Faculty Bibliography

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with high rates of psychiatric comorbidity, most notably substance use disorders, major depression, and other anxiety disorders. However, little is known about how these disorders cluster together among people with PTSD, if disorder clusters have distinct etiologies in terms of trauma type, and if they confer greater burden over and above PTSD alone. METHOD: Utilizing Latent Class Analysis, we tested for discrete patterns of lifetime comorbidity with PTSD following trauma exposure (n = 409). Diagnoses were based on the Structured Clinical Interview for DSM-IV (SCID). Next, we examined if gender, trauma type, symptom frequency, severity, and interference with everyday life were associated with the latent classes. RESULTS: Three patterns of lifetime comorbidity with PTSD emerged: a class characterized by predominantly comorbid mood and anxiety disorders; a class characterized by predominantly comorbid mood, anxiety, and substance dependence; and a relatively pure low-comorbidity PTSD class. Individuals in both high comorbid classes had nearly two and a half times the rates of suicidal ideation, endorsed more PTSD symptom severity, and demonstrated a greater likelihood of intimate partner abuse compared to the low comorbidity class. Men were most likely to fall into the substance dependent class. CONCLUSION: PTSD comorbidity clusters into a small number of common patterns. These patterns may represent an important area of study, as they confer distinct differences in risk and possibly etiology. Implications for research and treatment are discussed.

BACKGROUND: Our goal was to better understand distinct PTSD symptom presentations in Iraq and Afghanistan Veterans (N=227) and to determine whether those who killed in war were at risk for being in the most symptomatic class. METHODS: We used latent class analysis of responses to the PTSD checklist and logistic regression of most symptomatic class. RESULTS: We found that a four-class solution best fit the data, with the following profiles emerging: High Symptom (34% of participants), Intermediate Symptom (41%), Intermediate Symptom with Low Emotional Numbing (10%), and Low Symptom (15%). The largest group of individuals who reported killing (45%) was in the High Symptom class, and those who killed had twice the odds of being in the most symptomatic PTSD class, compared to those who did not kill. Those who endorsed killing a non-combatant (OR=4.56, 95% CI [1.77, 11.7], p<0.01) or killing in the context of anger or revenge (OR=4.63, 95% CI=[1.89, 11.4], p<0.001) were more likely to belong to the most symptomatic PTSD class, compared to those who did not kill. LIMITATIONS: The study was retrospective and cross-sectional. The results may not generalize to veterans of other wars. CONCLUSIONS: Killing in war may be an important indicator of risk for developing frequent and severe PTSD symptoms. This has implications for the mental healthcare of veterans, providing evidence that a comprehensive evaluation of returning veterans should include an assessment of killing experiences and reactions to killing.

Pavlovian threat (fear) conditioning (PTC) is an experimental paradigm that couples innate aversive stimuli with neutral cues to elicit learned defensive behavior in response to the neutral cue. PTC is commonly used as a translational model to study neurobiological and behavioral aspects of fear and anxiety disorders including Posttraumatic Stress Disorder (PTSD). Though PTSD is a complex multi-faceted construct that cannot be fully captured in animals PTC is a conceptually valid model for studying the development and maintenance of learned threat responses. Thus, it can inform the understanding of PTSD symptomatology. However, there are significant individual differences in posttraumatic stress that are not as of yet accounted for in studies of PTC. Individuals exposed to danger have been shown to follow distinct patterns: some adapt rapidly and completely (resilience) others adapt slowly (recovery) and others failure to adapt (chronic stress response). Identifying similar behavioral outcomes in PTC increases the translatability of this model. In this report we present a flexible methodology for identifying individual differences in PTC by modeling latent subpopulations or classes characterized by defensive behavior during training. We provide evidence from a reanalysis of previously examined PTC learning and extinction data in rats to demonstrate the effectiveness of this methodology in identifying outcomes analogous to those observed in humans exposed to threat. By utilizing Latent Class Growth Analysis (LCGA) to test for heterogeneity in freezing behavior during threat conditioning and extinction learning in adult male outbred rats (n = 58) three outcomes were identified: rapid extinction (57.3%), slow extinction (32.3%), and failure to extinguish (10.3%) indicating that heterogeneity analogous to that in naturalistic human studies is present in experimental animal studies strengthening their translatability in understanding stress responses in humans.

