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Recent research suggests people who report vaccine hesitancy may still get vaccinated; however, little is known about hesitancy among those who chose to vaccinate. The current study focused on individuals who received the coronavirus disease 2019 (COVID-19) vaccine despite their hesitancy, whom we refer to as "hesitant adopters." With the understanding that vaccine attitudes and vaccine behaviors may or may not be correlated, we examined the prevalence of COVID-19 vaccine hesitancy among those who have been vaccinated, how COVID-19 vaccine hesitancy varies across sociodemographic groups, and how COVID-19 vaccine hesitancy relates to other factors (prior health care access and influenza vaccination behavior over the past 5 years). Random digit dialing of telephone landlines and cell phones was used to contact potential survey respondents, rendering a sample of 1500 Arkansan adults. Approximately one-third of those who received a COVID-19 vaccine also reported some level of hesitancy. Among hesitant adopters, 5.3% said they were "very hesitant," 8.8% said they were "somewhat hesitant," and 17.1% said they were "a little hesitant." Black/African American and Hispanic/Latinx respondents reported more hesitancy than White respondents, and female respondents reported greater hesitancy compared to male respondents. Greater hesitancy was associated with non-metro/rural residence, forgoing health care due to cost, and lower influenza vaccination rates over the past 5 years. Findings suggest those who are hesitant may get vaccinated despite their hesitancy, illustrating the complexity of vaccination behaviors. Prevalence of hesitancy among the vaccinated has implications for communication strategies in vaccine outreach programs and may help to reduce stigmatization of hesitant adopters.

Background: Up to 50% of individuals with posttraumatic stress disorder (PTSD) endorse problematic alcohol use. Typically, these individuals present with more complex and often more severe PTSD symptoms than those who do not report problematic alcohol use. Emerging literature suggests that heightened symptoms of dissociation are likewise associated with greater PTSD symptom severity. Despite this knowledge, the role of dissociation in the relation between PTSD severity and alcohol-related problems has yet to be examined. Here, we explore the mediating role of dissociative symptomatology on the association between PTSD severity and alcohol-related problems within a PTSD treatment-seeking sample. Methods: Structural equation modeling was used to test the mediating role of dissociative symptomatology between PTSD severity and alcohol-related problems. Participants [N = 334; mean age (SD) = 44.29 (9.77), 50% female] were drawn from a clinical intake battery database for PTSD in-patient treatment services at Homewood Health Care, Guelph, ON, Canada. A subset of battery measures assessing PTSD severity, dissociative symptomatology, and alcohol-related problems were submitted to analysis. Results: A significant positive association emerged between PTSD severity and alcohol-related problems (β = 0.127, p < 0.05) in the absence of dissociative symptomatology. Critically, however, when added to this model, dissociative symptomatology (six unique facets of dissociation assessed by the Multiscale Dissociation Inventory) mediated the relation between PTSD severity and alcohol-related problems. Specifically, greater PTSD severity was associated with greater dissociative symptomatology (β = 0.566, p < 0.0001), which was in turn associated with greater alcohol-related problems (β = 0.184, p < 0.05). Conclusions: These results suggest that dissociative symptomatology plays a key role in explaining the relation between PTSD severity and alcohol-related problems. Future studies should examine the impact of targeting dissociative symptomatology specifically in treating individuals with PTSD who endorse alcohol-related problems.

Background Post-traumatic stress disorder affects 9% of individuals across their lifetime and increases nearly fourfold to 35% in Canadian public safety personnel (PSP). On-the-job experiences of PSP frequently meet criteria for traumatic events, making these individuals highly vulnerable to exposures of trauma and the negative consequences of PTSD. Few studies have reported on the clinical characteristics of Canadian samples of PSP and even fewer have examined the dissociative subtype of PTSD, which is associated with more severe, chronic traumatic experiences, and worse outcomes. Objective This study aimed to characterize dissociative symptoms, PTSD symptom severity, and other clinical variables among Canadian PSP with presumptive PTSD. Methods We sampled current and past PSP in Canada from both inpatient and outpatient populations (N = 50) that were enrolled in a psychological intervention. Only baseline testing data (prior to any intervention) were analysed in this study, such as PTSD symptom severity, dissociative symptoms, emotion dysregulation, and functional impairment. Results In our sample, 24.4% self-reported elevated levels of dissociation, specifically symptoms of depersonalization and derealization. Depersonalization and derealization symptoms were associated with more severe PTSD symptoms, greater emotion dysregulation, and functional impairment. Conclusions Nearly a quarter of this sample of Canadian PSP reported experiencing elevated levels of PTSD-related dissociation (depersonalization and derealization). These high levels of depersonalization and derealization were consistently positively associated with greater illness severity across clinical measures. It is imperative that dissociative symptoms be better recognized in patient populations that are exposed to chronic traumatic events such as PSP, so that treatment interventions can be designed to target a more severe illness presentation., HIGHLIGHTS 24.4% of traumatized Canadian public safety personnel reported elevated levels of depersonalization and derealization, which was associated with a severe illness profile characterized by greater trauma symptoms, emotional dysregulation, and difficulty with life tasks.

Background This study examined the complex relationships between sleep quality, depressive symptoms, and cognitive decline in older adults. We hypothesised that older age, lower education and greater medical comorbidities would each be associated with increased mild cognitive impairment (MCI) diagnosis risk through indirect effects via poorer sleep quality, and greater depressive symptomology. Methods 540 adults 44 years and over were recruited at the Brain and Mind Centre, Sydney, Australia. Participants underwent comprehensive psychiatric, neuropsychological, and medical assessment. Subjective sleep quality, current depressive symptomatology, and current medical burden were assessed. Results There were significant indirect effects of each of age, comorbidities and education, that operated via both sleep and depression. Younger age, greater comorbidities and fewer years’ education each predicted greater chance of MCI diagnosis via poorer sleep and in turn higher depressive symptomatology. Additionally, there was a significant direct effect of older age on MCI. Limitations The current study is cross-sectional and cannot determine whether poorer sleep quality and greater depressive symptomatology precede or arise as a result of the onset of cognitive decline in later-life. A longitudinal design may allow further explication of these relationships. Conclusions Both sleep and depression are linked with cognitive decline in older adults, with sleep disturbance appearing to predict depressive symptoms. These findings have implications for the management of MCI. Both greater depression symptomatology and sleep disturbance were shown to predict the risk of MCI diagnosis, with this effect strongest in those that are younger. Improved early detection and treatment of sleep problems in older adults may help prevent depressive symptom manifestation or exacerbation, in turn potentially reducing the risk of subsequent cognitive decline.

