Potential Vulnerability Marker Research Articles

No significant alteration in white matter microstructure in first-degree relatives of patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is characterized by structural alteration within white matter tissues of cortico-striato-thalamo-cortical, temporal and occipital circuits. However, the presence of microstructural changes in the white matter tracts of unaffected first-degree relatives of patients with OCD as a vulnerability marker remains unclear. Therefore, here, diffusion-tensor magnetic resonance imaging (DTI) data were obtained from 29 first-degree relatives of patients with OCD and 59 healthy controls. We investigated the group differences in FA using whole-brain analysis (DTI analysis). For additional regions of interest (ROI) analysis, we focused on the posterior thalamic radiation and sagittal stratum, shown in recent meta-analysis of patients with OCD. In both whole-brain and ROI analyses, using a strict statistical threshold (family-wise error rate [FWE] corrected p<.05 for whole-brain analyses, and p<.0125 (0.05/4) with Bonferroni correction for ROI analyses), we found no significant group differences in FA. Subtle reductions were observed in the anterior corona radiata, forceps minor, cingulum bundle, and corpus callosum only when a lenient statistical was applied (FWE corrected p<.20). These findings suggest that alterations in the white matter microstructure of first-degree relatives, as potential vulnerability markers for OCD, are likely subtle.

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders.

Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well as when and how these emotions are experienced or expressed. It is a focal overarching symptom in many severe and prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), and borderline personality disorder (BPD). In all these disorders, ED can manifest through symptoms of depression, anxiety, or affective lability. Considering the many symptomatic similarities between BD, ADHD, and BPD, a transdiagnostic approach is a promising lens of investigation. Mounting evidence supports the role of peripheral inflammatory markers and stress in the multifactorial aetiology and physiopathology of BD, ADHD, and BPD. Of note, neural circuits that regulate emotions appear particularly vulnerable to inflammatory insults and peripheral inflammation, which can impact the neuroimmune milieu of the central nervous system. Thus far, few studies have examined the link between ED and inflammation in BD, ADHD, and BPD. To our knowledge, no specific work has provided a critical comparison of the results from these disorders. To fill this gap in the literature, we review the known associations and mechanisms linking ED and inflammation in general, and clinically, in BD, ADHD, and BD. Our narrative review begins with an examination of the routes linking ED and inflammation, followed by a discussion of disorder-specific results accounting for methodological limitations and relevant confounding factors. Finally, we critically discuss both correspondences and discrepancies in the results and comment on potential vulnerability markers and promising therapeutic interventions.

Computational markers of risky decision-making predict for relapse to alcohol.

Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

Genotype-by-diagnosis interaction influences self-control in human cocaine addiction

Not everyone who uses drugs loses control over their intake, which is a hallmark of addiction. Although familial risk studies suggest significant addiction heritability, the genetic basis of vulnerability to drug addiction remains largely unknown. In the present study, we investigate the relationship between self-control, cocaine use, and the rs36024 single nucleotide polymorphism of the noradrenaline transporter gene (SLC6A2). We hypothesize that C-allele-carrying adults show impaired self-control, as measured by the stop-signal task and demonstrated previously in adolescents, and further exacerbated by chronic cocaine use. Patients with cocaine use disorder (CUD, n = 79) and healthy unrelated participants with no history of drug abuse (n = 54) completed the stop-signal task. All participants were genotyped for rs36024 allelic variants (CC/TT homozygotes, CT heterozygotes). We measured mean stop-signal reaction time, reflecting the ability to inhibit ongoing motor responses, reaction times to go stimuli, and the proportion of successful stops. CUD patients showed prolonged stop-signal reaction time, however, there was no main effect of rs36024 genotype. Importantly, there was a significant genotype-by-diagnosis interaction such that CUD patients with CC genotype had longer stop-signal reaction time and fewer successful stops compared with CC healthy controls and TT CUD patients. CT CUD patients showed an intermediate performance. Self-control deficits were associated with cocaine use disorder diagnosis, which interacts with the noradrenaline transporter rs36024 polymorphism. Our findings suggest that rs36024 may represent a potential genetic vulnerability marker, which facilitates the transition from first cocaine use to addiction by weakening the inhibitory control over behavior.

