Journal of Behavioral Medicine, Vol. 28, No. 1, February 2005 ( C© 2005)DOI: 10.1007/s10865-005-2561-0

The Validity of Beck Depression Inventory and HamiltonRating Scale for Depression Items in the Assessment ofDepression Among Patients with Multiple Sclerosis

Patricia J. Moran1,3 and David C. Mohr1,2

Accepted for publication: February 24, 2004

Measuring depression in patients with chronic illnesses such as multiple sclerosis (MS) is po-tentially complicated by the fact that several somatic symptoms of depression are also com-mon in chronic illnesses. Whether standard assessment measures such as the Beck DepressionInventory (BDI) and Hamilton Rating Scale for Depression (HRSD) should exclude certainsomatic symptoms when used in MS has been examined previously, but there is no clear con-sensus on this issue. The present study evaluated the utility of individual BDI and HRSDitems for assessing depression in MS patients by examining how individual items respondedto depression treatment in 42 (29 female) depressed MS patients. All 21 BDI items and 12of 17 HRSD items decreased significantly with treatment, suggesting that all BDI items tapdepression, as do 12 of 17 HRSD items. Thus, the present data support the inclusion of allBDI items when measuring depression in MS. Decisions on whether or not to use all HRSDitems or only the 12 shown here to capture depression may depend on the study purpose anddesign.

KEY WORDS: depression; Beck Depression Inventory; Hamilton Rating Scale for Depression; multiplesclerosis.

INTRODUCTION

It is widely recognized that chronic or seri-ous illness increases risk for depression (Cassemet al., 1995). Assessment of depressive symptoma-tology in these populations is commonly performedeither with self-report measures, such as the BeckDepression Inventory (BDI; Beck et al., 1961), orwith structured or semi-structured interviews such asthe Hamilton Rating Scale for Depression (HRSD)(Hamilton, 1960). It has long been suspected thatthe validity of such assessments may be compro-mised by the confounding of depressive and medical

1University of California, San Francisco, California.2VA Medical Center, San Francisco.3To whom correspondence should be addressed at Osher Cen-ter for Integrative Medicine, University of California, Box 1726,1701 Divisadero Street, Suite 150, San Francisco, California 941431726; e-mail: moranp@ocim.ucsf.edu

symptoms. The 21-item BDI, originally developedto measure level of depression in patients receivingcognitive-behavioral therapy, has been widely usedas a self-report measure of depression in a range ofpatient populations. The 17-item HRSD is one themost frequently-used and well-validated clinician-rated measures of depression severity.

While research on the application of the HRSDin medical populations is lacking, use of the BDIwith medical patients has received considerable em-pirical attention. The bulk of this research com-pares the predictive validity of the BDI to clinical orstructured interview diagnoses based on DSM-IV (orIIIR) criteria. These studies often find that the BDIdiscriminates depressed from non-depressed DSM-diagnosed medical patients, and conclude that thefull BDI is valid with these populations (e.g. patientswith diabetes, Lustman et al., 1997; chronic pain pa-tients, Geisser et al., 1997). DSM-based classificationis often considered the diagnostic gold standard in

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36 Moran and Mohr

these studies, but it is unclear whether DSM crite-ria clarify diagnostic issues in depressed medical pa-tients (von Ammon Cavanaugh, 1995), as the BDIand DSM criteria contain similar somatic symptoms.

Considerable attention has been paid to themeasurement of depression in multiple sclerosis(MS), a chronic neurological disorder that affectsnearly 350,000 people in the United States (Aikenset al., 1999; Huber et al., 1993, Mohr et al., 1997b;Nyenhuis et al., 1995). Depression is common amongMS patients (Joffe et al., 1987; Minden et al., 1987),with lifetime prevalence rates of major depressivedisorder (MDD) approximately 50% (Sadovnicket al., 1991). MS presents a particularly salient prob-lem in depression assessment because it can producea wide variety of symptoms that can also also occurin depression, including sexual dysfunction, debilitat-ing fatigue, cognitive difficulties, psychomotor retar-dation, mood changes, sleep changes, and emotionalchanges (Goodkin, 1992; Mohr and Dick, 1998; Mohret al., 1997a). This overlap can complicate the assess-ment of depression in patients with MS.

