|Year : 2020 | Volume
| Issue : 2 | Page : 79-84
Familial liability and age of onset among patients with major mental illness
Adetunji Obadeji1, Lateef Olutoyin Oluwole1, Christopher Goson Piwuna2
1 Department of Psychiatry, Faculty of Clinical Sciences, College of Medicine, Ekiti State University, Ado-Ekiti, Nigeria
2 Department of Psychiatry, Faculty of Medicine, University of Jos, Jos, Plateau State, Nigeria
|Date of Submission||13-Apr-2020|
|Date of Acceptance||20-Jul-2020|
|Date of Web Publication||16-Sep-2020|
Department of Psychiatry, Faculty of Clinical Sciences, College of Medicine, Ekiti State University, Ado-Ekiti
Source of Support: None, Conflict of Interest: None
Familial liability (FL) or susceptibility has been shown to increase the risk for psychotic disorders, however, little is known about FL among patients with major psychiatric disorders in Nigeria. This study aimed to determine the rate of FL and factors influencing the age of onset among patients with schizophrenia and bipolar disorders (BDs). This was a cross-sectional survey of patients with either diagnosis of BD or schizophrenia based on ICD-10 criteria. Data were collected through a pretested sociodemographic questionnaire, incorporating age, duration of illness, the onset of illness, and family history (FH) of mental illness. Data were presented as tables, charts, and bivariate analysis was performed to determine the relationship between variables. The level of significance was set at P < 0.05. Of the 235 participants, 66 (28.1%) had a FH of mental illness. The age of onset ranges from 12 to 70 years with a mean of 30.1 years (standard deviation = 11.1 years) and majority 85 (36.2%) were within the age group 30–39 years and had developed the illness before the age of 30 years (54.5%). The males were twice more likely to developed mental illness before the age of 30 years compared with their female counterparts (odds ratio [OR] = 2.42, [confidence interval (CI) = 1.40–4.25], [P = 0.013]), likewise, the singles compared with the ever-married (OR = 4.24, [CI = 2.45–7.34], [P = 0.000]). Although nearly a third of the participants had a FL to mental illness, there was no association between the age of onset and FH of mental illness. However, the males and the singles were more likely to have developed mental illness at an earlier age compared with their counterparts.
Keywords: Age of onset, bipolar disorder, familial liability, schizophrenia
|How to cite this article:|
Obadeji A, Oluwole LO, Piwuna CG. Familial liability and age of onset among patients with major mental illness. J Neurobehav Sci 2020;7:79-84
|How to cite this URL:|
Obadeji A, Oluwole LO, Piwuna CG. Familial liability and age of onset among patients with major mental illness. J Neurobehav Sci [serial online] 2020 [cited 2021 Jan 19];7:79-84. Available from: http://www.jnbsjournal.com/text.asp?2020/7/2/79/295157
| Introduction|| |
Schizophrenia and bipolar disorder (BD) are major psychiatric disorders with familial disposition. As noted by many researchers, the presence of family history (FH) is a major risk factor for these disorders.,, Several factors increase the risk of mental disorders in the general population. Of these, studies from the western world have repeatedly reported the role of heredity in the risk for mental illness.,, Familial liability (FL) or predisposition increases the risk of psychotic disorders by about five-fold independent of environmental influence., However, the additive effect of both environmental and familial predispositions increases the risk of developing psychotic disorders further.
Although schizophrenia is strongly associated with schizophrenia and related disorders among first-degree relatives, the presence of other psychiatric diagnoses among first-degree relatives increases the individual's risk of schizophrenia. According to Mortensen et al., the risk due to FH schizophrenia only is 6.0%, however, the population attributable risk due to FH of mental illness, in general, is about six times this value, thus showing the impact of other psychiatric disorders in predisposition to schizophrenia.