Does Cognitive Therapy Change the Early Maladaptive Schemas in Individuals with Alcohol Dependence? Evidence from a Randomized Controlled Trial.

Although early maladaptive schemas (EMSs) have been suggested as potential vulnerability markers for alcohol dependence (AD), there is less emphasis on addressing these schemas in substance abuse treatment programs. We thus aimed to examine the change in schemas in response to cognitive therapy in individuals with AD. In this an open-label randomized controlled study, individuals with alcohol dependence syndrome (ADS, n = 84) were randomized to the intervention group (n = 45), which received six cognitive therapy sessions combined with treatment as usual (TAU), or the control group (n = 39), which was on TAU only. Participants were assessed on the measures of EMSs, alcohol use severity, and perceived stress at baseline and posttreatment. The intervention group showed significant improvement in 5 out of 18 EMSs, that is, emotional deprivation, defectiveness, self-sacrifice, unrelenting standard, and negativity, compared to the control group, at the end of the treatment. There was a significant between-group effect for perceived stress but not for alcohol use severity. EMSs can be changed with cognitive therapy in individuals with AD and could be a crucial area to address in treatment programs. Further studies with long-term follow-up are warranted. The trial was registered with the Clinical Trials Registry-India (CTRI/2015/12/006441) on December 17, 2015.

The Extent of Endorsement of Distal to Proximal Dysfunctional Cognitions in Individuals with Alcohol Dependence: A Comparative Cross-Sectional Study in the Indian Context.

Background:Dysfunctional basic cognitions have been suggested as potential vulnerability markers for alcohol dependence (AD). Although there is a growing body of research on the role of distal cognitive vulnerability factors such as early maladaptive schema in the development of AD, little is known about the role of proximal cognitive factors such as cognitive distortions, dysfunctional attitude, and negative automatic thoughts.Methods:This comparative cross-sectional study aimed to examine dysfunctional cognitions in individuals with AD (n = 84) in comparison with healthy individuals (n = 60). The dysfunctional cognitions were assessed on the Young Schema Questionnaire third version of Short Form, Cognitive Distortion Scale, Dysfunctional Attitude Scale-Form A, and Automatic Thought Questionnaire. Multivariate analysis of covariance was conducted to analyze the group differences in dysfunctional cognitions.Results:After controlling for the group difference in employment status, 12 of 18 schemas were more prevalent in individuals with AD than in healthy individuals. Individuals with AD also scored higher on seven of 10 cognitive distortions, as well as in terms of dysfunctional attitude and negative automatic thoughts.Conclusion:Dysfunctional cognition may play a significant role in developing AD. The findings may enhance our understanding of the nature and severity of dysfunctional cognitions in the development of AD. The information may further assist the clinicians in implementing adequate intervention strategies to manage dysfunctional cognitions in individuals with AD.

Leukoaraiosis is associated with clinical symptom severity, poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage: a prospective multi-center cohort study.

Leukoaraiosis (LA) results from ischemic injury in small cerebral vessels, which may be attributable to decreased vascular density, reduced cerebrovascular angiogenesis, decreased cerebral blood flow, or microcirculatory dysfunction in the brain. In this study, we enrolled 357 patients with mild intracerebral hemorrhage (ICH) from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission, neurological function prognosis at 3 months, and 1-year stroke recurrence. Patients were divided into groups based on Fazekas scale scores: no LA (n = 83), mild LA (n = 64), moderate LA (n = 98) and severe LA (n = 112). More severe LA, larger hematoma volume, and higher blood glucose level at admission were associated with more severe neurological deficit. More severe LA, older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months. In addition, moderate-to-severe LA, admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence. These findings suggest that LA severity may be a potential marker of individual ICH vulnerability, which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH. Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols. This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University (approval No. 12) on March 10, 2011.

The Effects of Cannabis Use Frequency and Episodic Specificity Training on the Recall of Specific and Rewarding Events.

