Circadian Rhythm Disorders and Insomnia in Depression



In 2001, depressive disorders were estimated to be the leading cause of disability in the Americas, accounting for 8% of the total disability-adjusted life-years, the second leading cause of disability in Western Pacific countries and the third leading cause of disability in Europe, accounting for 6% of the total disability-adjusted life-years in these two regions (1). Depression was also associated with an increased mortality risk of 1.81 (1.58-2.07) in a meta-analysis of 25 community surveys involving more than 100,000 subjects (2).

CURRENT WORLDWIDE PREVALENCE OF DEPRESSION

Table 1 presents the epidemiological studies performed in general populations aged 14 years or older across the world. The studies are limited to those based on the DSM-IV, the ICD-10 or DSM-III-R classifications. Therefore, the table is not exhaustive and many valuable studies have been left out because they were based on small community samples or addressed special groups of the population such as the elderly.

The prevalences are provided according to three time frames (when available):

  • lifetime,
  • 12-months and
  • current (last month).

NORTH AMERICA

The most well known American studies are the Epidemiological Catchment Area study (ECA) and the National Comorbidity Survey (NCS) performed from 1990 to 1992 and its replication conducted in 2001-2002.

The ECA study, using DSM-III classification, estimated the 1-month prevalence of major depressive disorder between 1.7% and 3.4% of the ECA sites (3).

The first NCS reported a 1-month prevalence of major depressive disorder, DSM-III-R classification, of 4.9% in their national sample of 8,098 persons aged between 15 and 54 years (4).

The last NCS, using DSM-IV classification, found a 12-month prevalence of 6.6% in their national sample (5).

The MIDUS survey (6) found a 12-month prevalence of 14.1%.

Two Canadian surveys were published in the last decade. The oldest is based on the DSM-III-R classification (7) and reported a 12-month prevalence of 4.1%. The most recent study, based on DSM-IV, reported a 12-month prevalence of 7.4% (8).

SOUTH AMERICA

One Brazilian survey, using ICD-10 classification, reported a 1-month prevalence of 4.5%, and a 12-month prevalence of 7.1% (9).

EUROPE

Eight European surveys are presented in Table 1:

  • five are based on the DSM-IV classification (10-14);
  • two on the DSM-III-R (15,16) and/li>
  • one on the ICD-10 (17).


Table 1. Prevalence of Depression in the general population
Survey - CCHS: Canadian Community Health Survey; ANSMHWB: Australian national Survey of Mental health and Well-Being; NCS-R: National Comorbidity Survey Replication; NCS: National Comorbidity Survey; NEMESIS: Netherlands Mental Health Survey and Incidence Study; GHS-MH: German National Health Interview and Examination Survey, Mental Health Supplement; OHS-MHS: Ontario Health Survey - Mental Health Supplement; MIDUS: Midlife Development in the United States Survey; NSPM: National Survey of Psychiatric Morbidity of Great Britain
Instrument - CIDI: Composite International Diagnostic Interview; MINI: Mini International Neuropsychiatric Interview; FPI: Florence Psychiatric Interview
Type of diagnosis: Differential: when positive and differential diagnosis was performed; Positive: when only positive diagnosis was done
M: Male; F: Female; T: Total
Prevalence (%)
Author, year of publication, Survey Place N Age range Response rate Instrument Lifetime 12-months Current / 1-month
DSM-IV
Ohayon & Hong, 2006 (19) South Korea 3,719 ≥ 15 86.1% Sleep-EVAL M: 3.2
W: 4.0
T: 3.6
Molgat et al. 2004 (8) CCHS Canada 131,535 ≥ 18 91.9% CIDI-SFMD W: 5.3
M: 9.4
T: 7.4

