep duration, later chronotypes ate later and had

higher BMIs. Two recent studies have highlighted the

role of meal timing in weight loss. Garaulet and col-

leagues (2013) reported greater weight loss in par-

ticipants enrolled in a weight loss programme who

ate their main meal before 3:00 p.m. This study was

conducted in Spain, where the main meal is lunch.

Another study from this group reported greater

weight loss outcomes associated with a more robust

amplitude of their circadian rhythms and less frag-

mentation among obese women undergoing a weight

loss programme (Bandin et al., 2013). These studies

suggest that timing of eating is a potentially under-

studied factor in weight regulation and weight loss

outcomes.

Circadian misalignment in psychiatric disorders

Depression and seasonal affective disorder . There is a

long history of the investigation of circadian rhythms

and misalignment in depression (Borbely, 1982;

Germain & Kupfer, 2008). Early research into major

depression noted the predominance of early morn-

ing awakenings and shortened REM latency. Based

on these observations, researchers coined the ‘ phase

advance hypothesis ’ which posited that the biologi-

cal rhythm was advanced in respect to the sleep/

wake pattern (Kripke et al., 1983; Wehr et al., 1979).

Furthermore, changes in the light/dark schedule

were thought to be linked to SAD going back to the

earliest investigations into this disorder (Rosenthal

et al., 1984). However, later work in this area dem-

onstrated either no phase difference or a phase delay

compared to non-depressed individuals (von Zers-

sen et al., 1985). This observation of phase differ-

ences, rather than an advance or delay, led to the

‘ phase shift hypothesis ’ (Lam & Levitan, 2000; Lewy

et al., 2006, 2009).

Recent literature on depression and circadian

rhythms has focused attention on the alignment of

sleep to circadian rhythms, rather than a phase

advance or delay. Two small studies have evaluated

phase angle in major depressive disorder. Emens and

colleagues (2009) demonstrated that a shorter phase

angle between DLMO and sleep was correlated with

higher depressive symptoms among participants with

major depressive disorder. In another study, Hasler

and colleagues (2010) did not ﬁ nd a relationship

between DLMO and sleep with depressive symp-

toms. However, there were higher depressive symp-

toms in those with a shorter phase angle between

midpoint of the sleep period and core body tempera-

ture minimum. Meliska and colleagues (2011) dem-

onstrated a positive correlation between symptoms of

atypical depression (appetite, hypersomnia) and later

DLMO timing, but no association between atypical

depression symptoms and phase angle between mela-

tonin and sleep timing. These studies suggest that

rather than a phase advance or delay, it is possible

that alignment of sleep to circadian markers may be

an important marker of depression severity.

Bipolar disorder . Disruption of sleep and activity are

part of the key features that deﬁ ne bipolar disorder

(Cassidy et al, 1998; Wehr et al., 1987). Multiple stud-

ies using wrist actigraphy have demonstrated that indi-

viduals with bipolar disorder have less stable circadian

sleep/wake patterns, lower amplitude, lower daytime

activity and more fragmented nocturnal sleep com-

pared with those with unipolar depression or healthy

controls, even inter-episode (Jones et al., 2005; Rock

et al., 2014; Salvatore et al., 2008). There is only one

small study evaluating phase angle of circadian markers

and sleep among individuals with bipolar disorder

(Robillard et al., 2013). In this study, individuals with

bipolar disorder on average had later DLMO than indi-

viduals with unipolar major depressive disorder. The

results regarding phase angle were complicated. There

were no overall differences in phase angle between the

unipolar and bipolar groups. However, 10 participants

(ﬁ ve uniloplar/ﬁ ve bipolar) demonstrated abnormally

long phase angle, with DLMO occurring after their

habitual sleep onset time or after the end of saliva sam-

pling in this protocol ( ⬎ 2 h after habitual sleep onset

time). Results of these studies suggest that rhythms are

important in bipolar disorder but the role of misalign-

ment needs to be evaluated in further studies.

Other psychiatric disorders . Sleep problems and circa-

dian disruption are present in many other psychiatric

disorders beyond mood disorders. Signiﬁ cant circa-

dian disruption has been reported among individuals

with schizophrenia (Monti et al., 2013). Circadian

rhythms of individuals with schizophrenia have been

reported to be phase advanced (Rao et al., 1994),

delayed, or free running (Wulff et al., 2012) and mis-

aligned (Afonso et al., 2011; Bromundt et al., 2011).

Bromundt and colleagues (2011) reported bedtimes

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Circadian misalignment and health 149

before DLMO were common, particularly among

individuals with low amplitude of activity during the

day. A delay of melatonin timing and activity rhythms

have been reported among children and adolesents

with ADHD (van der Heijden et al., 2005; Van Veen

et al., 2010). In addition, differences in the timing of

melatonin offset relative to wake time have been

reported in ADHD compared to healthy controls

(Novakova et al., 2011).

Conclusion

The timing and alignment of circadian rhythms

are integral to the health and well-being of all organ-

isms, including humans. Misalignment of circadian

rhythms can occur when the individual ’ s sleep/wake

cycle is inappropriately timed relative to the biological

night, when eating is misaligned with other biological

rhythms, or there can even be misalignment between

the central (SCN) and peripheral rhythms (e.g. organ

or system). The consequences of circadian misalign-

ment include changes in dietary behaviour, appetite

regulation, glucose regulation and mood. The exper-

imental literature suggests that misalignment has

profound effects on processes that affect risk for car-

diovascular disease, diabetes, obesity and psychiatric

conditions. However, much is still not understood

about how misalignment contributes to disease risk.

