Download The Changing Epidemiologyof Depression

CLIN.CHEM.34/5,
807-812
(1988)
The Changing Epidemiologyof Depression
GeraldL Klerman1 and Myrna N. Welsaman2
At the clinical
level, we have seen the emergence
of a
subspecialtyof affective disorderswithin psychiatry. Mood
clinics,depressionunits,and affectivedisorderscentersare
appearing in many academic and clinical settings, where
clinical skill and knowledge can be concentratedand new
research furthered. By using structuredinterviewsand the
newer diagnosticsystems,systematicevaluationof patients
has contributedto improved care. Greater skill in psychopharmacology and in specialized psychotherapeutictechniques has resultedin reductionof hospitalizationand rates
for depression, shortened duration of illness, and, in some
instances, reports of reductionin suicide attempts and suicide deaths.
Depression is a highly prevalent disorder in the general
population. A number of its features are changing, so that
those currently at highest risk are adolescents and young
adults. At the same time, however, decreasing age-specific
rates in the elderly, increasing longevity, and a greater
proportion of the population surviving past the seventh
decade combine to produce an increase in the actual awnbers of elderly who are depressed (1).
Knowledge of the changing epidemiology of depression
has important
clinical and public health implications, as
well as being a topic of intrinsic scientific and social interest.
The Epldemiological Approach
Basic Concepts
Investigating the frequency of a disorder, such as depression, falls within the province of epidemiology, the scientific
discipline concerned with determining rates of disorders in
defined populations and investigating the variation in these
rates by characteristics of the individual, place, or time.
Historically, epidemiology has been focused mainly on infectious diseases, usually acute illnesses such as occur in
epidemics. However, in the last few decades, the epidemiological approach has been applied to the understanding of
chronic and non-infectious illnesses, such as cancers, coronary artery disease, and hypertension. The epidemiological
approaches have only recently been applied to specific
mental disorders (2,3).
Investigating changes in any medical disorder requires an
epidemiological approach, because diagnostic information
on large samples of persons, independent of whether they
are seeking or receiving treatment, is needed to obtain
accurate estimates of rates and of possible changes in these
rates. This approach is of particular importance for studies
of mental disorders. Many persons with mental disorders do
not receive treatment; if they do, frequently it is from nonpsychiatric
physicians or other sources from whom it is
‘Department
of Psychiatry, Cornell University Medical College,
New York, NY 10021.
2Department of Clinical and Genetic Epidemiology, New York
State Psychiatric Institute, College of Physicians & Surgeons,
Columbia University, New York, NY 10032.
difficult to obtain information. Gender and socio-economic
status influence the seeking of treatment by afflicted individuals; thus, women, the better educated, and the more
affluent are overrepresented in the treated population, affecting the accuracy of rate estimates. It must be pointed
out, however, that this pattern of treatment-seeking
also
characterizes
many non-psychiatric disorders.
Rates and Risk Factors
Some basic epidemiological
terms merit brief definition.
is the number of new cases of a disorder
occurring in the population per year. Data on incidence are
most relevant for understanding
the cause of a disorder.
Prevalence
is that proportion of the population with the
particular disorder at a given time. Prevalence is usually
divided into “point prevalence” (the rate of illness at a given
time) or “period prevalence” (the proportion of the population with the disorder within a period of time, usually a
month or a year). Incidence and prevalence are not identical
since there is a complex relationship based on the death
rate, chronicity, and time duration.
Lifetime prevalence is the lifetime likelthood of an individual having an episode of the illness. It is also useful to
calculate “morbid risk,” which estimates the prevalence for
the time during which the individual may be at risk. For
bipolar disorders, the period of risk for a first onset usually
begins with puberty and ends by age 60.
Risk factor is a characteristic
of the individual which
increases the likelihood of that individual developing the
disorder being studied. Risk factor is a statistical concept,
but knowledge about risk factors is valuable in providing
clues to etiology as well as planning preventive measures in
public health. Thus, for example, there appears to be a
reduction
in the U.S. death rate from coronary artery
disease owing to changes in cigarette smoking, diet, and
other behaviors on the part of the adult population, even
though the exact cause of arteriosclerosis has not yet been
determined.
