Santiago Papini

Combining seeking safety with sertraline for PTSD and alcohol use disorders: A randomized controlled trial.

OBJECTIVE The current study marks the first randomized controlled trial to test the benefit of combining Seeking Safety (SS), a present-focused cognitive-behavioral therapy for co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), with sertraline, a front-line medication for PTSD shown to also impact drinking outcomes. METHOD Sixty-nine participants (81% female; 59% African American) with primarily childhood sexual (46%) and physical (39%) trauma exposure, and drug dependence in addition to AUD were randomized to receive a partial-dose (12 sessions) of SS with either sertraline (n = 32; M = 7 sessions) or placebo (n = 37; M = 6 sessions). Assessments conducted at baseline, end-of-treatment, 6- and 12-months posttreatment measured PTSD and AUD symptom severity. RESULTS Both groups demonstrated significant improvement in PTSD symptoms. The SS plus sertraline group exhibited a significantly greater reduction in PTSD symptoms than the SS plus placebo group at end-of-treatment (M difference = -16.15, p = .04, d = 0.83), which was sustained at 6- and 12-month follow-up (M difference = -13.81, p = .04, d = 0.71, and M difference = -12.72, p = .05, d = 0.65, respectively). Both SS groups improved significantly on AUD severity at all posttreatment time points with no significant differences between SS plus sertraline and SS plus placebo. CONCLUSION Results support the combining of a cognitive-behavioral therapy and sertraline for PTSD/AUD. Clinically significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up, Moreover, greater mean improvement in PTSD symptoms was observed across all follow-up assessments in the SS plus sertraline group. (PsycINFO Database Record

Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study.

Background Neurobiological models of posttraumatic stress disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Specific deficits in extinction recall, the retention of learned extinction, have been demonstrated. While deficient extinction recall, and the associated activation pattern of prefrontal and hippocampal regions, distinguishes individuals with PTSD from controls, research has not yet examined changes following treatment. We examined the behavioral and neural correlates of extinction recall before and after cognitive behavioral treatment of PTSD. Methods Fifty-eight participants (30 with PTSD, 28 trauma-exposed matched controls) underwent a 2-day behavioral fear conditioning, extinction, and recall paradigm during functional magnetic resonance imaging (fMRI). The same procedures were repeated 10 weeks later, after PTSD patients had completed prolonged exposure treatment. We analyzed fMRI data from 32 subjects (16 PTSD; 16 controls) and skin conductance response (SCR) data from 33 subjects (16 PTSD; 17 controls). Neural activity during extinction recall, SCR, and PTSD symptoms were compared across groups and over time. Results PTSD patients exhibited pre- to post-treatment reduction in rostral anterior cingulate cortex (rACC) activation during extinction recall, and increase in functional coherence between the rACC and the ventromedial prefrontal cortex (vmPFC) and subgenual anterior cingulate cortex (sgACC). Reduced PTSD symptom severity from pre- to post-treatment was significantly associated with reduced subgenual ACC and parahippocampal activation during this task. SCR during the extinction recall phase did not significantly change with treatment in the PTSD group, but change in SCR was associated with reduction in PTSD symptom severity. Conclusions Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR) is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

Toward a translational approach to targeting the endocannabinoid system in posttraumatic stress disorder: A critical review of preclinical research

Despite the lack of clinical research, marijuana and synthetic cannabinoids have been approved to treat posttraumatic stress disorder (PTSD) in several states in the United States. This review critically examines preclinical research on the endocannabinoid system (ECS) in order to evaluate three key questions that are relevant to PTSD: (1) Does ECS dysfunction impact fear extinction? (2) Can stress-related symptoms be prevented by ECS modulation? (3) Is the ECS a potential target for enhancing PTSD treatment? Disruption of the ECS impaired fear extinction in rodents, and ECS abnormalities have been observed in PTSD. Targeting fear memories via the ECS had mixed results in rodents, whereas augmented cannabinoid receptor activation typically facilitated extinction. However, the translational value of these findings is limited by the paucity and inconsistency of human research. Further investigation is necessary to determine whether incorporating cannabinoids in treatment would benefit individuals with PTSD, with cautious attention to risks.

