| The association between atopic disorders and depression: The Northern Finland 1966 Birth Cohort Study | ||
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In Finland, diagnoses have been coded according to the International Classification of Diseases (ICD-7, up to 1968; ICD-8, 1969–1986; ICD-9, 1987–1995; ICD-10 1996 and thereafter) (World Health Organization 1967, 1977, 1993). From 1972 hospital diagnoses were obtained from the hospital discharge register maintained by the Finnish National Board of Health and later from the Hospital Care Register maintained by the National Research and Development Center for Welfare and Health until the end of 1997. These Finnish Hospital Discharge Registers (FHDR) cover all treatment episodes in general, mental, military, prison and private hospitals, as well as the inpatient wards of local health centers nation-wide. The FHDR contains the personal and hospital identification codes, data on age, gender, length of stay, and primary diagnosis at discharge, together with three subsidiary diagnoses. These register data have been shown to be of sufficiently high accuracy to be used in research (Poikolainen 1983, Keskimäki & Aro 1991, Näyhä 1992, Mähönen et al. 2000).
All cohort members having been admitted to a hospital during 1982–1997 (aged 16 to 31 years) due to a psychiatric disorder (i.e., ICD-8 290–309, 7092; ICD-9 290–316) were identified from the FHDR. Further, their hospital case notes were collected and the FHDR diagnoses were carefully validated by re-checking them against DSM-III-R criteria (American Psychiatric Association 1987, Isohanni et al. 1997, Moilanen et al. 2003).
In the original publications I and IV, those subjects who fulfilled the diagnostic criteria of major depression (DSM-III-R codes 296.2–296.3), depressive disorder Not Otherwise Specified (311.00) or dysthymia (300.40) were defined to suffer from hospital-treated depression.
In the original publications II–IV, data on self-reported lifetime doctor-diagnosed depression were obtained from the postal questionnaires of the 31-year follow-up survey. Cohort members were asked the following question: “Have you ever been diagnosed by a doctor as having depression or have you ever been treated by a doctor because of depression (yes/no).”
In the original publication III, information of depressive symptoms was determined through Hopkins Symptom Checklist-25 (HSCL-25), which is a 25-item shortened version of an 90-item questionnaire designed by Derogatis et al. (1973). HSCL-25 was included to the postal questionnaires of the 31-year follow-up survey. A depression subscale consists of 13 items: feeling low in energy/slowed down, blaming yourself for things, crying easily, loss of sexual interest or pleasure, feeling hopeless about the future, feeling blue, feeling lonely, thoughts of ending your life, feeling of being trapped or caught, worrying too much about things, feeling no interest in anything, feeling everything is an effort, feeling worthless (Winocur et al. 1984).
Cohort members estimated the severity of their depressive symptoms on a four-point scale ranging from 1 ("not at all") to 4 ("extremely"). Responses were summed and divided by the number of answered items to generate a “depression mean score” ranging from 1.0 to 4.0. This mean score was utilized to categorize the cohort members to subgroups according to the severity of their depressive symptoms. In addition to two commonly used mean scores of 1.55 and 1.75 (Nettelbladt et al. 1993, Sandanger et al. 1998), a cut-off point of 2.01 was also used in the original publication III, because it is known that duration of symptoms is an essential factor in the diagnosis of major depressive disorder, and because Winocur et al. (1984) have found that patients, who were considered to be highly symptomatic (i.e., had a score over 2.0), showed more consistent ratings over a whole follow-up period than subjects with lower scores (e.g., cut-off point < 2.0).
Hospital diagnosed atopic disorders of cohort members up to the age of 31 years were collected from central hospital files by the research group covering the years 1966–1971 (Moilanen & Rantakallio 1988), and extracted from the FHDR between the years 1972–1997. Cohort members, who had at least one of the following diagnoses: bronchial asthma (ICD-9 code 493), allergic rhinitis (477), or atopic eczema (691), were identified and considered to have an atopic disorder in the original publication I.