Objective: Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) present a complex and often severe clinical presentation within a concurrent disorders context. The objective of this study was to examine associations between PTSD symptoms and SUD outcomes to better understand the clinical phenomenon of comorbid PTSD and SUD. Multivariate statistical methods were used to test the hypothesis that elevated PTSD symptoms, both at the level of global severity and specific PTSD symptom clusters, are associated with greater substance use and related problems. Methods: Data were collected from an intake assessment battery within a specialized concurrent disorders outpatient service in Hamilton, ON. The sample comprised 326 participants (mean age = 37.19, 45.4% female). Structural equation models examined associations between PTSD and alcohol, cannabis, and substance use frequency and problems, controlling for age and sex. Alcohol was ultimately dropped from the model due to non-significant bivariate associations. Results: Higher global PTSD symptomatology was significantly associated with higher cannabis and other substance use frequency and related problems. Analyses using PTSD cluster scores showed higher scores for alterations in arousal were positively associated with cannabis-related problems, drug-related problems, and cannabis and other substance use frequency. Avoidance was significantly associated with cannabis frequency and cannabis-related problems. In general, effect sizes were small in magnitude, accounting for between 9% and 25% of variance. Conclusion: Significant cluster-level associations indicate the importance of specific PTSD symptoms (hyperarousal, avoidance) in relation to substance use when identifying therapeutic targets among individuals presenting with comorbid PTSD-SUD. This multivariate approach provides a higher resolution and potentially more clinically informative representation of the complex clinical presentation of PTSD and SUD in a concurrent disorder population and could guide the development of more effective treatment paths.

Background: Older adults living with amnestic mild cognitive impairment (aMCI) not only demonstrate impairments in Theory of Mind (ToM), relative to adults with non-amnestic MCI (naMCI), but are also at a higher risk of developing dementia. Objective: Our primary objective was to ascertain whether default mode network (DMN) functional connectivity was differentially associated with ToM abilities between MCI subgroups. Methods: Using functional magnetic resonance imaging, we investigated alterations in resting-state functional connectivity within the brain’s DMN in a sample of 43 older adults with aMCI (n = 19) and naMCI (n = 24), previously reported to demonstrate poorer ToM abilities. Results: Compared to naMCI, the aMCI subgroup revealed a significant association between poorer ToM performance and reduced functional connectivity between the bilateral temporal pole (TempP) and the left lateral temporal cortex (LTC) (LTC_L-TempP_L: b = –0.06, t(33) = –3.53, p = 0.02; LTC_L-TempP_R: b = –0.07,t(33) = –3.20, p = 0.03); between the right TempP and the dorsal medial prefrontal cortex (dMPFC) (b = –0.04, t(33) = –3.02, p = 0.03) and between the left and right TempP (b = –0.05, t(33) = –3.26, p = 0.03). In the naMCI subgroup, the opposite relationship was present between the bilateral TempP and the left LTC (Combined correlation: r = –0.47, p = 0.02), however, not between the right TempP and the dMPFC (r = –0.14, p = 0.51) or the left and right TempP (r = –0.31, p = 0.14). Conclusion: Our findings suggest that alterations in functional connectivity within the DMN involving temporal and frontal lobe regions are associated with ToM deficits in aMCI.

Objective Posttraumatic stress disorder (PTSD) has been associated with heightened impulsivity and risk-taking behaviors, including higher rates of substance use than individuals without PTSD. Although a number of studies suggest that impulsivity is associated with substance use in PTSD, the specific role of impulsivity in this common pattern of comorbidity remains unclear. The current study investigated associations between PTSD symptoms, substance use patterns, and impulsivity in a sample of adults. Method A total of 2,967 participants were recruited online through Amazon's Mechanical Turk. Participants who did not report at least one Criterion A traumatic event on the Brief Trauma Questionnaire were excluded. The remaining 1,609 trauma-exposed individuals were placed into either the probable PTSD group (n = 406) or the trauma-exposed non-PTSD group (n = 1,203) based on their PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PCL-5) score. Impulsivity was assessed via a delay discounting measure and the brief UPPS-P (urgency, premeditation, perseverance, sensation seeking, and positive urgency) Impulsive Behavior Scale. Alcohol and cannabis were assessed using the Alcohol Use Disorders Identification Test (AUDIT) and Cannabis Use Disorders Identification Test (CUDIT-R) scales, respectively. Results Probable PTSD participants exhibited steeper (more impulsive) delay discounting and endorsed more impulsive traits than participants in the trauma-exposed non-PTSD group. Moreover, the PTSD group reported significantly higher scores on both the AUDIT and CUDIT-R. Lastly, impulsive personality traits on the UPPS-P partially mediated the association between PTSD and both cannabis and alcohol use. Conclusions These findings suggest that trauma-exposed individuals who exhibit elevated PTSD symptoms show heightened impulsivity. It also appears that lower levels of impulsivity may serve as a protective factor among trauma-exposed individuals resilient to the development of PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-e4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-e4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.

Background Functional impairment among individuals with posttraumatic stress disorder (PTSD) represents a significant factor in recovery. Critically, functional impairment appears to persist following remission of PTSD symptoms. To date, work investigating functional impairment among individuals with PTSD has focused on PTSD symptom clusters, excluding other relevant symptoms, including emotion regulation difficulties and dissociative symptoms. Emerging work suggests that these symptoms may serve as important predictors of functional impairment among individuals with PTSD. Objective and methods The present study investigated the contributions of difficulties with emotion regulation, dissociative symptoms, and individual PTSD symptom clusters to functional impairment among an inpatient civilian sample who completed self-report assessments of PTSD symptoms, functional impairment, emotion regulation difficulties, and dissociative symptoms, upon admission to the program. Participants met criteria for probable PTSD as per the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and reported high rates of exposure to childhood abuse and neglect. Results Emotion regulation difficulties contributed significantly, while dissociative symptoms and PTSD arousal and reactivity symptoms showed a signal toward contributing significantly to a model accounting for variance in functional impairment among individuals with probable PTSD. Differential patterns of contributors emerged for the various domains of functional impairment measured. Conclusions These findings add to a growing body of literature highlighting the importance of emotion regulation difficulties, dissociative symptoms, and arousal and reactivity symptoms in contributing to functional impairment in this disorder. Recovery to premorbid functional status in PTSD may require interventions that target directly these symptoms. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Highlights • We compared ICNs between PTSD, dissociative subtype PTSD, and healthy controls. • Results revealed unique group connectivity to brain areas associated with PTSD symptoms. • Classification machine learning algorithms predicted diagnosis with high accuracy. • Alterations within ICNs may underlie unique psychopathology among PTSD subtypes., Intrinsic connectivity networks (ICNs), including the default mode network (DMN), the central executive network (CEN), and the salience network (SN) have been shown to be aberrant in patients with posttraumatic stress disorder (PTSD). The purpose of the current study was to a) compare ICN functional connectivity between PTSD, dissociative subtype PTSD (PTSD+DS) and healthy individuals; and b) to examine the use of multivariate machine learning algorithms in classifying PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our neuroimaging dataset consisted of resting-state fMRI scans from 186 participants [PTSD (n = 81); PTSD + DS (n = 49); and healthy controls (n = 56)]. We performed group-level independent component analyses to evaluate functional connectivity differences within each ICN. Multiclass Gaussian Process Classification algorithms within PRoNTo software were then used to predict the diagnosis of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. When comparing the functional connectivity of ICNs between PTSD, PTSD+DS and healthy controls, we found differential patterns of connectivity to brain regions involved in emotion regulation, in addition to limbic structures and areas involved in self-referential processing, interoception, bodily self-consciousness, and depersonalization/derealization. Machine learning algorithms were able to predict with high accuracy the classification of PTSD, PTSD+DS, and healthy individuals based on ICN functional activation. Our results suggest that alterations within intrinsic connectivity networks may underlie unique psychopathology and symptom presentation among PTSD subtypes. Furthermore, the current findings substantiate the use of machine learning algorithms for classifying subtypes of PTSD illness based on ICNs.