Incidence
Sources of Data about Epidemiology of Depression
l.a the last decade there has been a marked increase in
information on the epidemiology of depression, providing
data on overall rates of specific psychiatric disorders and
information about who is at increased risk in the general
population and in families. This increase in information is
due to advances in techniques of sampling and statistics
from social survey research and from epidemiology, as well
as from the achievements of clinical psychiatric research in
the development of reliable and valid methods for obtaining
more precise and reliable diagnoses (4).
During the last two decades there have been improved
diagnostic criteria for many mental disorders, based on type,
number, frequency, duration of symptoms, and exclusion
features. These criteria were codified in 1980 (5), and, based
on clinical and research experience, revised in 1987 as the
DSM-ffl-R (6).
In the mid-to-late
1970s, new diagnostic
methods
CLINICAL CHEMISTRY, Vol. 34, No. 5, 1988
were
807
applied to large samples in community surveys and to
family studies to provide information about rates and risk
factors for psychiatric disorders in general and for depression and mood disorders in particular.
The community studies include the NIMH Epidemiologic
Catchment Area Study, in which five university research
teams assessed over 18 000 persons selected from probability samples of non-institutionalized
persons living in five
urban areas in the U.S.: New Haven (Yale), Baltimore
(Johns Hopkins), St. Louis (Washington
University), Durham (Duke), and Los Angeles (UCLA). The study’s purpose
was to determine the rates and risks for major DSM-ffl
disorders and the treatment received for these disorders (7,
8). There also have been community surveys, done by
similar techniques, in Puerto Rico (9) and in New Zealand
(10).
The family genetic studies include relatives, both adults
and children, of probands (patients) with affective disorders.
They have had an important role in determining
familial
risk of disorders, particularly
for depression. These studies
include the NIMH Collaborative
Study (11), the Yale Family Study (12), and the NIMH Intra-Mural
Study (13).
The Clinical CondItions: Depression
Disorders
and Related Mood
The mood disorders (also called affective disorders) are a
group of mental conditions in which disturbances of emotions predominate.
While there is disagreement over which
emotions to include and how much significance should be
attached to various symptom patterns, there is consensus
that states of depression and mania constitute the major
mood disorders.
There are multiple forms of depression, notably dysthymia and schizoaffective disorder, but the best epidemiological evidence pertains to bipolar disorder and major depression. Transient moods of sadness and dysphoria are experienced by everyone and are not considered abnormal. In this
paper, we are mainly concerned with the clinical syndrome
of depression.
Depressive symptoms occur in a variety of medical and
mental illnesses. The clinical “depressive syndrome,” as
defined by DSM-ffl criteria, includes persistent mood disturbance, appetite change, and weight loss, changes in psychomotor activity, sexual dysfunction, and significant cognitive
changes manifested
by feelings of helplessness, hopelessness, and worthlessness, and associated with impairment of
functioning.
The Category of Mood Disorders
The identification of mood disorders as a separate category of psychiatric conditions has only gained acceptance in
the research and clinical community since the 1950s. Until
the promulgation of DSM-ffl in 1980, official diagnostic
systems, including the American Psychiatric Association’s
Diagnostic and Statistical Manual (APA-DSM) and the
World Health Organization’s International
Classification of
Diseases (WHO-lCD), did not include a separate category
for affective (mood) disorders. Rather, depressions and manic states were included either under psychotic or neurotic
conditions. Effective psychopharmacologic
agents further
contributed to the breakdown of the psychotic-neurotic
classification, particularly for depressions. Largely because
of the pattern of clinical actions of the tricycic antidepressants, monoamine oxidase inhibitors, electric convulsion
therapy, and lithium, it became increasingly useful clinical808
CLINICAL
CHEMISTRY,
Vol. 34, No. 5, 1988
ly and valid scientifically to group depressions togetherwhether psychotic or neurotic-and
elated states, including
manic-depressive
illness, cyclothymia, and hypomania, into
a broad category of affective disorders.
