Toxic mix of loss, humilition could spark depression, VCU study finds

Romantic breakups, for men and women, are the worst trigger

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RICHMOND, Va. – In addition to serious loss, humiliating events in a person’s life – particularly involving romantic breakups – appear to be strongly linked to risk for major depression, according to a study of more than 7,300 twins by researchers at Virginia Commonwealth University.

The study, published today (Aug. 11) in the Archives of General Psychiatry, is the largest study to date to use a rating system to assess the role that highly specific groups of

stressful life events play in sparking depression, anxiety and a combination of the two psychiatric disorders in both men and women. Previous studies involved much smaller samples and examined only women and depression.

“Love can make our life wonderful, but it also can make us miserable,” says psychiatric geneticist Kenneth S. Kendler, M.D., professor of psychiatry and director of the Virginia Institute for Psychiatric and Behavioral Genetics at VCU. Kendler was the lead author on the study.

“When we looked at stressful life events that predisposed men and women to the onset of episodes of depression, the most toxic combination was loss and humiliation that in some way directly devalued the individual in a core role,” Kendler said. “For both men and women, that combination was twice as potent for predisposing to depression as pure loss alone, such as death of a loved one. Most cases of combined loss and humiliation involved romantic breakups.

“For example, if your marriage breaks up, that’s a loss, and it’s reasonable to expect that you will experience aspects of grief, including sadness and loss of appetite. If your marriage breaks up, and your husband moves into a house a few doors away with a woman half his age, and he shows off his new girlfriend to your friends and family – that’s grief combined with humiliation. That combination is especially strongly linked to risk for a depressive episode.”

VCU researchers interviewed 7,322 male and female twins registered with VCU’s Mid-Atlantic Twin Registry (MATR) over several years in the early to mid 1990s to assess which stressful life events in the year preceding the interview appeared to have been linked to episodes of depression and anxiety. The twins at the time ranged in age from about 20 to 60. Of the 98,592 “person-months” considered, 4,251 person-months, or 4.3 percent of the total, contained a stressful life event.  

Using a five-point scale, the researchers rated stressful life events that were grouped into four broad dimensions of humiliation, entrapment, loss and danger and 15 categories that included 11 “personal” events (such as assault, divorce, separation, injury and job loss) and four “network” events (such as the death of someone close). On the scale, “0” meant the event had not occurred in the preceding year, and “4” meant that a severe level of the event had occurred. They matched those event ratings against three types of psychiatric episodes reported by the twins in the year preceding the interview: major depression, anxiety lasting at least two weeks and mixed depression/anxiety. 

Researchers found:

  • The risk for an episode of depression or a mixed episode of depression and anxiety was significantly increased in a month with high ratings for loss and humiliation. This was particularly true if the humiliation involved the split up of a relationship initiated by the other person or prompted by an infidelity or violence. The risk of depression that month was between 21 percent and 22 percent compared with a 10 percent risk for a depressive episode in a month where a loved one died but no humiliating event occurred. The impact of the events was short-lived and appeared to affect the risk for depression only in the month that the event occurred.

  • The risk for an episode of anxiety was significantly increased in the month following a month with high ratings for loss and danger. 

  • High ratings of entrapment predicted only onsets of mixed episodes of depression and anxiety and only within the month that the event occurred.

No sex differences were seen in the prediction of episodes of illness by event categories.

The study was funded by grants from the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

About the Virginia Institute for Psychiatric and Behavioral Genetics

The Virginia Institute for Psychiatric and Behavioral Genetics is a multi-disciplined, integrated research program of VCU’s Departments of Psychiatry and Human Genetics, focused on identifying genes and environments that cause psychiatric diseases and behavioral differences. For more, see