|Year : 2021 | Volume
| Issue : 1 | Page : 41-46
Role of age at onset in the clinical presentation of bipolar disorder in Indian population
Ajitabh Soni1, Paramjeet Singh2, Sunil Kumar2, Raghav Shah2, Lalit Batra2, Manoj Verma3
1 Department of Psychiatry, P.D.U. Medical College, Churu, Rajasthan, India
2 Department of Psychiatry, S.M.S. Medical College, Jaipur, Rajasthan, India
3 Department of Community Medicine, Dr. S.N. Medical College, Jodhpur, Rajasthan, India
|Date of Submission||30-Jan-2020|
|Date of Acceptance||21-Apr-2021|
|Date of Web Publication||17-Jun-2021|
Dr. Manoj Verma
C-157 Agrasen Nagar, Churu - 331 001, Rajasthan
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: The objective of this study was to determine any association of age at onset (AAO) with clinical presentation of bipolar disorder (BD) and family history of illness. Materials and Methods: A hospital-based cross-sectional observational study was conducted including 162 patients having a diagnosis of BD current episode manic. Individuals were divided into three subgroups according to AAO, i.e., early-onset BD (EOBD) (AAO ≤21 years), intermediate-onset BD (AAO – 22–34 years), and late-onset BD (AAO ≥35 years). The subgroups were compared on clinical variables; items of the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), and Scale for the Assessment of Positive Symptoms (SAPS); and family history of illness. Results: The early-onset group had significantly more episodes per year than the other groups (P < 0.001). The prevalence of family history of mood disorder was also significantly higher in the early-onset group than the other subgroups. AAO was found to be significantly associated with different items of YMRS, HAM-D, and SAPS. The early-onset group had higher rating on irritability, motor activity–energy, sexual interest, depressed mood, delusions, and thought disorders, whereas the late-onset group had higher rating on elevated mood. Conclusion: EOBD can be considered as a specific phenotype of BD, which is more homogenous, severe, and inheritable form of illness.
Keywords: Age at onset, bipolar disorder, depression, mania
|How to cite this article:|
Soni A, Singh P, Kumar S, Shah R, Batra L, Verma M. Role of age at onset in the clinical presentation of bipolar disorder in Indian population. Ind Psychiatry J 2021;30:41-6
Bipolar disorder (BD) is a chronic mental disorder characterized by alternating episodes of depression, euthymia, (hypo) mania, and mixed states. The usual age of onset of BD is before 30 years, and almost 90% of patients have onset before 50 years of age., BD has been reported to have a genetic basis with heritability of at least 60%–85%., A number of studies have attempted to identify the susceptibility loci adding evidence of linkage in multiple genomic regions. However, these genetic studies have given conflicting results; which may be due to the lack of consensus regarding the proper definition of the affected phenotype and the questionable homogeneity of bipolar illness.,, Thus, attention is shifting toward the study of clinical indicators of BD that are familial and may be useful for identifying inheritable forms of the illness.
Classifications such as the Diagnostic and Statistical Manual of Mental Disorders-5 defined certain specifiers of BD that have proven phenomenological relevance. However, most are of limited utility in identifying homogeneous subgroups. There is a necessity to identify reliably defined clinical features that are clinically valid and associated with underlying genetic process. These features can help in identifying genotypes and making informed treatment decisions.
There is considerable evidence to suggest that the clinical expression of BD differs according to age at onset (AAO), which has therefore been identified as a potential specifier of interest, especially patients having early onset of illness have specific clinical features and outcomes different from those of later onset of illness.,, In this regard, multiple admixture studies have revealed that such patients could be categorized into three homogeneous subgroups (early-onset BD [EOBD], intermediate-onset BD [IOBD], and late-onset BD [LOBD]).,,,,,,,
By making subgroups based on these cutoff points, the present study was aimed to compare the clinical presentation using the items of the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), and Scale for the Assessment of Positive Symptoms (SAPS) and to compare the presence of family history of the illness in Indian population. Such subgrouping may help in identifying phenotypes among BD patients.
| Materials and Methods|| |
A hospital-based cross-sectional observational study was conducted at the psychiatry department of the tertiary care hospital of western India. The study was conducted over a period extending from June 2018 to December 2018. Ethical clearance was taken from the research review board and ethical committee of the institution. Informed written consent was obtained from all the legal guardians of participants before inclusion in the study.