Alonso et al. 2004 (10) ESEMeD/MHEDEA Belgium, France, Germany, 21,425 ≥ 18 61.2% (45.9% to 78.6%) WMH-CIDI M: 8.9 M: 2.6
Italy, Netherlands, Spain W: 16.5 W: 5.0
T: 12.8 T: 3.9
Faravelli et al., 2004 (11) ESEMeD/MHEDEA Sesto Fiorentino, Italy 2,363 ≥ 14 94.5% I: MINI M: 1.8 M: 1.4
II: FPI W: 4.8 W: 3.8
T: 3.4 T: 2.7
Jacobi et al, 2004 (12) GHS-MH Germany 4,181 18-65 87.6% DIA-X/CIDI M: 11.1 M: 7.5 M: 4.2
W: 23.3 W: 14.0 W: 6.9
T: 17.1 T: 10.7 T: 5.6
Kessler et al., 2003 (5) NCS-R USA 9,090 ≥ 18 73.5% CIDI
T: 16.2 T: 6.6
Ohayon & Schatzberg 2003 (13) United Kingdom, Germany, Italy, Spain, Portugal 18,980 ≥ 15 80.4% Sleep-EVAL M: 3.1
W: 4.9
T: 4.0
Wilhelm et al., 2003 ANSMHWB (20) Australia 10,641 ≥ 18 78.1% CIDI M: 2.4
W: 3.9
T: 3.2
Ohayon et al., 1999 (14) United Kingdom 4,972 ≥ 15 79.6% Sleep-EVAL M: 4.2
W: 5.9
T: 5.0
DSM-III-R
Kawakami et al., 2004 (21) Gifu City, Japan 1,029 ≥ 20 56.9% UM-CIDI M: 3.1 M: 0.9 (6 ms)
W: 2.8 W: 1.4 (6 ms)
T: 2.9 T: 1.2 (6 ms)
Wang et al., 2000 (6) MIDUS USA 3,032 25-74 70.0% WHO CIDI-SF M: 10.0
W: 17.3
T: 14.1
Bijl et al., 1998 (15) NEMESIS Netherlands 7,076 18-64 70.0% WHO CIDI M: 10.9 M: 4.1 M: 1.9
W: 20.1 W: 7.5 W: 3.4
T: 15.4 T: 5.8 T: 2.7
Offord et al, 1996 (7) OHS-MHS Ontario, Canada 6,271 18-54 67.4% UM-CIDI M: 2.8
W: 5.4
T: 4.1
Blazer et al., 1994 (4) NCS USA 5,098 15-54 82.4% UM-CIDI M: 12.7 M: 3.8
W: 21.3 W: 5.9
T: 17.1 T: 4.9
Faravelli et al., 1990 (16) Florence, Italy 1,000 ≥ 15 Unknown SADS-L
T: 6.2 T: 2.8
Andrade et al., 2002 (9) Sao Paulo, Brazil 1,464 ≥ 18 65.2% WHO CIDI M: 13.5 M: 4.3 M: 3.2
W: 19.2 W: 9.2 W: 5.4
T: 16.8 T: 7.1 T: 4.5
Wilhelm et al., 2003 ANSMHWB (20) Australia 10,641 ≥ 18 78.1% CIDI M: 2.4
W: 4.2
T: 3.3
Jenkins et al.,1997 (17) NSPM Great Britain 10,108 16-65 79.4% CIS-R M: 1.7
W: 2.5
T: 2.1


As it can be seen, current prevalence of major depressive disorder ranges from 2.7% to 5.6% and 12-month prevalence from 3.9% to 10.7%.

The question is how different is this prevalence between European countries. There are two studies that assessed multiple countries with the same instrument for all the surveyed countries:

  • the Ohayon's study (13) obtained current prevalence of Depressive disorder lower in Italy (3.3%) and Spain (2.6%) compared to the other countries (UK: 5.0%; Germany: 5.1% and Portugal: 5.1%).
  • Prevalence rates in the ESMeD survey for each country are available only for mood disorders (18). They obtained lower 12-month prevalence in Italy (3.3%) and Spain (4.4%) compared with Belgium (5.2%), France (6.4%) and the Netherlands (5.1%).