Item-level data on the HRSD in MS patientshas not been previously reported, but the validityof the BDI for assessing depression in MS has beenevaluated. Mohr and colleagues (1997b) comparedthe relative contribution of each BDI item to to-tal score (i.e., relative scores) in MS patients versusclinically depressed non-medical patients and normalcollege students. They considered an item to be con-founded by MS symptoms if the percent contribu-tion to the total BDI score was significantly greaterin the MS group than both of the comparison groups(controlling for level of depression). They foundthat three BDI items (work-related problems, fa-tigue, and health concerns) had significantly greaterrelative scores in MS patients. The authors con-cluded that these items measured MS-disease symp-toms more than depression, and thus suggested thatthese items not be used in assessing MS patients fordepression.

A subsequent study by Aikens and colleagues(1999) reached a contradictory conclusion. These re-searchers examined the validity of the BDI in MS bycomparing item-level data of MS patients with othermedical patients (diabetes mellitus and chronic pain),patients with major depressive disorder (MDD), andhealthy controls. Despite concerns about the validityand reliability of relative scores, they examined rela-tive scores in order to enable comparisons with pre-vious research. When controlling for demographicvariables and depression severity, they found that

the relative contribution of one item (work difficulty)was higher in MS compared to healthy controls, butnot compared to MDD patients. There was also noevidence that internal consistency changed with thedeletion of purportedly confounded items. Together,these findings led the authors to conclude that BDIitems are not confounded with MS symptomatology.

To date, there is no clear consensus aboutwhether the assessment of depressive symptoms inMS should include or exclude somatic or func-tional items. The available studies rely on cross-sectional between-group comparisons. An alterna-tive approach to examining the utility of specificitems in assessing depressive symptomatology is toexamine item-level responses to depression treat-ment. Looking at individual items before and aftertreatment for depression is a particularly strong wayto examine this relationship because treatment es-sentially provides an experimental manipulation.

The purpose of the present study was to exam-ine how MS patients score on depression items oftwo commonly used measures of depression, the BDIand HRSD, when they are depressed versus not de-pressed. We selected patients who showed a reliablereduction in depression over the course of treatmentfor depression, and examined which items reflectedthe overall reduction.

MS is a chronic illness with fluctuating symp-toms. Most people with MS experience a fluctuatingdisease course with clearly-defined exacerbations, orepisodes of acute worsening of neurologic functionfollowed by partial or complete recovery periods freeof disease progression. Fluctuations in MS symptomscould therefore affect the reporting of depressivesymptoms in MS patients.

The present study is the first, to our knowledge,to examine the sensitivity of depression scale itemsin MS in the context of treatment for depression. Weanticipated that some somatic items on the BDI andHRSD would fail to show significant reductions withtreatment, while non-somatic items would improveover the course of treatment. Because previous re-search is mixed, we did not make predictions aboutspecific somatic items.

METHODS

Participants

We examined BDI and HRSD item meansin a sample of 42 depressed MS patients before

Depression Among Patients with Multiple Sclerosis 37

and after 16 weeks of treatment for depression.These participants were drawn from a larger com-parative outcome trial of three treatments for de-pression in patients with MS (Mohr et al., 2001a).Participants in the trial were randomly assigned toindividual cognitive-behavioral therapy, supportiveexpressive group therapy, and the antidepressantsertraline. Inclusion criteria for this study included(a) confirmed diagnosis of relapsing-remitting orsecondary-progressive MS (Poser et al., 1983; Lublinand Reingold, 1996); (b) a diagnosis of major depres-sive disorder (MDD) based on the Structural Clini-cal Interview for the DSM-IV (SCID) (First, Spitzeret al., 1995); (c) a score of 16 or more on the 17-item Hamilton Rating Scale for Depression (HRSD)(Hamilton, 1960; Whisman et al., 1989); and (d) ascore of 16 or more on the Beck Depression Inven-tory (BDI) (Beck et al., 1961). Exclusion criteria in-cluded (a) dementia defined as falling below the 5thpercentile in three of six areas of neuropsychologicalfunctioning (i.e. attention and concentration, speedof processing, executive functioning, verbal memoryand visual processing assessed with commonly usedtests); (b) current MS exacerbation (see Mohr et al.,2001a for a more detailed description of inclusionand exclusion criteria).