CONTEXT: Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder's pathogenesis and prophylaxis. OBJECTIVES: To describe discrete symptom trajectories and examine their relevance for preventive interventions. DESIGN: Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data. SETTING: Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity. PARTICIPANTS: Adult survivors of potentially traumatic events consecutively admitted to the hospital's emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months. APPROACH: We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8+/-5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8+/-42.4 days. CBT effectively reduced PTSD symptoms in the entire sample. MAIN OUTCOME MEASURE: Latent trajectories of PTSD symptoms; effects of CBT on these trajectories. RESULTS: THREE TRAJECTORIES WERE IDENTIFIED: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes. CONCLUSIONS: The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.

BACKGROUND: Several lines of evidence link cannabinoid (CB) type 1 (CB (1) ) receptor-mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB (1) receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD. METHODS: Medication-free participants were scanned during early abstinence 4 weeks after their last drink. Using positron emission tomography (PET) with a high-resolution research tomograph and the CB (1) receptor selective radiotracer [(11) C]OMAR, we determined [(11) C]OMAR volume of distribution ( V (T) ) values, a measure of CB (1) receptor density, in a priori selected brain regions in men with AD (n = 8, age 37.4 +/- 7.9 years; 5 smokers) and healthy control (HC) men (n = 8, age 32.5 +/- 6.9 years; all nonsmokers). PET images reconstructed using the MOLAR algorithm with hardware motion correction were rigidly aligned to the subject-specific magnetic resonance (MR) image, which in turn was warped to an MR template. Time-activity curves (TACs) were extracted from the dynamic PET data using a priori selected regions of interest delineated in the MR template space. RESULTS: In AD relative to HC, [(11) C]OMAR V (T) values were elevated by approximately 20% (p = 0.023) in a circuit, including the amygdala, hippocampus, putamen, insula, anterior and posterior cingulate cortices, and orbitofrontal cortex. Age, body mass index, or smoking status did not influence the outcome. CONCLUSIONS: These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB (1) receptors in AD. The current study design does not answer the important question of whether elevated CB (1) receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.

PURPOSE/OBJECTIVE: To investigate longitudinal trajectories of depression and anxiety symptoms following spinal cord injury (SCI) as well as the predictors of those trajectories. RESEARCH METHOD/DESIGN: A longitudinal study of 233 participants assessed at 4 time points: within 6 weeks, 3 months, 1 year, and 2 years from the point of injury. Data were analyzed using latent growth mixture modeling to determine the best-fitting model of depression and anxiety trajectories. Covariates assessed during hospitalization were explored as predictors of the trajectories. RESULTS: Analyses for depression and anxiety symptoms revealed 3 similar latent classes: a resilient pattern of stable low symptoms, a pattern of high symptoms followed by improvement (recovery), and delayed symptom elevations. A chronic high depression pattern also emerged but not a chronic high anxiety pattern. Analyses of predictors indicated that compared with other groups, resilient patients had fewer SCI-related quality of life problems, more challenge appraisals and fewer threat appraisals, greater acceptance and fighting spirit, and less coping through social reliance and behavioral disengagement. CONCLUSION/IMPLICATIONS: Overall, the majority of SCI patients demonstrated considerable psychological resilience. Models for depression and anxiety evidenced a pattern of elevated symptoms followed by improvement and a pattern of delayed symptoms. Chronic high depression was also observed but not chronic high anxiety. Analyses of predictors were consistent with the hypothesis that resilient individuals view major stressors as challenges to be accepted and met with active coping efforts. These results are comparable to other recent studies of major health stressors.