Furthermore, the aetiology of how individuals become

misaligned is not well understood. For example, in

DSPD, misalignment has been demonstrated between

sleep timing and circadian markers even when par-

ticipants are sleeping at their preferred sleep/wake

schedule, which suggests it is not only due to external

factors such as work and social schedules. Treatments

to shift and align circadian phase, such as bright light

and melatonin have shown promise in the treatment

of some conditions, such as depression and SAD

(Boyce & Hopwood, 2013; Lewy et al., 2009; Pail

et al., 2011). The application of aligning circadian

phase to other conditions such as cardiovascular dis-

ease, obesity and diabetes has not been well studied.

Experimental studies in animal models suggest that

altering meal timing may be a promising intervention

for weight regulation but this potential therapy is

beginning to be explored. Further research is needed

to understand the mechanisms that contribute to the

development of circadian misalignment, the links

between misalignment to disease development, and

ﬁ nally the role of improving circadian alignment in

the management of chronic illness.

Acknowledgements

We are grateful to Phyllis Zee for comments on pre-

vious drafts of this manuscript.

Declaration of interest: This project was sup-

ported by the US National Institutes of Health,

grant number 1K23HL109110. Dr Reid reports a

grant from Philips that is urelated to the work pre-

sented in this review. The authors alone are respon-

sible for the content and writing of the paper.

References

AASM . (2005) . International Classiﬁ cation of Sleep Disorders,

Second Edition: Diagnostic and Coding Manual . Westchester, IL:

American Academy of Sleep Medicine .

Abe , T. , Inoue , Y. , Komada , Y. , Nakamura , M. , Asaoka , S. ,

Kanno , M. , … Takahashi , K . (2011) . Relation between

morningness – eveningness score and depressive symptoms

among patients with delayed sleep phase syndrome . Sleep

Medicine , 12 (7) , 680 – 684 .

Adami , G.F. , Meneghelli , A. , & Scopinaro , N . (1999) . Night eat-

ing and binge eating disorder in obese patients . International

Journal of Eating Disorders , 25 (3) , 335 – 338 .

Afonso , P.

, Brissos , S. , Figueira , M.L. , & Paiva , T . (2011) .

Schizophrenia patients with predominantly positive symptoms

have more disturbed sleep – wake cycles measured by actigraphy .

Psychiatry Research , 189 (1) , 62 – 66 .

Ahn , Y.M. , Chang , J. , Joo , Y.H. , Kim , S.C. , Lee , K.Y. , & Kim , Y.S .

(2008) . Chronotype distribution in bipolar I disorder and

schizophrenia in a Korean sample . Bipolar Disorders , 10 (2) ,

271 – 275 .

Akerstedt , T . (1995) . Work hours, sleepiness and the underlying

mechanisms . Journal of Sleep Research , 4 (S2) , 15 – 22 .

Allison , K.C. , Engel , S.G. , Crosby , R.D. , de Zwaan , M. ,

O ’ Reardon , J.P. , Wonderlich , S.A. , … Stunkard , A.J . (2008) .

Evaluation of diagnostic criteria for night eating syndrome

using item response theory analysis . Eating Behaviors , 9 (4) ,

398 – 407 .

Ando , K. , Kripke , D.F. , & Ancoli-Israel , S . (2002) . Delayed and

advanced sleep phase symptoms . Israel Journal of Psychiatry and

Related Sciences , 39 (1) , 11 – 18 .

Arble , D.M. , Bass , J. , Laposky , A.D. , Vitaterna , M.H. , &

Turek , F.W . (2009) . Circadian timing of food intake contributes

to weight gain . Obesity , 17 (11) , 2100 – 2102 .

Baehr , E.K. , Eastman , C.I. , Revelle , W. , Olson , S.H. , Wolfe , L.F. ,

& Zee , P.C . (2003) . Circadian phase-shifting effects of

nocturnal exercise in older compared with young adults . Amer-

ican Journal of Physiology – Regulatory and Integrative Compara-

tive Physiology , 284 (6) , R1542 – 1550 .

Baehr , E.K. , Revelle , W. , & Eastman , C.I . (2000) . Individual dif-

ferences in the phase and amplitude of the human circadian

temperature rhythm: With an emphasis on morningness –

eveningness . Journal of Sleep Research , 9 (2) , 117 – 127 .

Bailer , U. , Wiesegger , G. , Leisch , F. , Fuchs , K. , Leitner , I. ,

Letmaier , M. , … Aschauer , H.N . (2005) . No association of

clock gene T3111C polymorphism and affective disorders . Euro-

pean Neuropsychopharmacology , 15 (1) , 51 – 55 .

Bandin , C. , Martinez-Nicolas , A. , Ordovas , J.M. , Madrid , J.A. , &

Garaulet , M . (2013) . Circadian rhythmicity as a predictor of

weight-loss effectiveness . International Journal of Obesity . doi:

10.1038/ijo.2013.211

Barger , L.K. , Wright , K.P. , Jr ., Hughes , R.J. , & Czeisler , C.A .

(2004) . Daily exercise facilitates phase delays of circadian mela-

tonin rhythm in very dim light . American Journal of

Physiology – Regulatory and Integrative Comparative Physiology ,

286 (6) , R1077 – 1084 .

Barnes , M . (2011) . Making Time Use Explicit in an Investigation of

Social Exclusion in the UK (RES-061-23-0122) . Swindon:

ESRC .

Int Rev Psychiatry Downloaded from informahealthcare.com by Northwestern University on 06/06/14

For personal use only.

