NESTTD Keynote April 30th 2011
June 27, 2011Keynote: Pierre Janet Memorial Lecture ISSTD 10/18/10
November 21, 2010Delayed Onset of Depression
June 15, 2009Teicher MH, Samson JA, Polcari A. Andersen SL. Length of time between onset of childhood sexual abuse and emergence of depression in a young adult sample. Journal of Clinical Psychiatry 2009; 70(5): 684-691
Synopsis
Depression is the most extensively documented outcome of exposure to CSA in adults (1), but in children the most discernible manifestations are sexualized behaviors rather than depression or PTSD (1). Despite the numerous studies demonstrating an association between exposure to CSA and emergence of depression, we are not aware of any studies that have specifically reported on the length of time between exposure to CSA and development of major depression. There are several possibilities. One is that depression follows rapidly on the heels of exposure to CSA. Another possibility is that depression emerges after exposure or risk of exposure to CSA has abated. A third possibility is that CSA does not directly lead to depression, but that it sensitizes the individual, enhancing their risk of developing depression as they pass through adolescents into adulthood as part of a neuromaturational process (2). A fourth possibility is that CSA could both sensitize and accelerate the process leading to an earlier age of onset, as has been reported to occur in patients with bipolar (3) or substance abuse disorders (4). Finally, episodes of major depression may emerge in sensitized individuals only if they are exposed to new losses or traumas, resulting in a variable onset times.
Determining the temporal relationship between CSA and onset of depression is difficult, as CSA usually occurs in individuals who have been, or will be, exposed to multiple other forms of trauma5, 6. However, delineating the time course is a fundamental prerequisite for designing intervention strategies to prevent or minimize the long-term sequelae of abuse and for interrupting the cycle of violence. To begin to address this issue we retrospectively examined the temporal relationship between CSA and depression in this group of 29 women who were exposed to CSA but to no other forms of trauma or severe early stress. These subjects were 20 ± 1.3 years old. All were in college, and 90% came from a middle class or higher socioeconomic status family (SES 2.3 ± 1.0). Reported perpetrators were part of the extended family and/or members of the community, with only three perpetrators being step-parents. None of the subjects in this sample reported experiencing CSA by their biological parents.
Psychiatric history was assessed by certified mental health clinicians using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) (7) and the Diagnostic Interview for Borderline Patients (DIB) (8). Age of onset was assessed as a part of this interview, which can be reliably determined through this form of assessment (9, 10). Kaplan-Meier analysis (SPSS version 11.0) provided mean survival time (±95% confidence interval [CI]) for onset of CSA, and from onset of CSA to emergence of depression.
Subjects who developed major depression (n=18) had the onset occur between 10–20 years of age (mean survival 15.0 years; 95% CI: 13.6–16.4 years). The average time from onset of CSA to onset of major depression, in those who developed depression, was 9.2 ± 3.6 years. Mean survival time from onset of CSA to onset of depression for the entire sample was 11.47 years (95% CI: 9.80–13.13 years). Mean survival from offset of CSA (first episode if there were multiple perpetrators) was 9.55 years (95% CI: 7.45–11.65 years). Figure 1 illustrates the number of cases with a history of depression who experienced CSA in a given year, and the cumulative prevalence of depression. Note that many of the subjects who went on to develop major depression experienced CSA at ages 5 and 6, and that 56% of depressive episodes began between 12–15 years of age.
Figure 1. Age of abuse and cumulative incidence of depression for 18 CSA subjects developing depression. Red line and left axis indicate number of subjects exposed to CSA at each age. Blue shaded area and right axis indicate the percentage of subjects who had an episode of major depression prior to or during each year of age (11).
The key finding of this formative study is that episodes of major depression did not immediately occur following exposure to CSA, but took several years to emerge. Further, the onset of depression did not directly coincide with the abatement of CSA. Rather, there was typically a long delay between exposure to CSA and onset of depression, with a surge in new cases occurring between 12–15 years of age. This is somewhat earlier than the peak surge of newly emergent cases reported to occur in a prospective longitudinal study of a contemporary birth cohort (12). Overall, these findings are compatible with the hypothesis that CSA sensitizes the individual to later emergence of depression during adolescence, and that it shifts the peak period of risk from mid-adolescence to early adolescence. This finding is consistent with a previous report of earlier age of onset of depression in women with histories of childhood abuse (13). Clinically, this is important information as it shows that there may be substantial time available in which to potentially intervene to minimize or preempt the most common major psychiatric consequences of CSA.