All participants received a screening evaluationthat included assessment of depression as well asinclusion/exclusion criteria. Depression assessmentswere repeated at the start of the treatment, andevery four weeks thereafter until the end of thetreatment at the 16th week. Patients were randomlyassigned to 16 weeks of weekly individual cognitive-behavioral therapy, weekly supportive expressivegroup psychotherapy (Spiegel, 2000), or sertraline.Thirty-eight percent of participants received indi-vidual CBT, 36% received group treatment, and26% received antidepressant medication. Completedetails on treatments, treatment assignment, andtreatment fidelity monitoring are described in Mohret al., (2001a).

In order to examine how MS patients rate de-pression symptoms when depressed versus not de-pressed, we selected patients who showed reliableimprovement in depression during treatment for in-clusion in the present study. To accomplish this, datawere only included from patients who completedeight or more weeks of treatment and who showeda reduction of two standard errors of measurement(SEM) or more on the BDI or HRSD (SEM forBDI = 3.26 SEM for HRSD = 3.20). To be included,patients were also required to have completed at

least eight weeks of treatment, as this is the minimaltreatment dose that can be expected to be sufficientto produce improvement across all treatment arms.

Assessment Measures

Beck Depression Inventory (BDI) (Beck et al.,1961) is a commonly used 21-item measure of de-pression. Table I lists all BDI items. Each item con-sists of four statements describing increasing intensi-ties of symptoms of depression. Items are rated on ascale from 0–3, reflecting how participants have feltover the past week. Possible scores range from 0–48;higher scores reflect more severe depressive sympto-motology. A review of research studies focusing onthe psychometric properties of the BDI revealed amean coefficient alpha of 0.86 in psychiatric popula-tions, indicating adequate internal consistency; con-current validities of the BDI with respect to clinicalratings and the HRSD were also high (correlationcoefficients were 0.72 and 0.73, respectively, for psy-chiatric patients; Beck et al., 1988).

Hamilton Rating Scale for Depression (HRSD)(Hamilton, 1960) is a semi-structured interview thatassesses depressive symptoms. To facilitate reliabil-ity, the present study used the more structured 17-item version (Whisman et al., 1989). Ratings weremade using the inclusive method based solely uponthe presence and severity of symptoms (Cohen-Coleand Harpe, 1987). No attempts were made to modifyratings of potentially confounded symptoms basedupon presumed etiology as such adjustments havebeen associated with lower reliability and validity(Koenig et al., 1997). Table II lists all HRSD items.Scores on the first 14 items are based on semi-structured interview of the patient about their expe-riences over the previous week. Scores on the last 3items (Insight, Psychomotor Retardation, and Psy-chomotor Agitation) are based on observations ofpatients behavior during the interview session. Inter-rater reliabilities for the HRSD were checked peri-odically and were consistently above 90.

RESULTS

Of the 42 participants who met criteria forthis study 29 (69%) were women. The majority ofthe sample identified as Caucasian (n = 34), andthe remainder identified as African-American, His-panic, Asian-American/Pacific-Islander, or “other.”Participants averaged 43.0 (SD = 10.3) years in age.

