Mood Disorders by Anda Gershon and Renee Thompson is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Permissions beyond the scope of this license may be available in our Licensing Agreement.
Everyone feels down or euphoric from time to time, but this is different from having a mood disorder such as major depressive disorder or bipolar disorder. Mood disorders are extended periods of depressed, euphoric, or irritable moods that in combination with other symptoms cause the person significant distress and interfere with his or her daily life, often resulting in social and occupational difficulties. In this module, we describe major mood disorders, including their symptom presentations, general prevalence rates, and how and why the rates of these disorders tend to vary by age, gender, and race. In addition, biological and environmental risk factors that have been implicated in the development and course of mood disorders, such as heritability and stressful life events, are reviewed. Finally, we provide an overview of treatments for mood disorders, covering treatments with demonstrated effectiveness, as well as new treatment options showing promise.
Figure 1: Perinatal depression following child birth afflicts about 5% of all mothers. An unfortunate social stigma regarding this form of depression compounds the problem for the women who suffer its effects. [Image: CC0 Public Domain]
The actress Brooke Shields published a memoir titled Down Came the Rain: My Journey through Postpartum Depression in which she described her struggles with depression following the birth of her daughter. Despite the fact that about one in 20 women experience depression after the birth of a baby (American Psychiatric Association [APA], 2013), postpartum depression—recently renamed “perinatal depression”—continues to be veiled by stigma, owing in part to a widely held expectation that motherhood should be a time of great joy. In an opinion piece in the New York Times, Shields revealed that entering motherhood was a profoundly overwhelming experience for her. She vividly describes experiencing a sense of “doom” and “dread” in response to her newborn baby. Because motherhood is conventionally thought of as a joyous event and not associated with sadness and hopelessness, responding to a newborn baby in this way can be shocking to the new mother as well as those close to her. It may also involve a great deal of shame for the mother, making her reluctant to divulge her experience to others, including her doctors and family.
Feelings of shame are not unique to perinatal depression. Stigma applies to other types of depressive and bipolar disorders and contributes to people not always receiving the necessary support and treatment for these disorders. In fact, the World Health Organization ranks both major depressive disorder (MDD) and bipolar disorder (BD) among the top 10 leading causes of disability worldwide. Further, MDD and BD carry a high risk of suicide. It is estimated that 25%–50% of people diagnosed with BD will attempt suicide at least once in their lifetimes (Goodwin & Jamison, 2007).
Everyone experiences brief periods of sadness, irritability, or euphoria. This is different than having a mood disorder, such as MDD or BD, which are characterized by a constellation of symptoms that causes people significant distress or impairs their everyday functioning.
Major Depressive Episode
A major depressive episode (MDE) refers to symptoms that co-occur for at least two weeks and cause significant distress or impairment in functioning, such as interfering with work, school, or relationships. Core symptoms include feeling down or depressed or experiencing anhedonia—loss of interest or pleasure in things that one typically enjoys. According to the fifth edition of the Diagnostic and Statistical Manual (DSM-5; APA, 2013), the criteria for an MDE require five or more of the following nine symptoms, including one or both of the first two symptoms, for most of the day, nearly every day:
These symptoms cannot be caused by physiological effects of a substance or a general medical condition (e.g., hypothyroidism).
Manic or Hypomanic Episode
The core criterion for a manic or hypomanic episode is a distinct period of abnormally and persistently euphoric, expansive, or irritable mood and persistently increased goal-directed activity or energy. The mood disturbance must be present for one week or longer in mania (unless hospitalization is required) or four days or longer in hypomania. Concurrently, at least three of the following symptoms must be present in the context of euphoric mood (or at least four in the context of irritable mood):
Manic episodes are distinguished from hypomanic episodes by their duration and associated impairment; whereas manic episodes must last one week and are defined by a significant impairment in functioning, hypomanic episodes are shorter and not necessarily accompanied by impairment in functioning.
