Post-traumatic change and resilience after childhood maltreatment: Impacts on maternal mental health over the postpartum period.

BACKGROUND: Mothers with a history of childhood maltreatment (CM) are particularly vulnerable to postpartum mental health changes. Variability in mental health trajectories is present over the first 18-months postpartum. Little is known about the potentially unique impacts of post-traumatic change or resilience on later postpartum mental health. METHODS: Participants (N = 97) completed questionnaires over the first 18-months postpartum measuring demographic risk, mental health symptoms, traumatic experiences, and resilience. Mothers also completed an interview measure coded for post-traumatic changes at 6-months postpartum. Multinomial logistic regression models examined post-traumatic change and resilience factors as predictors of mothers' longitudinal latent mental health trajectory. RESULTS: Three classes of latent postpartum mental health emerged: low-symptom, vulnerable, and chronic high-risk. Mothers reporting stronger positive post-traumatic changes were more likely to be in the low-symptom class than the chronic high-risk class (B = -1.082, p = .01). Mothers reporting stronger negative post-traumatic changes were more likely to be in the vulnerable class (B = 0.778, p = .006) or chronic high-risk class (B = 0.906, p = .046) than the low-symptom class. Resilience was not predictive of mental health class. LIMITATIONS: Findings are correlational, and causal effects between post-traumatic growth and mental health symptoms cannot be assumed. Mothers who consented to the interview may not be fully representative of all women who have experienced CM, limiting generalizability of findings. CONCLUSIONS: Positive post-traumatic change is associated with reduced psychopathology. These findings may assist in identification of mothers at greater risk of adverse postpartum outcomes and futher inform interventions focused on enhancing positive changes in post-traumatic cognitions.

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder.

BACKGROUND: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. METHODS: Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). RESULTS: Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028). LIMITATIONS: The modest sample size is the primary limitation. CONCLUSIONS: Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.

Differences in diagnostic rules used to determine borderline personality disorder impact prevalence and associations with clinically relevant variables: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions-III.

Borderline personality disorder (BPD) is a serious and understudied mental health condition associated with profound personal and public health consequences. Methodological differences in characterizing BPD may limit understanding the scope of the disorder's prevalence and effect. For example, using different diagnostic rules for BPD can affect apparent prevalence, comorbidity, and clinical presentation. This study examined how differences in diagnostic rules used to assign BPD diagnosis impacted its prevalence and associations with clinically relevant variables (e.g., demographics, comorbidity, treatment-seeking). Participants were a nationally representative sample of 36,309 noninstitutionalized U.S. adults. All variables were assessed via clinical interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-5). Six diagnostic rules determined BPD status. We used frequencies to examine prevalence rates of and associations between BPD and other clinical variables, and logistic regressions to examine the associations between each BPD variable and the other outcomes. The prevalence of BPD ranged widely-from 0.5% to 11.4%-per the diagnostic rule used. Associations between BPD diagnosis and various outcomes and clinical variables generally remained stable across all diagnostic rules, though effects became more extreme as diagnostic rules became more restrictive. Additionally, meaningful differences emerged as a function of the number of items used (30 vs. 18 items) even with no other changes to diagnostic rules. The field examining BPD and associated problem behaviors should critically consider how to most effectively characterize BPD to understand these problems more accurately and optimize the generalizability of findings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preliminary Study of White Matter Abnormalities and Associations With the Metabotropic Glutamate Receptor 5 to Distinguish Bipolar and Major Depressive Disorders.

Background: Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion-weighted MRI studies have suggested some common frontotemporal corticolimbic system white matter (WM) abnormalities across the disorders. However, critical to the development of more precise diagnosis and treatment is identifying distinguishing abnormalities. Promising candidates include more prominent frontotemporal WM abnormalities observed in BD in the uncinate fasciculus (UF) that have been associated with frontal-amygdala functional dysconnectivity, and with suicide that is especially high in BD. Prior work also showed differentiation in metabotropic glutamate receptor 5 (mGlu5) abnormalities in BD versus MDD, which could be a mechanism affected in the frontotemporal system. However, associations between WM and mGlu5 have not been examined previously as a differentiator of BD. Using a multimodal neuroimaging approach, we examined WM integrity alterations in the disorders and their associations with mGluR5 levels. Methods: Individuals with BD (N = 21), MDD (N = 10), and HC (N = 25) participated in structural and diffusion-weighted MRI scanning, and imaging with [18F]FPEB PET for quantification of mGlu5 availability. Whole-brain analyses were used to assess corticolimbic WM matter fractional anisotropy (FA) across BD and MDD relative to HC; abnormalities were tested for associations with mGlu5 availability. Results: FA corticolimbic reductions were observed in both disorders and altered UF WM integrity was observed only in BD. In BD, lower UF FA was associated with lower amygdala mGlu5 availability (p < .05). Conclusions: These novel preliminary findings suggest important associations between lower UF FA and lower amygdala mGlu5 levels that could represent a disorder-specific neural mechanism in which mGluR5 is associated with the frontotemporal dysconnectivity of the disorder.