BackgroundThe field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS).MethodsUsing Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD (n = 81); PTSD + DS (n = 49); and age-matched healthy trauma-unexposed controls (n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20].ResultsWe found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions.ConclusionThe current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.

BACKGROUND Obstructive sleep apnea is associated with an increased risk of developing mild cognitive impairment and dementia. Intermittent nocturnal hypoxemia in obstructive sleep apnea is associated with brain changes in key regions that underpin memory. OBJECTIVE To determine whether older adults with severe nocturnal hypoxemia would exhibit reduced functional connectivity within these regions, with associated deficits in memory. METHODS Seventy-two participants 51 years and over underwent polysomnography with continuous blood oxygen saturation recorded via oximetry. The oxygen desaturation index (ODI, 3% dips in oxygen levels per hour) was the primary outcome measure. ODI was split into tertiles, with analyses comparing the lowest and highest tertiles (N = 48). Thirty-five of the 48 participants from these two tertiles had mild cognitive impairment. Participants also underwent resting-state fMRI and comprehensive neuropsychological, medical, and psychiatric assessment. RESULTS The highest ODI tertile group demonstrated significantly reduced connectivity between the left and right parahippocampal cortex, relative to the lowest ODI tertile group (t(42) = -3.26, p = 0.041, beta = -1.99).The highest ODI tertile group also had poorer working memory performance. In the highest ODI tertile group only, higher left-right parahippocampal functional connectivity was associated with poorer visual memory recall (between-groups z = -2.93, p = 0.0034). CONCLUSIONS Older adults with severe nocturnal hypoxemia demonstrate impaired functional connectivity in medial temporal structures, key regions involved in sleep memory processing and implicated in dementia pathophysiology. Oxygen desaturation and functional connectivity in these individuals each relate to cognitive performance. Research is now required to further elucidate these findings.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Background The present study investigated Default Mode Network (DMN) functional connectivity in subjects with a lifetime history of major depression, comparing those with and without current sleep disturbance. Controls were included to assess DMN abnormalities specific to depression. Methods A total of 93 adults aged 50 years and over were recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. The sample comprised two groups, including 22 controls and 71 participants with a lifetime history of DSM-IV major depression (with depressive episode current or remitted). 52 of those with a lifetime history of depression also met criteria for Mild Cognitive Impairment (MCI). Participants underwent resting-state fMRI along with comprehensive psychiatric, neuropsychological, and medical assessment. Subjective sleep quality was assessed via the Pittsburgh Sleep Quality Index (PSQI). Sleep disturbance was defined as a PSQI score > 5. A total of 68% (n = 48) of cases with a lifetime history of depression met criteria for sleep-disturbance. DMN functional connectivity was assessed via ROI-to-ROI analyses. Results Relative to controls, those with lifetime major depression demonstrated significantly increased functional connectivity between the ventromedial prefrontal cortex and the temporal pole. Within the depression group (n = 48), those with current sleep disturbance had significantly increased connectivity between the anterior medial prefrontal cortex and both the parahippocampal cortex and the hippocampal formation, relative to those without sleep disturbance (n = 23). These results were present after controlling for MCI diagnosis. Conclusions Current sleep disturbance together with depression is associated with distinct abnormalities in DMN functioning incorporating regions responsible for self-reflection and declarative memory processes. Impaired sleep is associated with increased connectivity between these regions. Future studies may augment these findings with complementary imaging techniques including cortical thickness and diffusion tensor imaging, as well as high density electroencephalogram recording.

Background Posttraumatic stress disorder (PTSD) is characterized by dysregulated arousal and altered cardiac autonomic response as evidenced by decreased high-frequency heart rate variability (HF-HRV), an indirect measure of parasympathetic modulation of the heart. Indeed, subtle threatening cues can cause autonomic dysregulation, even without explicit awareness of the triggering stimulus. Accordingly, examining the neural underpinnings associated with HF-HRV during both sub- and supraliminal exposure to trauma-related cues is critical to an enhanced understanding of autonomic nervous system dysfunction in PTSD. Methods We compared neural activity in brain regions associated with HF-HRV in PTSD (n = 18) and healthy controls (n = 18) during exposure to sub- and supraliminal processing of personalized trauma-related words. Results As compared to controls, PTSD exhibited decreased HF-HRV reactivity in response to sub- and supraliminal cues. Notably, during subliminal processing of trauma-related versus neutral words, as compared to controls, PTSD showed decreased neural response associated with HF-HRV within the left dorsal anterior insula. By contrast, during supraliminal processing of trauma-related versus neutral words, decreased neural activity associated with HF-HRV within the posterior insula/superior temporal cortex, and increased neural activity associated with HF-HRV within the left centromedial amygdala was observed in PTSD as compared to controls. Conclusions Impaired parasympathetic modulation of autonomic arousal in PTSD appears related to altered activation of cortical and subcortical regions involved in the central autonomic network. Interestingly, both sub- and supraliminal trauma-related cues appear to elicit dysregulated arousal and may contribute to the maintenance of hyperarousal in PTSD. Hum Brain Mapp 38:4898–4907, 2017. © 2017 Wiley Periodicals, Inc.

