Importance of subsyndromal symptoms of depression in elderly patients

Importance of Subsyndromal Symptoms of Depression in Elderly Patients Mohit P. Chopra, M.D., Cynthia Zubritsky, Ph.D. Kathryn Knott, R.N., Thomas Ten Have, Ph.D. Trevor Hadley, Ph.D., James C. Coyne, Ph.D. David W. Oslin, M.D. Objective: There is a debate about the importance of subsyndromal symptoms of depression (SSD). The current study examined the cross-sectional and longitudinal significance of SSD in geriatric subjects both with and without a past history of major depression. Methods: Elderly primary-care subjects with SSD, both with (SSD
; N54) and without (SSD–; N204) a history of major depression, were compared with subjects with major depression (MDD; N111), minor depression (MinD; N74), and symptom-free comparison subjects (N59). Assessment domains included physical and psychological disability, health-care utilization, hopelessness, death and suicidal ideation, and a diagnostic evaluation at a 3-month follow-up. Results: Both subjects with SSD
and SSD– differed from the symptom-free comparison subjects on measures of psychological disability, hopelessness, and death ideation, with SSD
subjects being more severely psychologically disabled than SSD– subjects. There were few differences between SSD
and MinD subjects or those with MDD, except on measures of psychological disability. Finally, more than 24% of SSD
subjects progressed to meet criteria of MDD, MinD, or dysthymia over a 3-month period. Utilization of outpatient services did not differ among any of the depression groups or comparison subjects. Conclusions: SSD (with or without a past history of MDD) is associated with significant disability. Moreover, the risk of developing a diagnosis of MDD, MinD, or dysthymia is substantially elevated in subjects with a past history of MDD. (Am J Geriatr Psychiatry 2005; 13:597–606) pidemiological studies suggest that symptoms of depression below the criterion threshold of either major depression or dysthymia are more prevalent E than either of the nosological categories themselves.1 Adult patients with such depressive symptoms have been shown to experience significant psychological Received December 3, 2003; revised April 28, June 1, 2004; accepted June 8, 2004. From the Section on Geriatric Psychiatry, Dept. of Psychiatry, Univ. of Pennsylvania, Philadelphia, PA (MPC,KK,DWO), the Center for Clinical Epidemiology and Biostatistics, Univ. of Pennsylvania, Philadelphia, PA (TTH), the Center for Mental Health Care Policy and Services Research, Dept. of Psychiatry, Univ. of Pennsylvania (CZ,TH), the Dept. of Psychiatry, Univ. of Pennsylvania (JCC), the Center for the Study of Addictions, Dept. of Psychiatry, Univ. of Pennsylvania (DWO), and VISN 4 Mental Illness Research, Education, and Clinical Center at the Philadelphia VA Medical Center (DWO). Send correspondence and reprint requests to David W. Oslin, M.D., Univ. of Pennsylvania Health System, 3535 Market Street, Room 3002, Philadelphia, PA 19104. e-mail: oslin@mail. med.upenn.edu  2005 American Association for Geriatric Psychiatry Am J Geriatr Psychiatry 13:7, July 2005 597 AD Symptoms of Subsyndromal Depression disability2,3 and to have excess service-utilization,4 use of welfare benefits, and suicidal behavior, underscoring the importance of such symptoms. These observations are particularly relevant for geriatric psychiatry, where epidemiological studies suggest that the prevalence of major depressive disorder (MDD), as diagnosed with the criteria of the diagnostic systems, like the Diagnostic and Statistical Manual (DSM), is low.5,6 This has been attributed to the observation that clinically significant depression in the geriatric population may often fail to reach the threshold of MDD set by the DSM.7 Investigating the significance of subsyndromal depression in older adults is, hence, an important issue. Surveys carried out specifically in geriatric populations, including community-based,8 primary-care,9 and long-term care settings,10 confirm that subsyndromal depressive symptoms are indeed very common. As a result of the growing body of literature,11 the category of minor depression (MinD) has been included in Appendix B of the DSM-IV for further investigation. This category requires the presence of a total of 2–4 symptoms of depression, of which at least one should be depressed mood or anhedonia. Despite the clinical