150 K. G. Baron &. K. J. Reid

Baron , K.G. , Reid , K.J. , Kern , A.S. , & Zee , P.C . (2011) . Role

of sleep timing in caloric intake and BMI . Obesity , 19 (7) ,

1374 – 1381 .

Bass , J . (2012) . Circadian topology of metabolism . Nature ,

491 (7424) , 348 – 356 .

Benedetti , F. , Dallaspezia , S. , Colombo , C. , Pirovano , A. ,

Marino , E. , & Smeraldi , E . (2008) . A length polymorphism in

the circadian clock gene Per3 inﬂ uences age at onset of bipolar

disorder . Neuroscience Letters , 445 (2) , 184 –

187 .

Benedetti , F. , Serretti , A. , Colombo , C. , Barbini , B. ,

Lorenzi , C. , Campori , E. , & Smeraldi , E . (2003) . Inﬂ uence

of CLOCK gene polymorphism on circadian mood ﬂ uctua-

tion and illness recurrence in bipolar depression . American

Journal of Medical Genetics. Part B, Neuropsychiatric Genetics ,

123B (1) , 23 – 26 .

Benloucif , S. , Burgess , H.J. , Klerman , E.B. , Lewy , A.J. ,

Middleton , B. , Murphy , P. J. , … Revell , V.L . (2008) . Measuring

melatonin in humans . Journal of Clinical Sleep Medicine , 4 (1) ,

66 – 69 .

Bersani , F.S. , Iannitelli , A. , Pacitti , F. , & Bersani , G . (2012) .

Sleep and biorythm disturbances in schizophrenia, mood and

anxiety disorders: A review . Rivista di Psichiatria , 47 (5) , 365 – 375 .

Bijlenga , D. , Van Someren , E.J. , Gruber , R. , Bron , T.I. ,

Kruithof , I.F. , Spanbroek , E.C. , & Kooij , J.J . (2013) .

Body temperature, activity and melatonin proﬁ les in adults with

attention-deﬁ cit/hyperactivity disorder and delayed sleep: A

case-control study . Journal of Sleep Research , 22 (6) , 607 – 616 .

Birketvedt , G.S. , Florholmen , J. , Sundsfjord , J. , Osterud , B. , Din-

ges , D. , Bilker , W. , & Stunkard , A . (1999) . Behavioral and neu-

roendocrine characteristics of the night eating syndrome .

Journal of the American Medical Association , 282 (7) , 657 – 663 .

Boivin , D.B. , Czeisler , C.A. , Dijk , D.J. , Duffy , J.F. , Folkard , S. ,

Minors , D.S. , … Waterhouse , J.M . (1997) . Complex

interaction of the sleep-wake cycle and circadian phase

modulates mood in healthy subjects . Archives of General

Psychiatry , 54 (2) , 145 – 152 .

Borbely , A.A . (1982) . A two process model of sleep regulation .

Human Neurobiology , 1 (3) , 195 – 204 .

Boulos , Z. , Campbell , S.S. , Lewy , A.J. , Terman , M. , Dijk , D.J. , &

Eastman , C.I . (1995) . Light treatment for sleep disorders: con-

sensus report. VII. Jet lag . Journal of Biological Rhythms , 10 (2) ,

167 – 76 .

Boyce , P. , & Hopwood , M . (2013) . Manipulating melatonin in

managing mood . Acta Psychiatrica Scandinavica Supplementum ,

444 , 16 – 23 .

Bromundt , V. , Koster , M. , Georgiev-Kill , A. , Opwis , K.

Wirz-Justice , A. , Stoppe , G. , & Cajochen , C . (2011) .

Sleep – wake cycles and cognitive functioning in schizoph renia .

British Journal of Psychiatry , 198 (4) , 269 – 276 .

Brown , S.A. , & Azzi , A . (2013) . Peripheral circadian oscillators

in mammals . Handbook of Experimental Pharmacology , 217 ,

45 – 66 .

Burgess , H.J. , Revell , V.L. , Molina , T.A. , & Eastman , C.I . (2010) .

Human phase response curves to three days of daily melatonin:

0.5 mg versus 3.0 mg . Journal of Clinical Endocrinology and

Metabolism , 95 (7) , 3325 – 3331 .

Calugi , S. , Dalle Grave , R. , & Marchesini , G . (2009) . Night eating

syndrome in class II-III obesity: metabolic and psychopatho-

logical features. International Journal of Obesity (London) ,

33 (8) , 899 – 904 .

Cassidy , F. , Murry , E. , Forest , K. , & Carroll , B.J . (1998) . Signs

and symptoms of mania in pure and mixed episodes . Journal of

Affective Disorders , 50 (2 – 3) , 187 – 201 .

Chang , A.M. , Reid , K.J. , Gourineni , R. , & Zee , P.C . (2009) . Sleep

timing and circadian phase in delayed sleep phase syndrome .

Journal of Biological Rhythms , 24 (4) , 313 – 321 .

Chelminski , I. , Ferraro , F.R. , Petros , T. V. , & Plaud , J.J . (1999) .

An analysis of the ‘ eveningness – morningness ’ dimension in

‘ depressive ’ college students . Journal of Affective Disorders ,

52 (1 – 3) , 19 – 29 .

Chung , J.K. , Lee , K.Y. , Kim , S.H. , Kim , E.J. , Jeong , S.H. ,

Jung , H.Y. , … Joo , E.J . (2012) . Circadian rhythm characteristics

in mood disorders: Comparison among bipolar I disorder, bipo-

lar II disorder and recurrent major depressive disorder . Clinical

Psychopharmacology Neuroscience ,

10 (2) , 110 – 116 .