38 Moran and Mohr

Table I. BDI Item Scores Pre- and Post-Treatment for Depression in MS Patients

Mean SD

Pre-Tx Post-Tx Pre-Tx Post-Tx t p-value

BDI 1 Feeling sad 1.36 0.31 0.727 0.517 8.230 0.000BDI 2 Discouraged about future 1.12 0.45 0.633 0.633 5.292 0.000BDI 3 Feeling like a failure 0.88 0.31 0.739 0.517 4.625 0.000BDI 4 Anhedonia 1.43 0.71 0.668 0.554 5.041 0.000BDI 5 Guilt 0.79 0.21 0.750 0.470 4.625 0.000BDI 6 Deserving punishment 0.57 0.12 0.859 0.328 3.522 0.001BDI 7 Disappointment with self 1.05 0.50 0.697 0595 4.422 0.000BDI 8 Self-blame 1.14 0.48 0.647 0.552 5.990 0.000BDI 9 Suicidal ideation 0.52 0.07 0.505 0.261 5.820 0.000BDI 10 Crying 1.14 0.38 0.899 0.764 4.401 0.000BDI 11 Irritability 1.10 0.64 0.726 0.577 3.298 0.002BDI 12 Losing interest in others 1.14 0.64 0.647 0.618 4.583 0.000BDI 13 Indecisiveness 1.62 0.86 0.623 0.683 6.506 0.000BDI 14 Physical appearance 1.19 0.48 0.833 0.594 4.901 0.000BDI 15 Ability to work 1.57 0.86 0.668 0.566 5.545 0.000BDI 16 Sleep problems 1.48 0.83 0.969 0.794 3.865 0.000BDI 17 Fatigue 1.67 1.00 0.526 0.541 7.065 0.000BDI 18 Appetite 0.79 0.26 0.645 0.445 4.394 0.000BDI 19 Weight loss 0.52 0.17 0.890 0.377 2.555 0.014BDI 20 Concerns about health 1.24 0.45 0.850 0.593 5.506 0.000BDI 21 Sexual disinterest 1.36 0.79 0.983 0.842 3.937 0.000BDI TOTAL 23.67 10.52 6.849 6.508 10.905 0.000

Note. N = 42.

Nineteen (45%) were employed, while 23 (55%)were unemployed or on disability. Twenty-four(57%) were married or living with a partner, 18(43%) were single, separated, or divorced. Educa-tion ranged from 10–20 years, with an average of15.1 years. Participants had been diagnosed for anaverage of 6.6 (SD = 6.1) years, with a range of onemonth to 20 years. They reported that they had theirfirst symptom of MS for an average of 11.2 (SD =10.2) years, with a range of seven months to 35 years.

Pre- and post-treatment item means for eachitem on the BDI and HRSD were compared in pairedt-tests. The results of these t-tests are presented inTables I and II. The mean BDI and HRSD scoreswere 23.7 (SD = 6.9, range = 13–41) and 19.3 (SD =4.4, range = 10–30) at pre-treatment, and 10.5 (SD =6.5, range = 1–37) and 10.8 (SD = 5.3, range =1–21) at post-treatment, respectively. All 21 BDIitems showed statistically significant reductions withtreatment (p < 0.05).

Twelve of 17 HRSD items were significantlyreduced post-treatment (p < 0.05). Four HRSDitems did not reach statistical significance (p >

13). These included late insomnia (pre-treatmentx = 0.81, SD = 0.92, post-treatment x = 0.62, SD =0.83; t = 1.14, p = 0.26), insight (pre-treatment x =0.10, SD = 0.30, post-treatment x = 0.12, SD = 0.33;

t = −3.74, p = 0.71), psychomotor retardation (pre-treatment x = 0.19, SD = 0.40, post-treatment x =0.26, SD = 0.54; t = −0.77, p >0.45), and psychomo-tor agitation (pre-treatment x = 0.40, SD = 0.70,post-treatment x = 0.19, SD = 0.51; t = 1.55, p >

0.13). Change in somatic anxiety was marginallysignificant (pre-treatment x = 1.88, SD = 0.77, post-treatment x = 1.60, SD = 0.86; t = 2.02, p = 0.05).

DISCUSSION

The purpose of the present study was to eval-uate the utility of individual BDI and HRSD itemsfor assessing depression in MS patients. Among MSpatients who showed a reliable improvement in de-pression, 21 BDI items and 12 of 17 HRSD itemswere significantly reduced over the course of treat-ment. It is highly unlikely that these improvementswere due to changes in MS illness severity. BecauseMS is a progressive illness, basal levels of impair-ment or symptoms would not be expected to improveover 16 weeks. While symptoms do improve as MSexacerbations remit, patients in exacerbation wereexcluded at study entry, thereby precluding the possi-bility that symptom reduction could be due to remis-sion of MS exacerbation. Thus, we are confident that