importance of MinD, as increasingly recognized by research findings,9,12,13 a substantial number of individuals with symptoms of depression, such as poor energy or concentration, or sleep and appetite disturbances, do not meet the criteria for even minor depression. The importance of these depressive symptoms below the threshold of even MinD, the so-called subsyndromal symptoms of depression (SSD), has been studied less extensively, particularly in elderly subjects. Among younger and middle-aged adults, there are two parallel theories regarding the importance of SSD. There is evidence from the Psychobiology of Depression study14 that SSD is common during the longitudinal course of MDD, itself, because of partial remission of symptoms. Study subjects with residual SSD were seen to relapse into MDD sooner than those who had a complete remission of symptoms. However, a major limitation of this14 and other similar investigations15 is that they examined only those subjects who had met the symptom-threshold criteria for MDD. The other point of view suggests that clinically significant depression exists as a “spectrum,”16,17 starting with SSD, but ending with major depression 598 (with or without melancholic features). Such subsyndromal9 or “subdysthymic”18 depressive symptoms have been studied less extensively in elderly subjects, but have been shown to result in functional disability comparable to that seen in subjects with major depression. Furthermore, a proportion of such patients have progressed to develop MDD over time in both younger-adult19 and geriatric20 populations. Hence, although, in some instances, SSD may be an antecedent or sequela of MDD, the significance of subsyndromal symptoms that have never reached the threshold of MDD has not been specifically examined. Investigating the significance of SSD in a way that includes this “lifetime perspective” of having met the threshold for major depression is possible by considering SSD as two separate categories; that is, SSD in those with a past history of MDD, and SSD without such a history. For the purposes of the current report, we refer to these two subcategories as SSD
and SSD–. Examination of SSD in this manner is important not only because of its greater prevalence in elderly persons, but also because this would better characterize subsyndromal depression for the purposes of studying treatment interventions. Absence of clear definitions has been the limiting factor in the study of interventions for depressive conditions that fall short of MDD.21 Our hypotheses were that both subjects with SSD
and SSD– would experience greater psychological disability and burden of symptoms, from a public-health perspective, than symptom-free subjects, but be less impaired than subjects with MinD or MDD; that SSD
subjects would experience greater disability and symptom-burden than SSD– subjects; and that SSD
subjects would be more vulnerable to worsening of symptoms over time than SSD– subjects. Thus, our aim was to compare subjects with SSD
and SSD– to other categories and to each other on measures of public-health importance and outcome. METHODS Subjects and Recruitment This study was conducted as a site-specific component of a larger study, the Primary Care Research In Substance Abuse and Mental Health in the Elderly (PRISME) Study, which is a 10-site effectiveness trial Am J Geriatr Psychiatry 13:7, July 2005 Chopra et al. comparing enhanced referral care to specialty mental health services versus integrated-care models delivering mental-health–related treatment at the primarycare site for older adults suffering from depression, anxiety, and/or at-risk drinking.22 PRISME is a collaborative research study funded by the Substance Abuse and Mental Health Services Administration (SAMHSA), including its three centers: the Center for Mental Health Services (CMHS), Center for Substance Abuse Treatment (CSAT), and the Center for Substance Abuse and Prevention (CSAP). The Department of Veteran’s Affairs (VA), the Health Resources and Services Administration (HRSA), and the Centers for Medicare and Medicaid Services (CMS) provided additional funding and/or other support. Because the data analyzed during the current investigation were obtained at only two of the sites (the Philadelphia VAMC and the University of Pennsylvania), the findings should not be considered representative of the entire multisite study. The