Design and sample
We combined previously collected survey data from the Nord-Trøndelag Health Studies (HUNT/Young-HUNT) with prospectively collected health registry data, where HUNT surveys provided information on substantive exposures and covariates and health registries provided information on substantive outcomes of interest. Data sources were linked at the individual using person identification numbers assigned to all residents in Norway.
HUNT and Young-HUNT are large longitudinal general population studies covering a range of health-related topics, where all adults older than 20 and all adolescents between 13 and 20 years of age residing in Nord-Trøndelag county in Norway were invited to participate in these studies, respectively (24–26). The demographic structure of the county is reasonably representative of the Norwegian population (24–26).
We used data from two waves, collected in 1995-97, and 2006-08. The response rates for the surveys used ranged from 54.1–82.7% (24, 25). Detailed information on response rates, how nonparticipation was handled, and reasons for nonparticipation has been provided in HUNT and young-HUNT cohort description manuscripts (24–27). HUNT surveys provided information on parents, while Young-HUNT provided information on offspring; parents and offspring completed their HUNT questionnaires at approximately the same time and their responses were linked at the family level using the unique family numbers available from Statistics Norway. Because our aim was to examine the associations between exposures and outcomes in a sample that was not affected by a range of other risk factors - such as single-parent families - other potential risks were eliminated by study design and through the inclusion criteria focusing on 2-parent families only. Our analytical sample therefore consisted of family triads (N = 6,696) where the all age-eligible offspring (N = 8,773) and both parents had completed the surveys. All offspring were 13–19 years old when they participated in Young-HUNT and 14–33 years old in 2008 when registry follow-up started.
Ethics
Study participants provided informed consent. The study was approved by the Norwegian Data Protection Authority (# 38949) and the Regional Committees for Medical and Health Research Ethics (#2014/867). All procedures were performed in accordance with the relevant guidelines and regulations of these review boards.
Measures
Exposures
The primary exposure was based on previously identified constellations of maternal and paternal risk factors: education, drinking frequency and amount, and mental health (5). In the HUNT survey, the items: "How many times a month do you normally drink alcohol?" and "How many glasses of beer, wine, or spirits do you usually drink in the course of two weeks?" captured maternal and paternal drinking frequency and quantity respectively. Parental mental health symptoms were measured with the Hospital Anxiety and Depression Scale (HADS), where both parents completed the HADS scale as part of the HUNT survey (28, 29). HADS is commonly used to screen for anxiety and depression, where the summed scale scores translate to the following diagnostic categories 0–7 normal, 8–10 indicate mild symptoms; 11–14 moderate symptoms; and 15–21 severe symptoms (28). The number of years of completed education for each parent was obtained from Statistics Norway.
Based on these indicators, we previously identified five mutually exclusive risk constellations (5) using a Latent Profile Analysis (LPA)(30, 31). Table 1 provides a conceptual overview of these Latent Profiles (LP). In short, LP1 was characterized by low education for both parents, but otherwise no risk. LP2 was characterized by multiple risks; low education, mental health symptoms within a mild disorder range, and weekly binge drinking in both parents. LP3 was characterized by the lowest overall risk: some higher education, good mental health, and infrequent low-quantity drinking in both parents. In LP4, casual weekly drinking in both parents was the only potential risk factor. LP5 was characterized by multiple risk factors: frequent and high quantity drinking in both parents and mental health symptoms indicative of a mild disorder in fathers. We have previously shown increased risk for anxiety and depression diagnosis or treatment among offspring from risk constellations LP1 (i.e., low education in both parents) and LP5 (elevated drinking frequency and quantity in both parents, and elevated mental health symptoms in fathers)(5).
Table 1
Description of the parental risk constellations (Latent Profiles)
|
Latent profile 1
|
Latent profile 2
|
Latent profile 3
|
Latent profile 4
|
Latent profile 5
|
Characteristic
|
Low Education
|
Multiple risks: binge drinking and mental health symptoms in both parents
|
Low overall risk
|
Casual drinking in both parents
|
Multiple risks: frequent drinking both parents, mental health symptoms fathers
|
Participants, n(%)
|
|
|
|
|
|
Family a
|
4,857 (69.1%)
|
194 (2.8%)
|
1,444 (20.5%)
|
473 (6.7%)
|
61 (.9%)
|
Children
|
5,966 (68.0%)
|
246 (2.8%)
|
1,884 (21.5%)
|
598 (6.8%)
|
79 (.9%)
|
Education (years)b
|
|
|
|
|
|
Maternal
|
< 12
|
< 12
|
> 12
|
> 12
|
> 12
|
Paternal
|
< 11
|
< 12
|
> 14
|
> 12
|
> 12
|
Maternal drinking (weekly)c, d
|
|
|
|
|
|
Average quantity
|
1 drink
|
3.92 drinks
|
1.25 drinks
|
4.1 drinks
|
6.5 drinks
|
Average frequency
|
0.4 days
|
0.95 days
|
0.5 days
|
2.3 days
|
5.4 days
|
Paternal drinking (weekly)c, d
|
|
|
|
|
|
Average quantity
|
2 drinks
|
11.2 drinks
|
2.3 drinks
|
4.8 drinks
|
6.6 drinks
|
Average frequency
|
0.7 days
|
1.9 days
|
0.9 days
|
2 days
|
3 days
|
Mental health (HADS Score)c, e
|
|
|
|
|
|
Maternal
|
Normal range
|
Mild symtoms
|
Normal range
|
Normal range
|
Normal range
|
Paternal
|
Normal range
|
Mild symptoms
|
Normal range
|
Normal range
|
Mild symptoms
|
Notes: The original Latent profile analysis procedures utilized all indicators in their original format(5); to aid interpretation, we re-scaled the estimates to show average weekly drinking quantities and frequencies. Elevated levels of parental risk factors are shown in bold. aSome families had multiple children, therefore the number of children is greater than the number of families for each LP. bFrom the Statistics Norway records. cFrom parental self-reports. d Quantity = number of glasses of beer, wine, or liquor reported in HUNT surveys. e HADS (14-item Hospital Anxiety and Depression Scale) is commonly used to screen for anxiety and depression. Sum scores translate to the following diagnostic categories: 0–7 normal, 8–10 mild, 11–14 moderate, and 15–21 severe symptoms. |
Covariates
We included the following covariates: age at Young-HUNT participation, age at start of registry follow-up in 2008, and gender. We also included a measure of early mental health symptoms as self-reported in the Young-HUNT survey by the participants on the 5-item Hopkins Symptoms Checklist (SCL-5) (32). In line with previous reports, SCL-5 scores were categorized to reflect the top 25% of the distribution vs. rest (5, 32, 33), while missing responses (n = 138) were modeled as a separate category to prevent loss of data.
