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Heterogeneity in threat extinction learning: substantive and methodological considerations for identifying individual difference in response to stress

Galatzer-Levy, Isaac R; Bonanno, George A; Bush, David E A; Ledoux, Joseph E
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.
PMCID:3665921
PMID: 23754992
ISSN: 1662-5153
CID: 394072

Positron Emission Tomography Shows Elevated Cannabinoid CB (1) Receptor Binding in Men with Alcohol Dependence

Neumeister, Alexander; Normandin, Marc D; Murrough, James W; Henry, Shannan; Bailey, Christopher R; Luckenbaugh, David A; Tuit, Keri; Zheng, Ming-Qiang; Galatzer-Levy, Isaac R; Sinha, Rajita; Carson, Richard E; Potenza, Marc N; Huang, Yiyun
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.
PMCID:3418442
PMID: 22551199
ISSN: 0145-6008
CID: 178208

Trajectories of resilience, depression, and anxiety following spinal cord injury

Bonanno, George A; Kennedy, Paul; Galatzer-Levy, Isaac R; Lude, Peter; Elfstrom, Mangus L
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.
PMID: 22946611
ISSN: 0090-5550
CID: 226452

Beyond normality in the study of bereavement: heterogeneity in depression outcomes following loss in older adults

Galatzer-Levy, Isaac R; Bonanno, George A
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.
PMCID:4712952
PMID: 22472274
ISSN: 0277-9536
CID: 226462

The impact of killing and injuring others on mental health symptoms among police officers

Komarovskaya, Irina; Maguen, Shira; McCaslin, Shannon E; Metzler, Thomas J; Madan, Anita; Brown, Adam D; Galatzer-Levy, Isaac R; Henn-Haase, Clare; Marmar, Charles R
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
PMCID:3974970
PMID: 21658717
ISSN: 1879-1379
CID: 137879

Peritraumatic and trait dissociation differentiate police officers with resilient versus symptomatic trajectories of posttraumatic stress symptoms

Galatzer-Levy IR; Madan A; Neylan TC; Henn-Haase C; Marmar CR
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
PMCID:3974926
PMID: 21898602
ISSN: 1573-6598
CID: 140504

What we don't expect when expecting: evidence for heterogeneity in subjective well-being in response to parenthood

Galatzer-Levy, Isaac R; Mazursky, Heather; Mancini, Anthony D; Bonanno, George A
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.
PMID: 21553960
ISSN: 0893-3200
CID: 226472

August Aichhorn: a different vision of psychoanalysis, children, and society [Historical Article]

Galatzer-Levy, Isaac R; Galatzer-Levy, Robert M
Though August Aichhorn, in name, remains a significant figure in the history of psychoanalysis, his ideas have been all but abandoned in the modern clinical conception of the treatment of children and adolescents who act out. The current treatment of children and adolescents, so disturbed that their behavior demands treatment outside of their home environment, is currently rudderless and highly dependent on broad societal counter-transferential reactions to disturbed youth. We argue that not only does Aichhorn hold a distinguished position in the history of the treatment of youngsters, but that his ideas about the meaning of severely disruptive behavior as well as the techniques which align with those theories remain relevant and, if utilized, would improve the treatment of severely disturbed youth.
PMID: 18524091
ISSN: 0079-7308
CID: 226482

The revolution in psychiatric diagnosis: problems at the foundations [Historical Article]

Galatzer-Levy, Isaac R; Galatzer-Levy, Robert M
The third edition of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-III; 1974) not only revolutionized psychiatric diagnosis, it transformed and dominated American psychiatry. The nosology of psychiatry had been conceptually confusing, difficult to apply, and bound to widely questioned theories. Psychiatry and clinical psychology had been struggling with their scientific status. DSM attempted to solve psychiatry's problems by making psychiatry more like its authors' perception of general medicine. It tried to avoid theory, especially psychoanalytic theories, by discussing only observable manifestations of disorders. But DSM is actually highly theory-bound. It implicitly and powerfully includes an exclusively "medical" model of psychological disturbance, while excluding other psychiatric ideas. Its authors tried to meet what they saw as "scientific standards." To a surprising extent, DSM reflects its creators' personal distaste for psychoanalysis. The result is that DSM rests on a narrow philosophical perspective. The consequences of its adoption are widespread: it has profoundly affected drug development and other therapeutic studies, psychiatric education, attitudes toward patients, the public perception of psychiatry, and administrative and legal decisions. This article explores how DSM's most problematic features arise from its history in psychiatric controversies of the 1960s and its underlying positivistic philosophy.
PMID: 17468537
ISSN: 0031-5982
CID: 226492