The risk of offspring developing schizophrenia increases with increase in the number of parents with the history of mental illness, with both parents with history of schizophrenia, the risk increases to about four folds compared with just one of the parents with such history. Similarly, the risk of BDs increases to about five folds in offspring of couples with a history of BD compared to where only one of the parents is affected. This suggests as FL increases, the risk of developing both schizophrenia and BDs increases. Nevertheless, the risk of developing schizophrenia due to the presence of FH of psychiatric disorders decreased as the age of onset increases, and men were more at risk of both schizophrenia and BDs compared with women.,,
Studies have shown that positive FH of mental illness is associated with poor prognostic factors including early onset, increased frequencies of relapse or severity of episodes and substance misuse.,,, People with a positive FH of BD, recurrent depression, substance misuse, and other mental health difficulties are more likely to have an early age of onset of either schizophrenia or BDs. Patients with early-onset, on the other hand, were more likely to present with an increased level of cognitive impairment, impulsivity, and poor outcome., The severity of symptoms of illness may furthermore be influenced by the interaction between FH and gender.
In Nigeria, there are limited studies looking at the extent of FH among people with schizophrenia and BDs, and its relationship with age of onset. We, therefore, sought to determine the rate of occurrence of family liability, and identify factors associated with the age of onset as well as the relationship between positive FH and age of onset among patients with schizophrenia and BD.
| Materials and Methods|| |
Study setting and design
This cross-sectional survey was carried out at the Psychiatric outpatient of the Ekiti State University Teaching Hospital (EKSUTH), located in Ekiti State, Nigeria. The Hospital provides tertiary health care for people of the State and environs. Besides providing care in various specialties and subspecialties of Medicine, the hospital also provides mental health care for people of the state and its environs.
Study population and sampling
Participants were patients with either diagnosis BDs or schizophrenia based on ICD-10 criteria as evaluated by Consultant Psychiatrists attending the psychiatric outpatients of EKSUTH, Ado-Ekiti. In this study, consecutive patients with the diagnosis of either schizophrenia or bipolar affective disorders were recruited for the study through a convenient sampling technique. Data were collected over 3 months' period, with the mind that majority of the patients would have been seen at the out-patient clinic (based on the duration of appointment usually given).
Consecutive patients with the diagnosis of either schizophrenia or bipolar affective disorder were interviewed with pretested sociodemographic questionnaires, that incorporates the age, sex, duration of illness, the onset of illness, and duration on medications. A FH of mental illness was also elicited with a pretested questionnaire on history of similar illness or other mental illness in the first- or second-degree relatives. Due to the low level of knowledge of mental illness by the participants and record-keeping generally, participants were not asked for specific psychiatric diagnoses, but a history of mental illness in the first- and second-degree relatives.
The functional recovery was assessed by the managing physician who responded to the question “Considering your total clinical experience with this particular population of patients, how mentally ill is the patient at this time? to assess extent wellness compared with healthy individuals or someone with mental illness on a 7-point Likert scale based on their experience with this population of patients (7 = among the most extremely ill patients, 6 = severely ill, 5 = markedly ill, 4 = moderately ill, 3 mildly ill, 2 = borderline mentally ill, 1 = normal, not at all ill, and 0 = not assessed).
The age of onset was dichotomized into two, using the mean age of onset as the cut off. The first group was those who have developed the illness on or before the age of 30 years and those who developed the illness after the age of 30 years.
Inclusion and exclusion criteria
Patients younger than 17 years or had not been receiving treatment for up to 6 months or had comorbid mental illness were excluded from the study.
The study protocol was approved by the Research and Ethics Committee of the EKSUTH, Ado-Ekiti. Written informed consent was obtained from all participants before the questionnaires were administered. The confidentiality of information provided by the participants was also ensured.