References
1. Putnam FW. Ten-year research update review: child sexual abuse. J Am Acad Child Adolesc Psychiatry 2003;42:269-278
2. Andersen SL, Teicher MH. Stress, sensitive periods and maturational events in adolescent depression. Trends Neurosci 2008;31:183-191
3. Post RM, Leverich GS, Xing G, Weiss RB. Developmental vulnerabilities to the onset and course of bipolar disorder. Dev Psychopathol 2001;13:581-598.
4. Dube SR, Felitti VJ, Dong M, et al. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. Pediatrics 2003;111:564-572
5. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med 1998;14:245-258
6. Teicher MH, Samson JA, Polcari A, McGreenery CE. Sticks, stones, and hurtful words: relative effects of various forms of childhood maltreatment. Am J Psychiatry 2006;163:993-1000
7. Bremner JD, Steinberg M, Southwick SM, et al. Use of the Structured Clinical Interview for DSM-IV Dissociative Disorders for systematic assessment of dissociative symptoms in posttraumatic stress disorder. Am J Psychiatry 1993;150:1011-1014
8. Gunderson JG, Kolb JE, Austin V. The diagnostic interview for borderline patients. Am J Psychiatry 1981;138:896-903
9. Farrer LA, Florio LP, Bruce ML, et al. Reliability of self-reported age at onset of major depression. J Psychiatr Res 1989;23:35-47
10. Prusoff BA, Merikangas KR, Weissman MM. Lifetime prevalence and age of onset of psychiatric disorders: recall 4 years later. J Psychiatr Res 1988;22:107-117
11. Teicher MH, Samson JA, Polcari A, Andersen SL. Length of time between onset of childhood sexual abuse and emergence of depression in a young adult sample: a retrospective clinical report. J Clin Psychiatry 2009
12. Hankin BL, Abramson LY, Moffitt TE, et al. Development of depression from preadolescence to young adulthood: emerging gender differences in a 10-year longitudinal study. J Abnorm Psychol 1998;107:128-140
13. Gladstone GL, Parker GB, Mitchell PB, et al. Implications of childhood trauma for depressed women: an analysis of pathways from childhood sexual abuse to deliberate self-harm and revictimization. Am J Psychiatry 2004;161:1417-1425
Parental Verbal Abuse Affects Brain White Matter
January 17, 2009We have just published findings from my laboratory that are beginning to illuminate the neurobiological effects of exposure to parental verbal abuse. We had previously shown that exposure to high levels of parental verbal abuse had the same impact (based on symptom ratings) as witnessing domestic violence and extrafamilial sexual abuse. It had somewhat more impact than exposure to parental physical abuse, but less impact than familial sexual abuse. Hence, it appears to be a potent form of childhood adversity.
White Matter Tract Abnormalities in Young Adults Exposed to Parental Verbal Abuse
Synopsis
In this study we used a new MRI technique called diffusion tensor imaging (DTI) to ascertain whether exposure to a high level of parental verbal abuse (PVA) was associated with abnormalities in brain white matter (WM) tract integrity. The brain consists of regions of gray matter that contains the cell bodies and dendritic branches of neurons, and white matter, which are the myelinated axonal fiber tracts providing communication between neurons in different gray matter regions. We screen 1271 healthy young adults for exposure to childhood adversity, and collected DTI (Siemens 3.0 T Trio Scanner) on 16 unmedicated subjects with a history of high-level exposure to PVA but no other form of maltreatment (4M/12F, mean age 21.9±2.4 yrs), and 16 healthy controls (5M/11F, 21.0±1.6 yrs). Group differences in fractional anisotropy (FA), covaried by parental education and income, were evaluated using tract-based spatial statistics (TBSS), and correlated with symptom ratings and verbal IQ. FA is an index of the integrity of the fiber pathway. Reduced FA may indicate a reduction in myelin, number of axons, or diameter of axons.
