پیش بینی کاتکول آمین از نتایج سوگ درمانی پیچیده

Abstract Could sympathetic hyperarousal limit treatment success in complicated grief? The present study investigated persons with complicated grief, a chronic condition with distinct symptoms including persistent intense yearning and longing for the person who died, avoidance of reminders that the person is gone, deep relentless sadness, self-blame, bitterness, or anger in connection with the death, and an inability to gain satisfaction or joy through engaging in meaningful activities or relationships with significant others. Length of bereavement did not correlate with complicated grief scores. Catecholamines (i.e., epinephrine, norepinephrine, dopamine) in plasma were assessed pre- and post-psychotherapeutic treatment. Participants with the highest levels of epinephrine at pre-treatment had the highest levels of complicated grief symptoms at post-treatment, accounting for baseline levels of symptoms. This predictive relationship was not seen for depressive symptoms. The present study supports the hypothesis that catecholamine levels are affected by bereavement, and in turn, can affect the ability of those with complicated grief to benefit from psychotherapy.

1. Introduction The death of a loved one is a highly stressful event because of the permanent loss of an attachment figure. The attachment model states that when the loved one is unavailable, there is a resulting strong desire to be with the person and a sense of insecurity (Bowlby, 1969). There is evidence for the role of attachment relationships in autonomic regulatory processes (for a review, see Hofer, 1984). Bereavement triggers acute grief, a unique biobehavioral response (Shear and Shair, 2005). Acute grief is intensely painful and disruptive, but for most people, a natural healing process slowly integrates the reality of the death. However, for a subset of bereaved people, dysfunctional thoughts, maladaptive behaviors or ineffective emotion regulation complicate and prolong the process, resulting in a disorder termed complicated grief. Little information is available regarding autonomic regulatory processes in complicated grief, but there is some evidence for increased sympatho-adrenal-medulla (SAM) system activation with acute grief, and this could be a contributor to complicated grief. The present paper investigates whether sympathetic hyperarousal limits treatment success in complicated grief. Prior research demonstrates that acute grief is associated with increased urinary catecholamines (Jacobs, et al., 1986), increased heart rate (Buckley et al., 2012a and O'Connor et al., 2002), and cardiovascular disorders, including high blood pressure (Buckley, et al., 2011), stress cardiomyopathy (Wittstein, et al., 2005) and sudden cardiac death (Stroebe et al., 2007). During emotional activation, the SAM system releases epinephrine and norepinephrine, which increases heart rate. In addition, epinephrine increases peripheral resistance, and therefore increases blood pressure. In instances of stress cardiomyopathy (usually occurring after an acute emotional trigger, most frequently, notification of the death of a loved one), plasma catecholamine levels are extremely high from SAM activation (Wittstein, 2012). Higher grief intensity, as well as persistence and chronicity, is associated with greater physiological stress responsivity. In a small naturalistic study (n = 56) of adaptation at 1 and 2 months after bereavement, Jacobs and colleagues found that the subgroup whose separation anxiety symptoms worsened over the month (n = 24) compared to those that did not (n = 32) had higher urinary free cortisol levels (Jacobs, et al., 1987). In another study the stress of losing a family member was associated with the development of essential hypertension in the absence of other cardiovascular risk factors (Santic et al., 2006). These authors found that family members of deceased soldiers had a higher prevalence of arterial hypertension, accounting for a host of other cardiovascular risk factors and post-traumatic stress disorder (50.7% vs. 39.0%, p < 0.001.). The prevalence of hypertension decreased over time only in the bereaved group. Complicated grief, which affects about 10% of bereaved people, has been recognized for only a short time and is not yet in the official diagnostic nomenclature. As a result, there has been little study of the physiological profile of this chronic disabling condition (Shear et al., 2011). Complicated grief is characterized by a prolonged acute grief accompanied by dysfunctional thoughts, behaviors or emotions related to the death that interfere with the process of adaptation. One longitudinal study found that those with complicated grief at 6 months post-loss showed higher levels of hypertension at thirteen months (Prigerson, et al., 1997). We hypothesize that individuals with complicated grief continue to experience sympathetic stimulation generated by the emotional distress. The parent study (NIMH MH70741) for the current report is investigating the efficacy of complicated grief treatment in older adults. We conducted a pilot study of plasma catecholamines among a subgroup of participants in this study (n = 16) treated with either Complicated Grief Treatment (Shear et al., 2005) or Interpersonal Psychotherapy (Shear et al., 2005).1 The present paper reports results of baseline and post-treatment catecholamines in order to explore hypotheses about baseline catecholamines affecting responsiveness to treatment. To do so we measured peripheral epinephrine, norepinephrine and dopamine at pre- and post-treatment.