Data were analyzed using Statistical Package for Social Sciences (SPSS) version 25 (IBM Inc, IBM Inc. Armonk, New York, USA). Descriptive statistics including mean, frequency tables, and charts were performed to determine the distribution of characteristics of the variables studied. Chi-square test as well as the odds ratios were performed to determine the relationship between FH of mental illness, sociodemographic variables, and age of onset. A P ≤ 0.05 was adjudged statistically significant.
| Results|| |
A total of 235 patients with either schizophrenia or bipolar affective disorders took part in the study. Their ages range between 17 and 75 years with a mean of 38.5 years (standard deviation [SD] = 11.2 years). The age of onset ranges from 12 to 70 years with a mean of 30.1 years (SD = 11.1 years). As shown in [Table 1], the majority of participants 85 (36.2%) were within the age group of 30–39 years (36.2%), followed by those between 20 and 29 years (22.6%). Majority 128 (54.5%) developed the illness before the age of 30 years while 49 (21.4%) on or before the age of 21 years. Most of the participants were females 153 (61.5%), had tertiary education 129 (54.9%), single 119 (50.6%), and were employed 120 (51.1%).
[Table 2] shows the FH of illness and the diagnoses of the participants. A total of 203 (86.4%) had schizophrenia while the rest had bipolar affective disorder. Sixty-six (28.1%) had a FH of mental illness.
[Figure 1] shows the pie-chart showing the family relationship with the probands. The majority of the participants 24 (32%) reported siblings as relative with the history of mental illness, followed by mother (18%), and cousins were the least.
Relationships between the age of onset and participants' characteristics
[Table 3] shows the relationship between age of onset and participants' characteristics. Compared with the females, the males were more likely to developed mental illness before the age of 30 years (odds ratio [OR] = 2.42, [confidence interval (CI) = 1.40–4.25], [P = 0.013]). Similarly, the singles were over four times more likely to develop mental illness before the age of 30 years compared with those that were ever married (OR = 4.24, [CI = 2.45–7.34], [P = 0.000]). There was no statistically significant relationship between levels of education, participants' diagnosis, FH of mental illness, and age of onset of illness.
|Table 3: Relationship between the age of onset and participants' characteristics|
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Age of onset and functional recovery/severity of illness
[Figure 2] shows the relationship between age of onset and functional recovery/severity of illness. Compared with those with the onset of illness 30 years and above, a higher number of those with the onset of illness below 30 years were adjudged to be borderline to severely ill at the time of interview while a higher number of those that were rated normal had the onset of illness after the age of 30 years.
| Discussion|| |
Schizophrenia and BDs occur more frequently in first- and second-degree relatives of people with mental illness. In this study, nearly a third of the participants reported FH of mental illness suggesting a high genetic predisposition. A FH of schizophrenia for example, had been reported as the strongest single indicator for an individual with schizophrenic risk. The presence of an affected co-twin, first-degree, or second-degree relative increases the relative risk by about 2–38 times. Similarly, the risks of schizophrenia and BD in offspring of couples with schizophrenia and the other with BD were 15.6% and 11.7%, respectively, as against 4.4% in offspring where only one of the parents is affected. Familial predisposition has been reported to increase the risk of psychotic disorder by about five-fold independent of environmental influence., This suggests the effect of heritability in predisposition to schizophrenia and BD.
In this study, participants' age of onset ranges from 12 to 70 years with an average age of about 30 years, indicating most of the participants were relatively young. There was no significant difference in the age of onset of people with the diagnosis of schizophrenia and BD. This suggests that both disorders show a relatively young age of onset. Again, over half of the participants had developed mental illness before the age of 30 years while about one-fifth before the age of 21 years, denoting most had a relatively early age of onset. Similar to other psychiatric illnesses, most individuals with schizophrenia and BD developed these disorders in late adolescence or early twenties, with a slightly later onset in females., Several reasons have been deduced to explain this; the early adulthood represents a time of maturation and comes with its peculiar challenges., Studies have shown that patients with early-onset were more likely to show greater levels of cognitive impairment, a higher level of impulsivity as well as poor outcome., This may explain the lower-level functionality observed with most patients with early onset illness as noticed in this study.