methods described below conform to the general procedures of the multisite protocol, but also include details about procedures that were only conducted at the two Philadelphia sites. All patients age 65 and over who had an appointment with one of 34 primary-care clinicians (23 in the Philadelphia VA system and 11 in University of Pennsylvania Health System community practices) during the time between March 2000 and August 2001 were eligible for participation. During each week of the recruitment phase, a random subset of patients was selected from each practice’s appointment list. Primarycare clinicians could request that screening not be conducted on patients known to be terminally ill or severely cognitively impaired, or for those who they felt could not participate in the screening. The remaining patients were sent a letter from the office of their physician describing the screening procedures to be used to identify possible mental health conditions that may be present in the selected group. The subjects approached were invited to return a form if they did not wish to be contacted for telephone screening. Approximately 1 week before the scheduled medical appointment, the research staff, via telephone, contacted those who had not declined participation, to screen them for depression, anxiety, and “at-risk” drinking. For all stages of the project, informed consent was obtained in accordance with both the Philadelphia VAMC and Am J Geriatr Psychiatry 13:7, July 2005 University of Pennsylvania Institutional Review Board (IRB) regulations. Assessments The screening evaluation consisted of: • demographic information • the Blessed Orientation Memory Concentration (BOMC) test23,24 • the 12-item General Health Questionnaire (GHQ)25 • two screening questions for suicidal ideation, modified from the PRIME- MD, that inquired about passive death ideation and active suicidal ideation26 • quantity and frequency of alcohol use • an assessment for past history of major depression, ascertained by the subjects’ self-reports of a previous history of a 2-week period of depressive symptoms that either required treatment or caused significant disability. Subjects were ineligible to complete the screening session if there was evidence of severe cognitive deficit (BOMC of ⱖ16). For those completing the screening, a positive screen was determined by the presence of psychological symptoms, as evidenced by a score ⬎2 on the GHQ, or a response of “Yes” to one of the suicide questions, or consumption of ⱖ8 alcoholic drinks in the previous week or binges consisting of ⱖ4 drinks. Those screening positive and not receiving mental health or substance-abuse care from mental health or substance-abuse therapists during the previous 3 months were invited to receive further evaluation to diagnose any psychiatric condition that might be present, in accordance with the PRISME multisite protocol. Also, a random subset of 59 subjects who had screened negative (“symptom-free comparison group”) were also recruited for baseline evaluation and study participation at the two Philadelphia sites, with the aim of comparing those with any depressive symptoms to those without any symptoms at all. For the purposes of this investigation, only the subjects selected as the symptom-free comparison group and those screening positive on the GHQ were considered eligible for further analysis. Baseline Evaluation and Instruments Subjects who had screened positive, as well as subjects from the selected comparison group, were in- 599 AD Symptoms of Subsyndromal Depression vited to participate in a structured baseline evaluation. The baseline assessment included diagnostic evaluations for mood, anxiety, or alcohol-related disorders, in accordance with DSM-IV (APA) diagnostic criteria, and additional information about symptom severity and functional status. At other participating sites, baseline evaluations were stopped if the subjects did not meet formal diagnostic criteria for one of the study diagnoses. However, at the University of Pennsylvania and the Philadelphia VAMC sites, the complete baseline exam was administered to all consenting subjects who had screened positive. Baseline assessment instruments considered for this investigation were the following: symptoms. Hence, subjects with MinD had between 2 and 4 depressive symptoms present continuously for a 2-week period. SSD was limited to subjects who had