In several studies, prevalence peak among the youngest subjects (< 30 years old) (4,5,10) while in others the peak prevalence was among the 45 to 54 year-old group (13,20). Marital status and education were constantly found as predictors of Major Depressive Disorder in many studies and in different countries (3,5,14,20).

EPIDEMIOLOGY OF INSOMNIA IN THE GENERAL POPULATION

Since the end of seventies, more than 50 epidemiological studies have assessed the prevalence of insomnia symptomatology in the general population.

Methodologies have included face-to-face interviews, postal questionnaires, telephone interviews, or a combination of two of the above. The definition of insomnia also varied considerably from one survey to another:

  • Earlier studies evaluated insomnia based on the presence of DIS or DMS regardless the frequency or severity of the symptom or daytime consequences. It was done simply by asking about the presence of these symptoms. Subsequently, DIS or DMS were assessed using the frequency of the symptom, an occurrence of 3 nights or more per week being necessary for the symptom to be present.
  • Other studies asked about the severity of the symptoms for example, being bothered "a lot" or "not at all" by the symptom.
  • Other studies, in addition of assessing the presence of insomnia symptoms, inquired about daytime repercussions of these symptoms such as daytime sleepiness, irritability, depressive or anxious mood, or needing to seek help.
  • Finally, other studies inquired about dissatisfaction with sleep quantity or quality.

Table 2 gives the definitions used in epidemiological studies and prevalence of insomnia.



