Schizophrenia Research

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1 SCHRES-04797; No of Pages 6 Schizophrenia Research xxx (2011) xxx xxx Contents lists available at SciVerse ScienceDirect Schizophrenia Research journal homepage: PTSD'S mediation of the relationships between trauma, depression, substance abuse, mental health, and physical health in individuals with severe mental illness: Evaluating a comprehensive model Andrew M. Subica, Keith H. Claypoole, A. Michael Wylie University of Hawai i at Mānoa, 2350 Dole Street, Sakamaki C400, Honolulu, HI, USA article info abstract Article history: Received 22 July 2011 Received in revised form 26 October 2011 Accepted 28 October 2011 Available online xxxx Keywords: Trauma PTSD Severe mental illness Depression Physical health Objective: Following trauma exposure and PTSD, individuals with severe mental illness (SMI) frequently suffer a complex course of recovery complicated by reduced mental and physical health and increased substance abuse. The authors evaluated a theoretical PTSD-SMI model which theorizes that trauma, PTSD, depression, substance abuse, mental health, and physical health are interrelated and that PTSD mediates these relationships. Method: Participants were ethnoracially diverse individuals diagnosed with SMI (N=175) who were assessed for trauma exposure, severity of PTSD and depression, substance abuse, and overall mental and physical health functioning. Pearson's correlations were utilized to examine the relationships between study domains. The mediating effects of PTSD were assessed using regression coefficients and the Sobel test for mediation. Results: A majority of participants with SMI (89%) reported trauma exposure and 41% reported meeting diagnostic criteria for PTSD. On average, participants were exposed to over four types of traumatic events. Trauma, severity of PTSD and depression, substance abuse, and overall mental and physical health functioning were significantly interrelated. PTSD partially mediated the relationships between trauma and severity of depression and between trauma and overall mental health; PTSD fully mediated the trauma and overall physical health relationship. Discussion: Within an ethnoracially diverse SMI sample, trauma exposure and PTSD comorbidity were high and associated with severity of depression, substance abuse, overall mental health and physical health functioning. Supporting our theoretical PTSD-SMI model, PTSD mediated the adverse effects of trauma exposure on participants current severity of depression and overall mental and physical health functioning Elsevier B.V. All rights reserved. 1. Introduction 1.1. Trauma, PTSD, and severe mental illness The rates of individuals with severe mental illness (SMI) who experience traumatic events are high, ranging from 61% to 98% (Mueser et al., 1998; McFarlane et al., 2001; Cusack et al., 2004). The reported prevalence of PTSD in individuals with SMI ranges from 19% to 43% (Mueser et al., 1998; Cusack et al., 2004), greatly exceeding the 8 9% lifetime prevalence rate of PTSD reported in the general population (Breslau et al., 1991; Kessler et al., 1995). The high prevalence of trauma and PTSD among individuals with SMI can be partially explained by the diathesis-stress model which theorizes that psychiatric disorders, including PTSD, result from an Corresponding author at: 2530 Dole Street, Sakamaki C400, Honolulu, HI, USA. Tel.: ; fax: address: asubica@hawaii.edu (A.M. Subica). interaction between biological vulnerability toward mental illness and exposure to environmental factors such as trauma (McKeever & Huff, 2003). A biological vulnerability to SMI has also been linked to an increased likelihood of developing comorbid PTSD following trauma exposure (Mueser et al., 2002). Previous investigators examining the relationship between SMI and comorbid PTSD proposed a model theorizing that PTSD functioned to mediate the relationship between trauma and increased psychiatric symptom severity, substance abuse, and acute care utilization (Mueser et al., 2002). This model conceptualized PTSD as negatively affecting SMI directly through PTSD's core symptoms of avoidance, distress, and autonomic overarousal, and indirectly through substance abuse, revictimization, and reduced working alliance with providers. Subsequent research has supported this model by finding that many individuals with SMI have histories of trauma and substance abuse and consequently suffer related negative mental health outcomes (Gearon et al., 2003; Christensen et al., 2005) /$ see front matter 2011 Elsevier B.V. All rights reserved. doi: /j.schres