Unipolar Mood Disorders
Two major types of unipolar disorders described by the DSM-5 (APA, 2013) are major depressive disorder and persistent depressive disorder (PDD; dysthymia). MDD is defined by one or more MDEs, but no history of manic or hypomanic episodes. Criteria for PDD are feeling depressed most of the day for more days than not, for at least two years. At least two of the following symptoms are also required to meet criteria for PDD:
Like MDD, these symptoms need to cause significant distress or impairment and cannot be due to the effects of a substance or a general medical condition. To meet criteria for PDD, a person cannot be without symptoms for more than two months at a time. PDD has overlapping symptoms with MDD. If someone meets criteria for an MDE during a PDD episode, the person will receive diagnoses of PDD and MDD.
Bipolar Mood Disorders
Figure 2: Bipolar disorders are characterized by cycles of high energy and depression. [Image: Brett Whaley, https://goo.gl/k4HTR7, CC BY-NC 2.0, https://goo.gl/VnKlK8]
Three major types of BDs are described by the DSM-5 (APA, 2013). Bipolar I Disorder (BD I), which was previously known as manic-depression, is characterized by a single (or recurrent) manic episode. A depressive episode is not necessary but commonly present for the diagnosis of BD I. Bipolar II Disorder is characterized by single (or recurrent) hypomanic episodes and depressive episodes. Another type of BD is cyclothymic disorder, characterized by numerous and alternating periods of hypomania and depression, lasting at least two years. To qualify for cyclothymic disorder, the periods of depression cannot meet full diagnostic criteria for an MDE; the person must experience symptoms at least half the time with no more than two consecutive symptom-free months; and the symptoms must cause significant distress or impairment.
It is important to note that the DSM-5 was published in 2013, and findings based on the updated manual will be forthcoming. Consequently, the research presented below was largely based on a similar, but not identical, conceptualization of mood disorders drawn from the DSM-IV (APA, 2000).
In a nationally representative sample, lifetime prevalence rate for MDD is 16.6% (Kessler, Berglund, Demler, Jin, Merikangas, & Walters, 2005). This means that nearly one in five Americans will meet the criteria for MDD during their lifetime. The 12-month prevalence—the proportion of people who meet criteria for a disorder during a 12-month period—for PDD is approximately 0.5% (APA, 2013).
Although the onset of MDD can occur at any time throughout the lifespan, the average age of onset is mid-20s, with the age of onset decreasing with people born more recently (APA, 2000). Prevalence of MDD among older adults is much lower than it is for younger cohorts (Kessler, Birnbaum, Bromet, Hwang, Sampson, & Shahly, 2010). The duration of MDEs varies widely. Recovery begins within three months for 40% of people with MDD and within 12 months for 80% (APA, 2013). MDD tends to be a recurrent disorder with about 40%–50% of those who experience one MDE experiencing a second MDE (Monroe & Harkness, 2011). An earlier age of onset predicts a worse course. About 5%–10% of people who experience an MDE will later experience a manic episode (APA, 2000), thus no longer meeting criteria for MDD but instead meeting them for BD I. Diagnoses of other disorders across the lifetime are common for people with MDD: 59% experience an anxiety disorder; 32% experience an impulse control disorder, and 24% experience a substance use disorder (Kessler, Merikangas, & Wang, 2007).
Women experience two to three times higher rates of MDD than do men (Nolen-Hoeksema & Hilt, 2009). This gender difference emerges during puberty (Conley & Rudolph, 2009). Before puberty, boys exhibit similar or higher prevalence rates of MDD than do girls (Twenge & Nolen-Hoeksema, 2002). MDD is inversely correlated with socioeconomic status (SES), a person’s economic and social position based on income, education, and occupation. Higher prevalence rates of MDD are associated with lower SES (Lorant, Deliege, Eaton, Robert, Philippot, & Ansseau, 2003), particularly for adults over 65 years old (Kessler et al., 2010). Independent of SES, results from a nationally representative sample found that European Americans had a higher prevalence rate of MDD than did African Americans and Hispanic Americans, whose rates were similar (Breslau, Aguilar-Gaxiola, Kendler, Su, Williams, & Kessler, 2006). The course of MDD for African Americans is often more severe and less often treated than it is for European Americans, however (Williams et al., 2007). Native Americans have a higher prevalence rate than do European Americans, African Americans, or Hispanic Americans (Hasin, Goodwin, Stinson & Grant, 2005). Depression is not limited to industrialized or western cultures; it is found in all countries that have been examined, although the symptom presentation as well as prevalence rates vary across cultures (Chentsova-Dutton & Tsai, 2009).