Table 2: Definition and prevalence of insomnia in the general population
DIS: Difficulty initiating Sleep ; DS: Disrupted Sleep; EMA: Early morning awakening; NRS: non-restorative sleep
Author Year Place N Age Definition Prevalence (%) Male/Female
Karacan et al. (32) 1976 Alachua County, Florida, USA 1645 ≥ 18 Trouble with sleep often or all the times 10.9/15.4
Bixler et al. (22) 1979 Los Angeles, USA 1006 ≥ 18 Presence of DIS, DMS or EMA 28.9/34.8
Welstein et al. (26) 1983 San Francisco, USA 6340 ≥ 6 Presence of DIS, DMS or EMA 31.0
Karacan et al. (33) 1983 Houston, USA 2347 ≥ 18 Often or always has DIS or DMS 18.6/28.6
Lugaresi et al. (61) 1983 San Marino, Italy 5713 ≥ 3 Always or almost always has a bad sleep 9.9/16.8
Mellinger et al. (41) 1985 USA 3161 ≥ 18 Being bothered a lot by DIS, DMS or EMA 14.0/20.0
Klink & Quan (23) 1987 Tucson, USA 2187 ≥ 18 Presence of DIS, DMS or EMA 37.8
Gislason & Almqvist (38) 1987 Uppsala, Sweden 3201 men 30-69 Major complaints of DIS or DMS DIS: 6.9
DMS: 7.5
Liljenberg et al. (40) 1988 Gavleborg & Kopparberg counties, Sweden 3557 30-65 Great or very great DIS or DMS DIS: 5.1/7.1
DMS: 7.7/8.9
Ford & Kamerow (44) 1989 Baltimore, Durham, Los Angeles, USA 7954 ≥ 18 Presence of DIS, DMS or EMA >= 2 weeks, + seeking professional help for the problem, or using sleep medication, or interfering a lot with daily life 7.9/12.1
Quera-Salva et al. (25) 1991 France 1003 ≥ 16 Presence of DIS, DMS or EMA 48.0
Weyerer & Dilling (81) 1991 Upper Bavarian area, Germany 1536 ≥ 15 - Mild insomnia
- Moderate/severe insomnia
15.0
13.5
Klink et al. (24) 1992 Tucson, USA 2187 ≥ 18 Presence of DIS, DMS or EMA 34.1
Tellez-Lopez et al. (42) 1995 Monterrey, Mexico 1000 ≥ 18 Being bothered a lot by DIS, DMS or EMA/td> 16.4
Olson (36) 1996 Newcastle, Australia 535 ≥ 16 Difficulty sleeping often or always 17.3/24.9
Yeo et al. (57) 1996 Singapore 2418 15-55 Dissatisfaction with sleep 12.9/17.5
Ohayon (46,51) 1996 France 5622 ≥ 15 - DIS, DMS, EMA or NRS + daytime consequences
- Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
-12.7
-15.6/24.4
-5.6
Ohayon et al. (67) 1997 United Kingdom 4972 ≥ 15 - DIS, DMS, EMA or NRS + daytime consequences
- Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
9.1
6.8/10.6
6.4
Kageyama et al. (59) 1997 Tokyo, Maebashi, Nagasaki, Naha and Kawasaki, Japan 3600 wom. ≥ 20 - Dissatisfaction with sleep
- DSM-IV insomnia diagnoses/td>
11.2
4.4
Ohayon et al. (48) 1997 Montreal, Canada 1722 ≥ 15 - Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
8.7/13.2
4.4
Ancoli-Israel & Roth (27) 1999 USA 1000 ≥ 18 Difficulty sleeping on a frequent basis 9.0
Hoffmann (30) 1999 Belgium 1618 ≥ 18 - Having DIS, DMS or EMA at least 3 times per week
- DIS, DMS, EMA + daytime consequences
22.0
9.0
Hetta et al. (29) 1999 Sweden 1996 ≥ 18 - Having DIS, DMS or EMA at least 3 times per week
- DIS, DMS, EMA + daytime consequences
22.0
13.0
Vela-Bueno et al. (37) 1999 Madrid, Spain 1131 ≥ 18 - Having DIS, DMS or EMA at least 4 times per week
- Considered themselves insomniacs
17.7/27.4
7.8/14.4
Doi et al. (28) 2000 Japan 3030 ≥ 20 Often or always DIS, DMS or EMA 17.3
Leger et al. (34) 2000 France 12778 ≥ 16 - Having DIS, DMS or EMA at least 3 times per week
- DIS, DMS or EMA + daytime consequences
25.0/34.0
14.0/23.0
Ohayon & Zulley (45) 2001 Germany 4115 ≥ 15 - DIS, DMS, EMA or NRS + daytime consequences
- Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
8.5
5.6/8.2
6.0
Hajak (82) 2001 Germany 1913 ≥ 18 Severe insomnia 4.0
Pallesen et al. (56) 2001 Norway 2001 ≥ 18 DIS, DMS, EMA + daytime consequences 11.7
Ohayon & Smirne (52) 2002 Italy 3970 ≥ 15 - Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
10.1
6.0
Bixler et al. (63) 2002 Central Pennsylvania, USA 16,583 ≥ 20 - Complaint of insomnia >= 1year
- Difficulty sleeping (moderate to severe DIS, DMS, EMA or NRS)
5.9/9.0
21.7/23.1
Ohayon & Partinen (35) 2002 Finland 982 ≥ 18 - DIS, DMS, EMA or NRS >= 3 nights/week
- Dissatisfaction with sleep
- DSM-IV insomnia diagnoses
37.6
11.9
11.7
Ohayon & Hong (83) 2002 South Korea 3719 ≥ 15 - DIS, DMS, EMA or NRS >= 3 nights/week
- DSM-IV insomnia diagnoses
14.8/19.1
4.7/5.1
Kiejna et al. (60) 2003 Poland 47,924 ≥ 15 Suffering from insomnia 18.1/28.1
Ohayon & Paiva (55) 2005 Portugal 1858 ≥ 18 - DIS, DMS, EMA or NRS >= 3 nights/week
- Dissatisfaction with sleep
28.1
6.5/13.4


BINARY QUERY ABOUT THE PRESENCE OF INSOMNIA SYMPTOMS

In epidemiological studies, the binary query about the presence of insomnia symptoms gave high prevalence rates with an average around 33%:

  • One of the earliest epidemiological surveys on insomnia symptoms was carried out by Bixler et al. (22) in the metropolitan area of Los Angeles with 1,006 respondents aged 18 years or over. The overall prevalence of insomnia symptoms was 32.2% (DIS: 14.4%; DS: 22.9%; and EMA: 13.8%).
  • Subsequent studies (23-26) found a similar prevalence in the general population when inquiries were made about the presence of insomnia symptoms (Table 2).

