Background
Bipolar disorder (BD) affects approximately 0.4–1.1% of people worldwide, with males and females at equal risk. It is a significant public health issue due to the psychosocial impairment it causes, the substantial costs associated with medical care and disability, and the high suicide rate associated with this disorder.1 Individuals with BD tend to experience a lower quality of life and diminished work productivity (as lost time and absence costs).2
Furthermore, BD is frequently comorbid with several psychiatric (substance-abuse disorders and personality disorders) and medical health issues (hypertension, obesity, endocrine and lipoprotein metabolism disorder).3–5 Several studies suggest that the prevalence and clinical manifestations of BD may vary according to the gender of the affected individuals.6–8 For example, substance abuse disorders are more common in males, while females with BD are more prone to experiencing eating disorders.7,9
The prevalence of psychopathology among family members of BD individuals has been the focus of global research efforts, revealing a significantly higher occurrence of mood disorders. However, determining an exact figure for this is a challenge due to misdiagnoses and undiagnosed cases within relatives.8 Studies indicate that the lifetime prevalence of mood disorders among children of parents with BD reaches up to 48-63%.10,11 Studies compared first-degree relatives of individuals with BD to controls, without a family history of the disorder.7,11–13 These studies have shown consistently that first-degree relatives (such as parents or siblings) of individuals with BD are more likely to develop depressive, anxiety, and behavioral disorders, or to receive at least two lifetime psychiatric diagnoses and treatment, compared to participants in control groups.10
A study by Rasic et al.14 examined the risk of developing psychiatric disorders in offspring of parents with schizophrenia, BD, and major depressive disorder (MDD). It was found that high-risk offspring were 3.5 times more likely to develop the same disorder as their parents when they were compared to a control group. Research indicates that children of individuals with BD are up to nine times more likely to develop bipolar-type disorders and 2.5 times more likely to experience non-bipolar affective disorders.15 Moreover, meta-analysis estimated a high incidence of MDD and BD among first-degree relatives of individuals diagnosed with these disorders.16 Specifically, the odds of developing MDD were 2.5 times higher, and the odds of developing BD were nearly eightfold compared to control participants.16
The reasons for the high incidence of psychiatric disorders among family members of bipolar disorder individuals remain unclear. It appears that a combination of genetic risk factors, environmental influences, and psychosocial dynamics within family relationships may contribute to this phenomenon.17,18 These findings highlight the significant familial risk associated with BD and underscore the importance of early identification and intervention for at-risk individuals. The present study aims to explore the prevalence of psychopathology among the family members of participants with BD. To achieve this, we analyzed data from two Mexican sites (Mexico City and Monterrey) as part of the “Genetics of Bipolar Disorder in Latino Populations” study, which included direct diagnostic interviews.19
Materials and methods
The present cross-sectional study involved families (N=172), which met the previously established ascertainment criteria outlined in Gonzalez et al.19 study. The study was conducted in the only two Mexican sites of the above study, at Monterrey Nuevo León Mexico (Department of Psychiatry of the University Hospital, UANL and INFOSAME Institute at Monterrey Mexico), and Mexico City (Carraci Institute). While not all relatives could be recruited, the study included available family members (N=770) of participants with BD across two states in Mexico: Mexico City (N=426) and Monterrey (N=344). All families were ascertained through two probands with a history of BD. After obtaining informed consent, all participants underwent interviews using the Diagnostic Interview for Genetic Studies (DIGS)20 and the Family Interview for Genetic Studies (FIGS),21 along with a medical and psychiatric history assessment.
Diagnoses were made using the best estimation technique,22 DSM-5 criteria were applied for psychiatric diagnosis. Data were collected by fully trained psychiatrists, who underwent training for FIGS and DIGS as part of the “Genetics of Bipolar Disorder in Latino Populations” study. Psychiatric History and DIGS interviews mean to take 3–6 hours, while FIGS used to be complete in 45 min. Detailed genogram information was used to collect relative’s data.
The study was approved by local IRBs (Department of Psychiatry of the University Hospital, UANL) and granted by NIMH (5RO1MH069856). The participants received meal and travel expenses incentives. Incomplete or not accurate FIGS information were excluded.
We analyzed data from first-degree and second-degree family members of BD participants, with a focus on the prevalence of psychopathology. A comparison was made between first- and second-degree family members.