Czeisler , C.A. , Allan , J.S. , Strogatz , S.H. , Ronda , J.M. , Sanchez , R. ,

Rios , C.D. , … Kronauer , R.E . (1986) . Bright light resets the

human circadian pacemaker independent of the timing of the

sleep – wake cycle . Science , 233 (4764) , 667 – 671 .

Czeisler , C.A. , Duffy , J.F. , Shanahan , T.L. , Brown , E.N. ,

Mitchell , J.F. , Rimmer , D.W. , … Kronauer , R.E . (1999) .

Stability, precision, and near-24-hour period of the human cir-

cadian pacemaker . Science , 284 (5423) , 2177 – 2181 .

Dalle Grave , R. , Calugi , S. , Ruocco , A. , & Marchesini , G .

(2011) . Night eating syndrome and weight loss outcome in

obese patients . International Journal of Eating Disorders , 44 (2) ,

150 – 156 .

Desan , P.H. , Oren , D.A. , Malison , R. , Price , L.H. ,

Rosenbaum , J. , Smoller , J. , … Gelernter , J . (2000) . Genetic

polymorphism at the CLOCK gene locus and major depres-

sion . American Journal of Medical Genetics , 96 (3) , 418 – 421 .

Dibner , C. , Schibler , U. , & Albrecht , U . (2010) . The mammalian

circadian timing system: Organization and coordination of cen-

tral and peripheral clocks . Annual Review of Physiology , 72 ,

517 – 549 .

Dijk , D.J. , & Archer , S.N . (2010) . PERIOD3, circadian pheno-

types, and sleep homeostasis . Sleep Medicine Reviews , 14 (3) ,

151 – 160 .

Dijk , D.J. , Duffy , J.F. , & Czeisler , C.A . (1992) . Circadian and

sleep/wake dependent aspects of subjective alertness and cogni-

tive performance . Journal of Sleep Research , 1 (2) , 112 – 117 .

Drake , C.L. , Roehrs , T. , Richardson , G. , Walsh , J.K. , &

Roth , T . (2004) . Shift work sleep disorder: Prevalence and con-

sequences beyond that of symptomatic day workers . Sleep ,

27 (8) , 1453 – 1462 .

Drennan , M.D. , Klauber , M.R. , Kripke , D.F. , & Goyette , L.M .

(1991) . The effects of depression and age on the Horne –

Ostberg morningness – eveningness score . Journal of Affective

Disorders , 23 (2) , 93 – 98 .

Duffy , J.F. , Rimmer , D.W. , & Czeisler , C.A . (2001) . Association

of intrinsic circadian period with morningness – eveningness,

usual wake time, and circadian phase . Behavioral Neuroscience ,

115 (4) , 895 – 899 .

Duffy , J.F. , & Wright , K.P. , Jr . (2005) . Entrainment of the human

circadian system by light . Journal of Biological Rhythms , 20 (4) ,

326 – 338 .

Emens , J. , Lewy , A. , Kinzie , J.M. , Arntz , D. , & Rough , J .

(2009) . Circadian misalignment in major depressive disorder .

Psychiatry Research , 168 (3) , 259 – 261 .

Esquirol , Y. , Perret , B. , Ruidavets , J.B. , Marquie , J.C. ,

Dienne , E. , Niezborala , M. , & Ferrieres , J . (2011) . Shift work

and cardiovascular risk factors: New knowledge from the past

decade . Archives Cardiovascual Diseases , 104 (12) , 636 – 668 .

Etain , B. , Milhiet , V. , Bellivier , F. , & Leboyer , M . (2011) .

Genetics of circadian rhythms and mood spectrum disorders .

European Neuropsychopharmacology , 21 (Suppl.4) , S676 – 682 .

Fleig , D. , & Randler , C . (2009) . Association between chronotype

and diet in adolescents based on food logs . Eating Behaviors ,

10 (2) , 115 – 118 .

Foerch , C. , Korf , H.W. , Steinmetz , H. , & Sitzer , M . (2008) .

Abrupt shift of the pattern of diurnal variation in stroke

onset with daylight saving time transitions . Circulation , 118 (3) ,

284 – 290 .

Folkard , S. , Monk , T.H. , & Lobban , M.C . (1979) . Towards a

predictive test of adjustment to shift work . Ergonomics , 22 (1) ,

79 – 91 .

Int Rev Psychiatry Downloaded from informahealthcare.com by Northwestern University on 06/06/14

For personal use only.

Circadian misalignment and health 151

Fonken , L.K. , Workman , J.L. , Walton , J.C. , Weil , Z.M. ,

Morris , J.S. , Haim , A. , & Nelson , R.J . (2010) . Light at night

increases body mass by shifting the time of food intake . Proceed-

ings of the National Academy of Sciences of the United States of

America , 107(43) , 18664 – 18669 .

Gachon , F. , Nagoshi , E. , Brown , S.A. , Ripperger , J. , &

Schibler , U . (2004) . The mammalian circadian timing

system: From gene expression to physiology . Chromosoma ,

113 (3) , 103 – 112 .

Gamble , K.L. , May , R.S. , Besing ,

R.C. , Tankersly , A.P. , &

Fargason , R.E . (2013) . Delayed sleep timing and symptoms

in adults with attention-deﬁ cit/hyperactivity disorder: A con-

trolled actigraphy study . Chronobiology International , 30 (4) ,

598 – 606 .

Garaulet , M. , Gomez-Abellan , P. , Alburquerque-Bejar , J.J. ,

Lee , Y.C. , Ordovas , J.M. , & Scheer , F.A . (2013) . Timing of food

intake predicts weight loss effectiveness . International Journal of

Obesity , 37 (4) , 604 – 611 .