STUDIES USING FREQUENCY TO DETERMINE THE PREVALENCE OF INSOMNIA SYMPTOMS

Epidemiological studies using frequency to determine the prevalence of insomnia symptoms are the most common (27-37).

In some studies, the subjects had to make a subjective assessment of the frequency of the symptom on a four- or five-point scale (27,32,33,36): for example, never, sometimes, often or always; often or always being the cut-off point to determine the presence of insomnia.

Mostly, however, frequency of the symptom is assessed on a weekly basis (28,29,30,31,35,37): for example, never, one or two nights, three or four nights, five nights or more per week; a frequency of three nights or more per week being the cut-off used to conclude the presence of insomnia.

The prevalence of insomnia symptoms drops to around 16% to 21% when frequency is used to determine the presence of insomnia and has similar rates among countries (Table 2).

STUDIES USING SEVERITY OF THE SYMPTOMS

Epidemiological studies using severity of the symptoms (for example being bothered a lot; having great or very great DIS or DMS or a major complaint) gave prevalence of insomnia between 10% and 28% of the general population (38-42). In most of the studies that assessed the prevalence of insomnia symptoms accompanied with daytime consequences, the prevalence was much lower being about 10% (29,30,34,43-46). One study provided a higher prevalence than the other studies mainly because the rate was based on lifetime estimation (43).

DISSATISFACTION WITH THE QUANTITY OR QUALITY OF SLEEP

DISSATISFACTION WITH THE QUANTITY OF SLEEP

Can be expressed as a complaint of:

  • not sleeping enough

OR

  • sleeping too much.

Sleeping not enough has been reported with prevalence ranging from 20% to 41.7% in the general population (29, 46-50). Sleeping too much is far less frequent with prevalence ranging between 2.8% and 9.5% (22,44, 42).

DISSATISFACTION WITH THE QUALITY OF SLEEP

Has various definitions:

  • In some studies, participants were asked to assess their level of satisfaction with their sleep. The prevalence of individuals reporting being dissatisfied with their sleep ranged from 8% to 18.5% (45-48,51-57).
  • Other studies have inquired about perception of sleep as being poor or subjects considering themselves as being insomniac.

Between 10% and 18.1% of the population reported being poor sleepers of being insomniacs (37,58-61).

CHRONICITY OF INSOMNIA SYMPTOMS

Unfortunately, most of these studies did not provide any information about the chronicity of these symptoms.

Studies that assessed duration of insomnia symptoms showed that insomnia is mostly chronic (51,52,55,62, 63):

  • Only 4% of subjects with insomnia symptoms reported a duration of 1 month or less.
  • About 6% of these subjects evaluated the duration being between 1 and 6 months;
  • 5% said the duration is between 6 and 12 months and 85% mentioned a duration of 1 year or more (68% said it lasted 5 years or more) (62).

GENDER DIFFERENCES

Women are more likely than men to report:

  • insomnia symptoms (32,33,34 ,36,37,41,48,67),
  • daytime consequences (27,33,34,51),
  • dissatisfaction with sleep (51,67,103) and
  • to have insomnia diagnoses (72,73,81).

Women/men ratios for insomnia symptoms are about 1.4. The difference between women and men increases with age, the ratio of women/men being about 1.7 after 45 years of age. Women are twice more likely than men to have an insomnia diagnosis. Some studies have found that the prevalence of insomnia increases in menopausal women as compared to their younger counterparts (64,84,88).

AGE

Almost all epidemiological studies reported an increased prevalence of insomnia symptoms with age, reaching close to 50% in elderly individuals (>= 65 years old) (22,23,25,27,29,30,37, 45,46, 48,67, 89). However, the prevalence of insomnia with daytime consequences and the prevalence of sleep dissatisfaction have mixed results.

