Gender moderates the relationship between stressful life events and psychopathology: Findings from a national study

Journal of Psychiatric Research 107 (2018) 34–41

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Gender moderates the relationship between stressful life events and psychopathology: Findings from a national study

T

Jessica L. Armstronga,b, Silvia Ronzittia,b,c, Rani A. Hoffa,b,d, Marc N. Potenzab,e,f,g,∗ a

Veterans' Administration, Connecticut Healthcare System, CT, USA Department of Psychiatry, Yale University School of Medicine, CT, USA c Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy d Northeast Program Evaluation Center; Director, Evaluation Division, National Center for PTSD, CT, USA e Department of Neuroscience, Yale University School of Medicine, CT, USA f Child Study Center, Yale University School of Medicine, CT, USA g Connecticut Mental Health Center, CT, USA b

A R T I C LE I N FO

A B S T R A C T

Keywords: Stressful life events NESARC Psychiatric conditions Personality disorders Alcohol use disorder

Background: While data suggest a strong relationship between trauma exposure and psychopathology, less research has investigated relationships between psychopathology and stressful life events more broadly, and how these relationships may differ by gender. Aim: To examine strengths of associations between stressful life events and psychiatric disorders (i.e., past-year Axis I and lifetime Axis II, per DSM-IV) and how they may differ by gender. Methods: Data from Wave 1 of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC; n = 43,093) were analyzed using chi-square tests and multinomial logistic regression analyses. Participants were categorized according to occurrence of stressful life events (low, moderate, and high). Results: Women as compared to men were more likely to report moderate (p < 0.0001) or high occurrence stressful life events (p < 0.0001). Increasing experiences of stressful life events were associated with increasing odds of most past-year Axis I and lifetime Axis II disorders in both gender groups, with the largest odds typically observed in association with more frequent stressful life events. Associations between stressful life events and multiple psychiatric disorders were stronger in women compared to men. Conclusions: Stressful life events are associated with multiple Axis I and Axis II psychiatric disorders in both men and women. This relationship is moderated by gender. Screening female patients who endorse significant stressors for mood, anxiety, and substance-use problems might be particularly important. The stronger associations in women between stressful life events and personality disorders in particular warrant further investigation.

1. Introduction Data suggest strong relationships between trauma exposure and psychopathologies (e.g., Hasin and Grant, 2015; Kucharska, 2017a, 2017b; Overstreet et al., 2017; Reardon et al., 2014). Past trauma is associated with mood, anxiety, substance-use, and personality disorders (Galea et al., 2002; Koss et al., 2003; Reardon et al., 2014). A cumulative effect of traumatic experiences may exist such that more frequent experiences of trauma and victimization in the course of one's lifetime may be associated with greater mental health concerns (Hodges et al., 2013; Kira et al., 2014; Kucharska, 2017a; Palm et al., 2016). The relationships between stressful life events and psychopathology more

∗

broadly among the general adult population – irrespective of trauma or trauma-related conditions – are arguably less well understood. Some researchers have begun to evaluate the lasting and potentially serious impact that stressful life events, or significant experiences in one's life that involve sudden and lasting change, may produce (Buccheri, Musaad, Bost, Fiese, & the STRONG Kids Research Team, 2017). However, further research is needed to better understand how the occurrence of stressful life events may relate to the prevalence of psychiatric disorders in community samples. Gender-related differences in stress experiences and severity, as well as in the associations between traumas and psychopathologies, have been reported (Tolin and Foa, 2006). For example, differences in what

Corresponding author. Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT, 06519, USA. E-mail address: [email protected] (M.N. Potenza).

https://doi.org/10.1016/j.jpsychires.2018.09.012 Received 27 April 2018; Received in revised form 21 August 2018; Accepted 19 September 2018 0022-3956/ © 2018 Elsevier Ltd. All rights reserved.

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Quantitative analyses involving chi-square and logistic regression analyses were conducted to examine relationships.

is considered to be stressful by women and men have been identified (Chaplin et al., 2008; Keyes et al., 2012; Matud, 2004), including differences in appraisal of trauma and rates of psychopathology (Kucharska, 2017b). Women as compared to men have been reported to experience more sadness and anxiety in response to stress (Chaplin et al., 2008). Further, the associations between trauma and psychiatric diagnoses may vary according to gender (Kucharska, 2017b), with trauma potentially leading to different psychopathologies in women and men. Whether differences in the associations between stressful life events and adult psychopathologies are moderated by gender or merely reflect gender-related differences in the distribution of psychiatric disorders in the general population is unclear. While there is some evidence of connection between stress and psychiatric disorders (e.g., substance-use disorders (SUDs); Sinha, 2007, 2008), the extent to which stressful life events relate to psychopathologies and whether these relationships may differ between women and men is incompletely understood. The purpose of the current study is to extend previous work by examining relationships between stressful life events and psychopathologies in women and men and whether gender moderates the relationships between stressful life events and psychiatric disorders in the large, National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) sample. We utilized the NESARC database in order to investigate within-gender relationships and gender-related differences in the relationships between stressful life experiences and psychopathologies, including mood, anxiety, substance-use, and personality disorders (PDs). The specific hypotheses for this study were: (1) women, as compared with men, would report more stressful life events; (2) increases in stressful life events would be associated with more psychopathologies in both women and men; and, (3) gender would moderate the relationships between stressful life events and psychopathologies such that there would be stronger relationships between stressful life events and psychiatric disorders, particularly mood and anxiety disorders, in women as compared to men. Given the possibility that greater psychopathology may lead to more stressful life events and these relationships may differ across gender groups, we also explored relationships with lifetime PD measures.

