EARLY LIFE STRESS AND DEPRESSION Childhood trauma may lead to neurobiologically unique mood disorders
Adults with a history of child abuse or neglect may respond differently than other depressed patients to the usual treatments.
Brain structure changes? In addition to the neuroendocrine changes observed in patients with ELS, there is evidence that ELS may also alter brain structure. Reduced hippocampal volume is found in some but not all patients with unipolar depression.29 In patients with a history of depression who also have hippocampal atrophy, the extent of atrophy is greater in patients with higher total lifetime duration of depression.30,31
Patients with ELS also have been found to have decreased hippocampal volume.32,33 However, previous structural imaging studies have not controlled for the presence of ELS when attempting to determine the relationship between depression and structural changes in the hippocampus, and this methodologic confound may explain in part the inconsistent relationship between altered hippocampal volume and depression.
To evaluate this hypothesis, hippocampal volume was measured in depressed women with and without a history of ELS and in a control group of women. Reduced hippocampal volume was found to occur solely in depressed women with a history of ELS. Depressed women without ELS and women from the control group had similar hippocampal volumes.34 These data suggest that previous reports of reduced hippocampal size in patients with depression may in fact be related to a history of ELS rather than depression.
Treatment implications
The data discussed in this paper indicate that patients with depression and a history of ELS may constitute a unique subgroup among depressed patients as a whole. A growing body of evidence suggests that depressed patients with ELS may also be unique with respect to their response to treatment.
ELS has been found to impact the clinical response of patients to pharmacotherapy with either dysthymia or depression.35,36 Further, patients with depression and a history of ELS have been reported to exhibit increased rates of relapse following treatment of depression.37 The course of depression in individuals with ELS is often characterized by chronicity.
ELS and therapeutic response, Recently, our group has sought to determine whether ELS in patients with chronic depression moderates their response to pharmacotherapy or psychotherapy.38 In this study, data from a large multicenter trial39 originally designed to compare the relative efficacy of pharmacotherapy (nefazodone), psychotherapy (Cognitive Behavioral Analysis System of Psychotherapy), or their combination in the treatment of chronic depression was reanalyzed by stratifying patients based on the presence or absence of ELS. In the overall sample of patients with chronic depression, psychotherapy and pharmacotherapy were comparable in efficacy but significantly less effective than their combination.
ELS in chronically depressed patients was highly prevalent. Approximately one-third experienced loss of a parent before age 15, 45% experienced childhood physical abuse, 16% experienced childhood sexual abuse, and 10% experienced neglect. Most significantly, depressed patients with a history of ELS had a superior response to psychotherapy alone compared with antidepressant monotherapy. In addition, combination therapy was only slightly more effective than psychotherapy alone in the group of depressed patients with ELS.
These data suggest that ELS is common in the population of patients with chronic depression and that psychotherapy is a critical element in the treatment of depressed patients with ELS40 (Box). However, it will be important in future studies to ascertain whether the differences in treatment response for psychotherapy compared with antidepressant in patients with ELS and depression are able to be replicated with the SSRI class of antidepressants.
Assessment of trauma and neglect should be a standard component of the diagnostic interview. Patients with a history of early life stress (ELS) may present for treatment with complaints that represent depression, anxiety, or substance abuse, but they may also have complicated presentations involving psychotic or dissociative symptoms, reflecting the diagnostic comorbidity in this population.
How to identify ELS. No standardized office-based screening tools exist for ELS, and clinical interviewing is the primary means of assessing exposure to ELS. A common error in history-taking with this population, particularly in high-volume settings, is to merely ask patients whether they were abused or neglected as children or to elaborate only very slightly on this aspect of the history. We risk not finding information that is critical to understanding our patients if we assume they share a common definition of abuse and neglect with us, can recognize such events in their personal history, and are willing to share that information with us.
When framing questions about abuse or neglect, it is important to remember that our own sense of what constitutes neglect or abuse may be very different from what a patient thinks of as neglect or abuse. For example, some patients may not consider their experience as a child abusive because of a distorted sense of responsibility, possibly further exaggerated by comorbid depression (ie, “My parents locked me in the closet overnight all the time when I was a child because I deserved it.”)
Other patients may try to minimize the impact of the experience or the responsibility of the perpetrator and attempt to normalize it (ie, “My uncle used to touch me between my legs in the swimming pool but he didn’t mean anything by it; he did it to everybody.”)
Avoiding ‘false memories.’ As important as it is to identify abuse or neglect when it has occurred, it is equally important to avoid intensifying the impact of an incident of abuse or, worse, creating a “false memory” of abuse in suggestible patients (bearing in mind that there is no definitive way to exclude the presence of “suggestibility” in patients). Our task as clinicians is to help patients correctly identify experiences of abuse and neglect and understand their response to these experiences clinically to facilitate case formulation and a treatment plan.
Creating a therapeutic alliance. Abuse and neglect during early life fundamentally alter the core assumptions that patients have about trust and safety in their relationships with others. Not only does this potentially impact the disclosure by patients of the nature and extent of trauma they have experienced, but it can also slow the formation of an effective therapeutic alliance.
To that end, asking open-ended questions about neglect and specific forms of abuse, creating an atmosphere of safety and trust, and a warm, empathic, nonjudgmental manner are central to the accurate assessment of ELS and provide the foundation for treatment by establishing an effective therapeutic alliance.
Optimal treatment. No published clinical trials have specifically compared the relative efficacy of particular forms of psychotherapy or pharmacotherapy for depressed patients with a history of ELS. However, it is clear from the available data that psychotherapy should be considered a core component of treatment for these patients.
Because psychiatric comorbidity is common in these patients, their treatment should be individualized in a manner that accounts for and addresses depression as well as associated diagnoses such as panic disorder or posttraumatic stress disorder (PTSD) with disorder-specific psychotherapy. Pharmacotherapy in combination with psychotherapy may also be helpful to patients with ELS and depression, though definitive data are lacking.
Judicious combination of medications such as antidepressants and benzodiazepines, particularly in patients with comorbid panic or PTSD, in concert with psychotherapy probably constitutes optimal treatment.