Gaspar-Barba , E. , Calati , R. , Cruz-Fuentes , C.S. ,

Ontiveros-Uribe , M.P. , Natale , V. , De Ronchi , D. , &

Serretti , A . (2009) . Depressive symptomatology is inﬂ uenced

by chronotypes . Journal of Affective Disorders , 119 (1 – 3) ,

100 – 106 .

Gehrman , P. , Marler , M. , Martin , J.L. , Shochat , T. ,

Corey-Bloom , J. , & Ancoli-Israel , S . (2004) . The timing

of activity rhythms in patients with dementia is related to sur-

vival . Journals of Gerontology A , 59 (10) , 1050 – 1055 .

Germain , A. , & Kupfer , D.J . (2008) . Circadian rhythm distur-

bances in depression . Human Psychopharmacology , 23 (7) ,

571 – 585 .

Giglio , L.M. , Magalhaes , P. V. , Andersen , M.L. , Walz , J.C. ,

Jakobson , L. , & Kapczinski , F . (2010) . Circadian preference in

bipolar disorder . Sleep and Breathing , 14 (2) , 153 – 155 .

Gluck , M.E. , Geliebter , A. , & Satov , T . (2001) . Night eating syn-

drome is associated with depression, low self-esteem, reduced

daytime hunger, and less weight loss in obese outpatients . Obes-

ity Research , 9 (4) , 264 – 267 .

Goel , N . (2005) . Late-night presentation of an auditory stimulus

phase delays human circadian rhythms . American Journal of

Physiology – Regulatory and Integrative Comparative Physiology ,

289 (1) , R209 – 216 .

Goel , N. , Stunkard , A.J. , Rogers , N.L. , Van Dongen , H.P. ,

Allison , K.C. , O ’ Reardon , J.P. , … Dinges , D.F . (2009) .

Circadian rhythm proﬁ les in women with night eating syn-

drome . Journal of Biological Rhythms , 24 (1) , 85 – 94 .

Gonnissen , H.K. , Hursel , R. , Rutters , F. , Martens , E.A. , &

Westerterp-Plantenga , M.S . (2012) . Effects of sleep fragmenta-

tion on appetite and related hormone concentrations over 24 h

in healthy men . British Journal of Nutrition , 1 – 9 .

Gonnissen , H.K. , Mazuy , C. , Rutters , F. , Martens , E.A. ,

Adam , T.C. , & Westerterp-Plantenga , M.S . (2013) . Sleep archi-

tecture when sleeping at an unusual circadian time

and associations with insulin sensitivity . PLoS ONE , 8 (8) ,

e72877 .

Gronﬁ er , C. , Wright , K.P. , Jr ., Kronauer , R.E. , & Czeisler , C.A .

(2007) . Entrainment of the human circadian pacemaker

to longer-than-24-h days . Proceedings of the National

Academy of Sciences of the United States of America , 104(21) ,

9081 – 9086 .

Grundy , A. , Richardson , H. , Burstyn , I. , Lohrisch , C. ,

SenGupta , S.K. , Lai , A.S. , … Aronson , K.J . (2013) .

Increased risk of breast cancer associated with long-term

shift work in Canada . Occupational and Environmental

Medicine , 70 (12) , 831 – 838 .

Gumenyuk , V. , Howard , R. , Roth , T. , Korzyukov , O. , &

Drake , C.L . (2014) . Sleep loss, circadian mismatch, and abnor-

malities in reorienting of attention in night workers with shift

work disorder . Sleep , 37 (3) , 545 – 556 .

Gumenyuk , V. , Roth , T. , Korzyukov , O. , Jefferson , C. , Kick , A. ,

Spear , L. , … Drake ,

C.L . (2010) . Shift work sleep disorder is

associated with an attenuated brain response of sensory mem-

ory and an increased brain response to novelty: An ERP study .

Sleep , 33 (5) , 703 – 713 .

Hahm , B.J. , Jo , B. , Dhabhar , F.S. , Palesh , O. , Aldridge-Gerry , A. ,

Bajestan , S.N. , … Zeitzer , J.M . (2014) . Bedtime misalignment

and progression of breast cancer . Chronobiology International ,

31 (2) , 214 – 221 .

Hampton , S.M. , Morgan , L.M. , Lawrence , N. , Anastasiadou , T. ,

Norris , F. , Deacon , S. , … Arendt , J . (1996)

. Postprandial

hormone and metabolic responses in simulated shift work .

Journal of Endocrinology , 151 (2) , 259 – 267 .

Harb , A. , Levandovski , R. , Oliveira , C. , Caumo , W. ,

Allison , K.C. , Stunkard , A. , & Hidalgo , M.P . (2012) . Night

eating patterns and chronotypes: A correlation with binge eat-

ing behaviors . Psychiatry Research , 200 (2 – 3) , 489 – 493 .

Hardin , P.E. , Hall , J.C. , & Rosbash , M . (1990) . Feedback of

the Drosophila period gene product on circadian cycling of its

messenger RNA levels . Nature , 343 (6258) , 536 – 540 .

Harrison , Y . (2013) . The impact of daylight saving time on sleep

and related behaviours . Sleep Med Rev , 17 (4) , 285 – 292 .

Hasler , B.P. , Buysse , D.J. , Kupfer , D.J. , & Germain , A . (2010) .

Phase relationships between core body temperature, melatonin,

and sleep are associated with depression severity: Further evi-

dence for circadian misalignment in non-seasonal depression .

Psychiatry Research , 178 (1) , 205 – 207 .