2.2. Measures Self-reported measures of gender, age in years, race/ethnicity (African-American, Hispanic, Caucasian, and other), education, employment, and marital status were used. Racial/ethnic categories were non-mutually exclusive because respondents could endorse more than one category. The NESARC used reliable and valid structured diagnostic assessments from the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM IV version (AUDADIS-IV; Grant et al., 2003). The AUDADIS-IV has been found to detect psychiatric disorders in community samples (Grant et al., 2003). Data were collected during 2001–2002 through computer-assisted personal interviews. Dependent variables were DSM-IV past-year Axis I and lifetime Axis II disorders. The AUDADIS-IV allows for assessment of past-year diagnoses, prior to past-year diagnoses, and lifetime diagnoses, and excludes for illness and substance-induced symptoms where appropriate. Diagnostic variables for Axis I disorders included major depression, dysthymia, mania, and hypomania, panic disorder, social phobia, simple phobia, generalized anxiety disorder, alcohol abuse, alcohol dependence, drug abuse, drug dependence, and nicotine dependence. For the purposes of this study, only past-year Axis I diagnoses were examined to allow for a more precise assessment of these conditions that are less subject to recall bias. Seven DSM-IV Axis II PDs were also assessed, including cluster A (paranoid, schizoid), cluster B (antisocial, histrionic), and cluster C (avoidant, dependent, obsessive-compulsive) PDs. Time constraints and consideration for subject burden limited the assessment of all DSM-IV PDs (Grant et al., 2005). In contrast to the Axis I disorders described above and since Axis II disorders were considered to be temporally stable constructs, no time periods were applied during data collection. Thus, respondents were asked about how they felt or acted most of the time, throughout their lives, and regardless of situation. 2.3. Stressful life events

2. Methods The primary independent variable of interest in this study was based on twelve items from Wave 1 that assessed for the experience of stressful life events. Participants were asked to indicate whether or not they had experienced each of twelve specific events in the past year, including death of a friend or family member, financial crisis (e.g., bankruptcy or being unable to pay monthly bills), serious problems with significant others, violent crime victimization, and changes in job responsibilities or work hours (see Table 2). Thus, while not all events would meet Criterion A for post-traumatic stress disorder as traumatic events, they would be considered stressful to most people. This measure uses similar items to assess for stressful life events that have been validated and associated with general health items in other studies (Buccheri et al., 2017). For the purposes of this study, in order to create a categorical variable, we coded stressful life events as low (zero stress event items endorsed), moderate (one to two stress event items endorsed), and high (three or more stress event items endorsed).

2.1. Sample Data from Wave 1 of the NESARC were examined. The NESARC study methodology has been described previously (Barry et al., 2012, 2013; Desai and Potenza, 2008; Grant et al., 2003, 2004). Briefly, the NESARC, conducted by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the U.S. Census Bureau, surveyed a large community sample of U.S. residents (citizens and non-citizens) age 18 and over who were identified using multi-stage, stratified, cluster sampling. Respondents were living in non-institutionalized settings (i.e., jails, prisons, and hospitals were excluded), including individuals who lived in dormitories, group homes, shelters, facilities for housing workers, and other group living environments. African-American and Latino households, as well as respondents aged 18 to 24, were oversampled during data collection in order to ensure sufficient statistical power to examine patterns of alcohol use in minority populations and young people, who may otherwise have been under-represented in a simple random sample (American Psychiatric Association, 1994; Grant et al., 2003, 2004). Weights were calculated in order to adjust standard errors for over-sampling, cluster sampling, and non-response. The final sample included 43,093 respondents, representing an 81% response rate. All respondents provided written consent to participate in the initial study which was reviewed by an appropriate ethical committee, and the investigation was conducted in accordance with the Declaration of Helsinki. The current investigation was exempted from further formal IRB review because it utilizes de-identified data.

2.4. Data analyses The primary research questions concerned gender-related differences in the associations between stressful life events and psychiatric disorders. To investigate, we first examined the association between gender, stressful life events, and other socio-demographic variables in order to identify socio-demographic variables potentially influencing the relationship between gender, stressful life events, and psychiatric disorders. Next, unadjusted weighted rates of psychiatric disorders were calculated, stratified by both gender (male, female) and stressful life 35

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p < .0001). Women were more likely than men to report stressors relating to death or illness of loved ones, serious problems with friends, neighbors or relatives, and being unable to pay bills. In contrast, men were more likely than women to endorse work-related stressors.

