Abstract
Nonrandom mating in parents with schizophrenia or bipolar disorder increases the population-level genetic variance among the offspring generation and creates familial (risk) environments likely to be shaped by specific conditions. The objective of this study was to investigate the occurrence of mental disorder and levels of cognitive and social functioning in individuals who have children by partners with schizophrenia or bipolar disorder compared to controls. The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study conducted in Denmark between 2013 and 2016. This study focus on parents diagnosed with schizophrenia (n = 150) or bipolar disorder (n = 100) and control parents (n = 182), as well as their partners without schizophrenia or bipolar disorder (n = 440). We used linear mixed-effect models, and main outcomes were mental disorders, intelligence, processing speed, verbal working memory, and social functioning. We found that parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder and had poorer social functioning compared to parents having children by a partner without schizophrenia or bipolar disorder. Furthermore, parents having children by a partner with schizophrenia performed poorer on processing speed compared to parents in the control group. The presence of nonrandom mating found in this study has implications for our understanding of familial transmission of these disorders and our findings should be considered in future investigations of potential risk factors for children with a parent with schizophrenia or bipolar disorder.
Keywords: assortative mating, mental disorders, cognition, social functioning
Introduction
Nonrandom mating refers to a tendency for mated couples to be more similar regarding some phenotypic traits than would be the case if mating occurred completely at random.1 It is common in individuals with mental disorders, both within specific disorders and across the spectrum of mental disorders.2 Nonrandom mating may result from the initial selection of a mate (assortment), and/or by couples becoming increasingly alike when living together (convergence).3,4 For example, spousal correlations around 0.40 have been found for intelligence, which is believed to be related to initial selection of the mate3 (assortative mating). Social homogamy covers marriage between individuals that resemble each other in their social characteristics, such as socioeconomic status, educational attainment, religion, and age, traits with varying degree of influence from genetic factors.5,6 Assortative mating in the parental generation is expected to increase the population-level additive genetic variance of the phenotype in the next generation. The offspring inherits only one allele per locus from each parent and only additive effects are transmitted from a single parent to the offspring but, in the case of assortative mating where pairs of parents are genetically correlated with respect to alleles associated with phenotype, the offspring is also affected by nonadditive interactions.7,8 Thus, the offspring of women with intelligence above average and men with intelligence below average, or vice versa, would generally be of average intelligence. However, in assortative mating, a child with an above average intelligent mother is also likely to have an above average intelligent father and the offspring is likely to be more intelligent than average. The same mechanism may occur for other phenotypes than intelligence. Consequently, in assortative mating, the offspring is likely to differ more from the population mean than in the case of random mating. Assortative mating is thus expected to increase phenotypic and additive genetic variance in the population over multiple generations,9 although the impact may be limited and model specific.10
Assortative mating may play a key role in mental disorders because the person with close relation to an individual with a mental disorder is also likely to have a mental disorder, which may further affect the level of functioning for both partners and their offspring. Therefore, the rationale for investigating assortative mating in families where one of the parents suffers from schizophrenia or bipolar disorder is convincing: when one parent is ill, the care for the child will often depend on the other parent. Thus, assortative mating will most likely influence the level of functioning in the offspring, beyond the effect of genetic risk.
Assortative mating in parents with schizophrenia or bipolar disorder has effects on a population-level as it increases the genetic variance in the population among the offspring generation, but it also produces familial (risk) environments that are likely to be shaped by specific conditions.7 Prior studies have also focused on nonrandom mating in relation to mental disorders, intelligence, or level of functioning.2,3,5 However, most studies are of older date, have a small sample size or only considers one area of interest in their investigations. The objective of this study was to investigate if the partners of individuals with schizophrenia or bipolar disorder differed from the partners in a control group in terms of mental disorders, cognitive abilities, and social functioning. Furthermore, we aimed to compare parents with schizophrenia, bipolar disorder, or control parents with their coparents on cognitive abilities and social functioning.