Statistical Analysis
Descriptive statistics were calculated for all included variables. Comparative analyses were conducted using metric and parametric tests, as appropriate, and the probability of risk for psychopathology was assessed. To examine group differences by diagnosis and sex, Pearson’s chi-square test and Fisher’s exact test were applied. Age differences were analyzed using Student’s t-test. The association between psychopathology and specific family group characteristics was evaluated with multivariate analysis. Unless otherwise specified, a p-value < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS software, version 17.0.23
Results
Demographics
A total of 770 family members of participants with BD were interviewed. Of these, 61.9% (N= 477) were female and 38.1% (N= 293) were male. In terms of employment status, 57.7% (n = 434) were employed and 42.3% (N= 318) were unemployed (disability status was not evaluated). Regarding marital status, 46.1% (N= 348) were married, 39.1% (N= 295) had never been married, and 14.8% (N= 127) were divorced, widowed, or in a cohabiting union. Among the family members, 66.6% (N= 513) were first-degree relatives, while 33.4% (N= 257) were second-degree relatives.
Psychopathology in family members
In our analysis of a sample consisting of 770 family members, we found that 65.2% (502 individuals) exhibited psychiatric pathology. The prevalence rates of various psychiatric disorders were as follows: depressive disorders in 31.9% of the sample (N=246), BD in 21.1% (N=163), anxiety disorders in 12.7% (N=98), abuse and/or alcohol dependence in 14.5% (N=109), substance abuse and/or dependence in 5.9% (N=46), eating disorders in 1.4% (N=11), and psychotic disorders in 3.5% (N=27). (see Table 1).
We also analyzed the differences in psychiatric diagnoses among the 502 family members with psychopathology, focusing on variations by sex and the prevalence of psychiatric disorders (see Table 1). Our findings indicated a higher prevalence among females for Depressive Disorder (p = 0.010) and Anxiety Disorders (p = 0.026). No significant differences were found between sexes for BD and Psychotic Disorders. In contrast, males showed a higher prevalence of Alcohol Abuse and/or Dependence (p < 0.001) and Substance Abuse and/or Dependence (p < 0.001) (see Table 1).
While studying the comorbidities of the relatives with psychiatric disorders (N=502), it was found that 28.1% (N=141) had two or more comorbid disorders. Specifically, 22.5% (N=113) had two diagnoses, 4.4% (N=22) had three diagnoses, 1% (N=5) had four diagnoses, and 0.2% (N=1) had five simultaneous diagnoses (bipolar, depressive and anxiety disorders, dependence-abuse of alcohol and drugs).
Psychopathology in first-degree versus second-degree family members
First-degree family members showed a higher prevalence of psychopathology, with 70% (359 out of 513) affected, compared to second-degree relatives, where the prevalence was 55.6% (143 out of 257). This difference was statistically significant (p=0.001). BD showed a higher prevalence among first-degree family members (p < 0.001). In contrast, second-degree family members had a higher prevalence of depressive disorder (p = 0.013) and psychotic disorder (p = 0.027) (see Table 1 and Table 3). No significant differences were found for anxiety disorders, alcohol abuse and/or dependence, or substance abuse and/or dependence (see Table 2).
Multivariate analysis
The relationship between psychopathology and certain characteristics of family groups was examined. Being a first-degree family member of a participant with BD was found to increase the probability of developing psychopathology by 1.99 times (Odds Ratio, 95% Confidence Interval), with a significance level of p<.001. However, no associations were identified between the development of psychopathology and factors such as gender, employment status, or marital status.
Discussion
In this population-based study involving a Mexican cohort with BD, we identified several significant findings. First-degree family members exhibited a higher prevalence of psychopathology when they were compared to second-degree family members, with BD showing a particularly elevated rate. Additionally, second-degree family members showed a greater prevalence of depressive and psychotic disorders. Our study also revealed that depressive and anxiety disorders were more prevalent among females, while alcohol and substance abuse and/or dependence were more common in males. Our findings, based on a Mexican sample, support previous research that highlighted an increased risk for BD among first-degree family members of BD individuals, and a high prevalence of different psychopathology.13,17,24–26
Our study found that the rates of BD among first-degree family members reached as high as 18%, a figure surpassing those reported in previous research. Nonetheless, it aligns with the observed increase in psychopathology, which can be as high as 10% among the offspring of participants with BD.12,14,17,25 Most published literature primarily focuses on the risk and prevalence of psychiatric disorders in first-degree relatives of BD participants, leaving a gap in knowledge regarding the prevalence of psychopathology in second-degree relatives. In our study, second-degree family members exhibited a higher prevalence of depressive and psychotic disorders compared to first-degree family members. It is interesting that in first-degree family members, MDD was reported as one of the most common disorders in our study; notably, this fact was reversed, with higher prevalence for MDD in second-degree (58%) compared to first-degree family members (45.4%).27
Research has consistently shown that gender significantly influences the presentation of psychopathology within families.28 In line with this, our study shows that depressive and anxiety disorders were more prevalent among females, while alcohol and substance abuse and/or dependence were more common in males.29,30 It is noteworthy that in bipolar individuals, women are more likely to experience anxiety disorders and more severe depressive episodes. Conversely, men are more prone to develop substance abuse disorders.1 It has been suggested that sex-specific differences in brain structure and function could contribute to different psychopathological patterns observed in men and women with BD.31 Interestingly, in children at familial high risk for BD compared with a control group, sex-specific morphometric differences were found,32 possibly reflecting endophenotypic markers of risk linked to gender. However, genetic and nongenetic factors, as well as influence of culture, may contribute to the sex differences observed in our and other studies.33
The presence of certain comorbidities in family members of BP participants suggests that shared etiological factors, beyond just the bipolar disorder itself, contribute to the risk for these related conditions.