events (low, moderate, high). Finally, a series of logistic regression models were fit, where psychiatric-disorder-related variables were the dependent variables of interest and the three-level stressful life events variable, gender, and the interaction between stressful life events and gender were the independent variables of interest in models adjusting for previously identified socio-demographic variables. Analyses began by examining psychiatric disorders grouped into Axis I and Axis II disorders with findings considered significant at p < 0.05 (95% confidence interval (95%CI) not including 1). Given that significant findings were observed in women and men between stressful life events and psychopathology for each of these categories, follow-up analyses examined 3 categories of disorders within each Axis were examined: any mood, anxiety, or SUD for Axis I categories, and any cluster A PD, cluster B PD, cluster C PD for Axis II categories. Finally, when significant associations were found within these categories, analyses of individual disorders were conducted. The multivariate-adjusted gender-specific odds ratios (ORs) as well as the interaction odds ratios (IORs) and their associated 95%CIs are presented. Gender-specific ORs reflect the magnitude and direction of the association between category of stressful life events and psychiatric disorder of interest, separately for women and men. The IOR is the ratio of the gender-specific ORs (i.e., OR women/ORmen). An IOR that is statistically significant indicates that the strength of the association between category of stressful life events and psychiatric disorder of interest varies between women and men. Statistical significance was determined with the Wald F-test. Statistical analyses were performed in SAS (version 8; SAS Institute, 1999).

3.4. Stressful life events and psychiatric disorders Bivariate associations were observed between stressful life events and psychopathology in the entire sample and among female and male respondents, separately (Supplementary Table 2). In general, greater occurrence of stressful life events was associated with greater psychopathology in each gender across groupings of Axis I (mood, anxiety, substance use) and Axis II (clusters A, B, C) disorders and for each contributing disorder. Adjusted multivariate models confirmed these relationships in both women and men (Table 3). 3.5. Gender, stressful life events and psychopathology In adjusted models, gender was found to moderate some relationships between stressful life events and Axis I and Axis II psychopathology (Table 3). Stronger relationships were observed in female as compared to male respondents between high occurrence of stress and any past-year Axis I disorder (IOR = 1.16, p = 0.019). Further analysis indicated stronger relationships in women between high occurrence of stress and any anxiety disorder (IOR = 1.33, p = 0.003), particularly social phobia (IOR = 2.03, p < 0.001). A stronger relationship between high occurrence of stress and alcohol abuse or dependence (IOR = 1.36, p = 0.012) was also observed in women as compared to men. A stronger relationship was also observed in female as compared to male respondents between high occurrence of stress and any lifetime Axis II disorder (IOR = 1.36, p < 0.001). Specifically, stronger relationships between high occurrence of stress and any cluster A PD (IOR = 1.60, p < 0.001), particularly schizotypal PD (IOR = 1.40, p = 0.046), any cluster B PD (IOR = 1.60, p = 0.006), particularly antisocial PD (ASPD; IOR = 2.30, p < 0.001), and any cluster C PD (IOR = 1.43, p < 0.001), particularly obsessive-compulsive PD (OCPD; IOR = 1.42, p = 0.002) were observed in women as compared to men. Relationships between moderate occurrence of stress and psychopathologies were largely similar across gender groups, with the most statistically robust finding suggesting a stronger relationship with any cluster A PD in women as compared to men (OR = 1.29, p = 0.048).

3. Results 3.1. Sociodemographics and psychiatric disorders Of participants (n = 43,093), more were female (n = 24,575; 57%), and the sample had an average age of 46.4 years (SD = 0.81, range = 18–90). Supplementary Table 1 presents prevalence of psychopathology overall and by gender. About 29% of participants reported symptoms consistent with Any Axis I disorder in the past year, while 14.6% reported Any Axis II disorder in their lifetime; these prevalences did not significantly differ by gender. Before accounting for stressful life events, there were significant gender-related differences in the prevalences of all psychiatric disorders with the exception of hypomania, schizotypal PD, histrionic PD, and obsessive-compulsive PD. Women reported significantly higher rates of nearly all psychiatric disorders, excluding SUDs, paranoid PD, and antisocial PD, which were significantly higher in men.

4. Discussion The present study represents the first to our knowledge to investigate systematically within and across gender groups associations between stressful life events and psychopathology in the large, national NESARC sample. Findings of the current study largely support a priori hypotheses and suggest that there are gender-related differences in the prevalence and types of stressors. Whereas both moderate and high occurrence of stressful life events were associated with greater psychopathologies in both women and men, relationships were as strong or stronger in women, particularly in the high occurrence of stressful life events group. The stronger relationships between stressful life events and psychopathologies in women involved both Axis I (particularly anxiety) and Axis II (clusters A, B, and C) disorders, with significant findings also for alcohol-use disorders. Implications are discussed below.