2 2 A.M. Subica et al. / Schizophrenia Research xxx (2011) xxx xxx 1.2. Updated model of trauma-ptsd in individuals with SMI Using Mueser et al.'s (2002) model as a base, we integrated relevant findings to develop an updated PTSD-SMI model which proposes multiple direct and indirect effects of trauma and PTSD on depression, substance abuse, and overall mental and physical health for individuals with SMI (Fig. 1). At the outset, this model reflects our current understanding that for individuals biologically predisposed towards SMI, their risk for developing SMI may be influenced by pre-adult stressors such as negative family environment and adverse life events. Among high-risk individuals, these factors interact with genetic vulnerability to trigger the onset of psychosis and schizophrenia (Burman et al., 1987; McDonald & Murray, 2000; Bebbington et al., 2004). Similar exposure to adverse childhood experiences (ACE) has also been found to predict adult depression, psychosis, and use of psychotropic medication (Chapman et al., 2004; Whitfield et al., 2005; Anda et al., 2007). Our model predicts that trauma in individuals with SMI leads to increased difficulties with physical health and depression, in addition to the previously theorized mental health and substance abuse problems (Mueser et al., 2002). In this expanded model, PTSD is conceptualized as directly mediating trauma's relationships with depression, substance abuse, mental health, and physical health. We theorized depression to be a domain distinct from overall mental health due to robust findings indicating that among individuals with SMI, PTSD is associated with increased depressive symptomatology (Resnick et al., 2003) and incidence of major depression (McFarlane et al., 2001). Based on research indicating that trauma exposure, particularly to ACEs, and PTSD are associated with lower functioning on numerous indices of physical health in the general population (Felitti et al., 1998; Anda et al., 1999) and increased outpatient medical services usage for individuals with SMI (Cusack et al., 2004; Mueser et al., 2004), we included the domain of overall physical health. Multiple interrelationships between trauma, PTSD, and our model's domains of functioning are also predicted. We posit that PTSD leads to mental and physical health declines plus increased depression, substance abuse, and retraumatization which interact in a negative synergistic fashion. Although beyond the scope of this study, the long-term effects of this insidious cycle may continue for many years following onset of PTSD. This study's principal objective was to evaluate the viability of the proposed PTSD-SMI model among ethnoracially diverse individuals with SMI. We hypothesized that trauma exposure, PTSD, severity of depression, substance abuse, and overall mental and physical health functioning would be highly interrelated and that PTSD would serve to mediate the relationships between trauma and the domains of depression, substance abuse, mental health, and physical health. Such findings would support the proposed model's thesis that PTSD underlies the complex mental and physical health sequelae of trauma exposure in individuals with SMI. Based on Tolin and Foa's (2006) meta-analysis of gender differences in PTSD, we also expected female participants to report higher levels of PTSD and greater incidence of clinical PTSD than male participants. 2. Method 2.1. Participants Participants (N=175) were recruited from community mental health centers serving adults with SMI and primary diagnoses of schizophrenia spectrum or major mood disorders. Participants lacking English fluency were excluded from the study. The participants exhibited extensive ethnoracial diversity with 79% reporting an ethnoracial minority or multiracial identity. Table 1 summarizes the characteristics of the study sample Procedure The Institutional Review Board of the University of Hawai i approved the study. Participants were recruited through posting of study announcements at community mental health centers inviting participation in a study examining stressful life events and mental and physical health. Research assistants trained by the principal investigators in trauma assessment administered the study's measures to participants. After comprehensive description of the study, written informed consent was obtained from all participants. Pre-Adult Trauma 2 Substance Abuse 4 Overall Physical Health 5 Biological Predisposition Severe Mental Illness 1 Adult Trauma 2 Posttraumatic Stress Disorder (PTSD) 3 Overall Mental Health 6 KEY = Correlational Relationship = Mediating Relationship Depression 7 Fig. 1. Mediational model of trauma, PTSD, health, substance abuse, and severe mental illness. 1 Includes schizophrenia spectrum and major mood disorders with marked functional impairment, 2 Trauma Assessment of Adults Brief Revised Version (TAA; 2), 3 PTSD Checklist (PCL; 24), 4 CAGE-AID (28), 5 12-item Short Form Health Survey: Physical Health Composite Score (PCS-12; 25), 6 12-item Short Form Health Survey: Mental Health Composite Score (MCS-12; 25), 7 Patient Health Questionnaire-8 (PHQ-8; 27).