At the Crossroads: The Intersection of Substance Use Disorders, Anxiety Disorders, and Posttraumatic Stress Disorder

The co-occurrence of substance use disorders with anxiety disorders and/or posttraumatic stress disorder has been widely documented and when compared to each disorder alone, consistently linked to increased risk for a host of negative outcomes including greater impairment, poorer treatment response, and higher rates of symptom relapse. This article focuses on recent advances in the understanding and effective treatment of this common and highly complex comorbidity. Prevalence and epidemiological data are introduced, followed by a review of contemporary models of etiology and associative pathways. Conceptualizations of effective treatment approaches are discussed alongside evidence from the past decade of clinical research trials. Highlighted are ongoing questions regarding the benefit of sequential, parallel, and integrated approaches and the necessity of further investigation into the mechanisms underlying treatment efficacy. Lastly, recent contributions from neuroscience research are offered as a promising bridge for the development and testing of novel, interdisciplinary treatment approaches.

Greater hippocampal volume is associated with PTSD treatment response

Previous research associates smaller hippocampal volume with posttraumatic stress disorder (PTSD). It is unclear, however, whether treatment affects hippocampal volume or vice versa. Seventy-six subjects, 40 PTSD patients and 36 matched trauma-exposed healthy resilient controls, underwent clinical assessments and magnetic resonance imaging (MRI) at baseline, and 10 weeks later, during which PTSD patients completed ten weeks of Prolonged Exposure (PE) treatment. The resilient controls and treatment responders (n=23) had greater baseline hippocampal volume than treatment non-responders (n=17) (p=0.012 and p=0.050, respectively), perhaps due to more robust fear-extinction capacity in both the initial phase after exposure to trauma and during treatment.

Pathways to change: Use trajectories following trauma-informed treatment of women with co-occurring post-traumatic stress disorder and substance use disorders.

INTRODUCTION AND AIMS Despite advances towards integration of care for women with co-occurring substance use disorder (SUD) and post-traumatic stress disorder (PTSD), low abstinence rates following SUD/PTSD treatment remain the norm. The utility of investigating distinct substance use trajectories is a critical innovation in the detection and refining of effective interventions for this clinical population. DESIGN AND METHODS The present study reanalysed data from the largest randomised clinical trial to date for co-occurring SUD and PTSD in women (National Drug Abuse Treatment Clinical Trials Network; Women and Trauma Study). Randomised participants (n = 353) received one of two interventions in addition to treatment as usual for SUD: (i) trauma-informed integrative treatment for PTSD/SUD; or (ii) an active control psychoeducation course on womens health. The present study utilised latent growth mixture models (LGMM) with multiple groups to estimate womens substance use patterns during the 12-month follow-up period. RESULTS Findings provided support for three different trajectories of substance use in the post-treatment year: (i) consistently low likelihood and use frequency; (ii) consistently high likelihood and use frequency; and (iii) high likelihood and moderate use frequency. Covariate analyses revealed improvement in PTSD severity was associated with membership in a specific substance use trajectory, although receiving trauma-informed treatment was not. Additionally, SUD severity, age and after-care efforts were shown to be related to trajectory membership. DISCUSSION AND CONCLUSIONS Findings highlight the necessity of accounting for heterogeneity in post-treatment substance use, relevance of trauma-informed care in SUD recovery and benefits of incorporating methodologies like LGMM when evaluating SUD treatment outcomes.

Identifying profiles of recovery from reward devaluation in rats.

In humans and other mammals, the unexpected loss of a resource can lead to emotional conflict. Consummatory successive negative contrast (cSNC) is a laboratory model of reward devaluation meant to capture that conflict. In this paradigm, animals are exposed to a sharp reduction in the sucrose concentration of a solution after several days of access. This downshift in sucrose content leads to behavioral responses such as the suppression of consumption and physiologic responses including elevation of corticosterone levels. However, response heterogeneity in cSNC has yet to be explored and may be relevant for increasing the validity of this model, as humans demonstrate clinically meaningful heterogeneity in response to resource loss. The current analysis applied latent growth mixture modeling to test for and characterize heterogeneity in recovery from cSNC among rats (N=262). Although most animals exhibited recovery of consummatory behavior after a sharp drop in consumption in the first postshift trial (Recovery class; 83%), two additional classes were identified including animals that did not change their consumption levels after downshift (No Contrast class; 6%), and animals that exhibited an initial response similar to that of the Recovery class but did not recover to preshift consumption levels (No Recovery class; 11%). These results indicate heterogeneity in recovery from reward loss among rats, which may increase the translatability of this animal model to understand diverse responses to loss among humans.