This grouping together follows the logic of classification
that emerged in medicine in the late 18th and early 19th
centuries. Disorders in general medicine are classified either by etiology (e.g., infectious disease, trauma, genetic
disturbances, metabolic illnesses, nutritional deficiencies) or
by the bodily organ involved (e.g., cardiac disease, kidney
disease). For psychiatric illness, establishing the etiology
remains the highest ideal. However, only a fraction of the
mental disorders have had their etiologies conclusively
established.
Currently,
most diagnostic
and classification
systems
group the non-organic
disorders on the basis of the mental
faculty that is disturbed. The psychiatric equivalent of the
“organ” becomes the mental faculty. The division of mental
disorders into disorders of thinking
(schizophrenia
and
paranoia), disorders of memory (dementia), disorders of
affect (mood disorders and anxiety disorders), and disorders
of behavior (eating disorders, psychological dysfunctions,
sleep disorders, etc.) reflects this view of the “morphology” of
the mind.
Admittedly,
this approach to classification is far from
ideal. We do not know the normal physiological basis of
mood, let alone the anatomical areas of pathology underlying clinical conditions. The syndromes of depression are
regarded as disturbances in common pathophysiology. Thus,
psychiatric syndromes are logically equivalent to syndromes
in medicine such as hypertension, jaundice, and congestive
heart failure. These syndromes each have common presentations and share pathophysiological
processes resulting
from multiple and diverse etiologies. As with hypertension,
heart failure, and jaundice, the psychiatric syndromes of
depression and elation reflect such disturbances in pathophysiology.
Rationalefor DiagnosticCategories
Surveyed
in This Paper
The epidemiological
data on affective disorders in this
are divided into four groups: (a) depressive
symptoms, (b) bipolar disorder, (c) non-bipolar depression, and (d)
chronic depression (dysthymia).
(a) There is a reasonable international agreement about
the existence and measurement of depressive symptoms that
.may not be of sufficient intensity to warrant a clinical
diagnosis.
(b) There is strong agreement that the bipolar disorder
(defined by one or more episodes of mania) is a distinct
diagnostic entity.
(c) “Major depressives” include persons with the depressive syndrome but without evidence of history of mania,
sometimes called unipolar depression, or non-bipolar depression. It is a large and heterogeneous group. There is
considerable international
disagreement
about how to subdivide this group. For example, in the DSM-ffl (5) the
diagnostic classification for this group is major depression,
which is further divided as to recurrence or symptom proffle
(melancholia). The ICD-9 classifies depression according to
impairment
of reality testing, subdivided into psychotic and
neurotic features (14).
(d) There is a large group of persons in the community
who have chronic depressions.
These symptoms usually
cause distress and impairment of functioning, but seldom
require hospitalization. The DSM-ffl-R groups them togetharticle
er as “dysthymia,” and research has provided new knowledge about their epidemiology and response to pharmacological and psychotherapeutic
treatments.
Depressive Symptoms
Feelings of sadness and disappointment
are part of the
human condition. Intense, pervasive, and persistent symptoms that interfere with normal functioning
are usually
considered pathological, but the gradation from normal
mood to the clinical state is not well defined.
In recent years there has been considerable research on
self.report in inventories and rating scales measuring depressive symptoms. Cutoff points that distinguish
normal
mood from clinical states have been developed, but the
clinical significance of depressive symptoms remains uncertain. For example, it is not clear whether they are prodromal of a depressive syndrome, or what therapeutic interventions are warranted for depressive symptoms.
Some investigators
have applied depressive symptom
scales to community samples. Table 1 summarizes the
instrument and cutoff score used and the point prevalence of
depressive symptoms from 12 studies (15).
The cutoff scores fall between 0.8 and 1.5 standard deviation above the mean scores in each study. These scores
defme between 9% and 20% of the population as having
depressive symptoms.
Although many persons in the community have depressive symptoms, there is only a modest relationship between
high scores on a depressive symptom scale and meeting the
criteria for a depression disorder according to the Research
Diagnostic Criteria or the DSM-ffl (15). Many persons who
Table 1. PoInt Prevalence per 100 of Depressive
Symptoms
Place, time, and source
of study
Symptom
scale
CutOff
.com
Boston, 1978
Washington County,
Md. 1978
Zung
CES-D’
50
Canberra, Australia,
Zung
1978
Tennessee,
CES-D
New
Haven,
1977
Coon.