Figure 3: Adolescents experience a higher incidence of bipolar spectrum disorders than do adults. Making matters worse, those who are diagnosed with BD at a younger age seem to suffer symptoms more intensely than those with adult onset. [Image: CC0 Public Domain]
The lifetime prevalence rate of bipolar spectrum disorders in the general U.S. population is estimated at approximately 4.4%, with BD I constituting about 1% of this rate (Merikangas et al., 2007). Prevalence estimates, however, are highly dependent on the diagnostic procedures used (e.g., interviews vs. self-report) and whether or not sub-threshold forms of the disorder are included in the estimate. BD often co-occurs with other psychiatric disorders. Approximately 65% of people with BD meet diagnostic criteria for at least one additional psychiatric disorder, most commonly anxiety disorders and substance use disorders (McElroy et al., 2001). The co-occurrence of BD with other psychiatric disorders is associated with poorer illness course, including higher rates of suicidality (Leverich et al., 2003). A recent cross-national study sample of more than 60,000 adults from 11 countries, estimated the worldwide prevalence of BD at 2.4%, with BD I constituting 0.6% of this rate (Merikangas et al., 2011). In this study, the prevalence of BD varied somewhat by country. Whereas the United States had the highest lifetime prevalence (4.4%), India had the lowest (0.1%). Variation in prevalence rates was not necessarily related to SES, as in the case of Japan, a high-income country with a very low prevalence rate of BD (0.7%).
With regard to ethnicity, data from studies not confounded by SES or inaccuracies in diagnosis are limited, but available reports suggest rates of BD among European Americans are similar to those found among African Americans (Blazer et al., 1985) and Hispanic Americans (Breslau, Kendler, Su, Gaxiola-Aguilar, & Kessler, 2005). Another large community-based study found that although prevalence rates of mood disorders were similar across ethnic groups, Hispanic Americans and African Americans with a mood disorder were more likely to remain persistently ill than European Americans (Breslau et al., 2005). Compared with European Americans with BD, African Americans tend to be underdiagnosed for BD (and over-diagnosed for schizophrenia) (Kilbourne, Haas, Mulsant, Bauer, & Pincus, 2004; Minsky, Vega, Miskimen, Gara, & Escobar, 2003), and Hispanic Americans with BD have been shown to receive fewer psychiatric medication prescriptions and specialty treatment visits (Gonzalez et al., 2007). Misdiagnosis of BD can result in the underutilization of treatment or the utilization of inappropriate treatment, and thus profoundly impact the course of illness.
As with MDD, adolescence is known to be a significant risk period for BD; mood symptoms start by adolescence in roughly half of BD cases (Leverich et al., 2007; Perlis et al., 2004). Longitudinal studies show that those diagnosed with BD prior to adulthood experience a more pernicious course of illness relative to those with adult onset, including more episode recurrence, higher rates of suicidality, and profound social, occupational, and economic repercussions (e.g., Lewinsohn, Seeley, Buckley, & Klein, 2002). The prevalence of BD is substantially lower in older adults compared with younger adults (1% vs. 4%) (Merikangas et al., 2007).
Mood disorders are complex disorders resulting from multiple factors. Causal explanations can be attempted at various levels, including biological and psychosocial levels. Below are several of the key factors that contribute to onset and course of mood disorders are highlighted.
Figure 4: Romantic relationships can affect mood as in the case of divorce or the death of a spouse. [Image: CC0 Public Domain]
Research across family and twin studies has provided support that genetic factors are implicated in the development of MDD. Twin studies suggest that familial influence on MDD is mostly due to genetic effects and that individual-specific environmental effects (e.g., romantic relationships) play an important role, too. By contrast, the contribution of shared environmental effect by siblings is negligible (Sullivan, Neale & Kendler, 2000). The mode of inheritance is not fully understood although no single genetic variation has been found to increase the risk of MDD significantly. Instead, several genetic variants and environmental factors most likely contribute to the risk for MDD (Lohoff, 2010).
