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22 The APA Publishing Textbook of Mood Disorders, Second Edition
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substituted for the current categorical approach to diagnosis, 5) increasing compatibility between DSM-5 and ICD-11, 6) assessing the applicability of criteria across different
cultures, and 7) facilitating the diagnostic process in nonpsychiatric primary care set
tings. Discussions about these issues guided much of the DSM-5 developmental process and the coordination with the ICD-11 development until publication of DSM-5 in
2013. The major harmonization effort between the two classifications occurred in the
overall reorganization of the entire mental health classification to reflect a more devel
opmentally grounded and disorder spectrum–based organizational structure (Andrews et al. 2009). There was also the introduction of more dimensional measures in
DSM-5, particularly in the sections on the following: neurodevelopmental disorders,
schizophrenia spectrum and other psychotic disorders, bipolar and related disorders,
depressive disorders, substance-related and addictive disorders, somatic symptom
and related disorders, and personality disorders.
With regard to the mood disorders in DSM-5, the placement of bipolar disorder in
a separate chapter from the depressive disorders constituted a significant structural
change. The rationale for this move entailed a careful evaluation of 11 different validation criteria for the classification of schizophrenia, schizoaffective illness, bipolar disorder, major depressive disorder, and anxiety disorders. Relevant literature reviews
for each of these disorder groups were performed to assess the following validating
correlates: genetics, familiality, early environment, neural substrate, biomarkers, tem
perament, cognitive and emotional processing, symptomatology, comorbidity, course
of illness, and treatment response (Goldberg et al. 2009a). Based on these correlates, it
appeared that bipolar disorder was more closely related to schizophrenia than to unipolar major depressive disorder—with the latter more closely related to the anxiety
disorder spectrum. All of the mental disorders consisting of states with increased lev
els of anxiety, depression, fear, and somatic symptoms were conceptualized as emotional or internalizing disorders (Goldberg et al. 2009b). As a result of the remaining
clinical and validating distinctions between these conditions, the DSM-5 committee
decided to maintain separate categories for bipolar disorder, depressive disorders,
and anxiety disorders (Goldberg et al. 2010). However, the ICD-11 committee continued to group bipolar disorder with the mood disorders (Reed et al. 2019).
The bipolar and related disorders chapter of DSM-5 includes bipolar I disorder, bipolar II disorder, cyclothymic disorder, substance/medication-induced bipolar and
related disorder, bipolar and related disorder due to another medical condition, other
specified bipolar and related disorder, and unspecified bipolar and related disorder.
In DSM-5, the definition of a component manic episode has been changed from DSMIV Criterion A to read (additions underlined): “A distinct period of abnormally and
persistently elevated, expansive, or irritable mood and abnormally and persistently
increased goal-directed activity or energy
the day, nearly every day
Psychiatric Association 2013, p. 124). Criterion B of the manic episode criteria is
largely unchanged from DSM-IV and requires three or more of seven symptoms or
four of seven if the mood is only irritable. DSM-IV Criterion C, which excluded a
mixed episode, was dropped in DSM-5 in favor of including a mixed features specifier among 10 specifiers for the bipolar and depressive disorder conditions. Criterion
D in DSM-IV and Criterion C in DSM-5 require that the mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to
(or any duration if hospitalization is necessary)” (American
, lasting at least 1 week, and present most of
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necessitate hospitalization to prevent harm to self or others, or that psychotic features
are present.
The definition of a major depressive episode in the DSM-5 bipolar and depressive
disorder chapters is very similar to that in DSM-IV and requires five of nine symp
toms occurring over the same 2-week period. DSM-IV symptom A1 has been changed
to read (DSM-5 addition underlined) “depressed mood most of the day, nearly every
day, as indicated by either subjective report (e.g., feels sad, empty,
servation made by others (e.g., appears tearful).” It is interesting to note that the
“hopeless” symptom was previously included only in the dysthymia criteria of DSM
IV but had been included in the Patient Health Questionnaire–9 screening interview
for major depressive disorder that was developed by Robert Spitzer; this 27-point in
strument is recommended as a severity measure in DSM-5 (Spitzer et al. 1994). Criterion E, known as the bereavement exclusion in DSM-IV, was replaced in DSM-5 with
a note requiring clinical judgment to distinguish major depressive disorder from a
normal grief response to a significant loss. In addition, DSM-5 includes an extensive
footnote describing the difference between a major depressive episode and a normal
grief response. This modification in the criteria for a major depressive episode re
ceived a great deal of attention and attracted controversy during the development of
DSM-5, and is dealt with somewhat differently in ICD-11 (Zachar et al. 2017). In ICD
11, the diagnosis of major depressive disorder is not excluded in a person who is bereaved, but it requires a longer duration (i.e., at least 1 month) and the presence of
symptoms unlikely to be associated with a normal grief response, such as low selfworth, guilt not related to the lost loved one, psychotic symptoms, suicidal ideation,
or psychomotor retardation (Stein et al. 2020). These additional requirements in ICD
11 for the diagnosis in bereaved persons are similar to but less complete than the description differentiating normal grief from a major depressive episode in the DSM-5
criteria note and footnote.