CES-D
1975-1976
Washington County,
CES-D
Md. 1973-1974
Kansas City, Mo.
CES-D
1973
Kansas City, Mo. and CES-D
Washington
County, Md.
Women Total
9
11
19
32
17
13
19
16
6
11
16
16
16
16
1972
OARS
A number of community studies have examined
the
lifetime risk of bipolar disorder. The risk for both men and
women ranges from 0.24 to 0.88 per 100 (Table 2).
Social class. It is thought that bipolar disorder may occur
frequently in the upper socio-economic classes.
Race. One study found no relationship between race and
bipolar disorder; another found that blacks had a higher
15
19
bipolar disorder.
Table 2. LIfetime Risk per 100 of Bipolar Disorder’
1971-1973
North Carolina,
“Bipolar disorder” is diagnosed if at least one episode of
depression or one of mania, or both, occur during the
individual’s life. Bipolar disorder is of particular
significance, not only because of its dramatic clinical manifestations, but because family, twin, and adoption studies and
recent linkage studies identifying chromosomal location of
markers of putative genes support a genetic basis for some
forms of bipolar disorder. This diagnostic category is also
important theoretically, since there is epidemiological evidence of temporal trends for bipolar depression as well as for
major depression.
The essential diagnostic feature of bipolar disorder is the
occurrence of a manic episode during the individual’s life (6).
A manic episode is a distinct period of elevated, expansive
mood with associated symptoms of increased activity, flight
of ideas, inflated self-esteem, decreased need for sleep,
distractability, and excessive involvement in activities without recognition
of the high potential for painful consequences.
Because most persons who experience manic episodes
eventually develop a depressive episode, most, but not all,
investigators include manic episodes under bipolar disorder
(16).
admission rate for manic depressive illness than whites.
Marital status. Many studies suggest that bipolar disorder
may be slightly more common among single and divorced
persons. However, marital status may change as a result of
the disorder rather than as a cause of the disorder. We
cannot say that being single or divorced is a risk factor for
9
15
16
Manic States and Bipolar Disorder
LifetimePrevalence of Bipolar Disorder
Rates per 100
Men
were clinically depressed
were missed by a depression
symptom scale (a false-negative
rate) and smaller fractions
of persons who were not clinically depressed scored high on
depressive symptoms (a false-positive
rate). Many of the
misclassified
subjects included persons who denied their
symptoms or who experienced language difficulty, as well as
persons who had medical or psychiatric disorders other than
depression.
3
13”
16”
15”
Depression
Scal&’
16
12
21
17
Washington County,
CES-D
Md. 1971-1974
Kansas City, Mo.
CES-D
16
16
22
20
1971-1 974
Florida, 1967-1972
18-item index
25
13
24
19
CES-D indicates the Center forEpidemlologicalStudiesDepressionScale.
Indicatesthedepressionscale oftheDuke-OldAmericansResourcesand
Services (OARS) MultIdimensionalFunctionalAssessmentQuestionnaire.
Data are for subjects aged 65 yearsand older.
From: BoydJH, WeissmanMM. Epidemiologyof affectivedisorders:reexaminationand futuredirections.ArchGen PsychIatry1981 38:1401.
Plac., tim., and
source of study
Rates p.r 100, tot.l
(both sexes)
New Haven, Coon.
1975-1976
NewZealand,1967
England, 1961
Iceland, 1957-1 971
Denmark, 1951
a Studies of manic-depressive illness are omitted if bipolar
0.24
0.88
0.79
0.61
disorder is not
separated from nonbipolar disorder.
#{176}This
is the lifetime prevalence for bipolar type 1 (with mania). If bipolar type
2 (with hypomania) is included, the lifetime prevalence is 1.2 per 100.
From: Boyd JH, Weissman MM. Epidemiology of affective disorders: reexamination and future directions. Arch Gen Psychiatry 1981 ;38:1401.
CLINICAL
CHEMISTRY,
Vol. 34, No. 5,
1988
809
Family history. There is hard, good evidence for a genetic
component in the familial transmission
of bipolar disorder.
It is a major risk factor of bipolar disorder. People under the
age of 50 are at higher risk for a first attack of bipolar
disorder, whereas someone who already has the disorder
faces recurrent
manic or depressive
episodes
with age.