Depression Among Patients with Multiple Sclerosis 39

Table II. HRSD Item Scores Pre- and Post-Treatment for Depression in MS Patients

Mean SD

Pre-Tx Post-Tx Pre-Tx Post-Tx t p-value

HRSD1 Depressed mood 2.31 0.86 0.643 0.926 8.663 0.000HRSD2 Work & activities 2.31 0.83 1.000 0.935 8.011 0.000HRSD3 Interest in sex 0.93 0.48 0.838 0.740 3.029 0.004HRSD4 Appetite 0.55 0.24 0.633 0.532 2.680 0.011HRSD5 Weight loss 0.48 0.10 0.773 0.370 2.891 0.006HRSD6 Early insomnia 0.88 0.45 0.942 0.772 2.371 0.023HRSD7 Middle insomnia 1.10 0.69 0.958 0.897 3.061 0.004HRSD8 Late insomnia 0.810 0.62 0.917 0.825 1.135 0.263HRSD9 Fatigue, aches, etc. 1.74 1.40 0.445 0.627 2.864 0.007HRSD10 Guilt 1.71 0.62 0.891 0.731 7.838 0.000HRSD11 Suicide 0.57 0.05 0.859 0.216 4.224 0.000HRSD12 Tense/irritable/worry 1.79 1.26 1.001 0.798 2.945 0.005HRSD13 Somatic anxiety 1.88 1.60 0.772 0.885 2.016 0.050HRSD14 Health concerns 1.57 1.07 0.831 0.677 3.532 0.001HRSD15 Insight 0.10 0.12 0.297 0.328 −.374 0.710HRSD16 Psychomotor retardation 0.19 0.26 0.397 0.544 −0.771 0.445HRSD17 Psychomotor agitation 0.40 0.19 0.701 0.505 1.546 0.130HRSD TOTAL 19.31 10.83 4.431 5.296 9.460 0.000

Note. N = 42.

the observed reductions in BDI and HRSD symp-toms were associated with change in depression.

The fact that these BDI and HRSD items sig-nificantly decreased over treatment should not be in-terpreted as evidence that these items are not con-founded with MS. There are several reasons whyan item may be both sensitive to depression andbe confounded with MS. Mood states are known toaffect appraisal of physical symptoms (Salovey andBirnbaum, 1989; Leventhal et al., 1996). Even theHRSD, a semi-structured interview, is based largelyon patient report of subjective symptoms (mood,anhedonia, fatigue, etc.). Thus, it is possible that im-provements in depression also reduce patient ap-praisals of their MS symptoms. In addition, it is pos-sible that depression is a symptom of MS. Many ofthe cytokines (proteins) involved in auto-aggressiveimmune dysregulation in MS are also known tocause depressive symptoms (Dantzer, 2001). How-ever, treatment for depression can also reduce suchimmune dysregulation (Mohr, 2001b). Thus, thesedata cannot be used to determine the degree to whichthese BDI and HRSD items are confounded withMS. However, these findings do support the notionthat BDI items and 12 HRSD items capture changein depression.

Four HRSD items did not show significant re-ductions: psychomotor retardation, psychomotor ag-itation, insight and late insomnia. Changes in insight,psychomotor retardation and psychomotor agitation

may not have been observed for a number of reasons.Floor effects may have allowed little room for reduc-tions, as pre-treatment means for these three itemswere the lowest of all the HRSD items (0.10,0.19,and.40, respectively). In addition, unlike the otherHRSD items, these three items are based solely onthe rater’s objective observation rather than patient’ssubjective report, and thus were not influenced by pa-tients’ mood-related changes in appraisal.

The absence of a significant reduction in lateinsomnia is somewhat surprising. It is possible thatchange in sleep disturbances are somewhat differentin MS patients treated for depression as comparedwith medically healthy patients. There are numer-ous MS symptoms that might interfere with sleep inthe morning. For example, the severity of urinaryurgency or incontinence increase over time and aretherefore likely to exert their greatest effect on sleepat the end of the night. MS patients frequently man-age fatigue by taking naps during the day, which maydisrupt terminal sleep. It is unclear, however, whythese factors would specifically impact terminal sleepand not initial or middle sleep.

A fifth item, somatic anxiety/physical com-plaints was marginally significant (p = 0.05). Thisitem assesses the severity of and effect on daily func-tioning of numerous physical symptoms includinggastrointestinal symptoms of dry mouth, gas, in-digestion, diarrhea, cramps, and belching; heartpalpitations, headaches; hyperventilating, sighing;

40 Moran and Mohr

and frequent urination. Given the marginal findingwe cannot say whether this item captures changes indepression in MS.