A consecutive sample of 162 patients admitted to the inpatient department with a diagnosis of BD current episode manic (as per the Diagnostic and Statistical Manual of Mental Disorders-5 criterion) was included in the study. The diagnosis was confirmed by applying the Mini-International Neuropsychiatric Interview (MINI). Patients with history of intake of any psychiatric medicine in the last 2 weeks were excluded from the study because it can alter the severity of the symptoms. Patients suffering from mental retardation, dementia, comorbid psychiatric and substance-related disorder (as confirmed by using the MINI), and any other acute medical illness were excluded from the study.
Study participants were divided into three subgroups according to AAO, namely EOBD (AAO ≤21 years), IOBD (AAO = 22–34 years), and LOBD (AAO ≥35 years). There were 67, 59, and 36 patients in early, intermediate, and late-onset groups, respectively. The cutoff for AAO was determined on the basis of a review article by Geoffroy et al. The cutoff value of 21 years for early onset was also recommended in other studies.,
AAO was defined as “the age at which the patient first met criteria for a depressive episode, mania or hypomania as indicated by patient history, recall of family members and medical records.” This definition is close to the exact beginning of the illness and had been found to be highly reliable.
After applying stringent inclusion and exclusion criteria, participants were subjected to the tools of study. Clinical interviews and symptom ratings according to the YMRS, HAM-D, and SAPS were performed at the first presentation in the outpatient department.
These subgroups were compared with the following tools of the study:
- Sociodemographic and clinical variables – A semi-structured pro forma was used to record the sociodemographic variables including age, sex, residence, occupation, marital status, monthly income, and education. Items occupation, education, and monthly income were adopted from the modified Kuppuswamy's socioeconomic scale. This information was gathered from first-degree relatives and the patient himself
- Clinical assessment – The clinical variables were gathered through a clinical interview of participants and their immediate family members. The selection of clinical variables was based on literature review and clinical observation. The clinical variables included number and duration of the illness (chronicity) and AAO of the illness
- Family history of mood disorder in first-degree relatives – Familial psychiatric illness was investigated using the Family Interview for Genetics Studies applied by a trained psychiatrist. A complete family history of psychiatric illness of first-degree relatives was obtained from each proband and at least one first-degree relative. The information was supplemented by medical reports of relatives.
- Symptom-related variables – It was assessed using YMRS, HAM-D, and SAPS. Items were removed from the rating scales that were a priori considered redundant among them (i.e., similar symptoms rated more than once). Like, the HAM-D scale ratings of early, late, and middle insomnia; psychomotor agitation; and impaired insight were removed in favor of the YMRS ratings of items decreased sleep, disruptive or aggressive behavior, and impaired insight, respectively. The SAPS behavioral rating domain was removed in favor of YMRS ratings of disruptive or aggressive behavior and inappropriate appearance. The YMRS rating of content and language-thought disorder was removed in favor of the more comprehensive rating of delusion, hallucination, and thought disorder on the SAPS. Thus, a total of 24 symptom (9 from YMRS, 12 from HAM-D, and 3 from SAPS) ratings were analyzed.
Categorical/nominal variables were summarized as frequency and percentage and were analyzed using Chi-square test. Continuous variables were expressed as mean and standard deviation and were analyzed using one-way analysis of variance test or Kruskal–Wallis test as appropriate. The level of significance was set at P < 0.05. All analysis was performed using statistical software IBM SPSS Statistics for Windows, Version 19.0. (trial version) Armonk, NY: IBM Corp.
| Results|| |
A total of 162 patients were included in the final analysis. More than half (59.3%) of the patients were male. The three groups did not differ significantly regarding the gender distribution. Majority of the patients were from rural background (85.8%), married (74%), and belonged to lower socioeconomic status [Table 1].
There was a significant difference between the three subgroups regarding episodes per year; the early-onset group had significantly more episodes per year (P < 0.001) [Table 2]. The prevalence of family history of mood disorder was also significantly higher in the early-onset subgroup (P < 0.001) [Table 3].
|Table 2: Comparison of the subgroups on age of presentation, onset, and episodes per years|
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Among these 35 affected families of early-onset probands, 51 first-degree relatives were found to be affected from mood disorder. Among these 51 first-degree relatives, 33 (64.7%) precipitated illness before the age of 21 years which indicates that they lay in the same early-onset group.
