The modern nosology of psychiatric disorders in late. Age at Onset in Geriatric Bipolar Disorder

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1 Age at in Geriatric Bipolar Disorder Effects on Clinical Presentation and Treatment Outcomes in an Inpatient Sample Mary E. Wylie, M.D. Benoit H. Mulsant, M.D. Bruce G. Pollock, M.D., Ph.D. Robert A. Sweet, M.D. George S. Zubenko, M.D. Amy E. Begley, M.A. Michele Gregor, M.S.W. Ellen Frank, Ph.D. Charles F. Reynolds, III, M.D. David J. Kupfer, M.D. The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission. (Am J Geriatr Psychiatry 1999; 7:77 83) The modern nosology of psychiatric disorders in late life was defined in a series of landmark papers published by Roth and his associates more than 40 years ago. 1,2 In his listing of problems for further investigation, he stated, It should be possible, for example, from a comparison of cases of affective psychosis with their first attack after the age of 60 and those with attacks earlier, to learn something about the factors that decide whether breakdown will occur early or late in life. Since then, age at first onset of illness has emerged as a heuristically useful distinction. 3,4 Comparisons of older patients with early-onset and late-onset mood disorders have raised several key questions. For instance, do patients with late-onset illness suffer from a different disease from those with earlier onset? Is late-onset illness associated with a worse (or better) prognosis? Recent studies have addressed those issues in older patients with major depression. Alexopoulos and colleagues studies suggest the concept of vascular depression, in which subclinical vascular disorders play an important role in the onset and outcome of a significant subset of patients with late-onset depression. Patients with late-onset depression have been reported to be more likely to present with delusions, to have cognitive impairment, and to have a less favorable treatment course. 5,6 By contrast, other investigators have reported that elderly patients with older age at first episode of major depression showed a more rapid, sustained response profile. 7 Studies focusing on age at onset among older patients with bipolar disorder also have had contrasting results, as summarized in a 1992 review by Young and Klerman 4 and in a 1997 review by Young. 8 In the era before effective treatments, Wertham 9 reviewed the records of 2,000 inpatients who were admitted for manic attacks and related the age at onset to the duration of the manic episode. He found that chronic mania (episodes lasting 2 years or more) was correlated with first admissions of advanced and mature age. More recent investigations have found an association between older age at onset and neurological and other medical disorders. 10 In contrast, other studies found that patients with earlier age at onset tended to be more floridly psychotic. 11 To further examine the issue of differences between early- and late-onset groups with respect Received September 17, 1997; revised February 9, 1998; accepted February 24, From the Mental Health Clinical Research Center for Late- Life Mood Disorders (MH52247) and the Mental Health Clinical Research Center for Affective Disorders (MH30915), Department of Psychiatry, University of Pittsburgh Medical Center. Address correspondence to Dr. Wylie, Office 740-BT, Western Psychiatric Institute and Clinic, 3811 O Hara Street, Pittsburgh, PA Copyright 1999 American Association for Geriatric Psychiatry Am J Geriatr Psychiatry 7:1, Winter

2 Geriatric Bipolar Disorder to demographic and clinical characteristics, treatment parameters, and treatment outcomes during a shortterm psychiatric hospitalization, we explored our database of 791 geriatric inpatients, which yielded 62 patients 60 years of age with a primary DSM-III-R diagnosis of bipolar disorder, manic, mixed, or depressed. At the outset, it is necessary to address the issue of how patients were divided into early-onset and late-onset groups. There is no agreed-upon standard as to which age should be used as the dividing line. Every decade from the 20s to the 60s has been used. 12,13 In samples of patients of mixed ages, the median age at onset has generally been used as the criterion. The median age at onset in our patients was 49 years. Support for using this figure as a definition of late age-at-onset comes from a study of 393 patients with bipolar disorder from five countries in which 88% of all cases have an age at onset of less than 49 years. 