3 A.M. Subica et al. / Schizophrenia Research xxx (2011) xxx xxx 3 Table 1 Demographic characteristics of study sample. Demographic characteristic N % Gender Men Women Other 3 2 Age=47.6 years SD=11.1 Race Multiracial Asian Caucasian or White Native Hawaiian 14 8 Hispanic/Latino 8 5 Pacific Islander 6 3 Black or African American 1 1 American Indian 1 1 Adopted/prefer not to answer/missing 8 4 Education bhigh school graduate High school graduate or GED >High school graduate Prefer not to answer/missing 3 2 Marital status Single Married/living with partner 11 6 Divorced/separated/widowed Prefer not to answer/missing 3 2 Following the consent process, participants completed a series of self-report questionnaires while being monitored for signs or symptoms of emotional distress. None of the participants demonstrated difficulty or distress during data collection. Participants were provided coupons of nominal value in appreciation of their time and participation and a listing of community-based trauma resources Measures Trauma exposure was assessed via the Trauma Assessment of Adults Brief Revised Version (TAA) (Cusack et al., 2004), a selfreport screen with good psychometric properties modified for use with individuals with SMI. This study expanded the TAA to include a question adopted from the Traumatic Life Events Questionnaire (TLEQ) (Kubany et al., 2000) about childhood physical abuse. PTSD was assessed using the PTSD Checklist (PCL) (Weathers et al., 1993), a well-established instrument that yields PTSD symptom severity and diagnostic information. PTSD can be diagnosed using the PCL by applying DSM-IV criteria for PTSD to participants responses or by applying the optimal 50-point threshold for identifying PTSD (Weathers et al., 1993). PCL responses were based on the traumatic event reported by the participants on the TAA as most distressing at the time of assessment. Overall mental and physical health functioning were evaluated with the widely-used Medical Outcomes Study Short Form 12-Item Health Survey (SF-12) which has separate overall mental health (MSC-12) and physical health (PCS-12) domains (Ware et al., 1996). Severity of depression was measured using the Patient Health Questionnaire 8 (PHQ-8) (Kroenke & Spitzer, 2002), a measure of depression shown to have strong reliability and validity in health care settings. The PHQ-8 provides a cumulative score of depression severity and a 10-point threshold has been reported to be optimal for diagnosing major depression (Kroenke & Spitzer, 2002). Substance abuse was assessed using the CAGE-AID (Brown & Rounds, 1995), a brief measure of alcohol and drug use reported to possess good sensitivity and reliability Statistical analysis Data were examined for missing values, outliers, homogeneity, and normality. Descriptive statistics were completed to determine sample characteristics including prevalence of traumatic events and means and standard deviations of all clinical variables were calculated. To test the proposed PTSD-SMI model's hypotheses, correlation and mediation analyses between study domains were performed. Pearson's correlation coefficients were used to examine the relationships between trauma, PTSD, depression severity, substance abuse, and overall mental and physical health functioning. Mediation effects of PTSD on trauma's relationships with depression severity, substance abuse, and overall mental and physical health functioning were analyzed using Baron and Kenny's (1986) criteria for mediation. According to Baron and Kenny (1986), establishing mediation requires three elements: the predictor, mediator, and outcome variables must be significantly related; the mediator and outcome variables must remain significantly related after the predictor is controlled; and the significant relationship between the predictor and outcome variables must decrease after controlling for the mediator. Regression coefficients were utilized to establish mediation according to these guidelines and mediation was confirmed using the Sobel test of mediation via Preacher and Hayes (2004) macro. Due to multiple comparisons, p-values less than 0.01 were considered significant. 3. Results Almost nine out of 10 (89%) participants reported lifetime trauma exposure. Table 2 summarizes trauma prevalence by gender and event type. The most frequently reported trauma type was experiencing a serious accident, followed by childhood physical abuse, physical assault with a weapon, and sexual assault. Table 3 presents mean domain scores. The rate of clinical PTSD in the sample, applying DSM-IV criteria to PCL responses, was 41% with this subgroup of PTSD participants reporting a mean lifetime exposure to 5.34 (SD=2.82) traumatic event types. The rate of clinical PTSD using the 50-point diagnostic threshold was 32%. Although the mean PTSD score for women was higher than that for men, the difference did not reach significance. The difference between the proportion of women (46%) versus men (36%) who met diagnostic criteria for PTSD also did not reach significance (X 2 =2.51, df=2, p=0.29). Mean severity of participants depression was elevated with 38% of the sample exceeding the 10-point diagnostic threshold for major depression on the PHQ-8. Mean overall mental health and physical health functioning scores were a half-standard deviation or more below the normative 50-point general population means on the SF- 12 (Ware et al., 1996). Trauma exposure, severity of depression, Table 2 Prevalence of traumatic events by gender. Type of traumatic event Men (n=95) Women (n=77) Total (n=175) n (% of population) Child physical abuse 39 (41) 38 (49) 78 (45) Child sexual abuse 15 (16) 28 (36) 44 (25) (before age 13) a Child sexual abuse 18 (19) 32 (42) 52 (30) (before age 18) a Forced sexual assault a 21 (22) 36 (47) 58 (33) Physical assault with weapon 33 (35) 29 (38) 62 (35) Physical assault without 30 (32) 29 (38) 61 (35) weapon Witnessed serious violence or 38 (40) 14 (18) 53 (30) injury a Serious accident 56 (59) 32 (42) 90 (51) Natural disaster 35 (37) 26 (34) 61 (35) Serious illness 11 (12) 16 (21) 27 (15) Military/Combat experience 14 (15) 5 (6) 19 (11) Close friend or family member 18 (19) 18 (23) 37 (21) killed Other 33 (35) 32 (42) 65 (37) a Difference between male and female groups significant at 0.01 level.