Methods
Participants
The Danish High Risk and Resilience Study VIA 7 is a population-based study of a nationwide cohort conducted in Denmark from January 1, 2013 until January 31, 2016. The VIA 7 sample consists of 522 7-year-old children with no parent, one parent, or both parents diagnosed with schizophrenia or bipolar disorder. The design of VIA 7 has been described in detail elsewhere.11
Participants were identified in the Danish Civil Registration System12 and the Danish Psychiatric Central Research Register13 through linkage of the unique personal identification number assigned to all Danish citizens. The Danish Psychiatric Central Research Register contains data on all admissions to Danish psychiatric in-patient facilities and, from 1995, all contacts to outpatient psychiatric departments and visits to psychiatric emergency care units were included. Schizophrenia was defined as schizophrenia, delusional disorder, or schizoaffective disorder coded in accordance with the International Classification of Diseases, 10th revision or 8th revision (ICD-10: F20, F22, and F25 or ICD-8: 295, 297, 298.29, 298.39, 298.89, and 298.99) and bipolar disorder (ICD-10: F30 and F31 or ICD-8: 296.19 and 296.39).
We defined the index parent as the parent with a diagnosis of schizophrenia or bipolar disorder in the Danish registries. The parent in the control group with the same sex was defined as the index control parent. We defined the nonindex parent as the other biological parent (ie, the partner without a diagnosis of schizophrenia or bipolar disorder recorded in the Danish registries). Index parents from the control group and all nonindex parents could have any other mental disorder diagnosis. The demographic characteristics of the parents (index parents and nonindex parents) are presented in table 1.
Table 1.
Demographic Characteristics of Biological Parents (Nonindex Parents and Index Parents)
| P-value | ||||||
|---|---|---|---|---|---|---|
| Pairwise comparisons | ||||||
| SZ | BP | PBC | SZ vs PBC | BP vs PBC | BP vs SZ | |
| Nonindex parents, n | 186 | 114 | 192 | |||
| Female, n (%) | 82 (44.1) | 51 (44.7) | 83 (43.2) | 0.867a | 0.797a | 0.912a |
| Age at inclusion, mean (SD) | 38.77 (6.35) | 40.95 (5.37) | 40.77 (4.26) | 0.001 b | 1.000b | 0.002 b |
| Employed or studying, n (%; n = 474) | 133 (75.1) | 93 (85.3) | 179 (95.2) | <0.001 a | 0.003 a | 0.040 a |
| Education, n (n = 469) | 176 | 106 | 187 | |||
| Primary/lower secondary, n (%) | 31 (17.6) | 5 (4.7) | 10 (5.3) | 0.002 a | 0.276a | < 0.001 a |
| Upper secondary, vocational, short-cycle tertiary, n (%) | 86 (48.9) | 44 (41.5) | 89 (47.6) | |||
| Bachelor degree, equivalent or higher, n (%) | 59 (33.5) | 57 (53.8) | 88 (47.1) | |||
| Index parents, n | 200 | 116 | 204 | |||
| Female, n (%) | 111 (55.5) | 64 (55.2) | 115 (56.4) | 0.860a | 0.835a | 0.955a |
| Age at inclusion, mean (SD) | 38.10 (6.07) | 41.00 (6.99) | 40.62 (4.84) | <0.001 b | 1.000b | <0.001 b |
| Employed or studying, n (%; n = 497) | 93 (49.7) | 61 (56.0) | 185 (92.0) | <0.001 a | <0.001 a | 0.301a |
| Education, n (n = 481) | 178 | 109 | 197 | |||
| Primary/lower secondary, n (%) | 54 (30.3) | 10 (9.2) | 8 (4.1) | <0.001 a | 0.985a | <0.001 a |
| Upper secondary, vocational, short cycle tertiary, n (%) | 76 (42.7) | 45 (41.3) | 95 (48.2) | |||
| Bachelor degree, equivalent or higher, n (%) | 48 (27.0) | 54 (49.5) | 94 (47.7) | |||
| Cohabitation | ||||||
| Living together, n (%) | 82 (40.6) | 63 (52.5) | 169 (84.5) | <0.001 a | <0.001 a | 0.038 a |
Note. For siblings, parent information was included only for first sibling to ensure that the same parent was not counted twice. Nonindex parents: biological parents without a diagnosis of schizophrenia or bipolar disorder in the Danish registers. Index parents: parents with a diagnosis of schizophrenia or bipolar disorder or matched control parents.