14 After dividing our patients into two groups, the early-onset (age 49, n 32) and late-onset (age 49, n 30), we compared them on demographic and clinical characteristics, treatment parameters, and treatment outcome. This allowed us to address the question of how the groups differed and whether those differences may have enhanced or impeded treatment response to a short-term (mean: days) psychiatric hospitalization. METHODS Data were available for 791 patients admitted to the Western Psychiatric Institute and Clinic s Geriatric Clinical Research (inpatient) Unit between September 1, 1990, and December 15, Of these, 62 patients had a primary DSM-III-R diagnosis of bipolar disorder, manic, depressed, or mixed, and were currently age 60 or above. The diagnosis corresponding to the symptoms that precipitated the admission was recorded as the primary diagnosis. A total of 14 patients were excluded from our study because of a diagnosis of organic mood disorder. Those with a primary diagnosis of organic mood disorder were excluded, allowing us to study a group of elderly patients with conservatively defined DSM-III-R bipolar disorder. Of these, nine were depressed, two had manic episodes, and three had unspecified subtypes. Examples of etiologies were the following: one depressed patient had a B 12 deficiency, another patient s depressive episode was attributed to Parkinson s disease. One of the manic episodes was due to treatment with prednisone. Patients with a primary diagnosis of bipolar disorder NOS (including bipolar II) were also excluded. Regarding multiple admissions, the first admission with a primary diagnosis of bipolar disorder, manic, mixed, or depressed, was used. As previously described, 15 all patients admitted for at least 4 days received a comprehensive evaluation performed by a multidisciplinary team including an attending psychiatrist, a social worker, a physician s assistant (supervised by a geriatrician), an occupational therapist, a psychiatric nurse, and a trained research clinician, all with expertise in geriatric psychiatry. Activities of daily living (ADL) were rated by use of the OARS questionnaire. 16 The Cumulative Illness Rating Scale (CIRS) was obtained by the method described by Miller et al. 17 Also, on admission and at discharge, a structured assessment was performed by a trained research clinician who was not involved in the clinical care of patients. 18 This assessment yielded ratings on several instruments, including the Global Assessment Scale (GAS), 19 the Brief Psychiatric Rating Scale (BPRS), 20 and a standardized version of Folstein s Mini-Mental State Exam (MMSE). 21 During the study period, intraclass correlation coefficients measuring interrater reliability ranged from 0.73 to 0.99 for these measures. Shortly after the patient s discharge, consensus Axis I and Axis II diagnoses were established according to the criteria of the DSM-III-R. These research diagnoses were made at a weekly consensus conference attended by at least three faculty psychiatrists and the research staff. They considered information obtained from the patient, family, primary care physicians, ratings, and old records. The primary diagnosis, the age at onset of the primary psychiatric disorder, and additional Axis I and Axis II diagnoses were recorded. The age at onset was defined as the time at which the patient met full criteria for the disorder. Medical problems were coded on Axis III according to the ICD-9 classification system, 22 with the exception that mental disorders and diseases of the brain recorded on Axis I and II were not duplicated. For this study, a cerebrovascular disease risk/burden score (range: 0 7) was determined as follows: one of the authors (MW), who was blinded to age at onset, reviewed all consensus Axis III diagnoses and gave one point for each of these diagnoses: hypertension, diabetes, peripheral vascular disease, coronary artery disease, history of transient ischemic attack or stroke, atrial fibrillation, and carotid bruit. Because not all patients 78 Am J Geriatr Psychiatry 7:1, Winter 1999