Background: Growing evidence implicates subjective episodic memory, the retrieval of detailed, integrated, and personally relevant past events, as a marker of cognitive vulnerability in mental disorders. Frequent and problematic cannabis use is associated with deficits in objective episodic memory (verbal memory), but the relationship between subjective episodic memory deficits and frequency of cannabis use is unknown. Further, whether a brief intervention designed to enhance the specificity of event retrieval, such as the Episodic Specificity Induction (ESI), might effectively target such deficits among regular cannabis users is unexamined. This study was designed to examine subjective episodic memory as a potential marker of cognitive vulnerability among frequent cannabis users.Methods: Active cannabis users (n = 133) recruited from Amazon Mechanical Turk or Qualtrics Panels were randomized to receive an ESI-control or ESI session and were separated into those who used cannabis 1–25 days in the past month (low to moderate frequency group) and those who used 26–30 days (high frequency group), which facilitated a low to moderate use/ESI-control group (n = 78), low to moderate use/ESI group (n =15), high-use/ESI-control group (n = 20), and high-use/ESI group (n = 20). Following the ESI or ESI-control intervention, participants selected four, positive events from the prior day, described the who, what, and where of the events, and rated how specific (vividness) and rewarding (enjoyable, importance, and exciting) each event was on a 0–100 scale. Four two-way ANCOVAs (demographics and problematic cannabis use covariates) were performed to examine the effects of frequency of cannabis use group and ESI group on the specificity and reward ratings.Results: Lower vividness and excitement ratings were reported for those with high relative to low to moderate cannabis use frequency patterns (p < 0.05). Those who received ESI reported greater vividness, excitement, and importance ratings than the ESI-control group (p < 0.01). No significant interactions between frequency and ESI were found.Conclusion: Findings from the current exploratory study provide initial evidence suggesting that more frequent cannabis use may be associated with the retrieval of less specific and rewarding events relative to less frequent users. Further, ESI may improve such deficits. Future studies that recruit larger and more clinically serious samples of cannabis users appear warranted.

The role of stress reactivity and pre-injury psychosocial vulnerability to psychological and physical health immediately after traumatic injury

BackgroundTraumatic injuries can have long-term negative impacts on health, especially psychological health. A biopsychosocial approach is recommended to identify those likely to experience psychosocial stress, however large individual differences exist in stress reactivity and post-injury health that remain unexplored. Therefore, we investigated autonomic nervous system (ANS) stress responses and pre-existing psychosocial vulnerability as contributors to health in individuals who sustained a traffic-related injury. Methods120 adults with traffic-related injury and 112 non-injury controls underwent an integrative ANS (cardiac and skin conductance) assessment and a health-related assessment at 3–6 weeks post-injury. Propensity score matching based on six pre-injury psychosocial vulnerability factors (age, sex, education, prior mental/physical health, socioeconomic status) guided the definition of high vulnerability (HV) and low vulnerability (LV) injury subgroups, with the LV subgroup having similar propensity scores to non-injury controls. A three-group comparative analysis of ANS responsivity (baseline, reactivity, recovery/rebound) and post-injury health was performed. ResultsThe HV subgroup exhibited the most negative immediate post-injury mental health profile and less adaptive ANS response patterns, indicating greater stress vulnerability/reactivity. Significant differences were found for psychological health (elevated psychological distress and catastrophizing), but not physical health (injury factors, pain, fatigue, physical wellbeing). HV participants showed sympathetic predominance at resting baseline (lower parasympathetic activity and/or elevated heart rate) compared to the LV and control groups, as well as smaller parasympathetic decrease during a cognitive task compared to controls. Despite preserved capacity for restoring initial homeostasis in both injury subgroups during recovery, there was some indication of blunted post-task sympathetic deactivation (larger sympathetic decrease) and reduced overall ANS adaptability (reduction in total power of heart rate variability spectrum), suggesting relative reduced capacity to face stressors compared to controls. ConclusionsFindings suggest that baseline resting ANS regulation, particularly parasympathetic activity, and pre-injury psychosocial factors are key contributors to individual psycho-biological responses following traumatic injury, and are therefore potential stress vulnerability markers. Post-stress recovery patterns may represent a novel physiological signature for a “biological intrinsic” vulnerability early after the injury. These findings provide direction for improved early identification and management of injured individuals, including innovative preventive interventions that target ANS regulation.