The majority of the participants that were adjudged to have borderline to severe illness were more likely to have developed the illness before the age of 30 whereas those who were normal were more likely to have developed the illness after the age of 30 years. Studies have shown an association between age at onset and the outcomes.,, Patients who were relatively young at onset were more likely to have more hospitalizations, more negative symptoms, more relapses, and poorer social and occupational functioning.,
In this study, relative to their female counterparts, the males were more likely to develop a mental illness at an earlier age similar to other findings., This is not limited to schizophrenia alone but to BDs as well.,, Among patients with schizophrenia on the other hand, a meta-analysis showed that the presence of a FH of psychosis is associated with an earlier age at onset in both sexes, with male gender presenting with early onset in those without FH of mental illness. This is supported by a recent study focusing on illness course that reported no association between gender and age at onset after adjusting for severity of symptoms at presentation, suggesting early age at illness onset might be a pointer to increased genetic vulnerability with gender as a modifier. Nonetheless, the presence of accumulated trauma, obstetric complications, and cannabis use may explain the relatively lower the age at onset in males.,
Among patients with BDs on the other hand, studies examining the relationship between age at onset and gender have produced varying results.,,, Significantly, men had been reported to present with earlier onset of first-episode mania and BD compared to women,, while others had reported men and women had similar age of onset but differ in the type of episode at onset and comorbidity pattern.
Oftentimes, the onset symptoms of schizophrenia begin in the 2nd and 3rd decade of life, though the onset may be earlier or later, and may even extend to the 7th decade of life. This may explain the long-range of age-onset noted in the study. However, some authors had raised the possibility of those disorders occurring at the later end of life as other variants.,
Varying findings have been reported on the impact of the FL of mental illness.,, Positive first-degree FH of psychosis had been reported to be associated with younger age at onset., However, there was no significant relationship between familial predisposition and age of onset in this population. Other environmental factors such as trauma, life adversity, obstetric complications which are likely to be more prevalent in this environment may explain this finding. Nevertheless, the risk of developing schizophrenia as a result of familial disposition decreased as the age of onset increases. Furthermore, there was no significant difference in the age of onset of both schizophrenia and BD, suggesting similar factors may influence the age at onset.
Compared with those that were ever married, participants who were single were more likely to have developed the illness before the age of 30 years. Marriage has been reported to be associated with reduced risk of early onset of most mental disorders in both males and females., Nevertheless, individuals with major mental illness are at higher risk of marital dissolution, or less likely enter into new marriages. Although marriage acts as a protective factor, it may also act as a predisposing/precipitating factor for most psychiatric disorders. Nonetheless, longitudinal studies are needed to provide greater clarity on the temporal association between the age of onset of mental health symptoms and marital status.
A substantial number of participants had a FH of mental illness, mostly as siblings and parents. However, no association was found between age of onset and FH of mental illness, suggesting other factors may contribute to early onset. Males and singles were more likely to develop mental illness earlier compared with their females or ever married counterparts. Similarly, those with early age of onset were more likely to present with more severe form compared with those who developed the illness at an older age.
(Abbreviations: BD: Bipolar Disorder, FH: Family History, FL: Familial Liability, SPSS: Statistical Package for Social Sciences.)
Ethics committee approval: The ethics committee approval has been obtained from Ekiti State University Teaching Hospital with Ethics and Research committee report number of EKSUTH/A67/2019/09/019 (10 Oct 2019).
Patient informed consent: Informed consent was obtained.
Financial support and sponsorship
No funding was received.
Conflicts of interest
There is no conflicts of interest to declare.
Author contribution area and rate:
Adetunji Obadeji (%50): conception/design of the work, data acquisition, analysis interpretation and drafting and its critical revision for important intellectual content.
Lateef Olutoyin Oluwole (%28): involved in refining the conception of the work, the interpretation of data for the work and revising it critically for important intellectual content.
Christopher Goson Piwuna (%22): involved in refining the conception of the work, the interpretation of data for the work and revising it critically for important intellectual content.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Byrne M, Agerbo E, Mortensen PB. Family history of psychiatric disorders and age at first contact in schizophrenia: an epidemiological study. Br J Psychiatry Suppl 2002;43:s19-25. doi:10.1192/bjp.181.43.s19.
