In the DSM-5, depressive disorders include a number of conditions that can cause persistent sad, empty, or irritable moods, accompanied by physical and cognitive changes that affect the person's ability to function in everyday life. People often speak of feeling “depressed,” and of course everyone feels sad from time to time. These feelings, however, are a far cry from serious clinical depression.

Major depression involves emotional, behavioral, cognitive, and physical changes severe enough to disrupt a person's ordinary functioning. Some episodes can last as long as 20 weeks, subside, and later recur. People with major depression feel despairing and worthless. They feel unable to get up and do things; it takes an enormous effort even to get dressed. They may overeat or stop eating, have difficulty falling asleep or sleeping through the night, have trouble concentrating, and feel tired all the time. They lose interest in activities that usually give them satisfaction and pleasure.

One symptom of major depression is recurring thoughts of death, leading some sufferers to try to commit suicide. In the United States, suicide is the second leading cause of death among people ages 15 to 24, after accidents (Centers for Disease Control and Prevention, 2013). Most people with suicidal thoughts do not really want to die; they want relief from the terrible pain of feeling that nobody cares, that life is not worth living, that they have been failures to their families, and that they are a burden on those they love. One team of psychologists looked up the “warning signs of suicide” that can be found on the Internet. Of the 75 supposed indicators they found, only two are central: feelings of hopelessness and perceived burdensomeness (Mandrusiak et al., 2006; Van Orden et al., 2006).

Major depression occurs at least twice as often among women as among men, all over the world. However, because women are more likely than men to talk about their feelings and more likely to seek help, depression in males (who are more likely to commit suicide) is probably underdiagnosed. Men who are depressed often try to mask their feelings by withdrawing, abusing alcohol or other drugs, driving recklessly, or behaving violently (Canetto & Cleary, 2012). As Susan Nolen-Hoeksema, a leading depression researcher, put it, “Women think and men drink.” The biological underpinnings of depression are discussed in the video Depression.

At the opposite pole from depression is mania, an abnormally high state of exhilaration. Mania is not the normal joy of being in love or winning the Pulitzer Prize. Instead of feeling fatigued and listless, a manic person is excessively wired and often irritable when thwarted. Instead of feeling hopeless and powerless, the person feels powerful and is full of plans; but these plans are usually based on delusional ideas, such as thinking that she or he has invented something that will solve the world's energy problems. People in a state of mania often get into terrible trouble, for example, by going on extravagant spending sprees or making rash decisions.

When people experience at least one episode of mania, typically alternating with episodes of depression, they are said to have bipolar disorder (formerly called manic-depressive disorder). The great humorist Mark Twain had bipolar disorder, which he described as “periodical and sudden changes of mood . . . from deep melancholy to half-insane tempests and cyclones.” Other writers, artists, musicians, and scientists have also suffered from this disorder (Jamison, 1992). During the highs, many of these creative people produce their best work, but the price of the lows is disastrous relationships, bankruptcy, and sometimes suicide.

The DSM-5 has put bipolar disorders into their own category, as a bridge between depressive disorders and schizophrenia. The reason, as research is finding, is that symptoms and causes of bipolar disorder can overlap with those of depression and schizophrenia (and other disorders as well).

One of the great mysteries of depression is that most people who undergo a “depressing” experience do not become clinically depressed, and many people who are clinically depressed have not had objectively “depressing” experiences (Monroe & Reid, 2009). Most researchers thus emphasize a vulnerability–stress model of depression: how a person's vulnerabilities (genetic predispositions, personality traits, or habits of thinking) may interact with stressful events (e.g., violence, abuse, death of a loved one, or losing a job) to produce a given case (see Figure 15.1).

Let's consider the evidence for the central contributing factors to depression:

1. Genetic predispositions. Major depression is a moderately heritable disorder, so genes must be involved for some individuals. But so far the search for specific genes has been unsuccessful. One focus of investigation has been the genes that regulate serotonin, a neurotransmitter involved in mood. An early theory held that depression results from abnormally low levels of this neurotransmitter. However, many years of research have failed to support the notion that depression results from a simple neurotransmitter deficiency. Depleting animals of serotonin does not induce depression, nor does increasing brain serotonin necessarily alleviate it. The fact that some antidepressants raise serotonin levelsdoes not mean that low serotonin levels caused the depression—a common but mistaken inference (Kirsch, 2010; Lacasse & Leo, 2005).

   In 2003, in a study of 847 New Zealanders who had been followed from birth to age 26, researchers reported that those who had a short form of a serotonin receptor gene called 5-HTT were much more likely to become severely depressed in the aftermath of extremely stressful events than were people with a long form of this gene (Caspi et al., 2003). But subsequent meta-analyses of direct replications of the New Zealand study found no links among the 5-HTT gene, life stresses, and depression (Duncan & Keller, 2011; Risch et al., 2009).