SZ, parents with a diagnosis of schizophrenia and parents having a child by a partner with schizophrenia; BP, parents with a diagnosis of bipolar disorder and parents having a child by a partner with bipolar disorder; PBC, population-based controls.
aChi-squared test of independency in contingency table.
bOne-way ANOVA.
All participants provided written informed consent after having received both verbal and written information about the study. The study was approved by the Danish Data Protection Agency. The Danish Ministry of Health granted permission to retrieve the data from Danish registers. The study protocol was evaluated by the National Committee on Health Research Ethics and all procedures were performed according to their guidelines. However, according to Danish law, this type of study did not require their ethical approval.
Procedures
All assessors (psychologists, medical doctors, and nurses) attended a 1-week training course on the Schedules for Clinical Assessment in Neuropsychiatry, version 2.1 (SCAN 2.1),14 and experienced users (coauthor O.M., Professor in psychiatry, and coauthor A.T., Professor in child and adolescence psychiatry) supervised diagnoses at clinical conferences. Assessors were blinded to index parents register diagnoses. All assessors were trained, certified, and supervised on neuropsychological assessments by a specialist in child neuropsychology (coauthor J.R.M.J.). The majority of assessments were conducted at the Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark, and at the Research Unit, Mental Health Centre Copenhagen, Copenhagen, Denmark, whereas a minority of the assessments were made in the homes of the participating families if the home allowed for equal conditions as in the research sites (ie, a quiet room, a suitable work desk, and no distractions). Trained research assistants, who were blinded to the illness status of the parents and supervised by a specialist in clinical child psychology (coauthor N.H.), and the first author (A.N.G.) carried out the scoring of the neurocognitive tests.
Measures
The diagnostic interview SCAN 2.1 was used to estimate lifetime-ever ICD-10 diagnoses15 of the following mental disorders in nonindex parents: psychoactive substance use disorder (F10–F19), schizophrenia spectrum disorder (F20–29), manic episode and bipolar disorder (F30–31), depressive episode and recurrent depressive disorder (F32–33), or phobic and other anxiety disorders, including obsessive-compulsive disorder (F40–42) based on the hierarchical principles of ICD-10.
Levels of social functioning of nonindex and index parents were rated using the Personal and Social Performance scale (PSP).16 The PSP interview was rated based on social functioning during the previous month, and consensus meetings were held regularly to secure agreement among raters.
Intelligence was estimated with the Reynolds Intellectual Screening Test (RIST), an individually administered assessment scale consisting of a verbal subtest (Guess What) and a nonverbal subtest (Odd-Item Out). The RIST index is based on norms stratified on age (Danish Version, Hogrefe, Psykologisk Forlag A/S, Virum, provided by the publisher, 2011).17
Verbal working memory was assessed with letter-number sequencing from the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV),18 and processing speed was measured with coding from the WAIS-IV18,19 using age-corrected norms.
Statistical Analysis
The demographic and clinical characteristics of the 3 groups of parents (schizophrenia, bipolar disorder, and controls) were compared with one-way ANOVA or Pearson’s chi-squared test of independence. Families with 2 parents with schizophrenia or bipolar disorder were not included in the main analyses. The assumption of normality was met for the 3 neurocognitive variables (intelligence, verbal working memory, and processing speed) and for social functioning in both nonindex parents and index parents.
Chi-square test (or Fisher’s exact test when the numbers were small) were used to test for significant difference between the selected diagnostic categories for nonindex schizophrenia, nonindex bipolar disorder, and nonindex control parents. One-way random effects model were used to calculate intraclass correlations (ICC) between index parents and nonindex parents in the 3 groups (schizophrenia, bipolar disorder, and controls) for intelligence, verbal working memory, processing speed, and social functioning.