One environmental stressor that has received much support in relation to MDD is stressful life events. In particular, severe stressful life events—those that have long-term consequences and involve loss of a significant relationship (e.g., divorce) or economic stability (e.g., unemployment) are strongly related to depression (Brown & Harris, 1989; Monroe et al., 2009). Stressful life events are more likely to predict the first MDE than subsequent episodes (Lewinsohn, Allen, Seeley, & Gotlib, 1999). In contrast, minor events may play a larger role in subsequent episodes than the initial episodes (Monroe & Harkness, 2005).
Depression research has not been limited to examining reactivity to stressful life events. Much research, particularly brain imagining research using functional magnetic resonance imaging (fMRI), has centered on examining neural circuitry—the interconnections that allow multiple brain regions to perceive, generate, and encode information in concert. A meta-analysis of neuroimaging studies showed that when viewing negative stimuli (e.g., picture of an angry face, picture of a car accident), compared with healthy control participants, participants with MDD have greater activation in brain regions involved in stress response and reduced activation of brain regions involved in positively motivated behaviors (Hamilton, Etkin, Furman, Lemus, Johnson, & Gotlib, 2012).
Other environmental factors related to increased risk for MDD include experiencing early adversity (e.g., childhood abuse or neglect; Widom, DuMont, & Czaja, 2007), chronic stress (e.g., poverty) and interpersonal factors. For example, marital dissatisfaction predicts increases in depressive symptoms in both men and women. On the other hand, depressive symptoms also predict increases in marital dissatisfaction (Whisman & Uebelacker, 2009). Research has found that people with MDD generate some of their interpersonal stress (Hammen, 2005). People with MDD whose relatives or spouses can be described as critical and emotionally overinvolved have higher relapse rates than do those living with people who are less critical and emotionally overinvolved (Butzlaff & Hooley, 1998).
People’s attributional styles or their general ways of thinking, interpreting, and recalling information have also been examined in the etiology of MDD (Gotlib & Joormann, 2010). People with a pessimistic attributional style tend to make internal (versus external), global (versus specific), and stable (versus unstable) attributions to negative events, serving as a vulnerability to developing MDD. For example, someone who when he fails an exam thinks that it was his fault (internal), that he is stupid (global), and that he will always do poorly (stable) has a pessimistic attribution style. Several influential theories of depression incorporate attributional styles (Abramson, Metalsky, & Alloy, 1989; Abramson Seligman, & Teasdale, 1978).
Although there have been important advances in research on the etiology, course, and treatment of BD, there remains a need to understand the mechanisms that contribute to episode onset and relapse. There is compelling evidence for biological causes of BD, which is known to be highly heritable (McGuffin, Rijsdijk, Andrew, Sham, Katz, & Cardno, 2003). It may be argued that a high rate of heritability demonstrates that BD is fundamentally a biological phenomenon. However, there is much variability in the course of BD both within a person across time and across people (Johnson, 2005). The triggers that determine how and when this genetic vulnerability is expressed are not yet understood; however, there is evidence to suggest that psychosocial triggers may play an important role in BD risk (e.g., Johnson et al., 2008; Malkoff-Schwartz et al., 1998).
In addition to the genetic contribution, biological explanations of BD have also focused on brain function. Many of the studies using fMRI techniques to characterize BD have focused on the processing of emotional stimuli based on the idea that BD is fundamentally a disorder of emotion (APA, 2000). Findings show that regions of the brain thought to be involved in emotional processing and regulation are activated differently in people with BD relative to healthy controls (e.g., Altshuler et al., 2008; Hassel et al., 2008; Lennox, Jacob, Calder, Lupson, & Bullmore, 2004).
However, there is little consensus as to whether a particular brain region becomes more or less active in response to an emotional stimulus among people with BD compared with healthy controls. Mixed findings are in part due to samples consisting of participants who are at various phases of illness at the time of testing (manic, depressed, inter-episode). Sample sizes tend to be relatively small, making comparisons between subgroups difficult. Additionally, the use of a standardized stimulus (e.g., facial expression of anger) may not elicit a sufficiently strong response. Personally engaging stimuli, such as recalling a memory, may be more effective in inducing strong emotions (Isacowitz, Gershon, Allard, & Johnson, 2013).