Nicotine Use and Metabotropic Glutamate Receptor 5 in Individuals With Major Depressive and Posttraumatic Stress Disorders.

Metabotropic glutamate receptor 5 (mGluR5) dysregulation has been implicated in the pathophysiology of many psychiatric disorders, as well as nicotine use and dependence. We used positron emission tomography with [18F]FPEB to measure mGluR5 availability in vivo in 6 groups: (1) nicotine users (NUs) without other psychiatric comorbidities (n = 23); (2) comparison controls (CCs) without nicotine use or psychiatric comorbidities (n = 38); (3) major depressive disorder subjects with concurrent nicotine use (MDD-NU; n = 19); (4) MDD subjects without concurrent nicotine use (MDD-CC; n = 20); (5) posttraumatic stress disorder subjects with concurrent nicotine use (PTSD-NU; n = 17); and (6) PTSD subjects without concurrent nicotine use (PTSD-CC; n = 16). The goal of the study was to test the hypothesis that mGluR5 availability in key corticolimbic regions of interest (ROIs) is different in NU with versus without comorbid psychiatric disorders (ROI: dorsolateral prefrontal cortex [dlPFC], orbitofrontal cortex [OFC], ventromedial prefrontal cortex [vmPFC], anterior cingulate cortex [ACC], amygdala, hippocampus). We found that NU had 11%-13% lower mGluR5 availability in OFC, vmPFC, dlPFC, and ACC as compared with CC, while PTSD-NU had 9%-11% higher mGluR5 availability in OFC, dlPFC, and ACC compared with PTSD. Furthermore, relationships between mGluR5 availability and psychiatric symptoms varied as a function of psychiatric diagnosis among NUs. NU showed a negative correlation between mGluR5 and smoking cravings and urges (r's = -0.58 to -0.70, p's = 0.011 - 0.047), while PTSD-NU had the reverse relationship (r's = 0.60-0.71, p's = 0.013-0.035 in ACC, vmPFC, and dlPFC). These findings have substantial implications for our understanding of glutamate homeostasis in psychiatric subgroups and for identifying key neural phenotypes among NU. mGluR5 is a potential treatment target for precision medicine in individuals with nicotine use.

Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder.

BACKGROUND: Understanding the neurobiology underlying bipolar disorder (BD) versus major depressive disorder (MDD) is crucial for accurate diagnosis and for driving the discovery of novel treatments. A promising target is the metabotropic glutamate receptor 5 (mGluR5), a modulator of glutamate transmission associated with synaptic plasticity. We measured mGluR5 availability in individuals with MDD and BD for the first time using positron emission tomography. METHODS: Individuals with BD (n = 17 depressed; n = 10 euthymic) or MDD (n = 17) and healthy control (HC) individuals (n = 18) underwent imaging with [18F]FPEB positron emission tomography to quantify mGluR5 availability in regions of the prefrontal cortex, which was compared across groups and assessed in relation to depressive symptoms and cognitive function. RESULTS: Prefrontal cortex mGluR5 availability was significantly different across groups (F6,116 = 2.18, p = .050). Specifically, mGluR5 was lower in BD versus MDD and HC groups, with no difference between MDD and HC groups. Furthermore, after dividing the BD group, mGluR5 was lower in both BD-depression and BD-euthymia groups versus both MDD and HC groups across regions of interest. Interestingly, lower dorsolateral prefrontal cortex mGluR5 was associated with worse depression in MDD (r = -0.67, p = .005) but not in BD. Significant negative correlations were observed between mGluR5 and working memory in MDD and BD-depression groups. CONCLUSIONS: This work suggests that mGluR5 could be helpful in distinguishing BD and MDD as a possible treatment target for depressive symptoms in MDD and for cognitive alterations in both disorders. Further work is needed to confirm differentiating roles for mGluR5 in BD and MDD and to probe modulation of mGluR5 as a preventive/treatment strategy.