Bipolar disorder seems to be associated with the upper socioeconomic classes, although, again, this is not conclusively
established.
Major Depression
Much of the clinical and epidemiological
data concern
major depression. The epidemiology, family aggregation,
and clinical course of major depression
have been well
described. It is not a single disorder, rather, it represents a
clinical syndrome, which is the final symptomatic presentation of multiple etiologic and pathogenic mechanisms. Some
forms of major depression may be genetic; others may be
environmental;
still others may be the consequence
of
medical illness, changes in CNS biochemistry,
or the adverse effects of drugs used in the treatment
of medical
conditions,
as with hypertension.
In DSM-ffl, major depression groups with several forms of
depression were previously separated
into psychotic and
neurotic forms. While there is considerable
criticism that
the DSM-ffl concept of major depression
is too broad and allinclusive, it has good reliability in diagnostic studies and
has been the subject of intense investigations.
Prevalence
The prevalence rates for major depression are considerably higher than for bipolar disorder. There are significantly
higher rates for major depression in women than men. The
relation to sex vanes considerably
by age-in
particular,
women ages 18-44 are at highest risk-as
does the effect of
site, urban or suburban, for example (Figure 1).
Maies
0
0
Females
5
Ui
Li 4
z
Ui
-J
> 3
Ui
aI
2
I-
z
0
0
.41
I
/
Fig. 1. Major depression DSM-Ili: EpidemiOlOgiCCatchment Area Study
From:WelssmanMM. Advancesin psychiatric
epidemiology:
rates, and rieks for
major depression. Am J Pub Health 1987;77:447
810 CLINICAL CHEMISTRY, Vol. 34, No.5, 1988
Risk Factors
Sex. The higher rate of major depression in women is a
consistent
finding in many clinical and epidemiological
studies.
Age. Major depression is most common between the ages
of 18 and 44, and particularly
between 25 and 34 years.
Age of onset. There is evidence that the age of onset of
major depression is decreasing
and that this is part of the
birth-cohort
effect. The rates are increasing in the cohorts
(the “Baby Boomers”) who came to maturity after World
War II. Consequently, the clinician and the researcher can
expect to see a greater number of young persons who are
affected with major depression
and whose age at the time of
the first episode is younger than was true for patients seen
in previous eras.
Marital status. The prevalence rates are lowest in men
and women who are married and getting along with their
spouse, highest in unhappily
married women. Although
women normally have higher rates of depression than men,
the increased risk for major depression in an unhappy
marriage is nearly the same for men and women.
Depression affects equally the educated and uneducated,
the rich and the poor, white and black Americans, and blueand white-collar workers, with lower rates in rural areas
than in urban areas.
Dysthymia
A substantial portion of the population and a relatively
large proportion of those people seeing physicians
have
chronic, persistent, low-grade symptoms of depression (17).
The number and intensity of these symptoms may not meet
the DSM-ffl criteria for major depression,
but they often
result in considerable
impairment
of functioning
and increased use of health-care facilities.
Dysthymia is a highly prevalent chronic condition and is
more frequent among women up to age 65, unmarried
persons, and young persons with low income. It is associated
with increased use of general health and psychiatric services and of psychotropic drugs, particularly
minor tranquilizers, antidepressants,
and sleeping pills. It has high comorbidity
with other psychiatric
disorders, particularly
major depression, anxiety disorders, and substance abuse.
The fact that only 25-35% of cases (pure dysthymics) occur
in the absence of other psychiatric disorders raises questions
about its validity as a specific disorder. These “pure dysthymica” may be persons with early symptoms of another
disorder or may have symptoms associated
with medical
conditions.
Until recently, the study of the precise nature and frequency of these chronic depressive states has been limited
by variability in definition and by lack of population-based
data. Previous observations about dysthymia were based on
selected samples of persons coming to various treatment
settings. The DSM-ffl clarified the definition by including
descriptive
symptomatic
criteria for dysthymia
that are
based on phenomenology. In addition, preliminary
epidemiological data on dysthymia are now available.