screened positive on a screening instrument (the GHQ) for depression but did not meet criteria for MDD, MinD, GAD, panic disorder, psychosis, mania, or problem alcohol use. This method of defining the SSD group is similar to how other studies have identified subjects with subsyndromal depression. SSD defined with such strict criteria would exclude contributions to symptoms or disability that might be otherwise related to another psychiatric condition. Longitudinal Follow-Up • the Mini International Neuropsychiatric Interview (MINI), used to diagnose MDD, dysthymia, MinD, Generalized Anxiety Disorder (GAD), panic disorder, psychosis, and mania, in accordance with DSM-IV diagnostic criteria27 • the Medical Outcome Study, Short Form–36 (SF– 36),28 which was analyzed from the two component subscales: • the Physical Component Score (PCS), assessing the disability from physical complaints and medical problems, and • the Mental Component Score (MCS), which measures the disability and impairment in quality of life from psychological complaints • the Short Michigan Alcohol Screening Test–Geriatric Version (SMAST–G),29 to diagnose those with problem drinking • the Beck Hopelessness Scale,30 assessing the degree of hopelessness • the Paykel Scale for Suicidality,31 evaluating death or suicidal ideation or intent; and • the Cornell Medical Index,32 for information about medical treatment over the previous 3 months The depression-related diagnostic categories considered were major depressive disorder (MDD), dysthymia, and minor depression (MinD). Subjects with a history of MDD with psychotic symptoms were included for analysis, but those with a history of mania or hypomania, or a primary non-affective psychotic illness were excluded. MinD was defined as the presence of either or both of the core symptoms of depressed mood and/or anhedonia, along with 1–2 ancillary depressive symptoms, to a maximum of 4 total 600 As designed for the treatment component of the multisite study, all subjects were followed for 3 months after baseline assessment. No treatment was offered as part of the current study to the SSD or comparison subjects during this follow-up period. The follow-up evaluation was carried out with the MINI exam. Treatment was offered to those SSD and comparison subjects who met diagnostic criteria for MDD, MinD, or dysthymia at the 3-month follow-up as part of the multisite study protocol. We therefore limited the focus of this report to the 3-month followup assessment in order to exclude potential treatment effects. Statistical Analysis Statistical analyses used SPSS Version 11.5 for Windows. Descriptive analyses included means and standard deviations (SD) for continuous variables and frequencies for categorical variables. Analysis was carried by comparing both SSD
and SSD– subjects as separate categories. We acknowledge that this would mean doubling the number of comparisons, but this would also result in a more conservative estimate of the significance of the differences. Betweengroups comparisons were made by ANOVA, followed by the Tukey HSD (Honestly Significant Difference) procedure for pairwise comparisons for continuous measures and chi-square test for proportions. The groups were compared for differences in demographic characteristics at baseline, and variables on which the groups differed at baseline were entered as covariates for between-group comparisons on measures of outcome. Corrections for multiple Am J Geriatr Psychiatry 13:7, July 2005 Chopra et al. comparisons were made with Holm’s procedure,33 which involved multiplication of the significance (p) values by the rank-order number of the significance levels obtained during the multiple comparisons. All significance levels (p values) reported in the text were corrected for multiple comparisons after applying Holm’s procedure. Because the number of outpatient visits did not follow a normal distribution, analysis was carried out after a logarithmic transformation of this variable. Dichotomous variables, like proportion of subjects with suicidal ideation or depression at follow-up, were compared by use of logistic regressions, so that covariates could be entered into the equation. Finally, because the number of subjects with active suicidal ideation in some groups was very small, comparisons for this variable were made with Fisher’s exact test. RESULTS A total of 825 subjects screened positive