4 4 A.M. Subica et al. / Schizophrenia Research xxx (2011) xxx xxx Table 3 Clinical mean scores of study sample by gender. Total (mean±s.d.) (n=175) Trauma a,b 4.06±2.95 PTSD c 40.52±16.84 Depression d 8.23±6.00 Substance abuse e 1.45±1.55 Mental health f 44.12±10.01 Physical health g 41.99±9.92 a b c d e f g Trauma Assessment for Adults. Trauma refers to number of distinct types of traumatic events experienced. PTSD Checklist. Patient Health Questionnaire 8. CAGE-AID. 12-item Short Form Health Survey Mental Component Summary Scale. 12-item Short Form Health Survey Physical Component Summary Scale. substance abuse, and overall mental and physical health functioning did not differ by gender. As presented in Table 4, degree of exposure to traumatic events types demonstrated significant positive correlations with PTSD, severity of depression, and substance abuse, and negative correlations with both overall mental health and physical health functioning. PTSD evidenced similar but stronger correlations with depression severity, overall mental health, and physical health than with trauma. Severity of depression was negatively correlated with overall mental health and physical health functioning while substance abuse was negatively correlated with overall mental health functioning. Regression analyses and the Sobel test were employed to determine whether PTSD mediated the significant relationships between trauma and other domains. Table 5 provides the regression analyses results. PTSD and substance abuse were not significantly related at the pb0.01 level (β=0.18, p=0.02), leading substance abuse to be dropped from further mediation analysis. All remaining mediator outcome variable relationships remained significant after trauma was controlled. After controlling for PTSD, the strength of initial significant relationships between trauma and severity of depression and trauma and overall mental health decreased which suggested partial PTSD mediation. PTSD fully mediated the trauma and overall physical health relationship as the original significant relationship became non-significant after PTSD was added to the regression equation. Sobel's tests of the indirect effects of trauma on severity of depression (Z=4.31, pb0.001), overall mental health (Z= 3.37, pb0.001), and overall physical health (Z= 3.56, pb0.001) via PTSD were significant, converging with the regression analyses to indicate PTSD mediation. Table 4 Correlations between trauma, PTSD, depression, substance abuse, mental health, and physical health. Variable Trauma a 2. PTSD b Depression c Substance abuse d Mental health e Physical health f pb0.01. pb0.001 a Trauma Assessment for Adults. b PTSD Checklist. c Patient Health Questionnaire 8. d CAGE-AID. e 12-item Short Form Health Survey Mental Component Summary Scale. f 12-item Short Form Health Survey Physical Component Summary Scale. Table 5 Regression analyses of trauma and domain variables. Predictor variable Outcome variable b (SE) β t Trauma Depression 0.70 (0.15) Trauma a Depression 0.32 (0.15) Trauma Mental Health 1.13 (0.24) Trauma a Mental Health 0.68 (0.26) Trauma Physical Health 0.72 (0.25) Trauma a Physical Health 0.23 (0.26) b=unstandardized beta coefficient, SE=standard error, β=standardized beta coefficient, t=t-value pb0.05. pb0.01. pb a Trauma and PTSD included as predictor variables in regression to control for PTSD. 4. Discussion Our results aligned with reports of alarmingly heightened rates of trauma and PTSD among individuals with SMI (Cusack et al., 2004). The 89% trauma exposure rate and 41% PTSD prevalence rate reported in our ethnoracially diverse sample is consistent with previous trauma surveys of individuals with SMI (Mueser et al., 1998; Cusack et al., 2004) and is far greater than the reported incidence of trauma and PTSD in the general population (Breslau et al., 1991; Kessler et al., 1995). Participants average exposure to over four different traumatic event types further underscores the profound levels of lifetime trauma exposure among individuals with SMI. Our PTSD prevalence findings also confirm earlier reports that PTSD is a more common comorbid disorder with SMI than is conventionally recognized within public-sector settings (Grubaugh et al., 2011). In contrast to findings with the general population (Tolin & Foa, 2006), female participants did not report significantly greater rates and severity of PTSD than male participants, suggesting that perhaps women and men with SMI may be equally vulnerable to developing PTSD following trauma exposure. Our findings of no significant gender differences is consistent with prior studies of individuals with SMI reporting comparable rates of PTSD among women and men (Mueser et al., 2004; Cusack et al., 2006; O'Hare et al., 2007). Support was found for the majority of our PTSD-SMI model's hypothesized relationships. Corroborating previous trauma-smi research, experiencing more traumatic event types was associated with greater severity of PTSD (Gearon et al., 2003) and depression (McFarlane