Differential Role of mGluR5 in Cognitive Processes in Posttraumatic Stress Disorder and Major Depression.

Background: A robust literature supports the role of the metabotropic glutamate receptor type 5 (mGluR5) in cognitive functioning. mGluR5 is also implicated in the pathophysiology of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), which are characterized by cognitive alterations. However, the relationship between mGluR5 and cognition in MDD and PTSD has not yet been directly investigated. To address this gap, we examined the relationship between in vivo mGluR5 availability and cognition in PTSD, MDD, and matched healthy adults (HA). Methods: Individuals with PTSD (N = 28) and MDD (N = 21), and HA (N = 28) were matched for age, gender, and smoking status. Participants completed 18F-FPEB positron emission tomography (PET) scan, psychiatric and cognitive assessments. Results: Across models examining the relationship between mGluR5 availability and different domains of cognition across diagnostic groups, only the interaction of diagnosis*attention was significant (F 4,64 = 3.011, P = .024). Higher mGluR5 availability was associated with poorer attention in PTSD in 4 frontolimbic regions of interests (ROI's: OFC (r = -.441, P = .016), vmPFC (r = -.408, P = .028), dlPFC (r = -.421, P = .023), hippocampus (r = -.422, P = .025). By contrast, mGluR5 availability in the MDD group was positively related to Attention (ATTN) in the OFC (r = .590, P = .006), vmPFC (r = .653, P = .002), and dlPFC (r = .620, P = .004). Findings in the hippocampus for MDD followed the same pattern but did not survive correction for multiple comparisons (r = .480, P = .036). ATTN and mGluR5 availability were not significantly related in the HA group. Of note, in MANOVA analyses group*ATTN interaction results in the OFC did not survive multiple comparisons (P = .046). All other findings survived correction for multiple comparisons and remained significant when covarying for potential confounds (eg, depressed mood). Conclusions: We observed a significant relationship between frontolimbic mGluR5 availability and performance on tests of attention in individuals with MDD and PTSD. This finding aligns with animal work showing dysregulation in mGluR5 in cognitive functioning, and differed as a function of diagnosis. Results suggest interventions targeting mGluR5 may help bolster cognitive difficulties, highlighting the importance of employing different mGluR5 directed treatment strategies in MDD and PTSD.

Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder.

Intravenous (IV) subanesthetic doses of ketamine have been shown to reduce psychiatric distress in both major depressive (MDD) and posttraumatic stress disorder (PTSD). However, the effect of ketamine on cognitive function in these disorders is not well understood. To address this gap, we examined the effect of a single dose of IV ketamine on cognition in individuals with MDD and/or PTSD relative to healthy controls (HC). Psychiatric (n = 29; 15 PTSD, 14 MDD) and sex- age- and IQ matched HC (n = 29) groups were recruited from the community. A single subanesthetic dose of IV ketamine was administered. Mood and cognitive measures were collected prior to, 2 h and 1 day post-ketamine administration. MDD/PTSD individuals evidenced a large-magnitude improvement in severity of depressive symptoms at both 2-hours and 1 day post-ketamine administration (p's < .001, Cohen d's = 0.80-1.02). Controlling for baseline performance and years of education, IV ketamine induced declines in attention (ATTN), executive function (EF), and verbal memory (VM) 2 h post-administration, all of which had resolved by 1 day post-ketamine across groups. The magnitude of cognitive decline was significantly larger in MDD/PTSD relative to HC on attention only (p = .012, d = 0.56). Ketamine did not affect working memory (WM) performance. Cognitive function (baseline, change from baseline to post-ketamine) was not associated with antidepressant response to ketamine. Results suggest that while ketamine may have an acute deleterious effect on some cognitive domains in both MDD/PTSD and HC individuals, most notably attention, this reduction is transient and there is no evidence of ketamine-related cognitive dysfunction at 1 day post-administration.

Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT1A expression.

The long-term behavioral, psychological, and neurobiological effects of exposure to potentially traumatic events vary within the human population. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. The serotonin 1-A receptor (5-HT1A) is an inhibitory G protein-coupled serotonin receptor encoded by the HTR1A gene that plays a role in regulating serotonin release, physiological stress responding, and emotional behavior. Studies from the preclinical and human literature suggest that dysfunctional expression of 5-HT1A is associated with a multitude of psychiatric symptoms commonly seen in trauma-exposed individuals. Here, we synthesize the literature, including numerous preclinical studies, examining differences in alterations in 5-HT1A expression following trauma exposure. Collectively, these findings suggest that the impact of trauma exposure on 5-HT1A expression is dependent, in part, on trauma type and extent of exposure. Furthermore, preclinical and human studies suggest that this observation likely applies to additional molecular targets and may help explain variation in trauma-induced changes in behavior and treatment responsivity. In order to understand the neurobiological impact of trauma, including the impact on 5-HT1A expression, it is crucial to consider both trauma type and extent of exposure.

PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies.

Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals-with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology.

Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET.

The metabotropic glutamate receptor 5 (mGluR5) is a promising treatment target for psychiatric disorders due to its modulatory effects on glutamate transmission. Using [11C]ABP688, we previously showed that the rapidly acting antidepressant ketamine decreases mGluR5 availability. The mGluR5 radioligand [18F]FPEB offers key advantages over [11C]ABP688; however, its suitability for drug challenge studies is unknown. We evaluated whether [18F]FPEB can be used to capture ketamine-induced effects on mGluR5. Seven healthy subjects participated in three [18F]FPEB scans: a baseline, a same-day post-ketamine, and a 24-h post-ketamine scan. The outcome measure was VT/fP, obtained using a two-tissue compartment model and a metabolite-corrected arterial input function. Dissociative symptoms, heart rate and blood pressure increased following ketamine infusion. [18F]FPEB VT/fP decreased by 9% across the cortex after ketamine infusion, with minimal difference between baseline and 24-h scans. Compared to our previous work using [11C]ABP688, the magnitude of the ketamine-induced change in mGluR5 was smaller using [18F]FPEB; however, effect sizes were similar for the same-day post-ketamine vs. baseline scan (Cohen's d = 0.75 for [18F]FPEB and 0.88 for [11C]ABP688). [18F]FPEB is therefore able to capture some of the effects of ketamine on mGluR5, but [11C]ABP688 appears to be more suitable in drug challenge paradigms designed to probe glutamate transmission.

In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.

Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) to compare with that of healthy comparison controls (HC; n = 29). Volume of distribution was computed using a venous input function in the five key frontal and limbic brain regions. We observed significantly higher mGluR5 availability in PTSD compared with HC individuals in all regions of interest (P's = 0.001-0.01) and compared with MDD individuals in three regions (P's = 0.007). mGluR5 availability was not significantly different between MDD and HC individuals (P = 0.17). Importantly, we observed an up-regulation in mGluR5 availability in the PTSD-SI group (P's = 0.001-0.007) compared with PTSD individuals without SI. Findings point to the potential role for mGluR5 as a target for intervention and, potentially, suicide risk management in PTSD.

Lower synaptic density is associated with depression severity and network alterations.

Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [11C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls (n = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression.

A factor analytic evaluation of the World Health Organization Disability Assessment Schedule 2.0 among veterans presenting to a generalist mental health clinic.

The shift from a multiaxial system of diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) brought forth the discontinuation of the Global Assessment of Functioning (GAF). DSM-5 proposes the use of a more reliable method for assessing and describing disability, the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The WHODAS 2.0 is widely-used within the Department of Veterans Affairs (VA) and the Veterans Benefits Administration to guide clinical decision making and assist in decisions pertaining to financial compensation. While the WHODAS 2.0 purports to be well-validated for adults cross-culturally in clinical and non-clinical samples, research is limited pertaining to the factor structure of the WHODAS 2.0 in non-compensation seeking U.S. Veteran populations. This study evaluated the factor structure of the WHODAS 2.0 in a sample of 464 Veterans receiving VA mental healthcare. Exploratory and confirmatory factor analyses of the WHODAS 2.0 data were conducted. Analyses confirmed the hardiness of the WHODAS 2.0 for use with Veterans. However, exploratory analyses pointed to several items that may reduce the functioning of the questionnaire in clinical Veteran samples. Exploratory and confirmatory analyses indicated better model fit can be achieved.

Relation between sexual and gender minority status and suicide attempts among veterans seeking treatment for military sexual trauma.