3.2. Stressful life events The prevalences of low, moderate, and high occurrence of stressful life events at Wave 1 for the overall sample were 31.47% (n = 13,474), 45.07% (n = 19,300), and 23.46% (n = 10,046), respectively. In both women and men, stressful life events were associated with marital status, education, employment, age, and race/ethnicity. Generally, the low stressful life events groups, as compared to the moderate or high stressful life events groups, more frequently acknowledged being married, being older, and being of Caucasian descent. In contrast, the high stressful life events groups, as compared to the low stressful life events groups, more frequently acknowledged having a college or higher level of education and having fulltime employment (Table 1). 3.3. Individual stressful life events by gender

4.1. Gender and stressful life events The likelihoods of experiencing individual stressors differed by gender (Table 2). Women, in contrast to men, were more likely to endorse moderate (women: 45.55%, men: 44.43%) or high (women: 23.97%, men: 22.79%) frequency of stressful life events (χ2 = 26.62,

The finding that women endorsed stressful life events at higher rates than men extends previous work documenting that women are more likely to experience potentially traumatic events, more chronic and 36

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Table 1 Baseline sociodemographic characteristics of male and female respondents by stress level. Characteristics

Male Respondents (n = 18389)

Female Respondents (n = 24431)

Low Stress n = 6027 (32.78%)

Moderate Stress n = 8171 (44.43%)

High Stress n = 4191 (22.79%)

Low Stress n = 7447 (30.48%)

Moderate Stress n = 11129 (45.55%)

High Stress n = 5855 (23.97%)

n (%)

n (%)

n (%)

χ2

p

n (%)

n (%)

n (%)

χ2

p

Age (M)

48.67

47.00

37.84

F = 561.39

< .0001

51.00

49.02

38.58

F = 895.71

< .0001

Race/Ethnicity White Black Hispanic Other

4826 (80.07) 913 (15.15) 1327 (22.02) 2 (0.03)

6460 (79.06) 1399 (17.12) 1535 (18.79) 4 (0.05)

3193 (76.19) 854 (20.38) 830 (19.80) 0 (0.00)

23.21 47.51 22.83 2.03

< .0001 < .0001 < .0001 0.36

5657 (75.96) 1403 (18.84) 1531 (20.56) 3 (0.04)

8331 (74.86) 2401 (21.57) 1988 (17.86) 2 (0.02)

4128 (70.50) 1558 (26.61) 1046 (17.87) 0 (0.00)

56.30 117.18 24.74 2.66

< .0001 < .0001 < .0001 0.26

Marital Status Married Never Married Previously Married

3603 (59.78) 1077 (17.87) 1347 (22.35)

4839 (59.22) 1462 (17.89) 1870 (22.89)

1917 (45.74) 817 (19.49) 1457 (34.76)

299.89

< .0001

367.16

< .0001

3746 (50.30) 2444 (32.82) 1257 (16.88)

5495 (49.38) 3550 (31.90) 2084 (18.73)

2404 (41.06) 1733 (29.60) 1718 (29.34)

Education Less than HS HS Graduate Some College College or higher

1169 1722 1524 1612

1445 2303 2302 2121

(17.68) (28.19) (28.17) (25.96)

729 (17.39) 1190 (28.39) 1397 (33.33) 875 (20.88)

194.35

< .0001

1519 2350 1914 1664

2035 3252 3334 2508

(18.29) (29.22) (29.96) (22.54)

899 (15.35) 1638 (27.98) 2129 (36.36) 11.89 (20.31)

Employment Part-Time Full-Time Not Working

3846 (63.81) 344 (5.71) 1837 (30.48)

5091 (62.31) 533 (6.52) 2547 (31.17)

2576 (61.47) 371 (8.85) 1244 (29.68)

341.38

< .0001

4616 (41.48) 1329 (11.94) 5184 (46.58)

2958 (50.52) 885 (15.12) 2012 (34.36)

102.96 (19.40) (28.57) (25.29) (26.75)

41.97

< .0001 (20.40) (31.56) (25.70) (22.34)

< .0001 3017 (40.51) 762 (10.23) 3668 (49.25)

corticolimbic, and hyperarousal responses to stress (Bangassar and Valentino, 2014) may in part explain the current findings. Further research is needed to explain how gender-related differences in the perception of and response to stressful life events connect to mental health.

acute stress, more negative consequences related to stress, and differences in the appraisal of stress and trauma (Chaplin et al., 2008; Keyes et al., 2012; Kucharska, 2017b; Matud, 2004). With respect to individual stressors, themes of loss of relationships (e.g., death or illness of loved ones, problems with friends, neighbors or relatives) and financial stressors were more frequently endorsed by women, while stressors endorsed by men were largely related to employment. The particular themes identified by men and women in our study are partially consistent with themes observed in other studies (Brown et al., 2011; Matud, 2004; Stroud et al., 2002). For example, one study found relationship stressors as being more salient to men and health-related stressors as being more salient to women (Matud, 2004), while another found rejection stress as particularly salient to women and achievement stress as particularly salient to men (Stroud et al., 2002). Gender-based coping differences have been posited to increase women's vulnerability for developing specific stress-related disorders (Kelly et al., 2008; Kessler et al., 1995; Tamres et al., 2002; Tolin and Foa, 2006). Studies that account for gender-related differences in neuroendocrine,

4.2. Gender, stressful life events, and psychopathology Results suggest a positive correlation between increasing stressful life events and psychopathology, across gender groups and Axis I and II disorders. When gender moderated the relationships between stressful life events and psychopathology, there were stronger associations in women as compared with men, particularly for increasing stressful life events. These results are consistent with, and expand upon, studies that have found gender to moderate significant relationships between trauma and psychiatric symptoms, with stronger associations in women (Breslau and Anthony, 2007; Kucharska, 2017b). Prior prevalence studies have found women to have higher rates of internalizing disorders, such as mood and anxiety disorders, and men to have higher