Linear mixed-effect models were used as the data had a multilevel structure, and mixed models allow the use of all available data under the assumption that data is missing at random. The models were applied to test the difference between nonindex parents from the 3 groups as well as difference between nonindex parents and index parents in the 3 groups for each of the outcomes (intelligence, processing speed, verbal working memory, and social functioning), including parent status (nonindex parent or index parent), group (schizophrenia, bipolar disorder, and control), and interaction between parent status and group. Age and cohabitation were included in the models as covariates. Due to the risk of overcorrecting, we did not covary for socioeconomic status (education and employment), which is intrinsically associated with group status.
The outcome scores (intelligence, processing speed, verbal working memory, and social functioning) were standardized into z-scores for figure 1, and means and SDs of control nonindex parents were used as reference for nonindex parents and means and SDs of control index parents were used as reference for index parents. A negative z-score reflected poorer performance. All analyses were performed with Stata 15 statistical software. We used a significance level of 5%.
Fig. 1.
Performance on social functioning, intelligence, processing speed, and verbal working memory in index parents and nonindex parents. The outcomes scores are standardized into z-scores with means and standard deviation (SDs) of control nonindex parents as reference for nonindex parents and means and SDs of control index parents as reference for index parents. A negative z-score reflected poorer performance. Age and cohabitation are included in the models as covariates.
Results
Demographic and Clinical
Our study included data from 872 biological parents and, in 401 families, both biological parents (nonindex parents and index parents) participated in the study. See table 1 for demographic presentation of nonindex parents and index parents.
Outcome Data
Among nonindex parents having the child by a partner with schizophrenia, 71 (43.56%) had a lifetime-ever diagnosis of either substance use disorder (10.43%), schizophrenia spectrum disorder (6.13%), a manic episode or bipolar disorder (3.68%), depression (29.45%), or anxiety (11.04%). Among nonindex parents having children by a partner with bipolar disorder, 34 (35.79%) had a lifetime-ever diagnosis of either substance use disorder (6.32%), schizophrenia spectrum disorder (1.05%), a manic episode or bipolar disorder (0%), depression (22.11%), or anxiety (9.47%). Among controls, 33 (19.08%) of the nonindex parents had a lifetime-ever diagnosis of either substance use disorder (4.62%), schizophrenia spectrum disorder (1.16%), mania or bipolar disorder (0.58%), depression (12.72%), or anxiety (3.47%).
Nonindex parents having child by a partner with schizophrenia, nonindex parents having child by a partner with bipolar disorder, and nonindex parents from the control group differed significantly on lifetime-ever diagnoses of schizophrenia spectrum disorder (P = .012), manic episode and bipolar disorder (P = .050), depressive episode and recurrent depressive disorder (P = .001), and any of the selected lifetime-ever ICD-10 diagnoses (P < .001). They did not differ significantly on psychoactive substance use (P = .090) and phobic and other anxiety disorders, including obsessive-compulsive disorder (P = .056; table 2).
Table 2.
Diagnoses of Mental Disorders in Nonindex Parents (n = 439)
| SZ | BP | PBC | |
|---|---|---|---|
| n (%) | n (%) | n (%) | |
| Diagnostic categories (ICD-10) | (n = 163) | (n = 95) | (n = 181) |
| Psychoactive substance use (F10–F19)a | 17 (10.43%) | 6 (6.32%) | 8 (4.42%) |
| Schizophrenia spectrum disorder (F20–29)b | 10 (6.13%) | 1 (1.05%) | 2 (1.10%) |
| Manic episode and bipolar disorder (F30–31)b | 6 (3.68%) | 0 (0%) | 1 (0.55%) |
| Depressive episode and recurrent depressive disorder (F32–33)b | 46 (28.22%) | 21 (22.11%) | 21 (11.60%) |
| Phobic and other anxiety disorders including obsessive-compulsive disorder (F40–42)b | 5 (3.07%) | 8 (8.42%) | 5 (2.76%) |
| Any of the above diagnoses | 71 (43.56%) | 34 (35.79%) | 33 (18.23%) |
Note. Nonindex parents: biological parents without schizophrenia or bipolar disorder in the Danish registers.