3 Wylie et al. had imaging studies, scan findings were not included in this risk assessment. As described in the introduction, the patients were divided into two groups (early-onset and late-onset) by performing a median split of the ages at onset. Another way of analyzing these data would have been to use the age at onset as a continuous variable. However, in a test for bimodality, we observed that the distribution of age at onset was made up of two clusters. This observation was made by using a uniform-kernel density estimation and examining the cluster results across a range of radii or smoothing parameters of 6 to 20 (SAS PROC MODE- CLUS). 23 As the smoothing parameter increased, the number of clusters dropped from 2 to 1 at radii 14; however the hypothesis to test that the number of clusters 1 was significant (z 3.75; P 0.002), thus indicating that indeed two clusters were apparent. The median-split procedure yielded a group of 32 patients with early-onset (age 49) and a group of 30 patients with late-onset (age 49) disorder. Demographic and clinical characteristics, treatment parameters, and outcomes of patients with early- and late-onset bipolar disorder were then systematically compared; categorical variables were compared with chi-square analysis or Fisher s exact test, as appropriate, and continuous variables were compared with t-tests (or a nonparametric analog when appropriate). Ratings obtained at admission and at discharge were compared between groups with repeatedmeasures analysis of variance. Unless indicated otherwise, all variables are reported as mean standard deviation (SD). All tests were two-tailed. RESULTS The demographic characteristics of the entire group and the comparison between patients with early- and late-onset are presented in Table 1. Patients with earlierand later-onset bipolar disorder did not differ on any of the demographic variables studied (including age at study entry), except for their marital status: patients with earlier onset were more likely to be divorced or separated than those with later onset (25% vs. 3.3%), and later-onset patients were more likely to be married or living with someone than earlier-onset (18.7% vs. 50%; Fisher s exact test 0.02). Table 2 presents clinical characteristics of the groups. The mean age at onset for the Early group was 30.8 years. The mean age at onset for the Late group was 63.1 years. The late-onset group was significantly more likely to have psychotic features (73.3% vs. 43.8%; v 2 [1] 5.6; P 0.02) and to demonstrate cerebrovascular disease burden/risk (70% vs. 37.5%; v 2 [1] 6.6; P 0.01). Otherwise, patients with early- and late-onset bipolar disorder had a similar burden of medical illness, as reflected in mean number of active medical problems on Axis III, and were equally likely to be admitted for the treatment of a depressive episode as for a manic or mixed episode. Furthermore, symptom severity at admission (as reflected by mean BPRS scores) and cognitive or functional impairment (as reflected by mean MMSE and ADL or GAS scores, respectively) were similar in the two groups. Table 3 demonstrates the pharmacologic parity of treatment received by the two groups. The use of electroconvulsive therapy did not differ between groups. Table 4 summarizes the variables reflecting the impact of treatment during short-term psychiatric hospitalization. Overall, both groups exhibited significant clinical improvement, as reflected by a decrease in BPRS scores, an increase in MMSE scores, and an increase in GAS scores. There was a significant Time Group interaction difference for the two groups on the BPRS. The older-onset group had slightly worse BPRS scores on admission but improved more than the early-onset group. A minority of patients (8 of 62; 12.9%) required discharge to more restrictive living arrangements. However, most patients (54 of 62; 87.1%) were able to be discharged to living arrangements that were no more restrictive than those before hospitalization. The two age-groups did not differ in this regard. DISCUSSION The following findings allowed us to answer our question regarding how the groups differed and whether those differences had an impact on treatment response to a short-term psychiatric hospitalization. 1. Patients with late-onset bipolar disorder were more likely to have psychotic features. However, they were not only equally likely to have significant improvement in BPRS scores, but their speed of improvement exceeded that of the early-onset group. Our findings contrast with those of Rosen et al., 11 who found that patients with early-onset illness were likely to be more floridly psychotic than pa- Am J Geriatr Psychiatry 7:1, Winter