on the GHQ as part of the screening evaluation and were not currently severely cognitively impaired. Of these subjects, 182 (22.1%) refused or gave incomplete data as part of the screening and baseline assessment, and 79 (9.6%) did not complete the baseline examination because they were currently receiving mental health services. Also, 62 subjects (7.5%) were not included for participation because of a diagnosis of mania (N7), psychosis (N13), problem drinking (N6), generalized anxiety disorder (N15), or dysthymia (N21). Patients diagnosed with dysthymia were not included in the analysis because the number of subjects was too small for meaningful comparisons. Thus, the analytic sample consisted of 502 subjects, of whom 111 had MDD (22.1% of the analytic sample), 74 had MinD (14.7%), 258 had SSD (51.4%), and 59 were symptom-free comparison subjects (11.8%). Fifty-four of the 258 SSD subjects (20.9%) met criteria for a past history of MDD, as did 12 subjects (16.2%) with MinD. Table 1 presents demographic characteristics, mean GHQ scores, and number of medical problems at baseline, as well as any significant differences on these parameters between the five groups. The demographic characteristics of the sample are reflective of the practices participating in the study. There were Am J Geriatr Psychiatry 13:7, July 2005 significant overall differences between the groups in the proportion of male subjects (overall v2[4]10.5; p0.032), and in the mean number of comorbid medical problems between the groups (F[4, 462]8.1; p ⬍0.001), with significant pairwise comparisons presented in Table 1. Gender and number of medical problems were entered as covariates in subsequent analyses, except where noted. The mean GHQ scores between the groups were significantly different (F[4, 565]133.3; p ⬍0.001) and showed a stepwise increase as the symptom threshold of depression increased. Pairwise differences on the mean GHQ scores are presented in Table 1. Finally, the proportion of subjects with a past history of MDD was also significantly different between the groups (v2[2]24.9; p⬍0.001), and the pairwise comparisons were significant, except that the difference between MinD and comparison groups did not reach statistical significance (v2[1]3.5; p0.062). Table 2 presents the mean values or the proportions of subjects in each of the outcome measures. At the 3-month follow-up evaluation, 166 subjects (64.34%) in the SSD groups and 45 symptom-free comparison subjects (76.3%) were re-evaluated. The analysis of differences in outcome measures between the groups, correcting for differences in baseline and multiple comparisons, yielded a number of areas of significant difference. The exploratory nature of this analysis should be emphasized again, and the significance of the reported differences should be interpreted with caution, even when adjusted for multiple comparisons. The significant comparisons are presented below. The overall ANOVA between the groups for the disability resulting from physical illnesses (PCS score) was significant (F[4, 487]5.2; p ⬍0.001). Pairwise comparisons showed that there were significant differences between SSD– subjects and the comparison group (mean difference: –5.7; 95% confidence interval (CI): –8.4 to –2.9; HSD p ⬍0.001). The ANOVA for the differences in MCS scores was highly significant (F[4, 487]73.8; p ⬍0.001). All pairwise comparisons for the extent of psychological disability between the groups were also significant. SSD– subjects were significantly more impaired than symptom-free comparison subjects (mean difference: –5.7; 95% CI: –8.3 to –2.96; HSD p ⬍0.001), but also significantly better than SSD
subjects (mean difference: 4.95; 95% CI: 2.4 to 7.5; HSD p ⬍0.001), subjects 601 AD Symptoms of Subsyndromal Depression ing that the two groups were not as different on this measure. Subjects with MinD had a mean of 4.6 (SD: 7.3) outpatient visits during the preceding 3 months, being the group that utilized outpatient services the most among the different groups. The overall ANOVA between the groups did not, however, reach statistical significance (F[4, 521]1.8; p0.136), and none of the between-group comparisons were significant. Comparison of mean hopelessness scores resulted in a significant ANOVA between the groups (F[4, 521] with MinD (mean difference: 8.6; 95% CI: 6.1 to 11.1; HSD p ⬍0.001), and MDD (mean difference: 16.6; 95% CI: 14.4 to 18.8; HSD p ⬍0.001). Similarly, SSD