In summary, there is good evidence that12 HRSD items capture symptomatic changes associ-ated with reductions in depression. Interpreting nullfindings is more difficult, since our statistics controlfor type I error (α), which is the likelihood that anobserved change in scores is due to chance and notdue to any true underlying effect. Our statistics arenot able to control for Type II error (β), which isthe possibility that a failure to observe a change inscores by chance did not capture a true underlyingdifference. As such, we can be reasonably confidentin our observations of significant reductions in BDIand HRSD items. But our ability to interpret the re-maining 5 HRSD items is difficult. Using a criterionof p > 0.20 for accepting the null hypothesis (Cohen,1988), the HRSD late insomnia, psychomotor retar-dation, and insight items would be said not to changeduring treatment for depression. However, it shouldbe recognized that this criterion is not a true test ofType II error.

Several limitations should be noted. First, al-though repeated measures may counteract this draw-back, we had a relatively small sample, particularlyfor the number of comparisons made. In addition, thesmall sample size limited our power to detect signif-icant changes with treatment. While this strengthensour confidence in our findings with respect to itemsthat showed significant change over the course oftreatment, it is possible that in a larger sample moreor all HRSD items would have shown statistically sig-nificant reductions. Second, it would have been idealto compare the MS sample with a non-medical de-pressed sample treated for depression, in order to de-termine if patterns of response to treatment that weobtained are unique to MS or reflect broader trendsin depression treatment. For example, it is possiblethat certain symptoms, such as late insomnia, do notremit as quickly or as fully as other symptoms. Com-parison with a non-medical depressed sample wouldalso have allowed us to better understand the lackof remission observed in the three observation-baseditems on the HRSD, insight, retardation, and agita-tion. Third, the lack of a comparison group with an-other medical diagnosis limits the generalizability ofthese findings. Because people with MS experiencea broad range of symptoms and levels of disabil-ity (Noseworthy et al., 2000) we believe these find-ings are broadly applicable, however, in the absenceof data, this contention remains speculative. Finally,

although our sample, comprised primarily of Cau-casian females, is highly representative of the MSpopulation (MS is 2–3 times more common in womenthan men, and affects primarily Caucasian people),the generalizability of our findings to other ethnicand cultural groups is limited.

Accurate assessment of depression in MS andother chronical illnesses is critical. Depression neg-atively impacts not only quality of life (Amato et al.,2001) and psychosocial functioning (Coulehan et al.,1996), but also medical outcomes such as adherenceto treatment (Guiry et al., 1987; Stoudemire andThompson, 1983, Mohr et al., 1997a), length of hospi-tal stays (Koenig et al., 1989), and mortality (Frasure-Smith et al., 1995; Koenig et al., 1989; Hawton, 1981;Murphy et al., 1988).

Due to potential overlap in symptoms of de-pression and MS, assessment of depression is compli-cated. Whether standard assessment measures suchas the BDI are valid in MS has been examined previ-ously (Aikens et al., 1999; Mohr et al., 1997b). This isthe first study, to our knowledge, to examine the va-lidity of the BDI and HRSD in MS using a treatmentsample and the first study to examine the HRSDitems in MS. Our findings that five HRSD items maynot reflect treatment-related change in depressionsuggest that researchers may wish to consider the in-clusion of these items depending on the study aimsand design. For example, the HRSD may slightlyoverestimate depression in cross-sectional studies, al-though the low pre-treatment values suggest that thiseffect would be small. However, because any lackof change in these items would wash out in treat-ment outcome studies, investigators may want to re-port all items for the sake of consistency across stud-ies. Our current findings with respect to the BDIcontradict our previous conclusion that some BDIitems should be excluded (Mohr et al., 1997b). Thesefindings support Aikens and colleagues (1999) con-tention that the full BDI can and should be used withMS patients.

ACKNOWLEDGMENTS

This research was supported by research grantsRG2719 A1/2 from the National Multiple Sclero-sis Society and R01 MH59708 from the NIMH(PI, David C. Mohr). The preparation of thismanuscript was supported in part by a training grant,“Psychology and Medicine: An Integrative ResearchApproach,” NIH T32 MH 19391.