The epidemiological
data on bipolar disorder and major
depression suggest that the onset and highest risk periods
for major depression and bipolar disorder are in young
adulthood, while the risk for dysthymia is greatest in middle
and old age.
There is strong evidence from family and clinical studies
that major depression and dysthymia are overlapping disor-
ders. In approximately 40% of individuals coming for treatment of depression, the occurrence of major depression and
dysthymia, termed “double depression,” is evident. Family
studies indicate an increased risk of dysthymia in the firstdegree relatives of probands with major depression. Followup studies report that many patients with major depression
go on to become dysthymic.
The association
between these disorders is well established, but the mechanism
of the association is unclear.
Dysthymia may be a mild manifestation
of major depression
or it may be the consequence of untreated or only partly
resolved episodes of major depression that have become
chronic.
The finding of an age-related difference in peak prevalence rates of major depression and dysthymia suggests that
many cases of dysthymia are residual of episodes of major
depression. Because the onset of major depression is most
common in the late 20s, the high rates in the younger age
groups may be a reflection of new onset.
In summary, the epidemiological findings concerning the
age/sex-specific prevalence rates and co-morbidity of dysthymia are reasonably consistent across geographic areas in the
U.S. and are reasonably consistent with findings reported
from clinical studies. The times of onset and highest risk for
other affective disorders are young adulthood, with a residual of dysthymia in middle and older ages. Questions remain
about the uniqueness of dysthymia as a direct disorder.
Suicide
Suicide-attempted
or completed-is
often the outcome of
depression. The feelings of helplessness, hopelessness, and
powerlessness
that are evident in depression can lead to
suicidal intent. While there is not a direct relationship
between suicide and depression, they are nonetheless closely
related. Thus, the higher suicide rates indicate a changing
epidemiology of depression (18).
By the 1970s, clinical and epidemiological research had
revealed an alarming increase in this phenomenon, with the
highest rates registered in the “baby-boom” generation, the
birth cohort born in the decade after World War U.
The recent increase in death by suicide among adolescents
and young adults has prompted intense research to identify
risk factors that may be clinically relevant and that, it is
hoped, may contribute to public-health preventive efforts.
The rate for males is higher than that for females, with
white men more prone than black men. Recently, however,
there has been an alarming increase in the suicide rate
among black males, along with an increase in death by
homicide among black males (19).
Psychological autopsy studies indicate that a substantial
percentage of youth who commit suicide have a diagnosable
psychiatric disorder, including depression and affective dieorder. What is pervasive is the high rate of substance abuse
among these individuals. One study reported that upwards
of 30% to 40% of the youthful suicides have had substance
abuse as a concomitant.
Thus, the increase in suicide parallels the increase in
depression and affective disorders among adolescents and
young adults and the dramatic rise in drug abuse in these
age groups. Other significant risk factors are family history
with respect to suicide and affective disorder, and also a
history of previous attempts.
-39
Temporal Trends
1920-29
1910-19
S.f or. 1910
AGE IN YEARS
Interest in depression and related mood disorders has
increased rapidly over the past few decades, probably reflecting a true increase in the rates of depression. Recent
epidemiological
studies indicate there has been an overall
increase in depression since World War H, and a younger
age of onset (Figure 2). The evidence is best for major
depression, but there is some evidence that there have also
been temporal trends for bipolar disorder (13). The greater
professional
and public interest in depression, however,
probably reflects a true increase in prevalence. This is also
paralleled in an increase in suicide rates among adolescents
and young adults.
Changes in the epidemiology of depression are noted in
three aspects of depression: recent high rates, tendency of
recurrence, and mortality from suicide.
Supported by grants U-O1-MH-43077 and R-O1-MH-43044
from
the National Institutes of Mental Health: Alcohol, Drug Abuse and
Mental Health Administration; Public Health Service; US Department of Public Health Services, Washington, DC; and grant 86-212
from the John D. and Catherine T. MacArthur Foundation.
AGE IN YEARS
Fig. 2. Cumulative probability of diagnosable major depressive disorder
(u,e,) andfemalerelatives (lowe,) by birth cohort
From an interviewwith Gerald L Kierman,M.D.: the changingepidemiologyof
depression. Depression Dialogue, MerrellDow: November1985.
in male relatives
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