3. Results At the pre-treatment baseline, participants had a mean age of 64 (SD = 4.3). Participants were grieving the loss of a close relative or friend, including loss of a parent (44%), spouse (31%), child (6%), sibling (13%), or others (e.g., close friend). The length of bereavement varied widely, with a mean of 87 months (SD = 123.9), but a median of 38 months. However, the length of bereavement did not correlate with depression or complicated grief scores at pre-treatment or at post-treatment, and did not correlate with any of the biomarkers. The mean BMI was 25.7 (SD = 4.4). The paired-sample t-test for the BDI was significant (t = 8.03, p < .001). Additional demographics are in Table 1. Table 1. Demographic characteristics. Percentage Gender (female) 88% Ethnicity Caucasian 81% African-American 19% Marital status Never married 19% Married 19% Separated 6% Divorced 25% Widowed 31% Education Some college/AA 13% College degree 13% Some graduate school 18% Graduate/professional degree 56% Employment Full-time 18% Part-time 38% Retired 38% Unemployed 6% AA = associates degree. Table options The mean BDI score was 26.2 (SD = 7.5) at pre-treatment and 10.6 (SD = 6.5) at post-treatment. We grouped depression at post-treatment as high (BDI score of > 21) and low (BDI of < 21). Only one of the participants had a high level at post-treatment (although the BDI declined from 36 to 23). Two participants showed particularly long time since the death (425 and 344 months), and one of these had persistent levels of high depressive symptoms. The mean level ICG score at pre-treatment was 44.6 (SD = 11.5) and 23.5 (SD = 11.0) at post-treatment. The paired-sample t-test for the ICG was significant (t = 7.44, p < .001). We grouped ICG scores at post-treatment as high (ICG > 30) or low (ICG < 30), and 64.7% (n = 11) were low. The length of bereavement was not different between those with high or low post-treatment levels (F = 1.31, p = 0.27). Cronbach's alpha for the ICG was 0.84 at pre-treatment, and 0.88 at post-treatment and the two scores correlated at r = 0.45, p = 0.08. 3.1. Biomarkers Levels of plasma catecholamines can be seen in Table 2. To determine whether the biomarkers predicted treatment outcome, regression analyses were used. Epinephrine at pre-treatment predicted the post-treatment ICG score, accounting for the pre-treatment ICG score (F (16, 2) = 6.68, p = 0.01, βlogE = 0.53, βICG = 0.48). Those participants with the highest levels of epinephrine at pre-treatment had the highest levels of complicated grief symptoms at post-treatment. Outlying values did not account for the relationship ( Fig. 1). Norepinephrine and dopamine at pre-treatment were not significant predictors of post-treatment ICG, once pre-treatment ICG was entered into the analysis. These results did not change if age was included in the regression analysis, and age was not a significant predictor within the model. Unlike the predictive significance of pre-treatment epinephrine, when each of the catecholamines at post-treatment was used to predict simultaneous post-treatment ICG scores, none of the post-treatment levels (i.e., epinephrine, norepinephrine and dopamine) predicted post-treatment ICG scores, once pre-treatment ICG was accounted for. None of the three biomarkers significantly predicted the post-treatment BDI score, accounting for the pre-treatment BDI score. Table 2. Mean levels of catecholamines at two time points. Mean SD Dopamine (pre-treatment) 81.5 35.0 Norepinephrine (pre-treatment) 193.9 243.5 Epinephrine (pre-treatment) 49.3 11.1 Dopamine (post-treatment) 90.0 44.0 Norepinephrine (post-treatment) 223.3 345.9 Epinephrine (post-treatment) 40.5 20.4 Table options Scatterplot of the association between complicated grief symptoms and ... Fig. 1. Scatterplot of the association between complicated grief symptoms and pre-treatment epinephrine levels. ICG = Inventory of Complicated Grief.