Table 2 Stressful life event items by gender. Stressful Life Event Items

1. Did any of your family members or close friends die? 2. Did any of your family members or close friends have a serious illness or injury? 3. Did you move or have anyone new come to live with you? 4. Were you fired or laid off from a job? 5. Were you unemployed and looking for a job for more than a month? 6. Have you had trouble with your boss or a coworker? 7. Did you change jobs or job responsibilities or work hours? 8. Did you get separated or divorced or break off a steady relationship? 9. Have you had serious problems with a neighbor, friend, or relative? 10. Have you experienced a major financial crisis, declared bankruptcy or more than once been unable to pay your bills on time? 11. Did you or a family member have trouble with the police, get arrested, or sent to jail? 12. Were you or a family member the victim of any type of crime?

37

Women (n = 24431)

Men (n = 18319)

n (%)

n (%)

χ2

p

5640 (30.79) 5849 (31.95) 2662 (14.50) 1417 (7.72) 1801 (9.81) 1431 (7.80) 4015 (21.88) 1135 (6.18) 799 (4.36) 1878 (10.24)

33.76 144.32 1.08 110.99 23.28 1.55 14.86 6.20 103.01 74.66

< .0001 < .0001 .300 < .0001 < .0001 .214 < .001 .013 < .0001 < .0001

1043 (5.69) 1214 (6.62)

0.79 1.16

.375 .282

8139 9132 3825 1274 2064 1983 4964 1655 1621 3159

(33.45) (37.56) (14.86) (5.22) (8.46) (8.13) (20.35) (6.79) (6.65) (12.96)

1338 (5.49) 1551 (6.36)

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Table 3 Multivariate modeling results. Women

Men

Interaction Odds Ratio: Women v. Men

Moderate Stress vs. Low Stress

High Stress vs. Low Stress

Moderate Stress vs. Low Stress

High Stress vs. Low Stress

Moderate Stress vs. Low Stress

High Stress vs. Low Stress

OR (95% CI)

OR (95% CI)

OR (95% CI)

OR (95% CI)

IOR (95% CI)

IOR (95% CI)

Any Axis I Disorder

2.07 (1.92, 2.24)

4.96 (4.55, 5.39)

1.98 (1.82, 2.15)

4.27 (3.87, 4.69)

1.05 (0.94, 1.18)

1.16 (1.03, 1.32)

Any Mood Disorder Depression Dysthymia Mania Hypomania

2.49 2.68 1.61 2.19 2.36

(2.17, (2.29, (1.25, (1.52, (1.44,

2.86) 3.13) 2.06) 3.17) 3.87)

7.19 (6.27, 8.24) 7.39 (6.33, 8.63) 4.39 (3.43, 5.63) 7.00 (5.42, 10.92) 7.21 (4.52, 11.52)

2.69 2.54 2.54 3.81 3.16

(2.23, (2.02, (1.69, (2.30, (1.87,

3.26) 3.19) 3.82) 6.31) 5.35)

6.36 (5.27, 7.68) 6.39 (5.10, 7.99) 4.54 (3.01, 6.85) 9.10 (5.56, 14.89) 6.50 (3.88, 10.88)

0.93 1.06 0.63 0.58 0.75

(0.73, (0.80, (0.39, (0.31, (0.36,

1.17) 1.39) 1.02) 1.07) 1.54)

1.13 1.16 0.97 0.85 1.11

Any Anxiety Disorder Panic disorder Social Phobia Specific phobia Generalized Anxiety Disorder

1.95 2.16 2.04 1.74 2.53

(1.76, (1.67, (1.63, (1.54, (1.92,

2.17) 2.79) 2.56) 1.97) 3.34)

3.91 5.14 4.24 3.19 7.37

1.79 2.15 1.62 1.81 2.31

(1.54, (1.43, (1.24, (1.50, (1.49,

2.08) 3.24) 2.11) 2.19) 3.60)

2.94 4.82 2.09 2.72 6.10

1.09 1.00 1.26 0.96 1.10

(0.91, (0.62, (0.89, (0.77, (0.65,

1.31) 1.62) 1.79) 1.21) 1.85)

1.33 (1.10, 1.60) 1.07 (0.67, 1.70) 2.03 (1.42, 2.91) 1.17 (0.93, 1.48) 1.21 (0.73, 2.00)

Any Substance Use Disorder Alcohol abuse/dependence Nicotine dependence Drug abuse/dependence

1.85 2.14 1.82 2.29

(1.66, (1.74, (1.61, (1.38,

2.07) 2.63) 2.06) 3.81)

4.06 (3.63, 4.54) 4.67 (3.81, 5.72) 3.93 (3.47, 4.46) 7.56 (4.70, 12.18)

1.80 1.76 1.78 2.31

(1.63, (1.54, (1.58, (1.61,

1.98) 2.00) 2.01) 3.32)

3.72 (3.36, 4.12) 3.43 (3.01, 3.92) 3.53 (3.10, 2.00) 7.49 (5.34, 10.53)

1.03 1.22 1.02 0.99

(0.89, (0.95, (0.86, (0.53,

1.19) 1.56) 1.22) 1.85)