Other studies found lower rates in middle-aged individuals (59), while still other studies reported an increasing prevalence with age (34,37,44 , 46).

INCOME

Prevalence of insomnia is higher in individuals with lower incomes (22,26,48) and in those with lower education (22,44,85). However, these associations can be the result of other factors such as age.

The use of poverty index will provide a better indication of the association between insomnia and poverty.

PREVALENCE AND CONSEQUENCES OF SLEEP DISORDERS IN DEPRESSIVE ILLNESS

Epidemiological studies have consistently reported that a mental disorder is associated with 30% to 40% of insomnia complaints.

Subjects with insomnia exhibit symptoms of depression in 40% to 60% of the cases (41,64-66) and have a clinical depression in 10% to 25% of cases. (66-69).

In individuals with a current major depressive episode, the presence of insomnia symptoms was found in nearly 80% of the subjects (36,70,71,72).

Ten longitudinal studies (43,44,73-80) examined the relationship between the persistence of insomnia symptoms and the appearance of mental disorders:

  • Ford and Kamerow (44) found a high co-occurrence of insomnia complaints and mental disorders (40%). Insomnia complaints were associated with a higher risk (odds ratio of 39.8) for developing a new major depressive illness if they persisted over two interviews within a 12-month interval, but were not a significant factor if they ceased by the second interview.
  • Another study in young adults between 21 and 30 years of age (43) found that subjects with a history of insomnia were four times more likely to develop a new major depressive disorder in the 3.5 years following the initial interview.
  • Another survey followed up 2,164 individuals age 50 years and over in Alameda County (California) during a one-year period (73). The presence of major depression at the last assessment was eight times more likely to occur in individuals with insomnia on both assessments and 10 times more likely to occur in those who reported insomnia only on the last assessment. However, insomnia was a less important predictor of future depression than other depressive symptoms (anhedonia, feelings of worthlessness, psychomotor agitation/retardation, mood disturbance, thoughts of death) (73).
  • A study (62) examining the time sequence between insomnia and mood and anxiety disorders, reported that insomnia was present in 70% of cases with mood disorders and that it preceded the apparition of the mood disorders in nearly half of cases.

PLACE OF CIRCADIAN RHYTHM DISTURBANCES IN THE COURSE OF DEPRESSIVE DISORDERS

Although several epidemiological surveys have assessed insomnia in depressive disorders very few of them have attempted to describe which type of insomnia characterized depressed individuals. None of them have investigated abnormalities in the sleep/wake schedule to determine if circadian rhythm disturbances could be present. In one study (50), half of participants with comorbid mood and anxiety disorders and 40% of participants with only mood disorders reported difficulty initiating sleep or difficulty maintaining sleep compared to about a quarter of participants with anxiety disorder.

Another study reported that persistent disrupted sleep over a one-year period was associated with new onset of depression in the elderly (74).

A Japanese study (84) found that high CES-D score (>=25) was associated with short (less than 6 hours) and long sleep (9 hours or more), difficulty initiating sleep and difficulty maintaining sleep.

CONCLUSIONS

Considerable progress has been made in the understanding of the mechanisms involved in depressive disorders, as well as in the treatment.

Depression is not just a disease of the mind but is the result of complex interactions between genetic vulnerability, physiological, psychological and environmental factors.

Sleep is part of this equation.

We spend about one third of our lives in the enigmatic world of sleep whether we want to or not. Sleep is as vital a need as food and drink. Things tend to go wrong when sleep is disturbed. Each of us needs to sleep a specific amount of time each day in order to function optimally when we are awake.

In a sense, the quality of our daytime hours depends on the quality of our nighttime hours.

There is mounting evidence of a strong independent relationship between sleep disturbances and depressive disorders. However, more adequate description is this relationship at the epidemiological level is still lacking.

Indeed both cross-sectional and longitudinal studies rarely described this relationship beyond the mere association between insomnia and depression.

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Ohayon MM. Epidemiology of circadian rhythm disorders in depression. Medicographia 2007; 29:10-16.