Hatori , M. , Vollmers , C. , Zarrinpar , A. , DiTacchio , L. ,

Bushong , E.A. , Gill , S. , … Panda , S . (2012) . Time-restricted

feeding without reducing caloric intake prevents metabolic

diseases in mice fed a high-fat diet . Cell Metabolism , 15 (6) ,

848 – 860 .

Hayakawa , T. , Uchiyama , M. , Kamei , Y. , Shibui , K. , Tagaya , H. ,

Asada , T. , … Takahashi , K . (2005) . Clinical analyses of sighted

patients with non-24-hour sleep – wake syndrome: A study of 57

consecutively diagnosed cases . Sleep , 28 (8) , 945 – 952 .

Hirata , F.C. , Lima , M.C. , de Bruin , V.M. , Nobrega , P.R. ,

Wenceslau , G.P. , & de Bruin , P. F . (2007) . Depression in med-

ical school: The inﬂ uence of morningness – eveningness . Chrono-

biology International , 24 (5) , 939 – 946 .

Hoogendijk , W. J . , van Someren , E.J. , Mirmiran , M. ,

Hofman , M.A. , Lucassen , P. J. , Zhou , J.N. , & Swaab , D.F .

(1996) . Circadian rhythm-related behavioral disturbances

and structural hypothalamic changes in Alzheimer ’ s disease .

International Psychogeriatrics , 8 (Suppl.3) , 245 – 252 ; discussion

269 – 272.

Horne , J.A. , & Ostberg , O . (1976) . A self-assessment question-

naire to determine morningness – eveningness in human circa-

dian rhythms . International Journal of Chronobiology , 4 (2) ,

97 – 110 .

Ijaz , S. , Verbeek , J. , Seidler , A. , Lindbohm , M.L. , Ojajarvi , A. ,

Orsini , N. , … Neuvonen , K . (2013) . Night-shift work

and breast cancer – A systematic review and meta-analysis .

Scandinavian Journal of Work, Environment and Health , 39 (5) ,

431 – 447 .

Jakubowicz , D. , Barnea , M. , Wainstein , J. , & Froy , O . (2013) .

High Caloric intake at breakfast vs dinner differentially inﬂ u-

ences weight loss of overweight and obese women . Obesity ,

21 (12) , 2504 – 2512 .

Janszky , I. , Ahnve , S. , Ljung , R. , Mukamal , K. J. , Gautam , S. ,

Wallentin , L. , & Stenestrand , U . (2012) . Daylight saving time

shifts and incidence of acute myocardial infarction – Swedish

Intensive Care Admissions (RIKS-HIA) . Sleep Medicine , 13 (3) ,

237 – 242 .

Janszky , I. , & Ljung , R . (2008) . Shifts to and from daylight saving

time and incidence of myocardial infarction . New England Jour-

nal of Medicine , 359 (18) , 1966 – 1968 .

Int Rev Psychiatry Downloaded from informahealthcare.com by Northwestern University on 06/06/14

For personal use only.

152 K. G. Baron &. K. J. Reid

Lee , H.J. , Rex , K.M. , Nievergelt , C.M. , Kelsoe , J.R. , &

Kripke , D.F . (2011) . Delayed sleep phase syndrome is related

to seasonal affective disorder . Journal of Affective Disorders ,

133 (3) , 573 – 579 .

Levandovski , R. , Dantas , G. , Fernandes , L.C. , Caumo , W. ,

Torres , I. , Roenneberg , T. , … Allebrandt , K.V . (2011) . Depression

scores associate with chronotype and social jetlag in a

rural population . Chronobiology International , 28 (9) , 771 – 778 .

Lewy , A.J . (2007) . Melatonin and human chronobiology . Cold

Spring Harbor Symposia on Quantitative Biology

, 72 , 623 – 636 .

Lewy , A.J. , Ahmed , S. , Jackson , J.M. , & Sack , R.L . (1992) . Mela-

tonin shifts human circadian rhythms according to a phase-

response curve . Chronobiology International , 9 (5) , 380 – 392 .

Lewy , A.J. , Emens , J.S. , Songer , J.B. , Sims , N. , Laurie , A.L. ,

Fiala , S.C. , & Buti , A.L . (2009) . Winter depression: Integrating

mood, circadian rhythms, and the sleep/wake and light/dark

cycles into a bio-psycho-social-environmental model . Sleep

Medicine Clinics , 4 (2) , 285 – 299 .

Lewy , A.J. , Leﬂ er , B.J. , Emens , J.S. , & Bauer , V.K . (2006) . The

circadian basis of winter depression . Proceedings of the National

Academy of Sciences of the United States of America , 103(19) ,

7414 – 7419 .

Lockley , S.W. , Dijk , D.J. , Kosti , O. , Skene , D.J. , & Arendt , J .

(2008) . Alertness, mood and performance rhythm disturbances

associated with circadian sleep disorders in the blind . Journal

of Sleep Research , 17 (2) , 207 – 216 .

Lockley , S.W. , Skene , D.J. , Arendt , J. , Tabandeh , H. , Bird , A.C. ,

& Defrance , R . (1997) . Relationship between melatonin rhythms

and visual loss in the blind . Journal of Clinical Endocrinology and

Metabolism , 82 (11) , 3763 – 3770 .

Loros , J.J. , & Dunlap , J.C . (1991) . Neurospora crassa clock-con-

trolled genes are regulated at the level of transcription . Molecu-

lar and Cellular Biology , 11 (1) , 558 – 563 .

Lovato , N. , Gradisar , M. , Short , M. , Dohnt , H. , & Micic , G .