subjects were significantly worse, compared with symptom-free comparison subjects (mean difference: –10.6; 95% CI: –13.9 to –7.3; HSD p ⬍0.001), but were also significantly better than subjects with current MDD (mean difference: 11.7; 95% CI: 8.7 to 14.6; HSD p ⬍0.001). There was a difference, to a lesser extent, between the SSD
and MinD groups (mean difference: 3.4; 95% CI: 0.4 to 6.8; HSD p0.026), suggest- TABLE 1. Comparison of Demographic Details and Differences in Baseline Characteristics of the Subject Groups Subsyndromal Depression Symptom-Free Subjects (A) Past History Negative (B) Past History Positive (C) Minor Depression (D) Major Depressive Disorder (E) Sample size Age, years Gender (% men) Race (% white) GHQ score N59 75.7 (5.4) 64.4 83.1 0.4 (0.7) N204 74.8 (5.4) 71.1 70.6 4.4 (1.7) N54 73.3 (6.5) 53.7 79.7 5.2 (2.2) N74 76.2 (6.2) 67.6 63.5 5.7 (2.2) N111 74.4 (6.3) 74.8 64.9 7.4 (2.5) Number of medical problems Past history of major depression (% positive) 3.7 (1.9) 4.8 (2.2) 5.2 (2.3) 5.4 (2.5) 5.6 (2.3) 7.3 0 100 18.8 53.7 Significant Pairwise Comparisons* None C⬍E a None A⬍B b; A⬍C c; A⬍D d; A⬍E e; B⬍D f; B⬍E g; C⬍E h; D⬍E i; B⬍C j A⬍D k; A⬍E l; A⬍C m; A⬍B n A⬍E o; D⬍E p Note: Values are mean (standard deviation), unless otherwise indicated. GHQ: General Health Questionnaire. *Significant pairwise comparisons; p values mentioned are after correction for multiple comparisons: a 2 v [1]8.6; p0.033; b mean difference (MD)  –3.9; 95% confidence interval (CI): –4.5 to –3.4; Tukey honestly significant difference (HSD) p ⬍0.001; c MD  –4.7; 95% CI: –5.5 to –4.1; HSD p ⬍0.001; d MD  –5.1; 95% CI: –5.9 to –4.4; HSD p ⬍0.001; e MD  –6.9; 95% CI: –7.6 to –4.4; HSD p ⬍0.001; f MD1.2; 95% CI: 0.7 to 1.7; HSD p ⬍0.001; g MD2.8; 95% CI: 2.5 to 3.4; HSD p ⬍0.001; h MD2.2; 95% CI: 1.5 to 2.8; HSD p ⬍0.001; i MD  –1.8; 95% CI: –2.4 to –1.2; HSD p ⬍0.001; j MD  –0.8; 95% CI: 0.3 to 1.4; HSD p0.003; k MD  –1.8; 95% CI: –2.9 to –0.7; HSD p ⬍0.001; l MD  –1.95; 95% CI: –2.98 to –0.9; HSD p ⬍0.001; m MD  –1.5; 95% CI: –2.7 to –0.4; HSD p0.024; n MD  –1.1; 95% CI: –2.0 to –0.2; HSD p0.035; o v2[1]31.1; p ⬍0.001; p v2[1]18.5; p ⬍0.001. TABLE 2. Mean Values on Disability Measures, Service Utilization, Hopelessness, and Proportion of Patients With Death Ideation, Suicidal Ideation, and Progression of Diagnostic Category Among the Different Groups Subsyndromal Depression PCS score MCS score Number of outpatient visits Hopelessness Death Ideation (% of subjects) Suicidal Ideation (% of subjects) Developed major or minor depression or dysthymia, at 3 months (%) SymptomFree Subjects (N59) Past Depression History Negative (SSD–) (N204) Past Depression HistoryPositive (SS) (N54) Minor Depression (MinD) (N74) Major Depressive Disorder (MDD) (N111) 40.1 (7.6) 59.2 (4.9) 1.95 (1.9) 2.7 (2.2) 1.7 0 32.5 (9.9) 53.9 (7.8) 3.6 (5.3) 4.1 (3.3) 20.1 1.5 35.4 (10.4) 48.8 (9.2) 3.6 (5.2) 5.3 (3.6) 40.7 1.9 31.96 (10.4) 45.1 (11.5) 4.6 (7.3) 6.4 (4.1) 48.6 2.7 32.5 (10.8) 37.1 (11) 3.3 (3.2) 8.8 (5.5) 58.6 5.4 4.4 10.1 24.3 N/A N/A Note: Values are mean (standard deviation), unless otherwise indicated. PCS: Physical Component Score; MCS: Mental Component Score. 602 Am J Geriatr Psychiatry 13:7, July 2005 Chopra et al. 21.2; p ⬍0.001). SSD– subjects had higher scores than symptom-free subjects (mean difference: –0.28; 95% CI: –0.5 to –0.1; HSD p0.017), but were significantly better than MinD (mean difference: 0.4; 95% CI: 0.2 to 0.6; HSD p ⬍0.001) and MDD subjects (mean difference: 0.6; 95% CI: 0.4 to 0.8; HSD p ⬍0.001). Similarly, SSD
subjects had higher scores than the comparison group (mean difference: –0.5; 95% CI: –0.7 to –0.3; HSD p ⬍0.001), but lower scores than subjects with MDD (mean difference: 0.4; 95% CI: 0.2 to 0.6; HSD p0.003). The differences between subjects with SSD– and SSD
and those with SSD
versus MinD were not significant. The proportion of SSD– subjects reporting “passive” death ideation was significantly higher than in the symptom-free comparison group (odds ratio [OR]: 2.03; 95% CI: 1.2 to 3.4; Wald v2[1]7.8; p0.021), but also significantly lower than the MinD (OR: 0.68; 95% CI: 0.56 to 0.8; Wald v2[1]18.4; p ⬍0.001) and MDD (OR: 0.21; 95% CI: 0.13 to 0.33; Wald v2[1]42.1; p ⬍0.001) groups. Similarly, a significantly higher proportion of SSD