Background: Sleep disturbance is prevalent in MCI, and is a risk factor for cognitive deterioration. Objective: To identify functional connectivity deficits in the default mode network (DMN) in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to MCIs with intact sleep. Methods: Participants comprised 47 adults aged 55 years and over, recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. This sample contained 15 controls and 32 participants meeting criteria for MCI. Participants underwent resting-state fMRI and actigraphy, along with comprehensive neuropsychological, medical and psychiatric assessment. MCIs were split into two groups according to average wake after sleep onset (WASO) per night. WASO equal to or greater than 1 standard deviation (SD) above the control mean was deemed to reflect disturbed sleep. There were 11 patients in the MCI sleep-disturbed group, and 21 in the MCI sleep-intact group. Results: Relative to controls, MCIs demonstrated significant connectivity reductions between parietal and temporoparietal regions, and between temporal regions. Relative to MCIs with intact sleep, MCIs with sleep disturbance demonstrated reductions in functional connectivity between temporal and parietal regions, and between temporal and temporoparietal regions. Conclusions: MCIs with nocturnal awakenings demonstrate reductions in DMN connectivity. These reductions comprise brain regions that are crucially involved in sleep and memory processes. These results strengthen our previous findings, which found reduced connectivity in MCIs with self-reported sleep disturbances. Future studies may build on these findings through incorporating complementary neuroimaging techniques and experimental manipulations of sleep.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n = 84), PTSD+DS (n = 49), and age-matched healthy controls (n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

Among non-Hispanic whites, cardiovascular risk factors are associated with increased mortality and poorer cognition. Prevalence of cardiovascular risk factors among aging Hispanics is also high and Hispanics generally have poorer access to healthcare, yet they tend to have advantageous cardiovascular disease rates and outcomes and live longer than non-Hispanic whites, an epidemiological phenomenon commonly referred to as the Hispanic or Latino health paradox. Although robust data support these ethnic benefits on physical health and mortality, it is unknown if it extends to include cognition resilience advantages in older adulthood. The present study compared relationships between cardiovascular risk and cognition (executive functions and episodic memory) in late middle age and older Hispanics (n = 87) and non-Hispanic whites (n = 81). Participants were selected from the National Alzheimer's Coordinating Center and Alzheimer's Disease Neuroimaging Initiative databases. Hispanics and non-Hispanic white groups were matched on age (50–94 yr, mean age = 72 yr), education, gender, cognitive status (i.e., cognitively healthy versus mildly cognitively impaired), and apolipoprotein E4 status. History of hypertension and higher body mass index were both associated with poorer executive functions among Hispanics but not non-Hispanic whites. Our findings suggest greater vulnerability to impairments in executive functions among Hispanics with hypertension and obesity, contrary to the notion of a Hispanic health paradox for cognitive aging.

A growing body of literature suggests that obsessive-compulsive disorder (OCD) is a heterogeneous condition. The studies investigating symptom dimensions have been limited by numerous methodological differences and sample characteristics. The purpose of this study was to compare the two most commonly applied statistical techniques used in addressing this question in the same large cohort of individuals with OCD. Both cluster analysis and factor analysis were used to examine OCD symptom data as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom Checklist for 355 individuals with a primary diagnosis of OCD. The factor analysis revealed a three-factor model best described as symmetry obsessions/ordering compulsions, contamination obsessions/cleaning compulsions and aggressive obsessions/checking compulsions. In contrast, the cluster analysis yielded a stable four-cluster solution best described as symmetry obsessions/ordering compulsions, contamination obsessions/cleaning compulsions, aggressive-somatic-religious obsessions/checking compulsions and a mixed symptom profile. Although there was overlap in the models resulting from these two statistical approaches, cluster analysis better captured the dimensional nature of OCD by demonstrating the prevalence of symptom categories in each subgroup. Though both analyses are capable of providing similar outputs, the validity of these results is limited given the input of a priori symptom categories from the Y-BOCS.

Amygdala dysregulation has been shown to be central to the pathophysiology of posttraumatic stress disorder (PTSD) representing a critical treatment target. Here, amygdala downregulation was targeted using real-time fMRI neurofeedback (rt-fMRI-nf) in patients with PTSD, allowing us to examine further the regulation of emotional states during symptom provocation. Patients (n = 10) completed three sessions of rt-fMRI-nf with the instruction to downregulate activation in the amygdala, while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting (a) regulate trials, with (b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run not involving neurofeedback. Generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses were also computed to explore task-based functional connectivity and causal structure, respectively. It was found that PTSD patients were able to successfully downregulate both right and left amygdala activation, showing sustained effects within the transfer run. Increased activation in the dorsolateral and ventrolateral prefrontal cortex (PFC), regions related to emotion regulation, was observed during regulate as compared with view conditions. Importantly, activation in the PFC, rostral anterior cingulate cortex, and the insula, were negatively correlated to PTSD dissociative symptoms in the transfer run. Increased functional connectivity between the amygdala- and both the dorsolateral and dorsomedial PFC was found during regulate, as compared with view conditions during neurofeedback training. Finally, our DCM analysis exploring directional structure suggested that amygdala downregulation involves both top-down and bottom-up information flow with regard to observed PFC-amygdala connectivity. This is the first demonstration of successful downregulation of the amygdala using rt-fMRI-nf in PTSD, which was critically sustained in a subsequent transfer run without neurofeedback, and corresponded to increased connectivity with prefrontal regions involved in emotion regulation during the intervention. Hum Brain Mapp 38:541-560, 2017. © 2016 Wiley Periodicals, Inc.

The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype.

Key evidence points toward alterations in the neurocircuitry of large-scale networks among patients with posttraumatic stress disorder (PTSD). The pulvinar is a thalamic region displaying reciprocal connectivity with the cortex and has been shown to modulate alpha synchrony to facilitate network communication. During rest, the pulvinar displays functional connectivity with the posterior parietal cortex (PPC), a heteromodal network of brain areas underlying multisensory integration and socioaffective functions that are shown at deficit in PTSD. Accordingly, this study seeks to reveal the resting-state functional connectivity (rsFC) patterns of individuals with PTSD, its dissociative subtype (PTSD + DS) and healthy controls. A whole-brain rsFC analysis was conducted using SPM12 and PickAtlas. Connectivity was analyzed for the left and right pulvinar across groups of individuals with PTSD (n = 81), PTSD + DS (n = 49), and controls (n = 51). As compared to PTSD, controls displayed significantly greater pulvinar rsFC with the superior parietal lobule and precuneus. Moreover, as compared to PTSD + DS, controls showed increased pulvinar connectivity with the superior parietal lobule, inferior parietal lobule and the precuneus. PTSD groups did not display stronger connectivity with any region as compared to controls. Last, PTSD had greater rsFC in the supramarginal gyrus relative to PTSD + DS. Reduced connectivity between the pulvinar and PPC may explain impairments to autobiographical memory, self-referential processing, and socioaffective domains in PTSD and PTSD + DS even at "rest." Critically, these alterations appear to be exacerbated in individuals with PTSD + DS, which may have important implications for treatment.

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed-based resting-state functional connectivity of the anterior cerebellum (lobule IV-V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non-trauma-exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self-consciousness (temporo-parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito-frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.

Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared to controls. Here, we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioural symptoms. PTSD patients (n=49), with (n=13) and without (n=36) the dissociative subtype, and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared to the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception -implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.Neuropsychopharmacology accepted article preview online, 19 March 2015. doi:10.1038/npp.2015.79.