SZ, parents who have children by partners with schizophrenia; BP, parents who have children by partners with bipolar disorder; PBC, population-based controls.
aDiagnoses of substance use were rated for all nonindex parents.
bLifetime-ever diagnoses based on the hierarchical principles of the International Classification of Diseases, 10th revision (ICD-10).
ICC for intelligence between index parents and nonindex parents were 0.35 (95% CI: 0.20 to 0.49) for schizophrenia, 0.10 (95% CI: −0.12 to 0.31) for bipolar disorder, and 0.30 (95% CI: 0.15 to 0.43) for controls. We found no significant difference between the 3 study groups on intelligence as CIs were overlapping. ICC for verbal working memory between index parents and nonindex parents were 0.06 (95% CI: −0.11 to 0.23) for schizophrenia, 0.03 (95% CI: −0.18 to 0.24) for bipolar disorder, and 0.08 (95% CI: −0.07 to 0.22) for controls, with no significant difference between groups. ICC for processing speed between index parents and nonindex parents were −0.10 (95% CI: −0.26 to 0.07) for schizophrenia, 0.14 (95% CI: −0.07 to 0.35) for bipolar disorder, and 0.18 (95% CI: 0.03 to 0.32) for controls, and ICC for social functioning between index parents and nonindex parents were 0.23 (95% CI: 0.07 to 0.39) for schizophrenia, −0.00 (−0.22 to 0.21) for bipolar disorder, and 0.28 (0.14 to 0.41) for controls. We found no significant differences between groups for either processing speed or social functioning. See supplementary material.
Nonindex parents having children by a partner with schizophrenia had significantly lower scores on processing speed (Δ = −0.86 [95% CI: −1.45 to −0.27]) and social functioning (Δ = −7.24 [95% CI: −9.98 to −4.50]) compared to the nonindex parents in the control group and significantly lower scores on intelligence (Δ = −3.55 [95% CI: −5.71 to −1.38]) and social functioning (Δ = −4.63 [95% CI: −7.76 to −1.51]) compared to nonindex parents having children by a partner with bipolar disorder. See table 3 for the presentation of outcome data for 3 groups of nonindex and index parents.
Table 3.
Mean Differences Between Nonindex Parents and Index Parents, Respectively, From the 3 Groups (Schizophrenia, Bipolar Disorder, and Controls) on Performance on Intelligence, Processing Speed, Verbal Working Memory, and Social Functioning. The Presented Values Are Adjusted for Age and Cohabitation
| SZ | BP | PBC | Difference | |||
|---|---|---|---|---|---|---|
| SZ vs PBC | BP vs PBC | SZ vs BP | ||||
| Mean (95% CI) | Mean (95% CI) | Mean (95% CI) | Δ (95% CI) | Δ (95% CI) | Δ (95% CI) | |
| P e | P e | P e | ||||
| Nonindex parents | ||||||
| Variable | ||||||
| Intelligencea (n = 440) | 102.27 (100.93; 103.61) | 105.82 (104.11; 107.53) | 103.80 (102.54; 105.07) | −1.53 (−3.42; 0.36) | 2.02 (−0.12; 4.15) | −3.55 (−5.71; −1.38) |
| .113 | .064 | .001 | ||||