subjects experienced death ideation than did the symptom-free group (OR: 2.13; 95% CI: 1.4 to 3.2; Wald v2[1]13.1; p0.002). There was a less significant difference between subjects with SSD– and SSD
(OR: 2.5; 95% CI: 1.4 to 4.5; Wald v2[1]9.6; p0.010), and no differences between SSD
versus MinD, or SSD
versus MDD. Also, the proportion of subjects with active suicidal ideation was not significantly different between the groups, except between the SSD– and MDD groups (Fishers exact test, p0.02). Finally, 24.3% of the subjects with SSD
met criteria for MDD, MinD, or dysthymia at the 3-month follow-up period (Table 2). This was significantly higher when compared with the proportion of subjects with SSD– (OR: 3.53; 95% CI: 1.34 to 9.28; Wald v2[1]6.55; p0.033) and symptom-free comparison subjects (OR: 1.46; 95% CI: 1.06 to 2.02; Wald v2[1]5.24; p0.044). SSD– and symptom-free comparison subjects did not differ in this regard (OR: 1.02; 95% CI: 0.68 to 1.53; Wald v2[1]0.01; p0.931). All the analyses were repeated excluding the 12 of 74 subjects with MinD who had a past history of MDD, and the results were similar to those presented above. Also, the proportion of subjects from VA versus the university site did not differ between the groups (v2[4]7.8; p0.101). There were no differAm J Geriatr Psychiatry 13:7, July 2005 ences in the findings when site was co-varied in the analysis (details not presented). DISCUSSION Similar to the findings of previous studies, a large proportion of subjects screening positive for psychological distress (a significant score on the GHQ) were found not to meet the criteria for a diagnosis of dysthymia, major or minor depression or another major mental health problem. Almost three-quarters (74%) of these subjects with SSD did not have a history of major depression, suggesting that SSD is likely to occur, not only during the course of MDD, but also as an independent condition, perhaps uniquely in elderly subjects or in primary care. The highlight of the current investigation is that it examines the significance of both the possible contexts in which SSD can exist: SSD without a past history of MDD (SSD–) and SSD with a history of major depression (SSD
), and compares them with other categories. The results of this study demonstrate that subjects with SSD (both with and without a history of diagnosed depression [
and –]) differed from symptomfree subjects on most of the measures of outcome examined. This finding highlights the fact that depressive symptoms below the threshold of major or minor depression are important because they result in higher public-health measures of significance, such as disability and suicidal ideation. The risk of suicide is among the most dangerous, and possibly preventable, problems in old age, as demographic trends have repeatedly shown that successfully completed acts of suicide are highest in the geriatric population.34,35 The importance of hopelessness as a symptom predictor of future suicide attempts has also been well demonstrated.36,37 These findings underscore the importance of recognizing the two categories of SSD, with the aim of preventing morbidity and mortality in the geriatric population. SSD– subjects experienced disability from psychological symptoms that was significantly different from comparison subjects, indicating that the impairment in quality of life (QOL) from even one or two symptoms of depression is significant. This observation also lends support to the reports of earlier investigations that older adults are likely to experience de- 603 AD Symptoms of Subsyndromal Depression pression differently,38 possibly because they were less likely to endorse sadness as a symptom.39 These symptoms also resulted in greater physical disability than could be explained from differences in the number of medical problems when compared with symptom-free subjects. Earlier studies have shown that patients with minor and subthreshold depression experience greater severity of medical illnesses13 and were more likely to report functional disability in medical care settings.40 However, these subjects did not differ from the comparison subjects in the proportion that were diagnosed with a depressionrelated category over time. Hence, given the implications of the presence of these symptoms and the substantial proportion of persons experiencing them, the importance of subsyndromal symptoms alone (SSD–) needs further exploration. Similar to subjects with SSD–, SSD subjects who had a past history of major depression (SSD