1.09 (0.94, 1.27) 1.36 (1.07, 1.73) 1.12 (0.94, 1.33) 1.01 (0.56, 1.81)

Any Axis II Disorder

2.31 (2.06, 2.59)

5.93 (5.28, 6.66)

2.04 (1.82, 2.29)

4.37 (3.88, 4.92)

1.13 (0.96, 1.33)

1.36 (1.15, 1.60)

Any Cluster A Personality Disorder Paranoid Personality Disorder Schizotypal Personality Disorder

2.46 (2.07, 2.92)

7.01 (5.92, 8.30)

1.91 (1.59, 2.30)

4.38 (3.65, 5.26)

1.29 (1.00, 1.66)

1.60 (1.25, 2.05)

2.63 (2.14, 3.23) 2.11 (1.68, 2.66)

7.87 (6.43, 9.63) 5.22 (4.15, 6.55)

2.32 (1.81, 2.98) 1.90 (1.49, 2.42)

5.85 (4.59, 7.45) 3.73 (2.92, 4.77)

1.13 (0.82, 1.57) 1.11 (0.80, 1.56)

1.35 (0.98, 1.84) 1.40 (1.01, 1.94)

Any Cluster B Personality Disorder Antisocial Personality Disorder

2.63 (1.98, 3.50)

9.36 (7.13, 12.28)

2.44 (1.99, 2.98)

5.86 (4.81, 7.14)

1.08 (0.76, 1.53)

1.60 (1.14, 2.23)

3.44 (2.22, 5.32)

2.32 (1.86, 2.91)

5.84 (4.68, 7.27)

1.48 (0.90, 2.42)

2.30 (1.44, 3.69)

Histrionic Personality Disorder

2.16 (1.51, 3.09)

13.44 (8.85, 20.43) 6.77 (4.81, 9.53)

2.85 (1.94, 4.18)

5.93 (4.07, 8.64)

0.76 (0.45, 1.28)

1.14 (0.69, 1.89)

Any Cluster C Personality Disorder Avoidant Personality Disorder Dependent Personality Disorder Obsessive Compulsive Personality Disorder

2.20 (1.92, 2.52)

5.35 (4.66, 6.15)

2.01 (1.74, 2.32)

3.75 (3.22, 4.36)

1.10 (0.90, 1.34)

1.43 (1.17, 1.75)

2.09 (1.60, 2.72) 2.41 (1.38, 4.20) 2.17 (1.87, 2.52)

5.48 (4.23, 7.10) 5.25 (3.01, 9.18) 5.22 (4.48, 6.08)

2.23 (1.57, 3.16) 1.46 (0.66, 3.23) 1.96 (1.68, 2.29)

4.55 (3.22, 6.42) 3.70 (1.75, 7.83) 3.67 (3.13, 4.31)

0.94 (0.61, 1.45) 1.65 (0.63, 4.36) 1.11 (0.89, 1.37)

1.21 (0.79, 1.85) 1.42 (0.57, 3.55) 1.42 (1.15, 1.77)

(3.50, (3.98, (3.37, (2.80, (5.59,

4.36) 6.64) 5.34) 3.63) 9.70)

(2.52, (3.23, (1.57, (2.23, (3.97,

3.44) 7.20) 2.77) 3.33) 9.37)

(0.90, (0.88, (0.60, (0.47, (0.56,

1.42) 1.52) 1.55) 1.54) 2.22)

Axis I accounts for Past-year disorders at Wave 1; Axis II accounts for Lifetime disorders at Wave 1.

phobias, at higher rates than men (Bruce et al., 2005; Eaton et al., 2012; Kessler et al., 1993), prior research has found gender-related differences to be least pronounced for social anxiety disorder (Breslau et al., 2000). The stronger connection in the current study between increasing stressful life events and social phobia in women as compared to men warrants further examination. The finding of a stronger relationship in women between increasing stressful life events and alcohol-use disorders is consistent with prior reports of stress linked to increased drinking in women (Sinha, 2001), expanding on research highlighting the connection between early stress experiences and the development of SUDs (Khantzian, 1985; McClellan et al., 1997). Gender-related differences in emotional and craving responses to stress have been hypothesized to underlie the differential risk for alcohol-use disorders (Chaplin et al., 2008; Kajantie and Phillips, 2005). Gender-related differences in subjective, behavioral, physiological and craving responses to stress have been identified, with variability in their relationships to alcohol craving and substance use. For example, while women were more likely than men to report and show negative emotion following induced stress, negative emotion was related to alcohol craving in men only (Chaplin et al., 2008). Further, physiological stress responses, including gender-related differences in the hypothalamus-pituitary-adrenal (HPA) axis stress response (Kudielka and Kirschbaum, 2005), may also influence how men and women respond to psychosocial stressors in daily life (Chaplin et al.,

rates of externalizing disorders, such as ASPD and other PDs (Eaton et al., 2012; Hasin and Grant, 2015). Some explanations include a dimensional, gender-invariant, internalizing-externalizing liability model to explain such gender-related differences in these classes of disorders (Eaton et al., 2012), whereby these differences in prevalence originate at the level of latent internalizing and externalizing liabilities. However, in the context of moderate to high stressful life events, this internalizing-externalizing liability model does not fit these data, as women were more likely than men to endorse alcohol-use disorders and ASPD in the context of more versus less stressful life events. Findings related to gender, stressful life events, and individual psychiatric disorders are discussed below. 4.2.1. Axis I disorders There were stronger links for women versus men between increasing stressful life events and social phobia and between increasing stressful life events and alcohol-use disorders. Women tend to demonstrate greater fear and anxiety across the lifespan when compared to men (McLean and Anderson, 2009). Researchers have identified several factors that may contribute to women's greater vulnerability for fear, including negative affectivity, heightened anxiety sensitivity, use of emotion-focused coping, and gender-specific stressors and traumas (McLean and Anderson, 2009). However, while women have been found to develop anxiety disorders, including specific and social 38