There is limited study of suicidal behaviors among veterans identifying as sexual and gender minorities (SGMs), despite previous research indicating rates of suicide attempts are high within civilian SGM populations. Further, some research incorporating military service members suggests those identifying as SGMs are disproportionately exposed to military sexual trauma (MST), an additional risk factor for negative psychiatric sequelae. To address health care research disparities among minority veterans (i.e., women, those endorsing MST, SGMs), we examined presentations of veterans (N = 277) who attended initial consultation appointments for MST-related treatment and completed a semistructured clinical interview including demographic characteristics, history of suicide attempts (HSA), and a diagnostic evaluation. Twenty-eight (10.1%) veterans identified as SGMs. SGM/non-SGM groups were contrasted on suicidal and psychiatric morbidity outcomes. Overall, endorsement of HSA was high (30.7%). Despite similar clinical profiles, 53.6% of veterans who identified as SGM endorsed HSA in contrast with 28.1% of peers identifying as heterosexual and nontransgender, a significant effect of small-to-moderate size. Findings suggest assessment and clinical management of suicidality is of critical importance for clinicians providing services to veterans pursuing recovery from MST, generally, and may be especially so when delivering care to SGM. Further, results underscore the need for culturally competent delivery of trauma-focused interventions. (PsycINFO Database Record

Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence.

BACKGROUND: Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. METHODS: We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses. RESULTS: Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex (mPFC). Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD checklist (PCL-5; r= -.0.77, r=-0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (mPFC and cerebellum) and the supramarginal gyrus, in the PTSD group. CONCLUSION: We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.

Posttraumatic Stress Disorder Symptom Clusters and Acquired Capability for Suicide: A Reexamination Using DSM-5 Criteria.

This study used the interpersonal-psychological theory of suicide to explore the relationships among DSM-5 posttraumatic stress disorder (PTSD) symptom clusters derived from the six-factor anhedonia model and facets of acquired capability for suicide (ACS). In a sample of 373 trauma-exposed undergraduates, most PTSD symptom clusters were negatively associated with facets of ACS in bivariate correlations, but the anhedonia cluster was positively associated with ACS in regression models. Structure coefficients and commonality analysis indicated that anhedonia served as a suppressor variable for the other symptom clusters. Our findings further elucidate the complex relationship between specific PTSD symptom clusters and ACS.

A psychometric evaluation of the Posttraumatic Cognitions Inventory with Veterans seeking treatment following military trauma exposure.

Trauma-related beliefs have salient relationships to the development and maintenance of Posttraumatic Stress Disorder (PTSD) following stress exposure. The Posttraumatic Cognitions Inventory (PTCI) has the potential to be a standard assessment of this critical construct. However, some critical aspects of validity and reliability appear to vary by population. To date, the PTCI has not been psychometrically evaluated for use with military-specific traumas such as combat and military sexual trauma (MST). Based on exploratory and confirmatory analyses with 949 Veterans seeking trauma-focused treatment for military traumas, we found a four factor model (negative view of the self, negative view of the world, self-blame, and negative beliefs about coping competence) provided the best fit. In contrast, the original three factor model was not confirmed. Both models demonstrated convergent and discriminative validity. Although gender was associated with PTCI total and factor scores, differences did not persist after controlling for trauma type. MST was associated with higher PTCI scores even when controlling for gender, though the clinical magnitude of these differences is likely negligible. Internal reliability validity was demonstrated with PTCI total and subscale scores.

Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence.

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.

Preliminary evidence concerning the pattern and magnitude of cognitive dysfunction in major depressive disorder using cogstate measures.

BACKGROUND: Cognitive deficits are common in individuals with major depressive disorder (MDD), and are associated with treatment non-responsiveness and poorer functional outcomes. Characterization of the nature and magnitude of deficits in this population has been limited in part by lack of brief, practical, and well-validated assessment measures. The goal of this study was to use a brief, practical, and repeatable computerized cognitive test battery from Cogstate to examine differences in cognitive functioning between individuals with MDD and healthy controls. METHODS: Forty participants (22 healthy controls (HCs), 18 with MDD) completed a battery of six cognitive measures, as well as measures of intellectual functioning (intellect) and depressive symptom severity. A multivariate analysis of covariance (MANCOVA) was conducted to compare cognitive test performance across groups while controlling for intellect. RESULTS: Individuals with MDD had lower full-scale IQ scores on average, and performed worse on measures of visual attention (d=1.04), verbal learning (d=1.22) and memory (d=1.22), and visuospatial problem solving (d=0.80) than HCs after adjustment for differences in intellect. Psychomotor speed, visual memory, and working memory did not differ between groups. CONCLUSIONS: Cogstate measures appear to be sensitive in assessing deficits in attention, verbal learning and memory, and executive function in individuals with MDD. Further research will be useful in establishing the utility of Cogstate measures for standard use in research and clinical practice.