OBJECTIVE: Despite advances in our understanding of mental health issues among military forces, a large proportion of military personnel continue to exhibit deployment-related psychological issues. Recent work has identified symptoms of guilt and shame related to moral injury as contributing significantly to combat-related mental health issues. This systematic scoping review explores the association between morality and symptoms of guilt and shame within military forces. METHOD: A search of the literature pertaining to guilt, shame and morality within military samples was conducted. RESULTS: Nineteen articles were selected for review. There is strong evidence linking exposure to and the perceived perpetration of moral transgressions with experiences of guilt and shame. Critically, symptoms of guilt and shame were related to adverse mental health outcomes, particularly the onset of post-traumatic stress disorder (PTSD). No studies have explored moral judgment in conjunction with assessments of guilt or moral injury. CONCLUSION: These findings have important implications for the prevention and treatment of PTSD-related symptoms in military samples. By measuring moral judgment prior to deployment, it may be possible to predict the likelihood of incurring moral injuries and the development of associated symptoms. Early intervention programmes aimed at ameliorating guilt and shame are required to prevent the long-term development of deployment-related psychological distress. Language: en

The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype.

Background The vestibular system integrates multisensory information to monitor one's bodily orientation in space, and is influenced by interoceptive awareness. Post-traumatic stress disorder (PTSD) involves typically alterations in interoceptive and bodily self-awareness evidenced by symptoms of hyperarousal, as well as of emotional detachment, including emotional numbing, depersonalization, and derealization. These alterations may disrupt vestibular multisensory integration between the brainstem (vestibular nuclei) and key vestibular cortical regions (parieto-insular vestibular cortex, prefrontal cortex). Accordingly, this study examined functional connectivity of the vestibular system in PTSD and its dissociative subtype. Methods Using resting-state fMRI data in SPM12 and PickAtlas, a seed-based analysis was employed to examine vestibular nuclei functional connectivity differences among PTSD (n = 60), PTSD dissociative subtype (PTSD + DS, n = 41) and healthy controls (n = 40). Results Increased vestibular nuclei functional connectivity with the parieto-insular vestibular cortex and the dorsolateral prefrontal cortex (dlPFC) was observed in PTSD and in controls as compared to PTSD + DS, and greater connectivity with the posterior insula was observed in controls as compared to PTSD. Interestingly, whereas PTSD symptom severity correlated negatively with dlPFC connectivity, clinical measures of depersonalization/derealization correlated negatively with right supramarginal gyrus connectivity. Discussion Taken together, decreased vestibular nuclei functional connectivity with key cortical vestibular regions in the PTSD + DS as compared to PTSD group, and its negative correlations with PTSD and dissociative symptoms, suggest that dysregulation of vestibular multisensory integration may contribute to the unique symptom profiles of each group. Further research examining disruption of vestibular system neural circuitry in PTSD and its dissociative subtype will be critical in capturing the neurophenomenology of PTSD symptoms and in identifying psychotherapeutic techniques that target dysfunction related to the vestibular system.

An overly negative self-schema is a proposed cognitive mechanism of major depressive disorder (MDD). Self-schema - one's core conception of self, including how strongly one believes one possesses various characteristics - is part of semantic memory (SM), our knowledge about concepts and their relationships. We used the N400 event-related potential (ERP) - elicited by meaningful stimuli, and reduced by greater association of the stimulus with preceding context - to measure association strength between self-concept and positive, negative, and neutral characteristics in SM. ERPs were recorded from MDD patients (n=16) and controls (n=16) who viewed trials comprising a self-referential phrase followed by a positive, negative, or neutral adjective. Participants' task was to indicate via button-press whether or not they felt each adjective described themselves. Controls endorsed more positive adjectives than did MDD patients, but the opposite was true for negative adjectives. Patients had smaller N400s than controls specifically for negative adjectives, suggesting that MDD is associated with stronger than normal functional neural links between self-concept and negative characteristics in SM.

Objective Posttraumatic stress disorder (PTSD) is associated with decreased top–down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting‐state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age‐matched healthy trauma‐unexposed controls [n = 52]). Results: PTSD was characterized by a pattern of predominant bottom–up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top–down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper‐ vs. hypo‐emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom–up defensive fear processing versus enhanced top–down regulation. Hum Brain Mapp 38:5551–5561, 2017. © 2017 Wiley Periodicals, Inc.

OBJECTIVE: Although deficits in memory and cognitive processing are evident in post-traumatic stress disorder (PTSD), difficulties with social cognition and the impact of such difficulties on interpersonal functioning are poorly understood. Here, we examined the ability of women diagnosed with PTSD related to childhood abuse to discriminate affective prosody, a central component of social cognition. METHOD: Women with PTSD and healthy controls (HCs) completed two computer-based tasks assessing affective prosody: (i) recognition (categorizing foreign-language excerpts as angry, fearful, sad, or happy) and (ii) discrimination (identifying whether two excerpts played consecutively had the 'same' or 'different' emotion). The association of performance with symptom presentation, trauma history, and interpersonal functioning was also explored. RESULTS: Women with PTSD were slower than HCs at identifying happiness, sadness, and fear, but not anger in the speech excerpts. The presence of dissociative symptoms was related to reduced accuracy on the discrimination task. An increased severity of childhood trauma was associated with reduced accuracy on the discrimination task and with slower identification of emotional prosody. CONCLUSION: Exposure to childhood trauma is associated with long-term, atypical development in the interpretation of prosodic cues in speech. The findings have implications for the intergenerational transmission of trauma. Language: en

The N400 event-related brain potential (ERP), a negative voltage deflection occurring approximately 400ms after onset of any meaningful stimulus, is reduced in amplitude when the stimulus is preceded by related context. Previous work has found this N400 semantic priming effect to be decreased in schizophrenia, suggesting impairment in using meaningful context to activate related concepts in semantic memory. Thus, N400 amplitude may be a useful biomarker of abnormal semantic processing and its response to treatment in schizophrenia. To help assess the validity of N400 amplitude as a longitudinal measure in schizophrenia, we evaluated its test-retest reliability. ERPs were recorded in sixteen schizophrenia patients who viewed prime words, each followed at 300- or 750-ms stimulus-onset asynchrony (SOA) by a target that was either a related or unrelated word, or nonword. Participants' task was to indicate whether or not the target was a real word. They were retested on the same procedure one week later. Test-retest reliability was assessed by calculating Pearson's r and intraclass correlation coefficients (ICCs) across timepoints for N400 amplitudes for related and unrelated targets, at each SOA. Consistent with previous results, there were no significant differences between patients' N400 amplitudes for related and unrelated targets, at any SOA/timepoint combination. Pearson's r and ICCs for N400 amplitudes at Fz across timepoints were significant for both target types at each SOA (ranges: r 0.52-0.64, ICC 0.52-0.63; all p

Objective Although studies increasingly point toward problems with social cognition among individuals with posttraumatic stress disorder (PTSD), few studies have assessed empathic responding. The aim of the current study was to investigate empathic responding in women with PTSD related to childhood trauma, and the contribution of parental bonding to empathic abilities in this sample. Methods Participants with PTSD (n = 29) and sex- and age-matched healthy controls (n = 20) completed two self-report empathy measures, the Interpersonal Reactivity Index (IRI) and the Toronto Empathy Questionnaire (TEQ), and a self-report measure of attachment, the Parental Bonding Instrument (PBI). Results Women with PTSD, relative to controls, reported significantly lower levels of empathic concern (r = 0.29) and perspective taking (r = 0.30), yet significantly higher levels of personal distress (r = 0.45) on the IRI. Women with PTSD also reported elevated scores on the TEQ (η2 = 0.13). Levels of paternal care on the PBI, rather than childhood trauma severity or PTSD symptom severity best predicted perspective taking scores on the IRI in the PTSD sample (R2 = 0.20). Conclusion Women with PTSD associated with childhood trauma reported alterations among different domains of empathic functioning that may be related to low levels of paternal care.