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increasing stressful life events and OCPD. Prevalence estimates suggest that men are more likely than women to meet criteria for OCPD in the general population (Grant et al., 2004) and in the context of depression (Golomb et al., 1995). However, our results demonstrate that women with OCPD are more likely to experience multiple stressful life events. Researchers have documented associations between anxiety disorders and OCPD with anorexia in women (Strober et al., 2007). Perhaps shared genetic, neural, and behavioral mechanisms of anxiety disorders, anorexia, and OCPD reflecting stress vulnerability may help explain these results, although the extent to which individuals, and particularly women, through engaging in OCPD-related tendencies may experience more stressful life events also warrants consideration.

2008; Kajantie, 2008). While some prior studies have identified greater risk for alcohol-use disorders in men (Kessler et al., 1993), in the context of increasing stressful life events, women were significantly more likely than men to meet criteria for alcohol-use disorders in the current study. Gender-related differences involving specific risk and protective factors, motivations to use, patterns of use, rates of progression to dependence may link to stress responsiveness; future studies should consider how physiology and/or appraisal of stress may relate to the development of SUDs in women and men experiencing stressful life events. The absence of a stronger relationship between stress and psychopathology in women than men among those with depression is worth noting. Higher rates of depression have been well documented in women across the lifespan (Nolen-Hoeksema, 2001; Parker& Brotchie, 2010; Piccinelli and Wilkinson, 2000), and have been suggested to be influenced by stress (Hankin and Abramson, 2001). While women's prevalence rates of depression were significantly higher than men's in this study, these differences were no longer significant or pronounced when stress was accounted for in multivariate models. Recent findings suggest that acute stressors, in addition to externalizing psychopathology and failure to achieve goals, predict depression in men (Kendler and Gardner, 2014). Nuanced gender-related differences in the relationship between more prevalent stressful life experiences, responses to stress, and depression should be explored in future studies.

4.3. Limitations and strengths Multiple study limitations exist. Stressful life events were assessed using a relatively blunt measure. The 12-item checklist with dichotomous responses provided limited information about context, including the lengths of time since stressors were experienced by participants (i.e., participants were only asked about stressors within the past year). Information about only the nature of the stressful event – but not the subjective or physiologic response to the event – was measured. Further, the nature of the stress assessment measure did not allow for the detection of curvilinear associations between stressful life events and psychopathologies. Such curvilinear relationships have been reported and suggests that moderate (but not low or high) stress may build resilience (Seery et al., 2010; Russo et al., 2012; Sapolsky, 2015). More nuanced assessments of stress are warranted in future studies. More comprehensive stress assessments could account for contexts of, timings of, and responses to specific stressors. Further longitudinal research is needed in order to clarify the nature and directionality of the relationships between stressful life events and psychopathology. Data were cross-sectional and included retrospective assessments, limiting investigation into causal relationships and introducing potential recall biases. The NESARC did not assess all DSM-IV Axis I and Axis II disorders (e.g., stress-related illnesses like post-traumatic stress disorder) because of concerns about response burden. Future research examining the psychiatric correlates of stressful life events might benefit from the use of DSM-5 assessments and inclusion of measures that assess additional psychiatric diagnoses. Although we conducted multiple comparisons to evaluate the association between stressful life events, gender, and PDs, we did not reduce the alpha for statistical significance. Some forms of correction (e.g., Bonferroni) have been considered as overly conservative (Bender and Lange, 2001). Given the absence of correction for multiple comparisons, the findings should be considered as exploratory. Because of our large sample size, it is also possible that the gender-related differences in the relationships between stressful life events and psychopathology reached statistical significance without having a substantial clinical impact. On the other hand, the existence of these differences, in line with NIH efforts to understand better how gender may influence health, argue for the need for additional studies into the clinical impacts of specific stressful life events in women and in men. Finally, participants were restricted to non-treatment-seeking and non-institutionalized people, which limits the generalizability of findings. A strength is the large, national sample assessed using valid and reliable diagnostic measures. Thus, the study permits insight into how stressors relate to psychopathologies in women and men in the community in the United States. Important questions remain regarding the nature of the associations between stressors and psychopathologies. Further research is needed to help clarify the nature of the observed findings. Future longitudinal studies should examine relationships between stressful life events, responses to stress, and psychopathology in a gender-informed fashion. In order to contextualize when and in what settings these relationships develop, consideration of other factors (e.g., developmental, cultural,