(2013) . Delayed sleep phase disorder in an Australian school-

based sample of adolescents . Journal of Clinical Sleep Medicine ,

9 (9) , 939 – 944 .

Lucassen , E.A. , Zhao , X. ,

Rother , K.I. , Mattingly , M.S. ,

Courville , A.B. , de Jonge , L. , … Cizza , G . (2013) . Evening

chronotype is associated with changes in eating behavior, more

sleep apnea, and increased stress hormones in short sleeping

obese individuals . PLoS ONE , 8 (3) , e56519 .

Lundgren , J.D. , Allison , K.C. , Crow , S. , O ’ Reardon , J.P. ,

Berg , K.C. , Galbraith , J. , … Stunkard , A.J . (2006) . Prevalence

of the night eating syndrome in a psychiatric population . Amer-

ican Journal of Psychiatry , 163 (1) , 156 – 158 .

Lundgren , J.D. , Allison , K.C. , O ’ Reardon ,

J.P. , & Stunkard , A.J .

(2008) . A descriptive study of non-obese persons with night

eating syndrome and a weight-matched comparison group . Eat-

ing Behaviors , 9 (3) , 343 – 351 .

Mansour , H.A. , Talkowski , M.E. , Wood , J. , Chowdari , K.V. ,

McClain , L. , Prasad , K. , … Nimgaonkar , V.L . (2009) . Associa-

tion study of 21 circadian genes with bipolar I disorder,

schizoaffective disorder, and schizophrenia . Bipolar Disorders ,

11 (7) , 701 – 710 .

Mansour , H.A. , Wood , J. , Chowdari , K.V. , Dayal , M. ,

Thase , M.E. , Kupfer , D.J. , … Nimgaonkar , V.L . (2005) . Circa-

dian phase variation in bipolar I disorder . Chronobiology Inter-

national , 22 (3) , 571 – 584 .

Marshall , H.M. , Allison , K.C. , O ’ Reardon , J.P. , Birketvedt , G. , &

Stunkard , A.J . (2004) . Night eating syndrome among

nonobese persons . International Journal of Eating Disorders ,

35 (2) , 217 – 222 .

McCarthy , M.J. , & Welsh , D.K . (2012) . Cellular circadian

clocks in mood disorders . Journal of Biological Rhythms , 27 (5) ,

339 – 352 .

Meliska , C.J. , Martinez , L.F. , Lopez , A.M. , Sorenson , D.L. ,

Nowakowski , S. , & Parry , B.L . (2011) . Relationship of

Johansson , C. , Willeit , M. , Smedh , C. , Ekholm , J. , Paunio , T. ,

Kieseppa , T. , … Partonen , T . (2003) . Circadian clock-related

polymorphisms in seasonal affective disorder and their rele-

vance to diurnal preference . Neuropsychopharmacology , 28 (4) ,

734 – 739 .

Jones , S.H. , Hare , D.J. , & Evershed , K . (2005) . Actigraphic assess-

ment of circadian activity and sleep patterns in bipolar disorder .

Bipolar Disorders , 7 (2) , 176 – 186 .

Kabrita , C.S. , Hajjar-Muca , T.A. , & Duffy , J.F . (2014) .

Predictors of poor sleep quality among Lebanese university

students: Association between evening typology, lifestyle behav-

iors, and sleep habits . Nature and Science of Sleep , 6 , 11 – 18 .

Kantermann , T. , Juda , M. , Merrow , M. , & Roenneberg , T . (2007) .

The human circadian clock ’ s seasonal adjustment is disrupted

by daylight saving time . Current Biology , 17 (22) , 1996 – 2000 .

Kerkhof , G.A. , & Lancel , M . (1991) . EEG slow wave activity,

REM sleep, and rectal temperature during night and day sleep

in morning-type and evening-type subjects . Psychophysiology ,

28 (6) , 678 – 688 .

Khalsa , S.B. , Jewett , M.E. , Cajochen , C. , & Czeisler , C.A . (2003) .

A phase response curve to single bright light pulses in human

subjects . Joural of Physiology , 549 (3) , 945 – 952 .

Kim , S.J. , Lee , Y. J. , Kim , H. , Cho , I.H. , Lee , J.Y. , & Cho , S.J .

(2010) . Age as a moderator of the association between depres-

sive symptoms and morningness – eveningness . Journal of Psy-

chosomatic Research , 68 (2) , 159 – 164 .

Kitamura , S. , Hida , A. , Watanabe , M. , Enomoto , M. , Aritake-

Okada , S. , Moriguchi , Y. , … Mishima , K . (2010) . Evening pref-

erence is related to the incidence of depressive states

independent of sleep – wake conditions . Chronobiology Interna-

tional , 27 (9 – 10) , 1797 – 1812 .

Kleitman , N. , & Kleitman , E . (1953) . Effect of non-twenty-

four-hour routines of living on oral temperature and heart rate .

Journal of Applied Physiology: Respiratory, Environmental and

Exercise Physiology , 6 (5) , 283 – 291 .

Knauth , P. , Landau , K. , Droge , C. , Schwitteck , M. ,

Widynski , M. , & Rutenfranz , J . (1980) . Duration of sleep

depending on the type of shift work . International Archives of

Occupational and Environmental Health , 46 (2) , 167 – 177 .

Kohsaka , A. , Laposky , A.D. , Ramsey , K.M. , Estrada , C. ,

Joshu , C. , Kobayashi , Y. , … Bass , J . (2007) . High-fat diet dis-

rupts behavioral and molecular circadian rhythms in mice . Cell

Metabolism , 6 (5) , 414 – 421 .