To date, very few studies have focused on autobiographical memory in patients with bipolar disorder. We examined whether mood state at the time of event encoding (i.e., manic, depressed, euthymic) influences subsequent recollection in these patients. We administered the Autobiographical Interview, a method that allowed us to dissociate episodic and semantic aspects of autobiographical memory. We also compared the memory perspective from which patients recollected these events. Patients were selectively impaired in recollecting episodic details of events encoded during mania but not depression or euthymia. No significant differences emerged between patients and controls for recollection of non-episodic details, regardless of mood state. Patients with bipolar disorder were also more likely than matched controls to recall memories from an observer perspective. These preliminary findings indicate a moderating influence of mood state at the time of event encoding on the subsequent recollection of autobiographical events in patients with bipolar disorder.

Background Evidence suggests obesity exerts a negative impact on cognition. Major Depressive Disorder (MDD) is also linked to problems in cognitive functioning. Obesity is highly prevalent in individuals with MDD and is linked to a failure to return to a full level of functioning. The study’s objective was to investigate the effect of obesity on cognitive impairment in participants with MDD. Methods This study compared cognitive performance in obese individuals with MDD and two control populations (obese individuals without a psychiatric illness and non-obese controls). A standardized battery of neuropsychological tests specifically designed to assess performance in declarative memory, executive functioning, processing speed and attention was administered. Mood ratings, physical measurements, nutritional and health questionnaires were also completed. Results We observed a consistent pattern across measures of memory, executive functioning, attention and processing speed. Whereas healthy controls performed better than both bariatric groups across the majority of measures administered, bariatric controls tended to outperform bariatric MDD patients. Limitations The overall sample size of our study was small and thus largely explorative in nature. However, it provides compelling results (while controlling for extraneous variables such as medication load, nutritional status and common metabolic comordidities) that strongly urges for further investigation and study replication with larger sample sizes. Conclusions We found obesity has a subtle impact on cognition in obese individuals, and when obesity is present in individuals with MDD, this impact may be significant. It is important to minimize all modifiable variables that can add to cognitive burden in this population.

Background Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL-PAG) and ventrolateral PAG (VL-PAG) are thought to mediate active and passive defensive responses, respectively. Methods We examined PAG subregion (dorsolateral and ventrolateral) resting-state functional connectivity in three groups: PTSD patients without the dissociative subtype (n = 60); PTSD patients with the dissociative subtype (n = 37); and healthy controls (n = 40) using a seed-based approach via PickAtlas and SPM12. Results All PTSD patients showed extensive DL- and VL-PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls (n = 40). Although all PTSD patients demonstrated DL-PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL-PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum). Conclusions These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma-related disorders.

Objective The present study investigated resting fMRI connectivity within the default mode (DMN), salience (SN), and central executive (CEN) networks in relation to neurocognitive performance and symptom severity in trauma‐exposed patients with major depressive disorder (MDD). Method Group independent component analysis was conducted among patients with MDD (n = 21), examining DMN, SN, and CEN connectivity in relation to neurocognitive performance and symptom severity. Activation in these networks was also compared between the patient group and healthy controls (n = 20). Results Among the patient group, higher levels of performance on measures of verbal memory and executive functioning were related to increased connectivity within the DMN (i.e., inferior parietal lobe; precuneus). Greater depression severity was related to reduced connectivity between the SN and a node of the DMN (i.e., posterior cingulate cortex) and higher depersonalization symptoms were related to enhanced connectivity between the SN and a node of the DMN (i.e., middle temporal gyrus). Higher symptoms of depersonalization were also associated with reduced integration of the DMN with the medial frontal gyrus. Relative to controls, patients with MDD showed greater connectivity of the ventromedial prefrontal cortex within the DMN. Conclusion Intrinsic connectivity network patterns are related to cognitive performance and symptom presentation among trauma‐exposed patients with MDD.

This study aimed to identify default mode network (DMN) functional connectivity deficits in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to those with MCI and no sleep disturbance. A control group was included to aid in identifying DMN changes specific to MCI. A cross-sectional, single-center study was performed at the Brain and Mind Research Centre in Sydney, Australia. Participants (95 adults over the age of 65: 38 controls and 57 meeting criteria for MCI) underwent resting-state functional MRI along with comprehensive neuropsychological, medical, and psychiatric assessment. Self-report data were collected including sleep quality assessment via the Pittsburgh Sleep Quality Index. A total score of greater than 5 on the Pittsburgh Sleep Quality Index was used to signify the presence of significant sleep disturbance, as per commonly used methodology. Using this criterion, 53% (n = 30) of our MCI group were classified as sleep-disturbed. Whereas the total group of MCI subjects and controls demonstrated no significant differences, sleep-disturbed MCIs demonstrated increased connectivity between temporal and parietal regions, and decreased connectivity between the prefrontal cortex and the temporoparietal junction relative to sleep-disturbed controls. Relative to those MCIs without sleep disturbance, sleep-disturbed MCI participants demonstrated significantly diminished DMN connectivity between temporal and parietal regions, a finding that was particularly pronounced in amnestic MCI. Sleep disturbance in MCI is associated with distinct alterations in DMN functional connectivity in brain regions underpinning salient memory and sleep systems. Future studies may build on these results via experimental manipulation and objective measurement of sleep. (PsycINFO Database Record

Objectives Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest. Methods PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network (CAN)—including the ventromedial prefrontal cortex (vmPFC), amygdala, and periaqueductal gray (PAG)—were examined using a seed-based approach. Observed connectivity patterns were then correlated to resting HRV. Results In contrast to controls, individuals with PTSD exhibited lower HRV. In addition, whereas controls engaged a localized connectivity pattern of CAN-related brain regions, in PTSD, key CAN regions were associated with widespread connectivity patterns in regions related to emotional reactivity (vmPFC and amygdala to insular cortex and lentiform nucleus; PAG to insula) and motor readiness (vmPFC and amygdala to precentral gyrus; PAG to precentral gyrus and cerebellum). Critically, whereas CAN connectivity in controls was strongly related to higher HRV (insula, mPFC, superior frontal cortex, thalamus), HRV covariation was absent in PTSD subjects. Conclusions This study provides the first evidence for a specific psychophysiological–neuronal profile in PTSD individuals characterized by lower resting HRV and a lack of HRV covariation with CAN-related brain connectivity. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.