Bipolar I disorder in DSM-5 requires the presence of a manic episode that may have
been preceded by and may be followed by a hypomanic episode or a major depres
sive episode. Bipolar II disorder requires a current or past hypomanic episode and a
current or past major depressive episode. Cyclothymic disorder criteria are much more
long term and require at least 2 years (1 year in children and adolescents) of numerous periods with hypomanic symptoms that never meet criteria for a hypomanic episode and numerous periods with depressive symptoms that fail to meet criteria for a
major depressive episode. The hypomanic or depressive symptoms must cause clini
cally significant distress or impairment; they must be present for at least half of the 2or 1-year time frame and must never be absent for more than 2 months at a time. Sub-
stance/medication-induced bipolar and related disorder requires prior exposure to a substance or medication capable of producing bipolar symptoms; ICD-10-CM coding
instructions are provided for the various types of precipitating substances or medications (Centers for Medicare & Medicaid Services 2021). Likewise, bipolar and related
disorder due to another medical condition requires that the syndrome be the direct patho
physiological consequence of another medical condition. Following ICD-10 conventions, there are also other specified bipolar and related disorders, with examples of
subthreshold combinations of symptoms, and unspecified bipolar and related disorders,
for use in cases where the clinician opts not to specify the reasons why criteria are not
met for specific bipolar and related disorders.
or hopeless
) or ob-
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DSM-5 includes 10 similar specifiers that—with the exception noted below—can
be applied to either bipolar or depressive disorders:
1. With anxious distress
2. With mixed features
3. With rapid cycling (Note: applicable only to bipolar disorders)
4. With melancholic features
5. With atypical features
6. With mood-congruent psychotic features
7. With mood-incongruent psychotic features
8. With catatonia
9. With peripartum onset
10. With seasonal pattern
The added symptom profiles provided by the specifiers are intended to allow a more
dimensional description of the bipolar and depressive disorders without producing
the expanded number of separate categorical disorders that would otherwise result
from multiplying the number of specifiers by the number of separately identified dis
orders. ICD-11 uses the term qualifiers instead of specifiers to include refined (more dimensional) descriptions of current mood episodes, including prominent anxiety,
melancholy, current perinatal episode, seasonal patterns, and rapid cycling. Al
though ICD-11 does not include a mixed features qualifier for either bipolar or depressive disorders, it has retained the DSM-IV and ICD-10 “mixed-episode” category
for bipolar I disorder—most recent episode mixed, which was eliminated in DSM-5
(Stein et al. 2020).
The DSM-5 section on depressive disorders includes, for the first time, disruptive
mood dysregulation disorder, a condition that should not be diagnosed before age 6 or
after age 18 years. It requires severe recurrent temper outbursts and either verbal or
physical rage episodes (which can include physical aggression) that are out of proportion in intensity or duration to the situation or provocation. These outbursts occur
three or more times per week, and irritable or angry mood persists between outbursts
for most of the day, nearly every day, for 12 or more months. The major debate in de
veloping criteria for this disorder was that it was not considered to be bipolar disorder, conduct disorder, or intermittent explosive disorder, although it shares multiple
symptoms with each of these conditions. Disruptive mood dysregulation disorder
was not included in ICD-11, which considered it to be more similar to conduct disorder. Following publication of DSM-5, the borderline personality disorder advocacy
community expressed concern that this symptom profile may reflect a childhood onset of borderline personality disorder.