Within the psychosocial level, research has focused on the environmental contributors to BD. A series of studies show that environmental stressors, particularly severe stressors (e.g., loss of a significant relationship), can adversely impact the course of BD. People with BD have substantially increased risk of relapse (Ellicott, Hammen, Gitlin, Brown, & Jamison, 1990) and suffer more depressive symptoms (Johnson, Winett, Meyer, Greenhouse, & Miller, 1999) following a severe life stressor. Interestingly, positive life events can also adversely impact the course of BD. People with BD suffer more manic symptoms after life events involving attainment of a desired goal (Johnson et al., 2008). Such findings suggest that people with BD may have a hypersensitivity to rewards.
Evidence from the life stress literature has also suggested that people with mood disorders may have a circadian vulnerability that renders them sensitive to stressors that disrupt their sleep or rhythms. According to social zeitgeber theory (Ehlers, Frank, & Kupfer, 1988; Frank et al., 1994), stressors that disrupt sleep, or that disrupt the daily routines that entrain the biological clock (e.g., meal times) can trigger episode relapse. Consistent with this theory, studies have shown that life events that involve a disruption in sleep and daily routines, such as overnight travel, can increase bipolar symptoms in people with BD (Malkoff-Schwartz et al., 1998).
Figure 5: A number of medications are effective in treating mood disorders. Meditation, exercise, counseling and other therapies also show effectiveness for some disorders. [Image: CC0 Public Domain]
There are many treatment options available for people with MDD. First, a number of antidepressant medications are available, all of which target one or more of the neurotransmitters implicated in depression.The earliest antidepressant medications were monoamine oxidase inhibitors (MAOIs). MAOIs inhibit monoamine oxidase, an enzyme involved in deactivating dopamine, norepinephrine, and serotonin. Although effective in treating depression, MAOIs can have serious side effects. Patients taking MAOIs may develop dangerously high blood pressure if they take certain drugs (e.g., antihistamines) or eat foods containing tyramine, an amino acid commonly found in foods such as aged cheeses, wine, and soy sauce. Tricyclics, the second-oldest class of antidepressant medications, block the reabsorption of norepinephrine, serotonin, or dopamine at synapses, resulting in their increased availability. Tricyclics are most effective for treating vegetative and somatic symptoms of depression. Like MAOIs, they have serious side effects, the most concerning of which is being cardiotoxic. Selective serotonin reuptake inhibitors (SSRIs; e.g., Fluoxetine) and serotonin and norepinephrine reuptake inhibitors (SNRIs; e.g., Duloxetine) are the most recently introduced antidepressant medications. SSRIs, the most commonly prescribed antidepressant medication, block the reabsorption of serotonin, whereas SNRIs block the reabsorption of serotonin and norepinephrine. SSRIs and SNRIs have fewer serious side effects than do MAOIs and tricyclics. In particular, they are less cardiotoxic, less lethal in overdose, and produce fewer cognitive impairments. They are not, however, without their own side effects, which include but are not limited to difficulty having orgasms, gastrointestinal issues, and insomnia.
Other biological treatments for people with depression include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation. ECT involves inducing a seizure after a patient takes muscle relaxants and is under general anesthesia. ECT is viable treatment for patients with severe depression or who show resistance to antidepressants although the mechanisms through which it works remain unknown. A common side effect is confusion and memory loss, usually short-term (Schulze-Rauschenbach, Harms, Schlaepfer, Maier, Falkai, & Wagner, 2005). Repetitive TMS is a noninvasive technique administered while a patient is awake. Brief pulsating magnetic fields are delivered to the cortex, inducing electrical activity. TMS has fewer side effects than ECT (Schulze-Rauschenbach et al., 2005), and while outcome studies are mixed, there is evidence that TMS is a promising treatment for patients with MDD who have shown resistance to other treatments (Rosa et al., 2006). Most recently, deep brain stimulation is being examined as a treatment option for patients who did not respond to more traditional treatments like those already described. Deep brain stimulation involves implanting an electrode in the brain. The electrode is connected to an implanted neurostimulator, which electrically stimulates that particular brain region. Although there is some evidence of its effectiveness (Mayberg et al., 2005), additional research is needed.