   Nonetheless, research into gene–environment interactions continues. Children who are at high genetic risk for developing depression (or aggressive disorders or alcohol abuse) may grow up just fine if they have good parents who monitor and control their children's vulnerabilities to these disorders (Dick et al., 2011; Dougherty et al., 2011). Moreover, the relative influence of genetic and environmental factors varies over the lifespan. A review of eight studies of identical twins found that although genetic predispositions predicted the twins' levels of depression and anxiety in childhood and young adulthood, by middle adulthood environmental factors and life experiences had become more powerful influences (Kendler et al., 2011).

2. Violence, childhood physical abuse, and parental neglect. One of the most powerful environmental factors associated with clinical depression is repeated experience with violence. Inner-city adolescents of both sexes who are exposed to high rates of violence in their families or communities report higher levels of depression and more attempts to commit suicide than those who are not subjected to constant violence (Mazza & Reynolds, 1999). The World Health Organization conducted a massive international research project in 21 countries, involving more than 100,000 people over age 18. In rich and poor countries alike, the strongest predictors of suicide and attempted suicide were repeated experiences of sexual abuse and violence in childhood and adolescence (Stein et al., 2010).

   The effects of maltreatment in childhood on later depression are independent of all other childhood and adult risk factors (Brown & Harris, 2008; Widom, DuMont, & Czaja, 2007). A mechanism that might explain this increased risk is that prolonged stress in childhood puts the body's responses to stress in overdrive, so that it overproduces the stress hormone cortisol (Gotlib et al., 2008). People who are depressed tend to have high levels of cortisol, which can affect the hippocampus and amygdala, causing mood and memory abnormalities.

   Among adults, domestic violence takes a particular toll on women. A longitudinal study that followed men and women from ages 18 to 26 compared those in physically abusive relationships with those in nonabusive ones. Although depressed women were more likely to enter abusive relationships to begin with, involvement in a violent relationship independently increased their rates of depression and anxiety—but, interestingly, not men's (Ehrensaft, Moffitt, & Caspi, 2006).

3. Losses of important relationships. A third line of investigation emphasizes the loss of important relationships in setting off depression in vulnerable individuals. When an infant is separated from a primary attachment figure, the result is not only despair and passivity, but also harm to the immune system, which can later lead to depressive illness (Hennessy, Schiml-Webb, & Deak, 2009). Many people suffering from depression have a history of separations, losses, rejections, and impaired, insecure attachments (Cruwys et al., 2014; Hammen, 2009; Nolan, Flynn, & Garber, 2003; Weissman, Markowitz, & Klerman, 2000).

4. Cognitive habits. Finally, depression involves specific, negative ways of thinking about one's situation (Beck, 2005; Mathews & MacLeod, 2005). Depressed people typically believe that their situation is permanent (“Nothing good will ever happen to me”) and uncontrollable (“I'm depressed because I'm ugly and horrible and I can't do anything about it”). Expecting nothing to get better, they do nothing to improve their lives and therefore remain unhappy. When depressed and nondepressed people are put into a sad mood and given a choice between looking at sad faces or happy faces, depressed people choose the sad faces—a metaphor for how they process the world in general, attending to everything that confirms the gloominess of life rather than any of its joys (Joormann & Gotlib, 2007). And when asked to recall happier times, nondepressed people cheer up, but depressed people feel even worse, as if the happy memory makes them feel that they will never be happy again (Joormann, Siemer, & Gotlib, 2007).

   The cognitive biases associated with depression are not just correlates of the disorder. Longitudinal studies show that they play a causal role, interacting with severe life stresses to generate further depressive episodes (Hallion & Ruscio, 2011; Monroe et al., 2007). Depressed people, especially if they also have low self-esteem, tend to ruminate—brooding about everything that is wrong in their lives, persuading themselves that no one cares about them, and dwelling on reasons to feel hopeless. They have trouble preventing these thoughts from entering and remaining in their memory, which keeps them stewing in negative perceptions and unhappy past events (Joormann, Levens, & Gotlib, 2011; Kuster, Orth, & Meier, 2012; Moore et al., 2013). In contrast, nondepressed people who undergo stressful events are usually able to distract themselves, look outward, and seek solutions. Beginning in adolescence, women are much more likely than men to develop a ruminating, introspective style, which contributes both to longer-lasting depressions in women and to the sex difference in reported rates (Nolen-Hoeksema, 2004).

The factors we have described—genetics, violence, loss of important relationships, and cognitive habits and biases—combine in different ways to produce any given case of depression. That is why the same sad event—such as flunking a course, being dumped by a lover, or losing a job—can affect two people entirely differently: One rolls with the punch and another is knocked flat.