Manic, depressive, and psychotic symptoms revealed a significant difference in symptom profiles between the early, intermediate, and late-onset groups (P < 0.001). It was found that among different YMRS, HAM-D, and SAPS items, the EOBD group had significantly greater scores on irritability, motor activity–energy, sexual interest, depressed mood, delusions, and thought disorders than the other groups. Similarly, the LOBD group had a significantly greater score on elevated mood than the other groups [Table 4].
|Table 4: Comparison of the three subgroups on different items of Young Mania Rating Scale, Hamilton Depression Rating Scale, and Scale for the Assessment of Positive Symptoms Scale (data presented as mean and standard deviation)|
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| Discussion|| |
BD patients were divided into three subgroups based on AAO (EOBD, IOBD, and LOBD), and a significant difference was found between the three subgroups on clinical presentation (different items of YMRS, HAM-D, and SAPS scale) and the presence of family history of the illness. Similarly, a previous study had divided BD patients into early-onset (age ≤20 years), intermediate-onset (age >20 to ≤30 years), and late-onset (age >30 years) subgroups. They found early-onset patients having more scores in hypersexuality, disinhibition, depressed mood, psychotic symptoms, and overall severity, whereas late-onset patients had greater scores on the Depression Rating Scale. A study from Turkey also supported the hypothesis that adolescent-onset mania may be a different subtype than adult-onset mania with respect to type of episode, phenomenology, and clinical features.
In the present study, depressed mood had a higher rating in the EOBD subgroup than the other groups, as was similarly reported by other studies from different countries., Another finding of the present study was that the psychotic symptoms, including delusions and thought disorder, were more common in the early-onset group, as was similarly reported by other researchers. On the other hand, the LOBD group had a greater score on elevated mood. Supporting this, a study on geriatric population reported a greater average YMRS item rating for happiness and cheerfulness in elders with late onset compared to those with early-onset illness.
In this study, early-onset patients experienced more number of episodes per year than the other groups, which indicates that they are more prone to be rapid cyclers. Supporting this, a previous study also reported that onset before 19 years of age eventually leads to the development of rapid cycling.
Upon direct comparison of the EOBD and LOBD subgroups (the cutoff points were AAO before 18 years and after 40 years for the two subgroups), past literatures suggest that early-onset patients had more psychotic symptoms, mixed features, and family history of affective illness. EOBD and LOBD differ in clinical expression and familial risk and may therefore be considered to be different subtypes of manic-depressive illness.
The family history of illness was significantly higher in the EOBD subgroup in the current study, and most of the first-degree relatives (64.7%) lied in the same proband (early onset) which supports the hypothesis that EOBD is a more heritable form of illness. Similarly, studies have found that bipolar siblings are much more likely to belong to the same theoretical AAO subgroup than to different subgroups., This finding confirms intrafamilial correlation for AAO in bipolar affective disorder. The existence of three “AAO subgroups” and the clustering of siblings in the same subgroup might be attributable to different genetic vulnerability factors supporting the view of genetic heterogeneity in BD.
| Conclusion|| |
AAO of BD is significantly associated with their clinical presentation and prevalence of family history of illness. The EOBD subgroup had significantly greater scores on several YMRS, HAM-D, and SAPS items, and greater prevalence of family history of illness can be considered as a specific phenotype of BD patients, which is more homogenous, severe, and heritable form of illness, could be a potential target for future genetic researches. AAO can be used a valid marker to identify homogenous subgroups in BD patients.
Only patients of mania were included, and depressive patients were excluded for proper comparison of one aspect of illness. There is no standard definition of cutoff value of AAO, and the possibility of recall bias in reporting AAO could not be ruled out.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Bauer M, Unützer J, Pincus HA, Lawson WB. Bipolar disorder. Men Health Serv Res 2002;4:225-9.
Baldessarini RJ, Bolzani L, Cruz N, Jones PB, Lai M, Lepri B, et al.
Onset-age of bipolar disorders at six international sites. J Affect Disord 2010;121:143-6.
Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: How far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry 2003;64:161-74.
Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet C Semin Med Genet 2003;123:48-58.
Antypa N, Serretti A. Family history of a mood disorder indicates a more severe bipolar disorder. J Affect Disord 2014;156:178-86.
Badner JA, Gershon ES. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002;7:405-11.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Washington, DC: American Psychiatric Association; 2013.
Colom F, Vieta E. The road to DSM-V. Bipolar disorder episode and course specifiers. Psychopathology 2009;42:209-18.
Leboyer M, Kupfer DJ. Bipolar disorder: New perspectives in health care and prevention. J Clin Psychiatry 2010;71:1689-95.
Leboyer M, Henry C, Paillere-Martinot ML, Bellivier F. Age at onset in bipolar affective disorders: A review. Bipolar Disord 2005;7:111-8.