To assess the efficacy of alfaxalone as an anaesthetic induction agent for dogs aged less than 12 weeks.The study group comprised 25 juvenile dogs aged less than 12 weeks that were presented for surgical desexing. Dogs were aged by dentition, examined and weighed prior to premedication with acepromazine, atropine and morphine. At 20-30 min after premedication, animals were anaesthetised with intravenous alfaxalone administered to effect, using a target maximum expected dose of 2 mg/kg. Dogs were intubated and anaesthesia was maintained with isoflurane in oxygen administered with a non-rebreathing system. Subjective measures of anaesthetic quality and vital signs were recorded from enrollment to recovery. Descriptive and comparative statistics were used to analyse and present collected data.The mean (± SD) dose of alfaxalone for induction was 1.7 (± 0.3) mg/kg body weight. Subjective measures of anaesthetic quality indicated acceptable induction, maintenance and recovery standards. Measured cardiovascular and respiratory parameters were well maintained.Alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (Alfaxan®) is a suitable injectable anaesthetic induction agent for dogs aged less than 12 weeks requiring anaesthesia.

Purpose: To develop a simple correction approach to mitigate shading in 3 Tesla (T) breast MRI. Materials and Methods: A slightly modified breast receive (Rx) array, which we termed field shaping array (FSA), was shown to mitigate breast shading at 3T. In this FSA, one Rx element was selectively unblocked and tuned off the Larmor frequency during the transmit (Tx) phase. The current flowing in this element during Tx created a secondary transmit field; the vector addition of this field and the one created directly by the body coil resulted in a more uniform excitation profile over the entire breast area. The receive Rx element was returned to its intended tuning during the Rx phase, ensuring unperturbed signal reception. Results: Using the FSA, improved Tx field uniformity, better fat suppression, increased image homogeneity and reduced power deposition was seen in all volunteers studied. Conclusion: A simple modification of a standard breast Rx array, converting it to a field shaping array, was shown to mitigate breast shading in all volunteers studied. J. Magn. Reson. Imaging 2012;36:865–872. © 2012 Wiley Periodicals, Inc.

A substantial body of evidence suggests that autobiographical recollection and simulation of future happenings activate a shared neural network. Many of the neural regions implicated in this network are affected in patients with bipolar disorder (BD), showing altered metabolic functioning and/or structural volume abnormalities. Studies of autobiographical recall in BD reveal overgeneralization, where autobiographical memory comprises primarily factual or repeated information as opposed to details specific in time and in place and definitive of re-experiencing. To date, no study has examined whether these deficits extend to future event simulation. We examined the ability of patients with BD and controls to imagine positive, negative and neutral future events using a modified version of the Autobiographical Interview (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) that allowed for separation of episodic and non-episodic details. Patients were selectively impaired in imagining future positive, negative, and neutral episodic details; simulation of non-episodic details was equivalent across groups.

Individuals with major depressive disorder (MDD) demonstrate deficits in multiple social cognitive domains; however, systematic investigations of empathic responding have not been performed. Twenty patients with MDD completed two measures of empathy, the Interpersonal Reactivity Index (IRI: Davis, 1980, 1983) and the Toronto Empathy Questionnaire (TEQ: Spreng et al., 2009). Relative to matched controls, patients with MDD reported significantly reduced levels of empathy measured broadly on the TEQ and specifically in cognitive ('Perspective Taking') and affective ('Empathic Concern') domains captured by the IRI. A higher illness burden (i.e., greater number of past depressive episodes) was associated with greater reductions in perspective taking ability. This study provides early evidence of impaired empathic abilities in patients with MDD that may worsen with illness progression. Alternatively, reductions in perspective taking ability may contribute to a more severe course of illness in this population. Further longitudinal work is needed to characterize the relation between social cognitive performance and social functioning in this population.

Despite evidence of impairments in social cognition in patients with bipolar disorder (BD), systematic investigations of empathic responding in this population have not been conducted. The objectives of the current study were to investigate empathic responding in patients with BD in varying states of illness and to determine whether course of illness variables and symptom severity predicted responding. Twenty well-characterized patients with BD and 20 matched healthy control subjects completed the Interpersonal Reactivity Index (IRI) and the Social Adjustment Scale Self-Report (SAS-SR), self-report measures of cognitive and emotional empathy and of psychosocial functioning, respectively. Patients with BD reported significantly reduced levels of cognitive empathy ('Perspective Taking') and higher levels of personal distress in response to others' negative experiences than did controls. Altered affective empathic abilities correlated significantly with reduced psychosocial functioning in family, social and occupational domains and with increased symptom severity. This study provides preliminary evidence of alterations in empathic responding in patients with BD. Alterations in the ability to adopt the perspective of others may contribute to the difficulties in social communication inherent in this patient population. Additional studies, involving larger samples, are required to determine the contribution of social cognitive performance to impaired social functioning in BD.

Objectives: People with bipolar disorder (BD) and major depressive disorder (MDD) are at risk for premature death from various physical illnesses. A large component of this risk may be accounted for by an elevated risk of metabolic syndrome (MeS) and coronary heart disease (CHD). The objective of our study was to examine patients' physical health prior to first treatment and over 2 years of follow-up. Methods: Ten-year risk for CHD and incidence of MeS were calculated for newly diagnosed patients with MDD (n = 30) and BD (n = 24) at baseline and over a 2-year follow-up. Age and sex-matched control subjects were obtained from the National Health and Nutrition Examination Survey III dataset. Results: At baseline, 11.2% of patients met diagnostic criteria for MeS and this increased to 16.8% at follow-up. Women had higher rates of MeS but rates were similar across diagnosis. There was a significant increase within all MeS criteria. The 10-year CHD risk was low for patients at baseline and follow-up but increased across the follow-up period. Changes in CHD and MeS risk were not associated with a specific type of pharmacotherapy, as all medication classes appeared to increase risk. Conclusion: Prior to treatment, MeS and CHD risk rates for patients were similar to the general population, but their risk of CHD increased appreciably. Can J Psychiatry. 2010;55(6):362-368. Clinical Implications * Our study highlights a concerning clinical trend. Changes in risk for both CHD and the component illnesses that make up MeS occurred early in treatment in a young, physically healthy population. * While the focus in terms of risk management has been primarily on patients treated with atypical antipsychotics, we found significant changes also occurred in patients receiving antidepressants. * Appropriate screening protocols and treatments need to be implemented early in the management of patients with mood disorders. Limitations * As our study was longitudinal and followed young patients over 2 years, we had a high attrition rate, limiting our sample size at the 2-year mark. * While detailed information regarding medication use was obtained, the naturalistic nature of the study meant that patients often used numerous different medications, limiting precise comments on the risk carried by specific medication classes. * The study sample was also ethnically homogenous, and lacking some ethnic groups that may be at highest risk for metabolic dysregulation, thereby limiting the generalizability of the findings. Key Words: obesity, bipolar major depression, metabolic syndrome, cardiovascular disease Abbreviations used in this article AD antidepressant ATPIII Adult Treatment Panel III BD bipolar disorder BMI body mass index BP blood pressure CHD coronary heart disease HDL high-density lipoprotein MDD major depressive disorder MeS metabolic syndrome NCEP National Cholestoral Education Program NHANES National Health and Nutrition Examination Survey SCID Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Defined by a cluster of metabolic risk factors, MeS in turn serves as a multiplex risk factor for CHD.1 Numerous differing definitions of the MeS have been put forward by various agencies but the definition most consistently cited is that of the NCEP ATPIII introduced in 2001 and subsequently modified in 2004. By definition, MeS requires the presence of any 3 of the following 5 criteria: central obesity (a waist circumference of >102 cm [>40 in] in men, >88 cm [>35 in] in women); elevated triglycerides (>150mg/dL [>1.7 mmol/L] or specific treatment for this lipid abnormality); raised BP (systolic BP > 1 30 or diastolic BP > 85 mm Hg, or treatment of previously diagnosed hypertension); raised fasting glucose (> 1 00 mg/dL [>5 . …