Three WM tracts had significantly reduced FA: (1) arcuate fasciculus in left superior temporal gyrus, (2) cingulum bundle in the fusiform gyrus by the posterior tail of the left hippocampus, and (3) the left body of fornix. FA values were strongly associated with the maximal PVA scores (r=-0.806, P<10-7; r=-0.658, P<.0001; r=-0.584, P<.0001, respectively).
Figure 1. Three white matter tract regions (shown in red) that differed significantly in fractional anisotropy (FA) between subjects with history of exposure to high levels of parental verbal aggression and healthy controls. Region 1 contained fibers from arcuate fasciculus. Region 2 contained fibers from the cingulum bundle near the tail of the hippocampus. Region 3 is part of the left fornix (hippocampal efferents). Green shows the mean FA skeleton and background image is in MNI 152. Tractography from representative subjects show tracts passing through the region identified by TBSS.
FA in region 1 correlated with verbal IQ (r=0.405, P<.03). The arcuate fasciculus is the fiber pathway that connects Wenicke’s area in the temporal lobe to Broca’s area in the frontal lobe. It plays an important role in verbal comprehension and communication. FA in region 2 was inversely associated with ratings of depression (r=–0.442), dissociation (r=–0.447), and limbic irritability(r=–0.483). The cingulum bundle is the most prominent tract of the limbic lobe, and connects the limbic lobe with the neocortex, particularly the cingulate gyrus. FA in region 3 was inversely correlated with anxiety (r=–0.36) and somatization (r=–0.371). The fornix is a pathway that interconnects hippocampus with the septal area and mammillary bodies, and is known to play a role in anxiety and memory. Interestingly, the hippocampus receives serotonin fibers from the midbrain raphe via two pathways: the cingulum bundle (which predominantly innervates dorsal hippocampus), and the fornix (which innervates all portions). Hence, two of the fiber tracts with segments of reduced FA in PVA subjects, provide pathways for serotonin fibers to innervate the hippocampus.
This study provides the first evidence that high levels of parental verbal aggression may be a form of abuse or adversity that alters trajectories of brain development. It supports our previous hypothesis that different forms of childhood maltreatment will exert some comparable an array of consistent neurobiological effects (particularly on limbic regions or connection) as they are all stressors. However, different forms of abuse will also have some unique effects based on sensory systems activated that convey the aversive stimulus to specific parts of the brain that process and interpret the information.
Support
This work was supported, in part, by National Institute of Mental Health RO1 grants MH53636 and MH-66222, and National Institute of Drug Abuse RO1 grants DA-016934 and DA-017846 to MHT.
Abuse and Sensitive Periods
December 14, 2008Research from my laboratory, and from other labs here and abroad, have shown that exposure to childhood abuse is associated with alterations in brain structure and function. This research has largely focused on brain regions known to be susceptible to the effects of stress, such as the hippocampus. We have recently expanded our knowledge regarding the potential adverse effects of abuse by publishing the first preliminary data indicating that the neurobiological consequences of abuse depend on the age of exposure (Andersen et al 2008).
Andersen SL, Tomada A, Vincow ES, Valente E, Polcari A, Teicher MH (2008): Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. J Neuropsychiatry Clin Neurosci 20:292-301.
Synopsis:
Childhood Abuse and Regional Brain Development: Evidence for Sensitive Periods
Martin H. Teicher, Susan L. Andersen, Akemi Tomada, Evelyn Vincow, Elizabeth Valente, & Ann Polcari
Department of Psychiatry, Harvard Medical School; Developmental Biopsychiatry Research Program, McLean Hospital, Belmont MA 02478
Background
The brain is molded by experiences that occur throughout the lifespan. However, there are particular stages of development when experience exerts either a maximal (sensitive period) or essential (critical period) effect. Little direct evidence exists for sensitive or critical periods in human brain development. Based on differential rates of maturation specific brain regions should have their own unique periods of sensitivity to the effects of early experiences such as stress.
To ascertain if this is true in humans, the size of apriori selected target regions were measured from high-resolution volumetric MRI scans (1.5 T GE Echospeed) from unmedicated collegiate females with a history of repeated childhood sexual abuse and healthy sociodemographically comparable controls.