4 Geriatric Bipolar Disorder tients who had an older age at onset. It differs also from Broadhead and Jacoby s study 24 in which lateonset and early-onset patients had no difference in illness severity. Our finding of a Time Group difference favoring the late-onset group agrees with Young, 4 whose preliminary prospective data suggested less residual psychopathology at discharge and greater change in Mania Rating Scale scores among late-onset patients. 2. Patients with late-onset bipolar disorder were more likely to demonstrate cerebrovascular risk factors or clinical evidence of cerebrovascular disorders. TABLE 1. Demographic characteristics Whole Early Late Early vs. Late Group Test Statistic (N 62) (n 32) (n 30) (t or v2) [df] P Age, years [60] 0.96 Men, % [1] 0.32 White, % Fisher s exact test 0.20 Marital status, n (%) Married/Living with someone 21 (33.9) 6 (18.7) 15 (50.0) Fisher s exact test 0.02 Divorced/Separated 9 (14.5) 8 (25.0) 1 (3.3) Widowed 26 (41.9) 14 (43.8) 12 (40.0) Single 6 (9.7) 4 (12.5) 2 (6.7) Living arrangements at admission, n (%) Home alone 32 (54.2) 16 (50.0) 16 (59.3) Fisher s exact test 0.40 Home with part/full-time supervision 20 (33.9) 10 (31.3) 10 (37.0) Personal care, home 4 (6.8) 3 (9.3) 1 (3.7) Intermediate/Skilled care facility/long-term hospitalization 3 (5.1) 3 (9.4) 0 TABLE 2. Clinical characteristics Whole Early Late Early vs. Late Group Test Statistic (N 62) (n 32) (n 30) (t or v2) [df] P Age at onset, years [60] 0 Episode type, n (%) Depressed 23 (37.1) 13 (40.6) 10 (33.3) 0.4 [1] 0.55 Manic/Mixed 39 (62.9) 19 (59.4) 20 (66.7) With psychotic features, n (%) 36 (58.1) 14 (43.8) 22 (73.3) 5.6 [1] 0.02 Duration of current episode, months a [59] 0.51 Length of hospital stay, days a [60] 0.24 Brief Psychiatric Rating Scale (BPRS) at admission [55] 0.20 Mini-Mental State Exam at admission [48] 0.67 Activities of Daily Living at admission [52] 0.99 Global Assessment Scale (GAS) at admission [59] 0.28 Nonpsychotropic medications at admission, n (%) b [60] 0.24 Number of Axis III diagnoses c [60] 0.09 Index of cerebrovascular risk factors, n (%) 0 risk factors 29 (46.8) 20 (62.5) 9 (30.0) 1 risk factor 18 (29.0) 5 (15.6) 13 (43.3) 6.6 [1] risk factors 15 (24.2) 7 (21.9) 8 (26.7) Cumulative Illness Rating Scale (CIRS) Total [44] 0.82 Count [44] 0.76 Note: Means and standard deviations are reported in their original units. a Ln (X) transformation used for analyses. b Square-root (X 0.1) transformation used for analyses. c Ln (X 0.1) transformation used for analyses. 80 Am J Geriatr Psychiatry 7:1, Winter 1999

5 Wylie et al. The possibility of an association of cerebrovascular risk factors or clinically apparent disease with mood disorders has informed research on geriatric mood disorders for decades. In the older literature, when all mood disorders were studied together, Kay 25 found that 12% of his geriatric mood disorder sample with an early age at onset had focal neurologic signs, compared with 6% of those with late onset. More recently, elderly patients with mania were compared with elderly depressed patients. 26 Thirty-six percent of the manic patients had neurologic disorders, one-third of which were identified as cerebrovascular disease. Only 8% of the depressed patients had neurologic disorders. However, mania due to organic causes was not excluded, making this a more heterogeneous group than ours. Broadhead and Jacoby s prospective study 24 compared currently young patients with mania with currently older manic patients. The older group was then subdivided into early-onset TABLE 3. Pharmacologic treatment at time of discharge Whole Early Late Early vs. Late Group Test Statistic (N 62) (n 32) (n 30) (t or v2) [df] P On lithium, n [1] 0.96 Dose, mg [35] 0.93 Last available level, meq [33] 0.89 On carbamazepine, n Dose, mg Fisher s exact test 0.67 On valproic acid, n Fisher s exact test 0.76 Dose, mg , Last available level, ng/ml On antipsychotic agents, n [1] 0.40 Receiving ECT, n (%) 8 (12.9) 6 (18.8) 2 (6.7) Fisher s exact test 0.26 Note: ECT electroconvulsive therapy. TABLE 4. Outcomes Whole Early Late Early vs. Late Group Test Statistic (N 62) (n 32) (n 30) (F) [df] Brief Psychiatric Rating Scale (BPRS) ab Time [1,59] Group [1,59] 0.0 T G [1,59] 4.9 Mini-Mental State Exam (MMSE) a Time [1,54] 7.9 Group [1,54] 0.2 T G [1,54] 0.0 Global Assessment Rating Scale Time [1,60] (GAS) a Group [1,60] 0.7 T G [1,60] 0.2 P Number of nonpsychotropic (T [59] ): medications at discharge c Living arrangements at discharge, n (%) Home alone 19 (31.7) 8 (25.0) 11 (39.3) Home with part/full-time supervision 25 (41.7) 16 (50.0) 9 (32.1) Personal care home 11 (18.3) 5 (15.6) 6 (21.4) Fisher s exact test 0.50 Intermediate/Skilled care facility/ Long-term hospitalization 5 (8.3) 3 (9.4) 2 (7.2) Note: Means and standard deviations are reported in their original units. a Change from admission to discharge. b 1/Square-root (X) transformation used for analyses. c Square-root (X 0.1) transformation used for analyses. Am J Geriatr Psychiatry 7:1, Winter