| Verbal working memoryb (n = 439) | 10.17 (9.80; 10.53) | 10.31 (9.85; 10.77) | 10.43 (10.09; 10.77) | −0.26 (−0.77; 0.25) | −0.12 (−0.69; 0.46) | −0.14 (−0.73; −0.44) |
| .312 | .691 | .625 | ||||
| Processing speedc (n = 440) | 10.36 (9.94; 10.78) | 10.95 (10.42; 11.49) | 11.22 (10.83; 11.61) | −0.86 (−1.45; −0.27) | −0.27 (−0.93;0.39) | −0.59 (−1.27; 0.09) |
| .004 | .426 | .087 | ||||
| Social functioningd (n = 437) | 77.28 (75.35; 79.22) | 81.92 (79.44; 84.39) | 85.52 (82.69; 86.36) | −7.24 (−9.98; −4.50) | −2.61 (−5.70;0.49) | −4.63 (−7.76; −1.51) |
| <.001 | .099 | .004 | ||||
| Index parents | ||||||
| Variable | ||||||
| Intelligencea (n = 432) | 101.62 (100.23; 103.02) | 104.20 (102.54; 105.87) | 103.49 (102.22; 104.76) | −1.87 (−3.80; 0.06) | 0.71 (−1.39; 2.82) | −2.58 (−4.74; −0.42) |
| .058 | .508 | .019 | ||||
| Verbal working memoryb (n =423) | 9.99 (9.62; 10.38) | 10.86 (10.41; 11.31) | 10.73 (10.39; 11.07) | −0.73 (−1.26; −0.21) | 0.12 (−0.44; 0.69) | −0.86 (−1.45; −0.27) |
| .006 | .668 | .004 | ||||
| Processing speedc (n = 428) | 9.74 (9.31; 10.18) | 10.24 (9.72; 10.76) | 11.38 (10.98; 11.78) | −1.63 (−2.24; −1.03) | −1.14 (−1.79; −0.48) | −0.50 (−1.17; 0.18) |
| <.001 | .001 | .149 | ||||
| Social functioningd (n = 432) | 67.73 (65.72; 69.75) | 69.34 (66.94; 71.74) | 83.28 (81.46; 85.10) | −15.55 (−18.33; −12.77) | −13.94 (−16.98; −10.91) | −1.61 (−4.73; 1.51) |
| <.001 | <.001 | .312 |
Note. Nonindex parents: biological parents without a diagnosis of schizophrenia or bipolar disorder in the Danish registers. Index parents: parents with a diagnosis of schizophrenia or bipolar disorder or matched control parents.
SZ, parents with a diagnosis of schizophrenia and parents having a child by a partner with schizophrenia; BP, parents with a diagnosis of bipolar disorder and parents having a child by a partner with bipolar disorder. PBC, population-based controls.
aMeasured by the RIST index from Reynolds Intellectual Screening Test.
bMeasured by letter-number sequencing from the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV).
cMeasured by coding from WAIS-IV.
dMeasured by the Personal and Social Performance Scale.
eMeasured by mixed-effect statistical models.
Nonindex parents having a child by a partner with schizophrenia did not differ significantly from their index parent on intelligence and verbal working memory, but they had significantly higher scores on processing speed (Δ = −0.62 [95% CI: −1.19 to −0.05]) and social functioning (Δ = −9.54 [95% CI: −11.91 to −7.19]). Nonindex parents having children by a partner with bipolar disorder did not differ significantly from their index parent on intelligence, verbal working memory, and processing speed, but they had significantly higher scores on social functioning (Δ = −12.57 [95% CI: −15.57 to −9.58]; table 4 and figure 1).
Table 4.