Depression Among Patients with Multiple Sclerosis 41

REFERENCES

Aikens, J. E., Reinecke, M. A., Pliskin, N. H., Fischer, J. S., Wiebe,J. S., McCracken, L. M., and Taylor, J. L. (1999). Assessingdepressive symptoms in multiple sclerosis: Is it necessary toomit items from the original Beck Depression Inventory ? J.Behav. Med. 22: 127–142.

Barnwell, A. M., and Kavanaugh, D. J. (1997). Prediction ofpsychological adjustment to multiple scleorsis. Soc. Sci. Med.45: 411–418.

Beck, A. T., Ward, C. H., Medelson, M., Mock, J., and Erbaugh,J. (1961). An inventory for measuring depression. Arch. Gen.Psychiatry 4: 561–571.

Beck, A. T., Steer, R. A., and Garbin, M. G. (1988). Psychometricproperties of the Beck Depression Inventory: Twenty-fiveyears of evaluation. Clin. Psychol. Rev. 8: 77–100.

Cassem, E. H. (1995). Depressive disorders in the medically ill:An overview. Psychosomatics 36: 2–10.

Cohen-Cole, S.A., and Harpe, C. (1987). Diagnostic assessmentof depression in the medically ill. In Stoudemire, A., andFogel, B. S. (Eds.), Principles of medical psychiatry, Gruneand Stratton, New York, pp. 23–36.

Cohen, J. (1988). Statistical Power Analysis for the BehavioralSciences, 2nd ed., Hillsdale, Erlbaum, New Jersey.

Dantzer, R. (2001). Cytokine-induced sickness behavior: Mecha-nisms and implications. Ann. N. Y. Acad. Sci. 933: 222–234.

First, M. B., Spitzer, R. L., Gibbon, M., and Williams, J. B. (1995).Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition (SCID-I/P, Version 2.0). New York StatePsychiatric Institute, New York.

Geisser, M. E., Roth, R. S., and Robinson, M. E. (1997). Assessingdepression among persons with chronic pain using the Centerfor Epidemiological Studies-Depression Scale and the BeckDepression Inventory: A comparative analysis. Clin. J. Pain13: 153–170.

Gilchrist, A. C., and Creed, F. H. (1994). Depression, cog-nitive impairment and social stress in multiple sclerosis.J. Psychosomatic Med. 38, 193–201.

Goodkin, D. E. (1992). The natural history of multiple sclerosis. InRudick, R. A., and Goodkin, G. E. (Eds.), Treatment of Mul-tiple Sclerosis: Trial Design, Results, and Future Perspectives,Springer-Verlag, New York, pp. 17–46.

Gulick, E. E. (1997). Correlates of quality of life among personswith multiple sclerosis. Nurs. Res. 46: 305–311.

Hamilton, M. (1960). A rating scale for depression. J. Neurol.Neurosurg. Psychiatry 23: 56–62.

Hays, R. D., Marshall, G. N., Wang, E. Y. I., and Sherbourne,C. D. (1994). Four-year cross-lagged associations betweenphysical and mental health in the medical outcomes study.J. Consulting Clin. Psychol. 62: 441–449.

Huber, S. J., Rammohan, K. W., Bornstein, R. A., and Christy,J. A. (1993). Depressive symptoms are not influenced byseverity of multiple sclerosis. Neuropsychiatry Neuropsychol.Behav. Neurol. 6: 177–180.

Joffe, R. T., Lippert, G. P., Gray, T. A., Sawa, G., and Horvath, Z.(1987). Mood disorder and multiple sclerosis. Arch. Neurol.44: 376–378.

Kathol, R. G., and Petty, F. (1981). Relationship of depression tomedical illness: A critical review. J. Affect. Disor. 3: 111–121.

Katon, W., and Sullivan, M. D. (1990) Depression and chronicmedical illness. J. Clin. Psychiatry 56: 3–11.

Koenig, H. G., George, L. K., Peterson, B. L., and Pieper,C. F. (1997). Depression in medically ill hospitalized olderadults: Prevalence, characteristics, and course of symptomsaccording to six diagnostic schemes. Am. J. Psychiatry 154:1376–1383.