Subjects
Physically healthy, unmedicated, right-handed individuals aged 18–22 years with history of 3 or more episodes of forced contact childhood sexual abuse (CSA) prior to age 18. Subjects had no history of neurological disorders; psychotic disorders; pregnancy; past or present alcohol/substance abuse; in utero exposure to alcohol or drugs; complication during prenancy or delivery; physical abuse above shoulders; or exposure to any other forms of trauma. Abused and control subjects were predominantly middle class or above (96%) and the two groups were similar in measures of socioeconomic status (Hollingshead index (23): 2.3±0.9 versus 2.0±0.6; p = 0.17). Subjects were paid for their participation, provided written, informed consent, and the study was approved and monitored by the McLean Hospital Institutional Review Board.
•CSA group: 26 abused women (mean age = 20.0 yr).
•Controls: 17 women (mean age = 19.4 yr) with no current or past DSM-IV Axis I disorder and no history of abuse or exposure to other traumatic events.
MRI Methods
Volumetric brain images were acquired using a 1.5 T magnetic resonance scanner (Echospeed; General Electric Medical Systems, Milwaukee, WI, USA) . Hippocampus and amygdala were manually traced in their entirety according to the method detailed by Pruessner et al. (2000). Anatomical measurements of corpus callosum area were obtained from the midsagittal image. An automated algorithm created in NIH Image divided the manually-traced corpus callosum into seven regions as defined by Witelson (1989). Region 3, rostral body, was selected for sensitive period analysis as this region showed the greatest overall vulnerability to CSA in the present sample. Frontal cortex grey matter volume and intracranial volume were ascertained using a semi-automated program for cortical surface-based analysis (FreeSurfer; Dale et al., 1999; Fischl et al 1999, 2001).
Data Analysis
First, an exploratory analysis was performed using ANCOVA to compare brain regions in subjects who experienced CSA during a development stage (preschool 3-5 yrs, latency 6-8 yr, prepubertal 9-10 yr, pubertal 11-13 yr and adolescent14-16 yr) versus healthy controls (“abuse-control comparison”). If a brain region was vulnerable at a particular stage, it should differ in size in subjects who experienced abuse at that stage relative to controls. Further, if one developmental stage was markedly more vulnerable than another developmental stage, then subjects who experienced CSA during the vulnerable stage should also show differences in regional brain size compared to subjects who experienced CSA during other stages (“within abuse comparison”).
To compensate statistically for the number of multiple comparisons made in each analysis, a sequential Sidak Bonferroni-type multiple comparison procedure was used to adjust reported p-values {Sidak1967, Holland 1988}.
Second, path analysis was performed using structural equation modeling with Amos Graphics as a confirmatory statistical procedure. Path analysis was used to simultaneously examine the association between the density of abuse during each of the aforementioned stages and measures of the hippocampal volume, frontal cortex GMV, and midsaggital area of the rostral body of the corpus callosum.
Results
Figure 1. Effect of exposure to childhood sexual abuse during different developmental stages on measures of hippocampal volume during early adulthood. Data based on ANCOVA, with results expressed as effect size (eta-squared), indicating percent of variance that can be attributed to abuse during a given stage.
Figure 2. Path analysis based on structural equation modeling with Amos Graphics, showing the relationship between density of abuse during different developmental stages and measures of hippocampus, corpus callosum and frontal cortex size. Data were covaried by SES and measures of overall brain size (intracranial volume, midsagittal area, total gray matter volume).
Summary
Within the same group of subjects there were marked differences between regions in the stages of greatest vulnerability. The hippocampus was particularly sensitive to abuse reported to occur at 3-5 and 11-13 years of age. In contrast, the rostral body of the corpus callosum was affected by abuse reported to have occurred at ages 9-10, and prefrontal cortex by abuse at ages 14-16.
Discussion
Childhood abuse has been associated with vulnerability to a host of psychiatric disorders and behavioral problems. Based on the present findings, there may be different abuse-related syndromes associated with particular stages of abuse and specific regional brain changes.
Identifying sensitive periods may also provide insight into key ages at which stimulation or environmental enrichment may optimally benefit development of specific brain regions.
Support
Supported, in part, by RO1 awards from the National Institute of Mental Health (MH-53636, MH-66222) and National Institute of Drug Abuse (DA-016934, DA-017846) to MHT.