Mean Differences Within Pairs of Nonindex Parents and Index Parents in the 3 Groups (Schizophrenia, Bipolar Disorders, and Controls) on Performance on Intelligence, Processing Speed, Verbal Working Memory, and Social Functioning. The Presented Values are Adjusted for Age and Cohabitation
| Index parents | Nonindex parents | Δ (95% CI) | |
|---|---|---|---|
| Mean (95% CI) | Mean (95% CI) | ||
| Intelligencea | |||
| SZ | 101.62 (100.23; 103.02) | 102.27 (100.93; 103.61) | −0.65 (−2.29; 0.99) |
| BP | 104.20 (102.54; 105.87) | 105.82 (104.11; 107.53) | −1.62 (−3.69; 0.46) |
| PBC | 103.49 (102.22; 104.76) | 103.80 (102.54; 105.07) | −0.31 (−1.81; 1.19) |
| Verbal working memoryb | |||
| SZ | 9.99 (9.62; 10.38) | 10.17 (9.80; 10.53) | −0.17 (−0.67; 0.33) |
| BP | 10.86 (10.41; 11.31) | 10.31 (9.85; 10.77) | 0.55 (−0.08; 1.17) |
| PBC | 10.73 (10.39; 11.07) | 10.43 (10.09; 10.77) | 0.30 (−0.15; 0.76) |
| Processing speedc | |||
| SZ | 9.74 (9.31; 10.18) | 10.36 (9.94; 10.78) | −0.62* (−1.19; −0.05) |
| BP | 10.24 (9.72; 10.76) | 10.95 (10.42; 11.49) | −0.71 (−1.43; 0.01) |
| PBC | 11.38 (10.98; 11.78) | 11.22 (10.83; 11.61) | 0.16 (−0.37; 0.68) |
| Social functioningd | |||
| SZ | 67.73 (65.72; 69.75) | 77.28 (75.35; 79.22) | −9.54* (−11.91; −7.19) |
| BP | 69.34 (66.94; 71.74) | 81.92 (79.44; 84.39) | −12.57* (−15.57; −9.58) |
| PBC | 83.28 (81.46; 85.10) | 85.52 (82.69; 86.36) | −1.24 (−3.39; 0.91) |
Note. Nonindex parents: biological parents without a diagnosis schizophrenia or bipolar disorder in the Danish registers. Index parents: parents with a diagnosis schizophrenia or bipolar disorder or matched control parents.
SZ, parents with a diagnosis of schizophrenia and parents having a child by a partner with schizophrenia; BP, parents with a diagnosis of bipolar disorder and parents having a child by a partner with bipolar disorder; PBC, population-based controls.
aMeasured by the RIST index and Reynolds Intellectual Screening Test.
bMeasured by letter-number sequencing, the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV) and the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV).
cMeasured by WAIS-IV/WISC-IV.
dMeasured by the Personal and Social Performance Scale.. Measured by mixed-effect statistical models.
*P < .05.
Discussion
In this study, we aimed to describe patterns of nonrandom mating using a large population-based cohort of parents having children at the same age by a partner with schizophrenia, bipolar disorder, or neither of these 2 disorders. First, we found that parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder compared to parents having children by a partner without schizophrenia or bipolar disorder. Second, the ICC analyses revealed low resemblance between index parents and coparents regarding social functioning, intelligence, processing speed, and verbal working memory with no significant differences in resemblance between the 3 study groups. Third, parents having children by a partner with schizophrenia had lower levels of social functioning compared to parents having children by a partner with bipolar disorder and compared to parents having children by a partner without schizophrenia or bipolar disorder. Furthermore, parents having children by a partner with schizophrenia performed poorer on measures of processing speed and they performed poorer on scores of intelligence compared to parents having a child by a partner with bipolar disorder. Finally, we found that parents having children by a partner with schizophrenia did not differ significantly from parents with schizophrenia on intelligence and verbal working memory, but they performed better on processing speed and had higher levels of social functioning. Parents having children by a partner with bipolar disorder did not differ from parents with bipolar disorder on intelligence, verbal working memory, or processing speed, but they had better social functioning. Our results extend earlier work in this area, indicating that nonrandom mating is present in individuals with mental disorders.20,21 Based on a previous finding of assortative mating not being present in somatic disorders, a study suggested that the processes involved in assortative mating and their effect on genetic architecture may be limited to mental disorders.2
Owing to the relatively high heritability of cognitive abilities both in healthy families and families with schizophrenia,22 the observed association of phenotypes for cognitive abilities found in this study is most likely induced by the selection of partner based on the level of cognitive functioning (assortative mating). However, heritability of depression is lower compared to heritability of schizophrenia or bipolar disorder, indicating that environment (and thus the behavior of spouse) have a larger effect on depression than on bipolar disorder and schizophrenia.23 Therefore, it is reasonable to assume that the presence of a mental disorder in the index parent (eg, schizophrenia) could affect his or her partner (the nonindex parent) and spur the development of a disorder more sensitive to stress (eg, depression). This is supported by the results from this study where we found that individuals who have children by partners with schizophrenia more often present with a depression diagnosis.