In order to formulate a parsimonious tool to assess empathy, we used factor analysis on a combination of self-report measures to examine consensus and developed a brief self-report measure of this common factor. The Toronto Empathy Questionnaire (TEQ) represents empathy as a primarily emotional process. In three studies, the TEQ demonstrated strong convergent validity, correlating positively with behavioral measures of social decoding, self-report measures of empathy, and negatively with a measure of Autism symptomatology. Moreover, it exhibited good internal consistency and high test-retest reliability. The TEQ is a brief, reliable, and valid instrument for the assessment of empathy.

Background Patients with mood disorders have higher rates of obesity than the general population. With respect to this, little is known regarding how patient look like prior to treatment or the rates of change. Objective To identify changes in the rates of obesity in never-treated patients with mood disorder over 4 years of follow-up. Methods Sixty-six never-treated patients with mood disorders were evaluated via clinical interview, symptom assessment and body mass index (BMI). Patients were followed 4 years. Population attributable risk (PAR%) was calculated. Results Patients in underweight and normal weight groups fell by nearly 29%, with a corresponding increase in patients entering overweight and obese groups. Rates of PAR% increased to 16.0, a significant 5-point increase over baseline. Limitations This study had a small sample size and the population was ethnically homogenous. BMI was used as a maker of weight and not waist circumference. Conclusions Over 4 years there was a significant increase in BMI and the risk conferred by obesity. Shift from normal weight to overweight and obese is a significant risk for patients with a mood disorder and clinical programs should consider interventions that might ameliorate risk of this shift early in the course of the illness.

The anterior cingulate cortex (ACC) is implicated in the cognitive and affective abnormalities observed in mood disorders. Bilateral ACC volume reductions have been reported in patients with major depressive disorder (MDD) when compared to healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24(sg)), subcallosal gyrus (BA25), and paracingulate gyrus (BA32) in 65 patients receiving a first course of treatment for MDD and 93 healthy control subjects. Patients with more than three episodes of untreated MDD had smaller subcallosal gyrus volumes than healthy controls, while those with three or fewer past untreated episodes did not differ from controls. We also found preliminary evidence that medication-exposed patients had smaller SGPFC volumes than patients with no exposure to medication and healthy controls. There was no evidence that these effects related to mood state, duration of untreated illness, or to patient age. No differences were apparent in paracingulate gyrus volumes between patients and controls. These findings confirm the presence of ACC volume reductions in untreated patients with MDD and suggest that illness burden and short-term medication exposure mediate this change.

The majority of volumetric magnetic resonance imaging (MRI) studies of the hippocampus in patients with bipolar disorder (BD) show no differences in hippocampal volume between patients and healthy controls. Significant variability, however, exists in the medication status of patients included in these studies. In particular, treatment with lithium may exert long-term effects on hippocampal volume, influencing cognitive outcomes in BD patients.To our knowledge, no longitudinal volumetric study has been performed in patients with BD, which would allow for an examination of whether lithium therapy used to treat BD can exert a long-term effect on hippocampal volume.We examined the effects of lithium on hippocampal volumes and recollective memory performance over a period of 2 to 4 years in 12 patients with BD who had never received pharmacotherapy before lithium initiation.We found bilateral increases in volume of the hippocampus over time. We also found some evidence of improvement in verbal memory performance over the 4-year measurement period as assessed by the California Verbal Learning Test.Consistent with preclinical literature supporting the neuroprotective effects of lithium, long-term treatment is associated with preservation of recollective memory function and increased hippocampal size in vivo.

BackgroundDespite increasing awareness of the extent and severity of cognitive deficits in major depressive disorder (MDD), trials of cognitive remediation have not been conducted. We conducted a 10-week course of cognitive remediation in patients with long-term MDD to probe whether deficits in four targeted cognitive domains, (i) memory, (ii) attention, (iii) executive functioning and (iv) psychomotor speed, could be improved by this intervention.MethodWe administered a computerized cognitive retraining package (PSSCogReHab) with demonstrated efficacy to 12 stable patients with recurrent MDD. Twelve matched patients with MDD and a group of healthy control participants were included for comparison; neither comparator group received the intervention that involved stimulation of cognitive functions through targeted, repetitive exercises in each domain.ResultsPatients who received cognitive training improved on a range of neuropsychological tests targeting attention, verbal learning and memory, psychomotor speed and executive function. This improvement exceeded that observed over the same time period in a group of matched comparisons. There was no change in depressive symptom scores over the course of the trial, thus improvement in cognitive performance occurred independent of other illness variables.ConclusionsThese results provide preliminary evidence that improvement of cognitive functions through targeted, repetitive exercises is a viable method of cognitive remediation in patients with recurrent MDD.

Post-traumatic stress disorder (PTSD) is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA) and basolateral amygdala (BLA) during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26) as compared to non-trauma-exposed controls (n = 20). Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala seed during trauma processing in PTSD. Specifically, relative to controls, during subconscious processing, individuals with PTSD demonstrated increased connectivity of the CMA with the superior frontal gyrus, accompanied by a pattern of decreased connectivity between the BLA and the superior colliculus. During conscious processing, relative to controls, individuals with PTSD showed increased connectivity between the CMA and the pulvinar. These findings demonstrate alterations in amygdala subregion functional connectivity in PTSD and highlight the disruption of the innate alarm network during both conscious and subconscious trauma processing in this disorder.