A cross species study of heterogeneity in fear extinction learning in relation to FKBP5 variation and expression: Implications for the acute treatment of posttraumatic stress disorder

&NA; Deficits in fear extinction learning are hypothesized to underlie the development of posttraumatic stress disorder (PTSD). Such deficits may, in part, be due to genetic and epigenetic variation in the stress related gene FKBP5. Conversely, altering FKBP5 epigenetic responses during memory consolidation may rescue extinction deficits making it a target for acute intervention to prevent the development of PTSD. Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re‐experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM). Study 2 (Mice) tests if increasing doses of dexamethasone administered prior to extinction alters Fkbp5 mRNA production in the amygdala after extinction and recall and prevents the development of abnormal extinction phenotypes. In humans, abnormal extinction was associated with the TT homozygous genotype of FKBP5 SNPs RS9470080 and RS1360780, and hyperarousal symptoms. In mice, dexamethasone 300 &mgr;g/kg was associated with increased amygdala Fkbp5 mRNA following extinction and robust extinction learning while lower doses were not associated with amygdala Fkbp5 mRNA or differences in extinction learning. Further, mice that extinguished on dexamethasone 300 &mgr;g/kg maintained low levels of freezing behavior during recall training while mRNA levels were no longer elevated. Together, findings indicate that FKBP5 confers risk for fear extinction deficits. However, this risk may be ameliorated by increasing fkbp5 mRNA expression in the amygdala during memory consolidation making this mechanism a plausible point of acute intervention to prevent the development of PTSD. HighlightsDistinct trajectories of extinction learning are present across specifies (humans & mice).Human trajectories are associated with variation in FKBP5 and hyper‐arousal symptomatology of PTSD.Trajectories in mice are associated with fkbp5 mRNA expression in the amygdala.In mice, fkbp5 amygdala mRNA expression and extinction trajectory is altered by dexamethasone 300 &mgr;g/kg but not lower dosages.

Chronic cannabis use is associated with impaired fear extinction in humans

The use of fear conditioning and extinction paradigms to examine intermediate phenotypes of anxiety and stress-related disorders has facilitated the identification of neurobiological mechanisms that underlie specific components of abnormal psychological functioning. Across species, acute pharmacologic manipulation of the endogenous cannabinoid system has provided evidence of its critical role in fear extinction, but the effects of chronic cannabis on extinction are relatively understudied. In rats, chronic cannabinoid administration impairs fear extinction in a drug-free state. Here we examine whether chronic cannabis use is associated with impaired fear extinction in humans. Participants were healthy chronic cannabis users (n = 20) and nonuser controls with minimal lifetime cannabis use (n = 20) matched on age, sex, and race who all screened negative for psychiatric disorders. A 2-day differential fear conditioning paradigm was used to test the hypothesis that chronic cannabis use would be associated with impaired extinction of the skin conductance response. Consistent with hypotheses, chronic cannabis use was associated with reduced within-session extinction of skin conductance response on Day 1 (d = 0.78), and between-session extinction on Day 2 (d = 0.76). Unexpectedly, cannabis use was also associated with reduced subjective differentiation between threat and safety stimuli during conditioning. Replication and translation of findings are necessary to test potential mechanisms directly and examine whether impairments can be reversed pharmacologically or after a period of cannabis abstinence.

Psychometric Properties of the Modified Posttraumatic Stress Disorder Symptom Scale among Women with Posttraumatic Stress Disorder and Substance Use Disorders Receiving Outpatient Group Treatments.

OBJECTIVE The use of psychometrically sound measures to assess and monitor PTSD treatment response over time is critical for better understanding the relationship between PTSD symptoms and Substance Use Disorder (SUD) symptoms throughout treatment. We examined the psychometric properties of the Modified Posttraumatic Stress Disorder (PTSD) Symptom Scale, Self-Report (MPSS-SR). METHODS Three hundred fifty three women diagnosed with co-occurring PTSD (full or sub-threshold) and SUD who participated in a multisite treatment trial completed the MPSS-SR at pre-treatment, weekly during treatment, and posttreatment. Reliability and validity analyses were applied to the data. RESULTS Internal consistency was excellent throughout the course of the trial demonstrating the MPSS-SRs high reliability. Strong correlations between MPSS-SR scores and the Brief Symptom Inventory and the Clinician Administered PTSD Scale (CAPS) severity scores demonstrated the MPSS-SRs convergent and concurrent validity. We conducted a classification analysis at posttreatment and compared the MPSS-SR at various cutoff scores with the CAPS diagnosis. A cutoff score of 29 on the MPSS-SR yielded a sensitivity rate of 89%, a specificity rate of 77%, and an overall classification rate of 80%, indicating the measures robust ability to accurately identify individuals with PTSD in our sample at posttreatment. CONCLUSIONS Findings support the use of the MPSS-SR as a reliable and valid tool to assess and monitor changes in PTSD symptoms over the course of treatment and as an alternative to structured clinical interviews to assess PTSD symptoms among populations with SUDs.