Kendler KS, Davis CG, Kessler RC. The familial aggregation of common psychiatric and substance use disorders in the national comorbidity survey: A family history study. Br J Psychiatry 1997;170:541-8.
Klein DN, Lewinsohn PM, Rohde P, Seeley JR, Shankman SA. Family study of co-orbidity between major depressive disorder and anxiety disorders. Psychol Med 2003;33:703-14.
Jeppesen P, Larsen JT, Clemmensen L, Munkholm A, Rimvall MK, Rask CU, et al
. The CCC2000 birth cohort study of register-based family history of mental disorders and psychotic experiences in offspring. Schizophr Bull 2015;41:1084-94.
Laursen TM, Labouriau R, Licht RW, Bertelsen A, Munk-Olsen T, Mortensen PB. Family history of psychiatric illness as a risk factor for schizoaffective disorder: A danish register-based cohort study. Arch General Psychiatry 2005;62:841-8.
Mortensen PB, Pedersen MG, Pedersen CB. Psychiatric family history and schizophrenia risk in Denmark: Which mental disorders are relevant? Psychol Med 2010;40:201-10.
van Os J, Hanssen M, Bak M, Bijl RV, Vollebergh W. Do urbanicity and familial liability coparticipate in causing psychosis? Am J Psychiatry 2003;160:477-82.
Gottesman II, Laursen TM, Bertelsen A, Mortensen PB. Severe mental disorders in offspring with 2 psychiatrically ill parents. Arch General Psychiatry 2010;67:252-7.
Aleman A, Kahn RS, Selten JP. Sex differences in the risk of schizophrenia: Evidence from meta-analysis. Arch General Psychiatry 2003;60:565-71.
Kennedy N, Boydell J, Kalidindi S, Fearon P, Jones PB, van Os J, et al
. Gender differences in incidence and age at onset of mania and bipolar disorder over a 35-year period in Camberwell, England. Am J Psychiatry 2005;162:257-62.
Ochoa S, Usall J, Cobo J, Labad X, Kulkarni J. Gender differences in schizophrenia and first-episode psychosis: A comprehensive literature review. Schizophr Res Treatment 2012;2012:916198.
Esterberg M, Compton M. Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients. Psychiatry Res 2012;197:23-8.
Kao YC, Liu YP. Effects of age of onset on clinical characteristics in schizophrenia spectrum disorders. BMC Psychiatry 2010;10:63.
Nuhu FT, Eseigbe EE, Issa BA, Gomina MO. Strong family history and early onset of schizophrenia: About 2 families in Northern Nigeria. Pan Afr Med J 2016;24:282.
Post RM, Altshuler L, Kupka R, McElroy SL, Frye MA, Rowe M, et al
. Multigenerational positive family history of psychiatric disorders is associated with a poor prognosis in bipolar disorder. J Neuropsychiatry Clin Neurosci 2015;27:304-10.
Chou IJ, Kuo CF, Huang YS, Grainge MJ, Valdes AM, See LC, et al
. Familial aggregation and heritability of schizophrenia and Co-aggregation of psychiatric illnesses in affected families. Schizophr Bull 2017;43:1070-8.
Gogtay N, Vyas NS, Testa R, Wood SJ, Pantelis C. Age of onset of schizophrenia: Perspectives from structural neuroimaging studies. Schizophr Bull 2011;37:504-13
Häfner H, Maurer K, Löffler W, Fätkenheuer B, an der Heiden W, Riecher-Rössler A, et al
. The epidemiology of early schizophrenia. Influence of age and gender on onset and early course. Br J Psychiatry Suppl 1994;23:29-38.
Pantelis C, Velakoulis D, Wood SJ, Yücel M, Yung AR, Phillips LJ, et al
. Neuroimaging and emerging psychotic disorders: The Melbourne ultra-high risk studies. Int Rev Psychiatry (Abingdon, England) 2007;19:371-81.