Major depressive disorder is largely unchanged from DSM-IV, with the exception of
the addition in DSM-5 of hopelessness as an example of depressed mood and the
elimination of the bereavement criteria for depressive episode. The addition of the
specifier “with anxious distress” requires at least two of five symptoms that include
feeling keyed up or tense, feeling unusually restless, difficulty concentrating because
of worry, fear that something awful may happen, and feeling that the individual
might lose control of himself or herself. Severity is rated according to number of
symptoms as mild (2/5), moderate (3/5), moderate-severe (4–5/5), or severe (4–5/5
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with motor agitation) (American Psychiatric Association 2013, p. 184). This severity
specifier was added when it was found in the DSM-5 field trials that a separate diag
nosis of anxious depression was not reliably diagnosed, even though a majority of
people with major depressive disorder are found to have significant anxiety (Regier
et al. 2013).
Persistent depressive disorder (dysthymia) was introduced into DSM-5 to combine
DSM-IV dysthymia that required a 2-year duration and DSM-IV chronic major de
pressive episode that also required a 2-year duration. Several key studies had been
unable to find any difference in correlates or outcomes for these two conditions.
Premenstrual dysphoric disorder, which was included in the DSM-IV appendix “Conditions for Further Study,” was studied extensively between 1994 and 2012 and shown
to have the requisite syndrome pattern and clinical distress and disability to be recog
nized as a disorder, as well as a good response to recognized treatments. The treatment
responses were sufficient to receive an FDA indication for antidepressant medica
tions—a rare accomplishment for a mental disorder not recognized in DSM-IV.
Substance/medication-induced depressive disorder, depressive disorder due to another
medical condition, other specified depressive disorder, and unspecified depressive disorder
have a structure and rationale similar to the bipolar disorders with identical modifiers
discussed above.
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Future of Mood Disorder Classification
Although the current DSM and ICD classifications of mood disorder have largely retained specific categorical diagnoses with explicit diagnostic criteria, the many overlaps in criteria produce very porous boundaries across spectra of disorders in the
depressive and bipolar disorder groups. The requirement for clinically significant dis
tress or impairment for almost all other DSM and ICD disorders means that some
combination of depressive and anxiety symptoms is inevitably present in most men
tal disorders. The research screening instrument that is most frequently used in epidemiological and many clinical studies to detect the clinical significance criteria is the
Kessler Psychological Distress Scale (either the 6-item [K6] or the 10-item [K10] ver
sion), which covers a broad range of depressive and anxiety symptoms (Andrews and
Slade 2001). The presence of depressive and anxiety symptoms in virtually all clinically significant mental disorders is widely understood to result in high levels of comorbidity between specific mental and addictive disorders. This finding also results
in spectra disorders, with porous instead of the strict boundaries between categorical
disorders envisioned by the Robins and Guze (1970) validation criteria.
As genetic research has advanced with genome-wide association studies (GWASs)
of specific mental disorders, there have been increasing requirements for linking the
large number of genetic variants with component traits and symptom profiles of
thousands of people diagnosed with these disorders (Lee et al. 2013). The very heterogeneous nature of specific mental disorders has led NIMH to establish the Research
Domain Criteria (RDoC), a research program that supports a dimensional characteri
zation of research subjects (Insel et al. 2010). The cross-diagnostic symptom domains
of interest include negative valence systems, positive valence systems, cognitive systems, systems for social processes, and arousal/modulatory systems. Both animal
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and human subjects may be assessed in these domains using progressively more
complex units of analysis, including genetic, molecular, cellular, neurocircuitry, phys
iological, and behavioral studies. Ideally, results from such studies should be linked
to the clinical patient profiles that are routinely assessed for the thousands of patients
in genetic studies with DSM and ICD diagnostic criteria (Cuthbert 2014; Regier 2015;
Vaidyanathan et al. 2015). Unfortunately, such linkages are not routinely leaping the
bench-to-bedside implementation hurdles. By taking a more clinically informed em
pirical approach to dimensional diagnoses of mental disorders, the Hierarchical Typology of Psychopathology (HiTOP) has initiated a much more detailed description
of traits, symptoms, and syndromes that has a better chance of linking to GWAS and
RDoC correlates than the current heterogeneous DSM and ICD disorder groups (Ko
tov et al. 2017). Nonetheless, application of dimensional trait and symptom profiles
to patients is difficult in routine clinical settings, and further automation of such as
sessments will be needed before DSM and ICD diagnostic practices are replaced in
such settings (Ruggero et al. 2019).
In the immediate future, DSM-5 is the standard classification system for clinical
diagnosis of mental disorders in the United States, with diagnostic codes drawn from
ICD-10-CM for all medical records. DSM-5 is also the standard classification system
for clinical trials research in the United States and much of the international scientific
community.