We included the following covariates: age at Young-HUNT participation, age at start of registry follow-up in 2008, and gender. We also included a measure of early mental health symptoms as self-reported in the Young-HUNT survey by the participants on the 5-item Hopkins Symptoms Checklist (SCL-5) (32). In line with previous reports, SCL-5 scores were categorized to reflect the top 25% of the distribution vs. rest (5, 32, 33), while missing responses (n = 138) were modeled as a separate category to prevent loss of data.
We included the following covariates: age at Young-HUNT participation, age at start of registry follow-up in 2008, and gender. We also included a measure of early mental health symptoms as self-reported in the Young-HUNT survey by the participants on the 5-item Hopkins Symptoms Checklist (SCL-5) (32). In line with previous reports, SCL-5 scores were categorized to reflect the top 25% of the distribution vs. rest (5, 32, 33), while missing responses (n = 138) were modeled as a separate category to prevent loss of data.
Outcomes
Information on our substantive outcomes of interest – that is, the recurrence of anxiety and depression over the 7-year study period -- were obtained from the Norwegian primary- and specialist health registries where all contacts with primary and specialist health care services for all somatic and psychiatric conditions are recorded at the patient-level. In this study we used registry records in the primary and specialist healthcare services that included anxiety/depression codes, recorded annually between 2008 and 2014. Table 2 gives an overview of the included diagnostic codes from the International Classification of Primary Care (ICPC) and International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). We examined two related outcomes; 1) the total number of calendar years the offspring were in contact with the healthcare services. This was calculated based on an individual’s contacts with the health care services during each calendar year. 2) The total number of offspring's contacts with the healthcare services for anxiety/depression during the study period (2008–2014). Both outcomes were based on the combined primary and specialist healthcare registry records.
Table 2
Codes for anxiety and depression, as identified in the primary and specialist healthcare registries
Registry for primary healthcarea
|
Registry for specialist healthcareb
|
ICPC codesc
|
ICD-10 codesd
|
P01
|
Feeling anxious/nervous/tense
|
F30 – F39
|
Mood (affective) disorders
|
P03
|
Feeling depressed
|
F40 – F48
|
Anxiety, dissociative, stress-related, somatoform, and other non-psychotic mental disorders
|
P73
|
Affective psychosis
|
|
P74
|
Anxiety disorder/anxiety state
|
|
P76
|
Depressive disorder
|
|
|
P79
|
Phobia/compulsive disorder
|
|
|
Notes: aControl and Reimbursement to Practitioners in Primary Healthcare for Seeing and Treating Patients' Database (CPHR). bThe Norwegian Patient Registry (NPR). cICPC=International Classification of Primary Care. dICD 10 = International Statistical Classification of Diseases and Related Health Problems 10th Revision. |
Analyses
As the number of a) years in contact with, and b) of actual contacts with the healthcare services for anxiety and depression are technically counts, and as the majority of our participants were not registered as having contact with the healthcare services for these problems (i.e., there was an excess of "zeros" in our data), our primary analysis was a count regression model, specifically, zero-inflated negative binomial (ZINB) regression. As zero-inflated models address both zero-inflation and over-dispersion problems, they are well-suited for mental health services research where studied outcomes often have low-prevalence rates (34, 35).
ZINB models consist of two components; the first models "zeroes" (the likelihood of no contact with the healthcare services in our case), while the second one models counts (the number of years, and the number of actual contacts with the healthcare services for anxiety and depression problems in our case). Thus, a ZINB model was estimated for each one of our outcomes, where the count components of these models specifically address our substantive questions of disorder(s) recurrence; that is, the duration of, and number of repeated contacts with the healthcare system for anxiety and depression disorders. Identical sets of predictors were included in the zero-inflated and the count component; the key exposure (parental risk constellations) was modeled as a categorical variable with the low-risk group, LP3, as the reference. To aid in the results interpretation, we reported the adjusted odds ratios (aORs) of no contact versus contact with the healthcare services for the zero-inflated component, and the adjusted incidence rate ratios (aIRRs) for the count component of both models.
All analyses were conducted in Stata using the -zinb command (36), where robust standard errors were estimated based on family-level clusters using the vce (cluster) option. All estimates were thus adjusted for within-family nesting (37) .