) differed from symptom-free comparison subjects on most of the outcome measures examined, except PCS scores. They, however, showed greater psychological impairment than the SSD– group, underscoring the possible long-term impact of having met the threshold of major depression in the past. However, probably the most important finding of this investigation was the fact that the SSD
group differed from both the symptom-free subjects and the SSD– group in that a greater proportion of subjects progressed to meet criteria for major or minor depression or dysthymia, even during short-term follow-up. These differences were statistically significant, highlighting the negative forebodings of a positive past history of MDD in the context of current subsyndromal symptoms. This finding also suggests that there may be value to prospectively monitoring this group closely with a goal to preventing relapse. There is increasing appreciation that often recovery from major depression may be only partial, leading to subsyndromal symptoms,14,15 and the finding of early relapse in SSD
subjects also highlights the importance of treating MDD to complete remission. The findings of this report should be interpreted in light of certain limitations. There may be concerns about generalization beyond the specific clinics participating because of geographical variations in treatment access or other unmeasured confounds. Next, although dysthymic disorder is a clinically important form of depression, patients with dysthymia were not 604 included in the analysis because of their small numbers. Also, the 3-month follow-up period is relatively short, and it can be argued as to whether this is adequate time to observe progression into the categories of major or minor depression. However, this finding must be interpreted in light of the fact that the study population was a preselected group that had screened positive for distress. Other limitations include the lack of validation of administering the MINI to elderly subjects by trained research assistants and the difficulty in determining a previous history of depression. We relied on patient self-report of past episodes, which has been shown to be likely to underestimate the actual number of patients with such a history.41 However, we would like to emphasize that the differences reported were significant even after covarying for baseline characteristics and correcting for multiple comparisons, and the analysis has the advantage of studying a large number of elderly subjects. For many years, psychiatry has been concerned about the threshold of significance for mood disorders. Undoubtedly, the established diagnostic categories have demonstrated good validity. However, recent interest has also focused on the importance of subsyndromal symptoms, and it has become apparent that subsyndromal depression is both very common and is associated with significant disability and risk for future episodes of MinD or MDD. This move to further understand subsyndromal depression is important because, thus far, there is only limited understanding about the implications and treatment of these conditions. Robust effect sizes, as have been shown for major depression, are absent when treatments such as antidepressant medications are used for minor depression.21 The findings of the current evaluation would suggest that SSD
may be a condition that requires closer monitoring and even targeted treatment and that SSD– may be a construct for further research of its implications and possible intervention strategies, as needed. However, despite the argument to recognize SSD,42 assigning its diagnostic significance remains a challenge.43 This study was presented in parts at the 2003 and 2004 Annual Meetings of the American Association for Geriatric Psychiatry (AAGP), held at Honolulu, HI, and Baltimore, MD. We express our gratitude to the clinicians and staff in Am J Geriatr Psychiatry 13:7, July 2005 Chopra et al. each of the participating primary-care clinics for supporting this work. This work was funded by SAMHSA (#) 1UD1SM53033; the Dept. of Veterans Affairs; National Institute of Mental Health Grant 1K08MH01599; National Institute of Mental Health Grant 5P30MH52129; and the Mental Illness Research, Education, and Clinical Center at the Philadelphia VAMC. References 1. 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