4.2.2. Axis II disorders There were stronger links for women as compared to men between increasing stressful life events and schizotypal PD, ASPD, and OCPD. Gender-related differences in course, outcome, symptomatology and risk factors for schizophrenia have been identified (Lewis, 1992); however, while schizotypal PD may be considered along a continuum of schizophrenia-related disorders, less data are available on gender-related differences in schizotypal PD (Reynolds et al., 2000). Gender-related differences in the individual features of schizotypal PD have been found among college students, with women scoring higher on the more positive schizotypal characteristics (e.g., ideas of reference, odd beliefs/ magical thinking) and men scoring higher on eccentric/odd behavior (Raine, 1992; Roth and Baribeau, 1997). Significant gender-related differences in the factor structure or factor inter-correlations of schizotypal PD have not yet been identified in general or clinical populations (Reynolds et al., 2000). Further study of gender-related differences with individuals with schizotypal PD and/or schizotypal personality features during the context of increasing stressful life events is needed. In our study, the relationship between stressful life events and ASPD was robust, and was significantly stronger in women than in men. While prevalence rates show that men are more likely than women to be diagnosed with ASPD (Alegria et al., 2013; Compton et al., 2005; Eaton et al., 2012; Grant et al., 2004), research on early risk factors of antisocial behavior has not identified meaningful gender-related differences in neurocognitive deficits nor family adversity (Moffitt et al., 2001). Research on gender-related differences in correlates of ASPD has identified more frequent experiences of childhood neglect, sexual abuse, parent-related adverse effects in childhood, and adverse effects in adulthood for women with ASPD as compared with men with ASPD (Alegria et al., 2013). Further, women with ASPD have higher rates of victimization, greater impairment, lower social support, and higher rates of aggressiveness and irritability, suggesting that this population may have increased mental health needs when compared to men with ASPD (Alegria et al., 2013). There is evidence of high comorbidity among PDs, SUDs, and other disorders related to emotion regulation and/or impulse problems more broadly, and the negative impacts of stress on emotion regulation and impulse control have also been documented (Trull et al., 2010). Further research with men and women is needed to enrich our understanding of these relationships. We observed a stronger relationship in women versus men between 39

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class-related) is warranted. Results suggest the need for gender-sensitive assessments of stressful life events and psychopathology and that policy and treatment guidelines should consider gender-related differences in stressors experienced and stress responsiveness.

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Funding support No financial support was received for data collection for this study. Dr. Armstrong's work on this project was supported with resources and the use of facilities at VA Connecticut Healthcare System, West Haven, CT, as a VA advanced addiction psychology fellow funded through VA Office of Academic Affiliations. Dr. Ronzitti currently receives support as a VA advanced medical informatics postdoctoral fellow funded through VA Office of Academic Affiliations. Dr. Hoff has no financial disclosures to declare for her work on this project. Dr. Potenza's involvement was supported by the National Center for Responsible Gaming through a Center of Excellence grant, the Connecticut Department of Mental Health and Addiction Services and the Connecticut Council on Problem Gambling. The views presented in this manuscript are those of the authors and do not necessarily reflect those of the funding agencies. The content of the manuscript does not necessarily reflect the views of any of the funding agencies. Conflicts of interest and disclosures The views expressed in this manuscript are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. The authors report no conflict of interest with respect to the content of this manuscript. Dr. Potenza has consulted for and advised Rivermend Health, Opiant/Lightlake Therapeutics and Jazz Pharmaceuticals; received research support (to Yale) from the Mohegan Sun Casino and the National Center for Responsible Gaming; consulted for legal and gambling entities on issues related to impulse control and addictive behaviors; provided clinical care related to impulse control and addictive behaviors; performed grant reviews; edited journals/ journal sections; given academic lectures in grand rounds, CME events and other clinical/scientific venues; and generated books or chapters for publishers of mental health texts. The other authors report no disclosures with commercial interests. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.jpsychires.2018.09.012. References Alegria, A.A., Petry, N.M., Liu, S.M., Blanco, C., Skodol, A.E., Grant, B., Hasin, D., 2013. Sex differences in antisocial personality disorder: results from the national epidemiological survey on alcohol and related conditions. Pers. Disord. 4 (3), 214–222. https://doi.org/10.1037/a0031681. American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. DSM-IV, Washington, D.C. Bangassar, D.A., Valentino, R.J., 2014. Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front. Neuroendocrinol. 35 (3), 303–319. Barry, D.T., Pilver, C., Potenza, M.N., Desai, R.A., 2012. Prevalence and psychiatric correlates of pain interference among men and women in the general population. J. Psychiatr. Res. 46, 118–127. Barry, D.T., Pilver, C.E., Hoff, R.A., Potenza, M.N., 2013. Pain interference and incident mood, anxiety, and substance-use disorders: findings from a representative sample of men and women in the general population. J. Psychiatr. Res. 47, 1658–1664. Bender, R., Lange, S., 2001. Adjusting for multiple testing – when and how? J. Clin. Epidemiol. 54 (4), 343–349. Breslau, N., Anthony, J.C., 2007. Gender differences in the sensitivity to posttraumatic stress disorder: an epidemiological study of urban young adults. J. Abnorm. Psychol. 116, 607–611.

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