Studies of individual differences in bereavement have revealed prototypical patterns of outcome. However, many of these studies were conducted prior to the advent of sophisticated contemporary data analytic techniques. For example, Bonanno et al. (2002) used rudimentary categorization procedures to identify unique trajectories of depression symptomatology from approximately 3 years prior to 4 years following conjugal loss in a representative sample of older American adults. In the current study, we revisited these same data using Latent Class Growth Analysis (LCGA) to derive trajectories and test predictors. LCGA is a technique well-suited for modeling empirically- and conceptually-derived heterogeneous longitudinal patterns while simultaneously modeling predictors of those longitudinal patterns. We uncovered four discrete trajectories similar in shape and proportion to the previous analyses: Resilience (characterized by little or no depression; 66.3%), Chronic Grief (characterized by depression following loss, alleviated by 4 years post-loss; 9.1%), _Pre-existing Chronic Depression (ongoing high pre- through post-loss depression; 14.5%), and Depressed-Improved (characterized by high pre-loss depression that decreases following loss; 10.1%). Using this analytic strategy, we were able to examine multiple hypotheses about bereavement simultaneously. Health, financial stress, and emotional stability emerged as strong predictors of variability in depression only for some trajectories, indicating that depression levels do not have a common etiology across all the bereaved. As such, we find that identifying distinct patterns informs both the course and etiology of depression in response to bereavement.

Research has consistently demonstrated that stress reactions to potentially traumatic events do not represent a unified phenomenon. Instead, individuals tend to cluster into prototypical response patterns over time including chronic symptoms, recovery, and resilience. We examined heterogeneity in a posttraumatic stress disorder (PTSD) symptom course in a sample of 178 active-duty police officers following exposure to a life-threatening event using latent growth mixture modeling (LGMM). This analysis revealed 3 discrete PTSD symptom trajectories: resilient (88%), distressed-improving (10%), and distressed-worsening (2%). We further examined whether trait and peritraumatic dissociation distinguished these symptom trajectories. Findings indicate that trait and peritraumatic dissociation differentiated the resilient from the distressed-improving trajectory (trait, p < .05; peritraumatic, p < .001), but only peritraumatic dissociation differentiated the resilient from the distressed-worsening trajectory (p < .001). It is essential to explore heterogeneity in symptom course and its predictors among active-duty police officers, a repeatedly exposed group. These findings suggest that police officers may be a highly resilient group overall. Furthermore, though there is abundant evidence that dissociation has a positive linear relationship with PTSD symptoms, this study demonstrates that degree of dissociation can distinguish between resilient and symptomatic groups of individuals

This study examined the relationship between killing or seriously injuring someone in the line of duty and mental health symptoms in a sample of police officers (N = 400) who were first assessed during academy training and at five additional time points over three years. We found that nearly 10% of police officers reported having to kill or seriously injure someone in the line of duty in the first three years of police service. After controlling for demographics and exposure to life threat, killing or seriously injuring someone in the line of duty was significantly associated with PTSD symptoms (p < .01) and marginally associated with depression symptoms (p = .06). These results highlight the potential mental health impact of killing or seriously injuring someone in the line of duty. Greater attention to mental health services following these types of exposures can serve as a preventative measure for police officers who have been negatively impacted

A recent article in New York Magazine echoed what psychological studies of parenthood have consistently demonstrated since the 1970s: "Most people assume that having children will make them happier. Yet a wide variety of academic research shows that parents are not happier than their childless peers, and in many cases are less so" (Senior, 2010). There is consistent evidence that, as opposed to other life events that cause transient disruptions in life satisfaction, becoming a parent appears to cause harm to individual subjective well-being (Twenge, Campbell, & Foster, 2003), and that this harm is sustained over time (Clark, Diener, Georgellis, & Lucas, 2008). The current investigation was predicated on the concern that these findings may be the result of the methodology used to examine them. As the experience of parenthood does not represent a unified phenomenon, we employed a methodological approach that allows for the exploration of heterogeneity as well as its predictors. By modeling heterogeneous trajectories within a prospective design from 4 years prior to 4 years after the birth of a parent's first child, we find that the majority of individuals (84.2%) demonstrate no long-term effects on life satisfaction in response to childbirth. Only a small percentage demonstrate the sustained declines (7.2%), and a significant cohort, previously unobserved in the literature, demonstrate dramatic and sustained improvements in response to parenthood (4.3%), providing compelling evidence for heterogeneity in life satisfaction among parents. Key demographic covariates that distinguish between trajectories of response are also explored.