In the 31-year follow-up survey, skin prick tests to three of the most common allergens in Finland (i.e., cat, birch, and timothy grass) and the house dust mite (Dermatophagoides pteronyssinus) were carried out. Histamine dihydrochloride (10 mg per ml) and diluent of the allergen extracts were used as positive and negative controls, respectively. After 15 minutes, skin reactions to each allergen were recorded as the average of the maximum wheal diameter and the diameter perpendicular to the maximum value. In the original publication II, subjects with a wheal reaction ≥3 mm (i.e., skin prick test positive) to one or more of the four allergens tested were considered to be "atopic", based on the biological approach in that paper. In the publications III and IV, the term “positive skin prick test response” was preferred to the term "atopic", because the concept of atopic disorder was considered in a more clinical sense in those papers. All prick-tested subjects had a positive reaction to histamine, but subjects with positive reactions to the negative control were rejected.
In clinical practice, the presence of atopy requires not only a positive skin prick test response but also clinical symptoms of allergy (Wamboldt et al. 1998). Therefore, data on a cohort member’s lifetime history of allergic diseases were gathered from postal questionnaires of the 31-year follow-up survey. Each person was asked to evaluate if, "he/she has ever had the following allergy-related symptoms or diseases: asthma, allergic rhinitis, atopic eczema, and/or allergic conjunctivitis.(yes/no)?” Symptoms of allergies were considered to be present if a cohort member had at least one of these self-reported allergic disorders/symptoms.
Data on the family histories of atopies were obtained through questionnaires included in the 31-year follow-up survey and posing the following, separate questions: “Have your a) father, b) mother or c) “any of your siblings” suffered from asthma, allergic rhinitis, or atopic eczema (yes/no)?”. Parental/sibling atopy were considered to be present if at least one of the parents/at least one sibling had or had had asthma, allergic rhinitis or atopic eczema.
In the original publication IV, data on self-reported doctor-diagnosed clinical histories of allergic disorders were obtained from the postal questionnaires of the 31-year follow-up survey. Cohort members were asked the question: “Have you ever been diagnosed by a doctor as having or having had the following allergy-related symptoms or diseases: asthma, allergic rhinitis, atopic eczema, and/or allergic conjunctivitis, or have you ever been treated by a doctor due to the following allergy-related symptoms or diseases: asthma, allergic rhinitis, atopic eczema, and/or allergic conjunctivitis (yes/no)?”. Clinical history of allergic disorders was considered to be present if a cohort member had ever had at least one of these self-reported doctor-diagnosed allergic disorders/symptoms.
The confounding variables used in the original publications I–IV are presented in Table 1. A father’s social class, the dwelling place and a mother’s parity were used as potential confounding factors, because in previous studies, they were shown to be associated with atopic disorders (Kilpeläinen et al. 2000, Pekkanen et al. 2001b, Williams et al. 1994) and depression (Kemppainen et al. 2000, Lenzi et al. 1993, Väisänen 1975).
Table 1. Confounding variables used in the original publications (I–IV)
| Confounding variables | Original publication |
|---|---|
| Father’s social class in 1966 | I–IV |
| Dwelling place in 1966 | II–IV |
| Mother’s parity in 1966 | II–IV |
| Cohort member’s hospital-diagnosed psychiatric diseases | II |
| Pregnancy of a cohort member (in females) | II |
| Use of oral contraceptives (in females). | II |
| Dwelling place in 1980 | I |
| Gender of a cohort member | I |
| Maternal smoking during pregnancy | IV |
| Cohort member’s regular daily smoking at the age of 31 | IV |
A father’s social class in 1966 was defined according to the father’s occupation and its prestige in 1966 (Sosiaaliryhmitys 1954, Rantakallio 1969, Rantakallio 1979). In the highest social stratum, class I, the father’s occupation has the highest prestige and usually required academic education. Examples of occupations in social class I are elementary school teachers, general practitioners, professional engineers and priests. Fathers from social class II were professionals with lower valuation and shorter education than in class I, e.g., office managers and ship’s engineers. Social class III consisted of skilled workers like clerks and stewards, and class IV contained unskilled workers like night watch men and office boys as well as persons on a disability pension. Farmers formed social class V. In all original publications, the father’s social class was re-categorized to three subgroups: classes I–II/classes III–IV/farmers.