et al., 2001), increased substance abuse (Briere et al., 1997), and decreased overall mental health (Calhoun et al., 2006) and physical health functioning (Cusack et al., 2004). Moreover, increased PTSD severity was more strongly associated with greater severity of depression and lower overall mental and physical health function than increased trauma exposure alone. Increased severity of depression was associated with decreased overall mental and physical health functioning while increased substance abuse was associated with decreased overall mental health. Thus, our model's proposed negative interactive cycle between trauma, PTSD, depression, substance abuse, mental health, and physical health was partly confirmed. These findings imply that for individuals with SMI and comorbid PTSD, there will be an increased likelihood that difficulties in one area of health functioning may be expected to detrimentally affect associated domains of functioning. Finally, as first conceptualized by Mueser et al. (2002) and elaborated upon in our model, this study's results indicate that PTSD mediates the clinical sequelae of trauma in individuals with SMI, completely underlying trauma's negative effects on overall physical health functioning and partially underlying trauma's negative effects on severity of depression and overall mental health functioning. Based on these findings, it is not the exposure to trauma per se but more the development of PTSD that appears to put individuals with SMI at increased risk for a more complex course of illness involving

5 A.M. Subica et al. / Schizophrenia Research xxx (2011) xxx xxx 5 negative interactions between depression and overall mental and physical health function. Study limitations include our cross-sectional design which restricts causal inferences and recruitment via convenience sampling which limits generalizability to other individuals with SMI. The limited scoring range of the substance abuse measure (the four-point CAGE-AID) may have contributed to the weak or absent substance abuse relationships with PTSD and physical health that have been previously noted to exist among individuals with SMI (Christensen et al., 2005; Larson et al., 2005). Finally, in results not reported above, we found that participants reported experiencing a number of SMI-related stressful experiences not included in the trauma measure (TAA) including incarceration, restraint, suicide attempts, and homelessness. These distressing experiences did not meet DSM-IV A1/A2 criteria for a precipitating PTSD event and their exclusion may have resulted in an underestimation of the actual prevalence of our participants history of exposure to traumatic-type events. In brief, the current analyses more directly test and extend previous findings that trauma and PTSD are highly prevalent and underestimated stressors facing individuals with SMI and that the presence of PTSD is often associated with greater impairments across a range of mental and physical health functioning indices. That is, the current data suggests that PTSD likely partially or fully mediates the relationship between trauma and other important indices of functioning. In this regard, PTSD clearly magnifies the overall illness burden of this population and should be aggressively targeted in public-sector settings. The use of assessment and treatment protocols focusing on trauma, PTSD, and depression can alleviate this burden along with closer monitoring and integrated treatment of comorbid medical disorders. As this study reflects a preliminary evaluation of our PTSD-SMI model, derived from an earlier model (Mueser et al., 2002), subsequent research may wish to examine, challenge, and expand the conceptualization of this model. Future studies may consider collecting more detailed data on illness severity such as diagnoses, disability, and hospitalization and care utilization rates, as well as measures of employment and psychosocial support to further our understanding of the factors that influence the complex relationships between trauma, PTSD, and SMI. Given the high comorbidities of PTSD and SMI, research such as this provides impetus to consider the extent of the pernicious influence of PTSD and its sequelae on the course of SMI, and also offers enhanced implications for the comprehensive treatment needed to support the recovery of individuals with SMI who also suffer from histories of trauma and PTSD. Role of funding source Funding support for this study was provided by the State of Hawai'i Department of Health. The Department of Health had no further role in study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the paper for publication. Contributors All authors collaborated in completing this study. A.M. and K.C. designed the updated PTSD-SMI model and study protocol, and contributed to the data analysis and interpretation. A.M. managed the literature searches, supervised the collection of data, and wrote the first draft of the manuscript. 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