Wood SJ, Pantelis C, Velakoulis D, Yücel M, Fornito A, McGorry PD. Progressive changes in the development toward schizophrenia: Studies in subjects at increased symptomatic risk. Schizophr Bull 2008;34:322-9.
Immonen J, Jääskeläinen E, Korpela H, Miettunen J. Age at onset and the outcomes of schizophrenia: A systematic review and meta-analysis. Early Interv Psychiatry 2017;11:453-60.
Käkelä J, Panula J, Oinas E, Hirvonen N, Jääskeläinen E, Miettunen J. Family history of psychosis and social, occupational and global outcome in schizophrenia: A meta-analysis. Acta Psychiatrica Scandinavica 2014;130:269-78.
Esterberg ML, Trotman HD, Holtzman C, Compton MT, Walker EF. The impact of a family history of psychosis on age-at-onset and positive and negative symptoms of schizophrenia: A meta-analysis. Schizophr Res 2010;120:121-30.
Drake RJ, Addington J, Viswanathan AC, Lewis SW, Cotter J, Yung AR, et al
. How age and gender predict illness course in a first-episode nonaffective psychosis cohort. J Clin Psychiatry. 2016;77:e283-9. doi: 10.4088/JCP.14m09369. PMID: 26890690.
Stepniak B, Papiol S, Hammer C, Ramin A, Everts S, Hennig L, et al
. Accumulated environmental risk determining age at schizophrenia onset: a deep phenotyping-based study. Lancet Psychiatry 2014;1:444-53. doi: 10.1016/S2215-0366(14)70379-7. Epub 2014 Nov 5. PMID: 26361199.
Kawa I, Carter JD, Joyce PR, Doughty CJ, Frampton CM, Wells JE, et al
. Gender differences in bipolar disorder: Age of onset, course, comorbidity, and symptom presentation. Bipolar Disorders 2005;7:119-25.
Raymont V, Bettany D, Frangou S. The Maudsley bipolar disorder project. Clinical characteristics of bipolar disorder I in a Catchment area treatment sample. Europ Psychiatry 2003;18:13-7.
Viguera AC, Baldessarini RJ, Tondo L. Response to lithium maintenance treatment in bipolar disorders: Comparison of women and men. Bipolar Disorders 2001;3:245-52.
Howard R, Rabins PV, Seeman MV, Jeste DV, Late-Onset The I. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: An international consensus. Am J Psychiatry 2000;157:172-8.
Maglione JE, Thomas SE, Jeste DV. Late-onset schizophrenia: Do recent studies support categorizing LOS as a subtype of schizophrenia? Curr Opin Psychiatry 2014;27:173-8.
Ritsner M, Ratner Y, Gibel A, Weizman R. Familiality in a five-factor model of schizophrenia psychopathology: Findings from a 16-month follow-up study. Psychiatry Res 2005;136:173-9.
Ritsner MS, Ratner Y, Gibel A, Weizman R. Positive family history is associated with persistent elevated emotional distress in schizophrenia: Evidence from a 16-month follow-up study. Psychiatry Res 2007;153:217-23.
Hilker R, Helenius D, Fagerlund B, Skytthe A, Christensen K, Werge TM, et al
. Is an early age at illness onset in schizophrenia associated with increased genetic susceptibility? Analysis of data from the nationwide Danish twin register. EBioMedicine 2017;18:320-6.
Mojtabai R, Stuart EA, Hwang I, Eaton WW, Sampson N, Kessler RC. Long-term effects of mental disorders on marital outcomes in the National Comorbidity Survey ten-year follow-up. Soc Psychiatry Psychiatr Epidemiol 2017;52:1217-26.
Scott KM, Wells JE, Angermeyer M, Brugha TS, Bromet E, Demyttenaere K, et al
. Gender and the relationship between marital status and first onset of mood, anxiety and substance use disorders. Psychol Med 2010;40:1495-505.
Mina S. Predictors of marriage in psychiatric illness: A review of literature. J Psychiatry Psychiatric Disord 2019;3:014-022.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]