Koorengevel , K.M. , Beersma , D.G. , den Boer , J.A. , &

van den Hoofdakker , R.H . (2003) . Mood regulation in seasonal

affective disorder patients and healthy controls studied in forced

desynchrony . Psychiatry Research , 117 (1) , 57 – 74 .

Kripke , D.F. , Elliott , J.A. , Youngstedt , S.D. , & Rex , K.M . (2007) .

Circadian phase response curves to light in older and young

women and men . Journal of Circadian Rhythms , 5 , 4 .

Kripke , D.F. , Rex , K.M. , Ancoli-Israel , S. , Nievergelt , C.M. ,

Klimecki , W. , & Kelsoe , J.R . (2008) . Delayed sleep phase cases

and controls . Journal of Circadian Rhythms , 6 , 6 .

Kripke , D.F. , Risch , S.C. , & Janowsky , D . (1983) . Bright

white light alleviates depression . Psychiatry Research , 10 (2) ,

105 – 112 .

Labyak , S. , Lava , S. , Turek , F. , & Zee , P . (2002) . Effects of

shiftwork on sleep and menstrual function in nurses . Health

Care for Women International , 23 (6 – 7) , 703 – 714 .

Lahti , T.A. , Haukka , J. , Lonnqvist , J. , & Partonen , T . (2008a) .

Daylight saving time transitions and hospital treatments due to

accidents or manic episodes . BMC Public Health , 8 , 74 .

Lahti , T.A. , Leppamaki , S. , Lonnqvist , J. , & Partonen , T . (2008b) .

Transitions into and out of daylight saving time compromise

sleep and the rest – activity cycles . BMC Physiology , 8 , 3 .

Lam , R.W. , & Levitan , R.D . (2000) . Pathophysiology of

seasonal affective disorder: A review . Journal of Psychiatry

and Neuroscience , 25 (5) , 469 – 480 .

Int Rev Psychiatry Downloaded from informahealthcare.com by Northwestern University on 06/06/14

For personal use only.

Circadian misalignment and health 153

Paudel , M.L. , Taylor , B.C. , Ancoli-Israel , S. , Blackwell , T. ,

Stone , K.L. , Tranah , G. , … Ensrud , K.E . (2010) . Rest/

activity rhythms and mortality rates in older men: MrOS Sleep

Study . Chronobiology International , 27 (2) , 363 – 377 .

Paudel , M.L. , Taylor , B.C. , Ancoli-Israel , S. , Stone , K.L. ,

Tranah , G. , Redline , S. , … Ensrud , K.E . (2011) . Rest/activity

rhythms and cardiovascular disease in older men . Chronobiology

International , 28 (3) , 258 – 266 .

Perry-Jenkins , M. ,

Goldberg , A.E. , Pierce , C.P. , & Sayer , A.G .

(2007) . Shift work, role overload, and the transition to parent-

hood . Journalof Marriageand the Family , 69 , 123 – 138 .

Rand , C.S. , Macgregor , A.M. , & Stunkard , A.J . (1997) . The night

eating syndrome in the general population and among postop-

erative obesity surgery patients . International Journal of Eating

Disorders , 22 (1) , 65 – 69 .

Rao , M.L. , Gross , G. , Strebel , B. , Halaris , A. , Huber , G. ,

Braunig , P. , & Marler , M . (1994) . Circadian rhythm of

tryptophan, serotonin, melatonin, and pituitary hormones

in schizophrenia . Biological Psychiatry , 35 (3) , 151 – 163 .

Regestein , Q.R. , & Monk , T.H . (1995) . Delayed sleep phase

syndrome: A review of its clinical aspects . American Journal of

Psychiatry , 152 (4) , 602 – 608 .

Reid , K.J. , Chang , A.M. , Dubocovich , M.L. , Turek , F.W. ,

Takahashi , J.S. , & Zee , P.C . (2001) . Familial advanced sleep

phase syndrome . Archives of Neurology , 58 (7) , 1089 – 1094 .

Reid , K.J . (2011) . Jet Lag Disorder. In A.Y. Avidan and P.C. Zee

(Eds.), Handbook of sleep medicine (379-386) . Philadelphia,

PA: Lippincott Williams & Wilkins .

Reid , K.J. , Jaksa , A.A. , Eisengart , J.B. , Baron , K.G. , Lu , B. ,

Kane , P. , … Zee , P.C . (2012) . Systematic evaluation of

Axis-I DSM diagnoses in delayed sleep phase disorder and

evening-type circadian preference . Sleep Medicine , 13 (9) ,

1171 – 1177 .

Reutrakul , S. , Hood , M.M. , Crowley , S.J. , Morgan , M.K. ,

Teodori , M. , Knutson , K.L. , & Van Cauter , E . (2013) . Chrono-

type is independently associated with glycemic control in type

2 diabetes . Diabetes Care , 36 (9) , 2523 – 2529 .

Robillard , R. , Naismith , S.L. , Rogers , N.L. , Ip , T.K. ,

Hermens , D.F. , Scott , E.M. , & Hickie , I.B . (2013) . Delayed

sleep phase in young people with unipolar or bipolar affective

disorders . Journal of Affective Disorders , 145 (2) , 260 – 263 .

Rock , P. , Goodwin , G. , Harmer , C. , & Wulff , K . (2014) .

Daily rest – activity patterns in the bipolar phenotype: A con-

trolled actigraphy study . Chronobiology International , 31 (2) ,

290 – 296 .

Roenneberg , T. , Allebrandt , K.V. , Merrow , M. , & Vetter , C . (2012) .

Social jetlag and obesity . Current Biology , 22 (10) , 939 – 943 .