ICD-11 was approved by the World Health Assembly in May 2019 (World Health
Organization 2019) but will not be available for official adoption in any WHO mem
ber country until 2022. Each member state of the United Nations and WHO must decide when it will transition from ICD-10 to the new ICD-11 classification and coding
system. For the United States, this transition will require the federal government to
discontinue use of the ICD-10-CM alphanumeric coding system (A00.00–Z99.99) and
adopt the ICD-11 numeric-alpha-numeric system (01A00.00–99Z99.99). Considering
that it took 23 years of negotiations from the WHO release of ICD-10 in 1992 to the
U.S. adoption of ICD-10-CM in 2015, it is unclear how long it will take to negotiate
resistance from electronic health record and health insurance companies to repro
gram their coding systems and adopt ICD-11.
Nevertheless, DSM-5 is largely similar to ICD-11 in organization and content (Regier et al. 2020). Because DSM-5 maintains this compatibility with the ICD-10-CM
codes, one can expect that the annual ICD-10-CM coding updates will gradually adopt
many of the ICD-11 substantive revisions over the next decade. This is similar to how
ICD-9-CM, issued in 1979 with numeric codes (000.00–999.99), gradually changed to
adopt the DSM-III disorders in 1980 and the DSM-IV disorders in 1994. By 2015, when
the United States discontinued ICD-9-CM and adopted ICD-10-CM, all of the DSM-IV
diagnoses had been incorporated into ICD-10, and some of the DSM-5 disorder
changes were ready for incorporation into the first annual revisions of ICD-10-CM. Because each ICD edition coding change substantially increased the number of coding
options, the major problem with adopting new, more complex substantive diagnoses
while continuing to use older ICD codes is that there are insufficient coding options to
fully capture the new disorders. The same will be true until ICD-11 and its associated
codes become the international standard for clinical mental disorder diagnoses.
To develop phenotypic diagnoses for research that can be linked more closely with
genotype-validating criteria, there will still need to be a paradigm shift in clinical de-
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scriptions of large patient populations. This shift will inevitably require a greater degree of dimensional assessments to match the dimensional complexity of genetic risk
profiles (e.g., Manhattan plots). A step in this direction was provided by the DSM-5
Alternative Model for Personality Disorders (in DSM-5 Section III, “Emerging Mea
sures and Models”), which enabled a more dimensional assessment of component
traits and impairments of personality disorders that could be matched with genetic
traits.
It remains to be seen whether the RDoC approach to classifying biological traits or
the HiTOP approach of classifying phenotypic traits and symptoms will ultimately
lead to an international research standard (Krueger and Bezdjian 2009). How future
DSM and ICD revisions adapt to such paradigm changes will depend on the explanatory power that these approaches bring to the development of new treatments for
mood and all other mental disorders.
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CHAPTER 3
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Epidemiology and Burden
of Mood Disorders
Ronald C. Kessler, Ph.D.
Andrew A. Nierenberg, M.D.
Brenda W.J.H. Penninx, M.D., Ph.D.
Philip S. Wang, M.D., Dr.P.H.
Hans-Ulrich Wittchen, Ph.D.
Hannah N. Ziobrowski, Ph.D., M.P.H.
In this chapter, we review the literature on the descriptive epidemiology and
burden of mood disorders worldwide. Data on these topics have increased substan
tially over the past two decades as governments have implemented epidemiological
surveys to provide guidance for mental health policy planning (Kawakami et al. 2020;
Stagnaro et al. 2018), meta-analyses have been conducted using these epidemiological surveys (Charlson et al. 2016; Whiteford et al. 2016), and policy proposals have
been developed based on the results of these meta-analyses (Patel et al. 2016; Vigo et
al. 2016). The realizations that mood disorders are highly prevalent and that they
have substantial costs to the individuals experiencing them, as well as to their families and society emerged for the first time among health policy analysts as a result of
the World Health Organization’s (WHO’s) 1996 Global Burden of Disease (GBD)
Study (Murray and Lopez 1996). In that study, researchers attempted to quantify the
relative importance of diverse illnesses with a metric other than mortality by taking
into consideration the comparative effects of different illnesses on impaired role functioning. After considering the data in this way, the GBD researchers concluded that
mental and substance use disorders, which do not figure prominently as causes of
mortality, are the most burdensome class of disorders in the world, accounting for
nearly one-fourth of all years lived with disability (Alonso et al. 2013; James et al.
2018). Mood disorders are the most important mental or substance use disorders in
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