6 Geriatric Bipolar Disorder and late-onset groups. In the first comparison, 20% of elderly patients had a first manic episode closely related temporally to a cerebral organic disease. By contrast, none of the young manic group had a physical illness associated with their first manic episode. However, when the geriatric patients were subdivided into early- and late-onset groups, they had no significant difference in rate of cerebral organic disease. Our finding that late-onset patients were more likely to demonstrate cerebrovascular risk factors or disease is in agreement with Alexopoulos et al. s findings 5 in elderly depressed patients and suggests the need for further studies focusing on different etiologic mechanisms for late-onset compared with early-onset bipolar disorder. 3. Patients with early-onset disorder were more likely to be divorced or separated than patients with late onset. Our finding contrasts with another study (Carlson et al. 27 ), in which both early- and late-onset patients had similarly high divorce rates, but it appears consistent with the literature indicating a disruptive effect of bipolar illness on marriage. 13 The higher incidence of marital disruption in the earlyonset group may reflect the increased number of years that the marriages were exposed to the effect of the illness or the effect of the illness on the earlier stages of marriage. 4. Both groups of patients were highly likely to be discharged to settings that were no more restrictive than those before admission. Both early- and lateonset groups were likely to show significant improvement, and 87% of the total were able to return to settings no more restrictive than those at admission. Our finding agrees with Dhingra and Rabins study, 28 in which 91% of patients were improved at the time of discharge from the hospital. Broadhead and Jacoby 24 also found no significant difference between the early- and late-onset groups with regard to treatment and discharge from the hospital. However, it is important to note that our outcomes were short-term; longer-term follow-up has revealed significant morbidity and mortality rates in older patients with mania. 25,29 Factors that may limit the generalizability of our study include the selection of the patient population. We excluded patients with DSM-III-R defined organic mood disorder, thereby ruling out from study syndromes that other investigators have found responsible for many cases of late-onset mania. This exclusion eliminated a total of 14 patients (see Methods section), two of whom had manic episodes. The exclusion of these few was unlikely to have introduced a large bias into the findings. Patients whose primary diagnosis was dementia were also excluded from study even if they were known to have carried a diagnosis of bipolar disorder before the onset of dementia. These exclusions limited the heterogeneity of our sample but allowed us to study a group that met conservatively applied DSM-III-R criteria for bipolar disorder and thus to compare them with cases in the literature that met similarly strict criteria for bipolar mood disorder. Nonetheless, in spite of our attempt to exclude patients with organic precipitants, 53% of our patients had one or more risk factors for cerebrovascular disease, raising the possibility that our patients may have had neurological contribution to the manifestation of mania in late life. A second limiting factor is the difficulty of ascertaining the exact age at onset and comparing it with studies that may have used different criteria. For example, earlier literature often used first hospitalization as the criteria for onset, whereas more recently the criterion has been the age at which the patient met full diagnostic criteria for the disorder. Some investigators have proposed using the age at first onset of symptoms that caused impairment, a practice that would lower the onset age of bipolar disorder by about 8 years. 30 Even when criteria for age at onset are agreed upon, Wiener et al. 31 found that raters agreed on age at onset in only 80% of cases even when informants and structured interviews are used. A third issue is whether age at onset should be analyzed as a continuous variable. We chose to take a dichotomous approach, as indicated by the analysis of bimodality and, as is consistent with literature, in order to facilitate comparisons. A fourth caution regarding generalizability is that our patients could have either manic, mixed, or depressed episodes of bipolar disorder, whereas other studies only included manic or mixed episodes. Finally, our study was retrospective and needs to be replicated prospectively, with more control and standardization of treatment. In conclusion, we found that although patients with a later onset of bipolar disorder had a greater chance of having psychotic features and cerebrovascular risk/burden, they were as likely as the early-onset group to have highly significant improvement in BPRS, GAS, and MMSE, and were as likely to be discharged to 82 Am J Geriatr Psychiatry 7:1, Winter 1999