Leventhal, E. A., Hansell, S., Diefenbach, M., Leventhal, H.,and Glass, D. C. (1996). Negative affect and self-report ofphysical symptoms: Two longitudinal studies of older adults.Health Psychol. 15: 193–199.

Lublin, F. D., and Reingold, S. C. (1996). Defining the clinicalcourse of multiple sclerosis: Results of an internationalsurvey. Neurology 46: 907–911.

Lustman, P. J., Clouse, R. E., Griffith, L. S., Carney, R. M., andFreedland, K. E. (1997). Screening for depression in diabetesusing the Beck Depression Inventory. Psychosom. Med. 59:24–31.

Minden, S. L., Orav, J., and Reich, P. (1987). Depression inmultiple sclerosis. Gen. Hosp. Psychiatry. 9: 426–434.

Mohr, D. C., and Dick, L. P. (1998). Multiple sclerosis. InCamic, P. M., and Knight, S. (Eds.), Clinical Hand-book of Health Psychology: A Practical Guide to Effec-tive Interventions, Hogrefe and Huber, Seattle, pp. 313–348.

Mohr, D. C., Goodkin, D. E., Gatto, N., and Vander Wende(1997a). Depression, coping and level of neurologicalimpairment in multiple sclerosis. Mult. Scler. 3: 254–258.

Mohr, D. C., Goodkin, D. E., Likosky, W., Beutler, L., Gatto, N.,and Langan, M. K. (1997b). Identification of Beck DepressionInventory items related to multiple sclerosis. J. Behav. Med.20: 405–412.

Mohr, D. C., Boudewyn, A. C., Goodkin, D. E., Bostrom, A., andEpstein, L. (2001a). Comparative outcomes for individualcognitive-behavior therapy, supportive-expressive grouppsychotherapy, and sertraline for the treatment of depressionin multiple sclerosis. J. Consulting Clin. Psychol. 69: 942–949.

Mohr, D. C., Goodkin, D. E., Islar, J., Hauser, S. L., and Genain,C. P. (2001b) Treatment of depression is associated with sup-pression of nonspecific and antigen-specific T(H)1 responsesin multiple sclerosis. Arch. Neurol. 58(7): 1081–1086.

Noseworthy, J. H., Lucchinetti, C., Rodriguez, M., andWeinshenker, B. G. (2000). Multiple sclerosis. N. Eng.J. Med. 343: 938–952.

Nyenhuis, D. L., Rao, S. M., Zajecka, J. M., Luchetta, T.,Bernardin, L., and Garron, D. C. (1995). Mood disturbanceversus other symptoms of depression in multiple sclerosis.JINS, 291–296.

Pakenham, K. I. (1999). Adjustment to multiple sclerosis: Appli-cation of a stress and coping model. Health Psychol. 18: 383–392.

Poser, C. M., Paty, D. W., Scheinberg, L., McDonald, W. I., Davis,F. A., Ebers, G. C., Johnson, K. P., Sibley, K. P., Silberberg,D. H., and Tourtellotte, W. W. (1983). New diagnostic criteriafor multiple sclerosis. Ann. Neurol. 13: 227–231.

Robertson, M. M., and Katona, C. L. E. (1997). Depression andPhysical Illness. Wiley, Chichester.

Rodin, R., Craven, J., and Littlefield, C. (1991). Depression in theMedically Ill: An Integrated Approach, Brunner/Mazel, NewYork.

Sadovnick, A. D., Eisen, K., Ebers, B. C., and Paty, D. W. (1991).Cause of death in patients attending multiple sclerosis clinics.Neurology 41: 1193–1196.

Salovey, P., and Birnbaum, D. (1989). Influence of mood onhealth-relevant cognitions. J. Pers. Soc. Psychol. 57: 539–551.

von Ammon Cavanaugh, S. (1995). Depression in the medicallyill: Critical issues in diagnostic assessment. Psychosomatics36: 48–59.

Whisman, M. A., Strosah, K., Fruzzetti, A. E., Schmaling, K. B.,Jabobson, N. S., and Miller, D. M. (1989). A structured in-terview version of the Hamilton Rating Scale for Depression:Reliability and validity. Psychol. Assess. 1: 238–241.