First-degree relatives of individuals with BD exhibit an elevated risk for a range of psychiatric and medical comorbidities relative to the general population, including anxiety disorders, personality disorders, substance-use disorders, type 2 diabetes, and ischemic heart disease. These familial associations are largely attributable to the heritability of BD, supporting the hypothesis that shared genetic and etiological mechanisms underlie the increased susceptibility to these conditions among family members.34
There is a scarcity of literature on comorbidity among relatives of individuals with BP in the Mexican population. When comparing prevalence rates with those reported in Hispanic/Latino populations living in the United States, it is important to consider that some studies suggest lower rates among recent immigrants similar to those reported in Mexico, compared to those who have resided in the U.S. for longer periods.35 Other research has documented persistently high rates of psychiatric comorbidities and related health conditions in Hispanic populations in the U.S., including depression, anxiety, and substance-use disorders, findings that are consistent with our study.36
Understanding the key components of psychopathology in relatives of individuals with BD is complex, as it is linked to genetic, psychological, familial, and contextual factors. For instance, children of parents with BD are nine times more likely to develop BD themselves and are also significantly more likely to experience other affective and anxiety disorders compared to children of nonaffected parents.17 Moreover, living with someone who has BD can create significant psychological and emotional stress for family members, potentially triggering or worsening mental health issues among them. The unpredictable mood cycles associated of BD and the emotionally charged atmosphere it creates can lead to increased anxiety, depression, and other mental health disorders in those close to the affected individual with BD.37,38 It has been recognized that living with family members with uncontrolled mental health conditions is an adverse childhood experience.39 This could account for psychopathology found in our and other studies with first-degree family members.40
The primary goal of the present study was to examine whether certain psychiatric disorders tend to cluster within family members of BD participants. Our findings indicate that being a first-degree family member carries an odds ratio of 1.99 to exhibit psychopathology. Our finding, with a sample of Mexican participants, reinforces evidence from previous family studies that highlighted the increased risk of psychopathology in first-degree family members of individuals with BD.41,42 Understanding the risk of psychopathology in family members of participants with psychiatric disorders is crucial not only for early identification but also for potential intervention strategies for at-risk populations.
Limitations
While our study included many participants, there are some limitations in the design. First, the sample in this study was highly selective, as families were chosen based on having multiple relatives affected by BD. Additionally, because we did not conduct a follow-up assessment, it remains uncertain whether more participants in our sample would develop psychopathology over time, including BD. Therefore, it may not be appropriate to generalize our findings to less-selective samples. While an effort was made to obtain data from all family members with detailed genograms, there were some missing data that could influence the final results of the study. While the best estimation method was realized to maximize diagnostic validity in our sample, several limitations are found including subjectivity, inter-rater variability, and lack of true validation due to no actual gold standard to confirm BD. Finally, we did not study past trauma in participants.
Conclusion
Our study with the Mexican population and its results are closely linked to previous research on the prevalence of psychopathology among family members of individuals with BD. These studies show similar findings to ours concerning specific pathologies and the relative risk analysis in these at-risk populations.
Our study, conducted within a Mexican cohort, aims to deepen the understanding of the pathology and its varied presentations in different cultural settings.
Our findings regarding the differences in psychopathology prevalence requires replication in future studies involving the Mexican and Hispanic populations, incorporating controlled analyses of potential associated risk factors. Added to the genetic and neurobiological mechanisms, these studies need to incorporate the impact of sociocultural and environmental factors to understand their contribution to BD. The contribution of future studies of BD presents a complex challenge whose results could impact the treatment and understanding of BD individuals and their families, for medical and behavioral health services.