The presented findings are important as they reveal potential risk factors for children born to a parent diagnosed with schizophrenia or bipolar disorder, which involves both genetic and environmental exposures.24 For example, it has been suggested that impaired cognitive functions are related to some of the difficulties concerning parental role functioning for parents with schizophrenia like creating routines and regularity, providing sensitive responsiveness and warmth, and giving appropriate stimulation and support to the child.25 This means that the main responsibility for parenting is often on the other parent, who may also have to pay extra attention to the ill parent’s mental health status at the same time. Therefore, these families are likely to have special needs and need extra support.26,27 Otherwise, there is a substantial risk that it will affect the upbringing of the children in the high-risk families in addition to the effects of genetic risk.
Strengths and Limitations
To our knowledge, The Danish High Risk and Resilience Study VIA 7 is the largest and most representative family sample of both biological parents of 7-year-old children with one parent with a severe mental disorder. Using this representative population-based sample is a major strength of our study. Earlier work has considered the validity of both affective and psychotic register-based diagnoses and found sufficiently high validity to allow them to be used in research studies.28,29 Despite these strengths, our findings should also be interpreted in the context of several limitations. Our definition of mating is limited to parents, ie, to couples having offspring. Individuals with severe mental disorders are less likely to have children than the general population; this is the case for both men and women with schizophrenia and for those with bipolar disorder.30,31 Both of the explored disorders are known to have onset during childbearing and in the early years of life,30,31 and compared to childless individuals with schizophrenia, parents with schizophrenia are more likely to have had better premorbid social adjustment and to become ill at a later age.32–34 Thus, parents with schizophrenia or bipolar disorder may represent a selected group of higher functioning individuals with schizophrenia and bipolar disorder, and our results may not be representative for all individuals with schizophrenia or bipolar disorder. Nevertheless, when comparing the PSP total score of parents with schizophrenia from our sample with another comparable sample,35 we found a similar level of social functioning.
Conclusion
In this unique and large population-based sample, we showed that almost half of the parents who have children by a partner with schizophrenia and one-third of parents having children by a partner with bipolar disorder present with a mental disorder compared to less than one-fifth of parents having children by a partner without these disorders. Furthermore, parents who have children by a partner with schizophrenia or bipolar disorder have poorer social functioning and parents who have children by a partner with schizophrenia have lower levels of cognitive functioning compared to parents who have children by partners without these disorders. These findings add important knowledge to the understanding of the familial transmission of schizophrenia and bipolar disorder and for the totality of risk factors facing the offspring. The findings presented in this study should be considered in future investigation of potential risk factors for children with a parent with schizophrenia or bipolar disorder.
Supplementary Material
Acknowledgments
The authors would like to express their gratitude to the dedicated families participating in the study; to M. Skjærbæk, A. Søndergaard, M. Gregersen, A. Ranning, H. Jensen, M. Melau, and C. Gregersen for contributing to data collection; to C. Bøcker Pedersen and M. Giørtz Pedersen for retrieving the register extract; to M. Chaine for help with data management; and to P.B. Mortensen, T. Werge, D. Hougaard, and A. Børglum for collaboration in iPSYCH. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors have approved the final version of the manuscript. The authors have declared that there are no conflicts of interest in relation to the subject of this study.
Funding
This work was supported by the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) (grant numbers R248-2017-2003, R155-2014-1724, and R102-A9118), Aarhus University, Aarhus University Hospital Psychiatry, the Mental Health Services of the Capital Region of Denmark, and the Beatrice Surovell Haskell Fund for Child Mental Health Research of Copenhagen. The sources of funding had no involvement in the study design, data collection, data analysis, interpretation, writing the manuscript, or decision to submit the manuscript for publication.
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