Several psychosocial treatments have received strong empirical support, meaning that independent investigations have achieved similarly positive results—a high threshold for examining treatment outcomes. These treatments include but are not limited to behavior therapy, cognitive therapy, and interpersonal therapy. Behavior therapies focus on increasing the frequency and quality of experiences that are pleasant or help the patient achieve mastery. Cognitive therapies primarily focus on helping patients identify and change distorted automatic thoughts and assumptions (e.g., Beck, 1967). Cognitive-behavioral therapies are based on the rationale that thoughts, behaviors, and emotions affect and are affected by each other. Interpersonal Therapy for Depression focuses largely on improving interpersonal relationships by targeting problem areas, specifically unresolved grief, interpersonal role disputes, role transitions, and interpersonal deficits. Finally, there is also some support for the effectiveness of Short-Term Psychodynamic Therapy for Depression (Leichsenring, 2001). The short-term treatment focuses on a limited number of important issues, and the therapist tends to be more actively involved than in more traditional psychodynamic therapy.
Patients with BD are typically treated with pharmacotherapy. Antidepressants such as SSRIs and SNRIs are the primary choice of treatment for depression, whereas for BD, lithium is the first line treatment choice. This is because SSRIs and SNRIs have the potential to induce mania or hypomania in patients with BD. Lithium acts on several neurotransmitter systems in the brain through complex mechanisms, including reduction of excitatory (dopamine and glutamate) neurotransmission, and increasing of inhibitory (GABA) neurotransmission (Lenox & Hahn, 2000). Lithium has strong efficacy for the treatment of BD (Geddes, Burgess, Hawton, Jamison, & Goodwin, 2004). However, a number of side effects can make lithium treatment difficult for patients to tolerate. Side effects include impaired cognitive function (Wingo, Wingo, Harvey, & Baldessarini, 2009), as well as physical symptoms such as nausea, tremor, weight gain, and fatigue (Dunner, 2000). Some of these side effects can improve with continued use; however, medication noncompliance remains an ongoing concern in the treatment of patients with BD. Anticonvulsant medications (e.g., carbamazepine, valproate) are also commonly used to treat patients with BD, either alone or in conjunction with lithium.
There are several adjunctive treatment options for people with BD. Interpersonal and social rhythm therapy (IPSRT; Frank et al., 1994) is a psychosocial intervention focused on addressing the mechanism of action posited in social zeitgeber theory to predispose patients who have BD to relapse, namely sleep disruption. A growing body of literature provides support for the central role of sleep dysregulation in BD (Harvey, 2008). Consistent with this literature, IPSRT aims to increase rhythmicity of patients’ lives and encourage vigilance in maintaining a stable rhythm. The therapist and patient work to develop and maintain a healthy balance of activity and stimulation such that the patient does not become overly active (e.g., by taking on too many projects) or inactive (e.g., by avoiding social contact). The efficacy of IPSRT has been demonstrated in that patients who received this treatment show reduced risk of episode recurrence and are more likely to remain well (Frank et al., 2005).
Everyone feels down or euphoric from time to time. For some people, these feelings can last for long periods of time and can also co-occur with other symptoms that, in combination, interfere with their everyday lives. When people experience an MDE or a manic episode, they see the world differently. During an MDE, people often feel hopeless about the future, and may even experience suicidal thoughts. During a manic episode, people often behave in ways that are risky or place them in danger. They may spend money excessively or have unprotected sex, often expressing deep shame over these decisions after the episode. MDD and BD cause significant problems for people at school, at work, and in their relationships and affect people regardless of gender, age, nationality, race, religion, or sexual orientation. If you or someone you know is suffering from a mood disorder, it is important to seek help. Effective treatments are available and continually improving. If you have an interest in mood disorders, there are many ways to contribute to their understanding, prevention, and treatment, whether by engaging in research or clinical work.
Books: Recommended memoirs include A Memoir of Madness by William Styron (MDD); Noonday Demon: An Atlas of Depression by Andrew Solomon (MDD); and An Unquiet Mind: A Memoir of Moods and Madness by Kay Redfield (BD).
Web: Visit the Association for Behavioral and Cognitive Therapies to find a list of the recommended therapists and evidence-based treatments.
Web: Visit the Depression and Bipolar Support Alliance for educational information and social support options.