The dwelling place in 1966 was defined according to the place of residence of the mother at the time of delivery, and it was divided into urban/rural categories in the original publications II–IV (Rantakallio 1969, Rantakallio et al. 1992). The dwelling place of the family in 1980 (urban/rural) was used in the original publication I (Rantakallio et al. 1992).
A mother’s parity (number of deliveries) in 1966 was used in the original publications II–IV. Parity status was defined as grand multiparity (Juntunen 1997, Kemppainen et al. 2000), if the mother had undergone six or more deliveries (yes/no).
Hospital-diagnosed psychiatric diseases (yes/no) were also used as a potential confounder in the original study II, because psychiatric disorders had been shown to be associated with physical illnesses (Mäkikyrö et al. 1998), and because of the high amount of co-morbidity between depression and other psychiatric disorders (Beekman et al. 2000, Kessler et al. 1996, Kool et al. 2000, Zisook et al. 1999). Psychiatric diagnoses (i.e., ICD-8 290–309, ICD-9 290–316, and ICD-10 F00–F69) of cohort members were obtained from the FHDR, and thereafter validated in detail as described in chapter 4.2.1.1 (Isohanni et al. 1997, Moilanen et al. 2003). In the original publication II, hospital-diagnosed psychiatric diseases were defined to be present if a cohort member had been admitted to hospital due to any of the above mentioned psychiatric disorders at least once before the age of 32.
Reproductive experience causes long-term psychological and physiological effects (Hucke et al. 2001). Further, female sex hormones may play a role in the mechanisms associated with both depression (Freeman 2001, Joffe & Cohen 1998) and atopic disorders (Balzano et al. 2001, Stubner et al. 1999). Therefore, the following variables were used as potential confounding factors in females in the original study II: a) a pregnancy of a cohort member (at least one pregnancy before the age of 31, yes/no), and b) the use of oral contraceptives (yes/no). This information was extracted from the postal questionnaires of the 31-year follow-up survey.
In previous studies, also exposure to tobacco smoke in utero and current own smoking have been shown to be associated with atopic disorders (Backer et al. 2002, Devereux et al. 2002) and depression (Fergusson et al. 1998, Dierker et al. 2002). Therefore, maternal smoking during pregnancy (yes/no) (Rantakallio et al. 1992, Järvelin et al. 1997, Räsänen et al. 1999) and a cohort member’s regular daily smoking at the age of 31 were used as potential confounding factors in the original publication IV.
Details with regard to the variable of maternal smoking during pregnancy had been obtained from the mothers of the probands during the time of their pregnancies and their visits to the antenatal clinics, and also after the delivery (Rantakallio 1969, Rantakallio et al. 1992). Maternal smoking was classified as “yes”, if the mother had smoked during the pregnancy (after second month of the pregnancy) and “no” if the mother did not smoke or had stopped before the pregnancy (Järvelin et al. 1997, Räsänen et al. 1999).
Data on a cohort member’s regular daily smoking habits at the age of 31 were obtained through postal questionnaires of the 31-year follow-up survey by posing the following questions: “Have you ever smoked in your life?” If the answer was “yes”, then cohort members were questioned “Do you smoke at present?” with several alternatives to the answer (Isohanni et al. 2001). A subject’s own regular daily smoking was dichotomized as follows: regular smokers [i.e., smoking on 7 days a week] versus occasional [i.e., smoking less than on 7 days per week] and non-smokers (Isohanni et al. 2001).