7 Wylie et al. the same setting from which they had come. Our study confirms that short-term psychiatric hospitalization offers an effective vehicle for the treatment of most cases of severe bipolar disorder in elderly patients, and thus there are grounds for optimism for those who treat geriatric patients with conservatively defined bipolar mood disorder. This work was supported in part by NIMH grants MH52247, MH30915, MH19986, and MH References 1. Roth M: The natural history of mental disorder in old age. Journal of Mental Science 1955; Kay D, Roth M, Hopkins B: Affective disorders arising in the senium, I: their association with organic cerebral degeneration. Journal of Mental Science 1955; 101: Alexopoulos GS, Young RC, Meyers BS, et al: Late-onset depression (review). Psychiatr Clin North Am 1988; 11: Young RC, Klerman GL: Mania in late life: focus on age at onset (review). Am J Psychiatry 1992; 149: Alexopoulos GS, Meyers BS, Young RC, et al: Clinically defined vascular depression. Am J Psychiatry 1997; 154: Alexopoulos GS, Meyers BS, Young RC, et al: The course of geriatric depression with reversible dementia : a controlled study. Am J Psychiatry 1993; 150: Dew MA, Reynolds CF, Houck PR, et al: Temporal profiles of the course of depression during treatment: predictors of pathways toward recovery in the elderly. Arch Gen Psychiatry 1997; 54: Young RC: Bipolar mood disorders in the elderly. Psychiatr Clin North Am 1997; 20: Wertham FI: A group of benign chronic psychoses: prolonged manic excitements. Am J Psychiatry 1929; 9: Krauthammer C, Klerman GL: Secondary mania: manic syndromes associated with antecedent physical illness or drugs. Arch Gen Psychiatry 1978; 35: Rosen LN, Rosenthal NE, Van Dusen PH, et al: Age at onset and number of psychotic symptoms in bipolar I and schizoaffective disorder. Am J Psychiatry 1983; 140: Yassa R, Nair NP, Iskandar H: Late-onset bipolar disorder (review). Psychiatr Clin North Am 1988; 11: Goodwin FK, Jamison KR: Manic-Depressive Illness. New York, Oxford University Press, Angst J, Grof P: The course of monopolar depressions and bipolar psychoses, in Lithium in Psychiatry: A Synopsis. Edited by Villeneuve A. Quebec, Canada, Les Presses de L Universite Laval, 1976, pp Zubenko GS, Mulsant BH, Rifai AH, et al: Impact of acute psychiatric inpatient treatment on major depression in late life and prediction of response. Am J Psychiatry 1994; 151: Fillenbaum GG, Smyer MA: The development, validity, and reliability of the OARS multidimensional functional assessment questionnaire. J Gerontol 1981; 36: Miller MD, Paradis CF, Houck PR, et al: Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992; 41: Mulsant BH, Stergiou A, Keshavan MS, et al: Schizophrenia in late life: elderly patients admitted to an acute care psychiatric hospital. Schizophr Bull 1993; 19: Endicott J, Spitzer RL, Fleiss JL, et al: The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976; 33: Overall JE, Gorham DR: The Brief Psychiatric Rating Scale. Psychol Rep 1962; 10: Molloy DW, Alemayehu E, Roberts R: Reliability of a standardized Mini-Mental State Exam compared with the traditional Mini-Mental State Exam. Am J Psychiatry 1991; 148: U.S. Department of Health and Human Services: InternationalClassification of Diseases, 9th Revision. Washington, DC, National Center for Health Statistics, SAS/STAT Software: Changes and Enhancements through Release Cary, NC, SAS Institute Inc., Broadhead J, Jacoby R: Mania in old age: a first prospective study. Int J Geriatr Psychiatry 1990; 5: Kay D: Observations on the natural history and genetics of old age psychoses: a Stockholm material. Proc R Soc Med 1959; 52: Shulman KI, Tohen M, Satlin A, et al: Mania compared with unipolar depression in old age. Am J Psychiatry 1992; 149: Carlson GA, Davenport YB, Jamison K: A comparison of outcome in adolescent- and later-onset bipolar manic-depressive illness. Am J Psychiatry 1977; 134: Dhingra U, Rabins PV: Mania in the elderly: a 5 7-year follow-up. J Am Geriatr Soc 1991; 39: Tohen M, Shulman KI, Satlin A: First-episode mania in late life. Am J Psychiatry 1994; 151: Egeland JA, Blumenthal RL, Nee J, et al: Reliability and relationship of various ages of onset criteria for major affective disorder. J Affect Disord 1987; 12: Wiener P, Alexopoulos GS, Kakuma T, et al: The limits of historytaking in geriatric depression. Am J Geriatr Psychiatry 1997; 5: Am J Geriatr Psychiatry 7:1, Winter