Bellivier F, Golmard JL, Rietschel M, Schulze TG, Malafosse A, Preisig M, et al.
Age at onset in bipolar I affective disorder: Further evidence for three subgroups. Am J Psychiatry 2003;160:999-1001.
Bellivier F, Etain B, Malafosse A, Henry C, Kahn JP, Elgrabli-Wajsbrot O, et al.
Age at onset in bipolar I affective disorder in the USA and Europe. World J Biol Psychiatry 2014;15:369-76.
Bellivier F, Golmard JL, Henry C, Leboyer M, Schürhoff F. Admixture analysis of age at onset in bipolar I affective disorder. Arch Gen Psychiatry 2001;58:510-2.
Hamshere ML, Gordon-Smith K, Forty L, Jones L, Caesar S, Fraser C, et al.
Age-at-onset in bipolar-I disorder: Mixture analysis of 1369 cases identifies three distinct clinical sub-groups. J Affect Disord 2009;116:23-9.
Lin PI, McInnis MG, Potash JB, Willour V, MacKinnon DF, DePaulo JR, et al.
Clinical correlates and familial aggregation of age at onset in bipolar disorder. Am J Psychiatry 2006;163:240-6.
Ortiz A, Bradler K, Slaney C, Garnham J, Ruzickova M, O'Donovan C, et al.
An admixture analysis of the age at index episodes in bipolar disorder. Psychiatry Res 2011;188:34-9.
Severino G, Manchia M, Contu P, Squassina A, Lampus S, Ardau R, et al.
Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system. Bipolar Disord 2009;11:215-20.
Tozzi F, Manchia M, Galwey NW, Severino G, Del Zompo M, Day R, et al.
Admixture analysis of age at onset in bipolar disorder. Psychiatry Res 2011;185:27-32.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al.
The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59 Suppl 20:22-33.
Geoffroy PA, Etain B, Scott J, Henry C, Jamain S, Leboyer M, et al.
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset. J Physiol Paris 2013;107:278-85.
Benazzi F. Classifying mood disorders by age-at-onset instead of polarity. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:86-93.
Carlson GA, Bromet EJ, Sievers S. Phenomenology and outcome of subjects with early- and adult-onset psychotic mania. Am J Psychiatry 2000;157:213-9.
Egeland JA, Blumenthal RL, Nee J, Sharpe L, Endicott J. Reliability and relationship of various ages of onset criteria for major affective disorder. J Affect Disord 1987;12:159-65.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: Reliability, validity and sensitivity. Br J Psychiatry 1978;133:429-35.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.
Andreasen NC. Scale for the Assessment of Positive Symptoms (SAPS). Iowa City: University of Iowa; 1984.
Bairwa M, Rajput M, Sachdeva S. Modified Kuppuswamy's socioeconomic scale: Social researcher should include updated income criteria, 2012. Indian J Community Med 2013;38:185-6.
] [Full text]
Ernst CL, Goldberg JF. Clinical features related to age at onset in bipolar disorder. J Affect Disord 2004;82:21-7.
Maxwell ME. Family Interview for Genetic Studies (FIGS): A Manual for FIGS. Bethesda, MD: Clinical Neurogenetics Branch, Intramural Research Program, National Institute of Mental Health; 1992.
Azorin JM, Bellivier F, Kaladjian A, Adida M, Belzeaux R, Fakra E, et al.
Characteristics and profiles of bipolar I patients according to age-at-onset: Findings from an admixture analysis. J Affect Disord 2013;150:993-1000.
Erkiran M, Karamustafalioğlu N, Tomruk N, Kahraman E, Alpay N. Phenomenological differences between adolescent and adult onset mania: A comparative study. Turk Psikiyatri Derg 2003;14:21-30.
Patel NC, Delbello MP, Keck PE Jr., Strakowski SM. Phenomenology associated with age at onset in patients with bipolar disorder at their first psychiatric hospitalization. Bipolar Disord 2006;8:91-4.
Schürhoff F, Bellivier F, Jouvent R, Mouren-Siméoni MC, Bouvard M, Allilaire JF, et al.
Early and late onset bipolar disorders: Two different forms of manic-depressive illness? J Affect Disord 2000;58:215-21.
Broadhead J, Jacoby R. Mania in old age: A first prospective study. Int J Geriatr Psychiatry 1990;5:215-22.
[Table 1], [Table 2], [Table 3], [Table 4]