Reduced cortical gyrification in the posteromedial cortex in unaffected relatives of schizophrenia patients with high genetic loading

Although abnormal cortical gyrification has been consistently reported in patients with schizophrenia, whether gyrification abnormalities reflect a genetic risk for the disorder remains unknown. This study investigated differences in cortical gyrification between unaffected relatives (URs) with high genetic loading for schizophrenia and healthy controls (HCs) to identify potential genetic vulnerability markers. A total of 50 URs of schizophrenia patients and 50 matched HCs underwent T1-weighted magnetic resonance imaging to compare whole-brain gyrification using the local gyrification index (lGI). Then, the lGI clusters showing significant differences were compared between the UR subgroups based on the number of first-degree relatives with schizophrenia to identify the effect of genetic loading on cortical gyrification changes. The URs exhibited significantly lower cortical gyrification than the HCs in clusters including medial parieto-occipital and cingulate regions comprising the bilateral precuneus, cuneus, pericalcarine, lingual, isthmus cingulate, and posterior cingulate gyri. Moreover, URs who had two or more first-degree relatives with schizophrenia showed greater gyrification reductions in these clusters than those who had at least one first-degree relative with schizophrenia. Our findings of reduced gyrification in URs, which are consistent with accumulated evidence of hypogyria observed in regions showing patient-control differences in previous studies, highlight that such hypogyria in posteromedial regions may serve as a genetic vulnerability marker and reflect early neurodevelopmental abnormalities resulting from a genetic risk for schizophrenia.

Anti-Apolipoprotein A-1 IgG Influences Neutrophil Extracellular Trap Content at Distinct Regions of Human Carotid Plaques.

Background: Neutrophils accumulate in atherosclerotic plaques. Neutrophil extracellular traps (NET) were recently identified in experimental atherosclerosis and in complex human lesions. However, not much is known about the NET marker citrullinated histone-3 (H3Cit) expression and functionality in human carotid plaques. Moreover, the association between the proatherosclerotic autoantibody anti-apolipoprotein A-1 (anti-ApoA-1 IgG) and NET has never been investigated. Methods: Atherosclerotic plaques have been obtained from 36 patients with severe carotid stenosis that underwent carotid endarterectomy for severe carotid stenosis. Samples were sectioned into upstream and downstream regions from the same artery segment. Plaque composition and expression of NET markers neutrophil elastase (NE) and H3Cit were quantified by immunohistochemistry. H3Cit expression and function was evaluated by immunofluorescence and confocal analysis in a subset of patients. Results: Pathological features of vulnerable phenotypes were exacerbated in plaques developed at downstream regions, including higher accumulation of neutrophils and enhanced expression of NE and H3Cit, as compared to plaques from upstream regions. The H3Cit signal was also more intense in downstream regions, with significant extracellular distribution in spaces outside of neutrophils. The percentage of H3Cit colocalization with CD66b (neutrophils) was markedly lower in downstream portions of carotid plaques, confirming the extrusion of NET in this region. In agreement, the maximum distance of the H3Cit signal from neutrophils, extrapolated from vortex distance calculation in all possible directions, was also higher in downstream plaques. The serum anti-ApoA-1index positively correlated with the expression of H3Cit in downstream segments of plaques. Expression of the H3Cit signal outside of neutrophils and H3Cit maximal distance from CD66b-positive cells increased in plaques from serum positive anti-ApoA-1 patients compared with serum negative patients. Conclusion: NET elements are differentially expressed in upstream versus downstream regions of human carotid plaques and may be influenced by circulating levels of anti-ApoA-1 IgG. These findings could warrant the investigation of NET elements as potential markers of vulnerability.

Variability in Hourly Activity Levels: Statistical Noise or Insight Into Older Adult Frailty?

Frailty is associated with lower mean activity; however, hourly activity is highly variable among older individuals. We aimed to relate frailty to hourly activity variance beyond frailty's association with mean activity. Using the 2010-2011 National Social Life, Health and Aging Project wrist accelerometry data (n = 647), we employed a mixed-effects location scale model to simultaneously determine whether an adapted phenotypic frailty scale (0-4) was associated with the log10-mean hourly counts per minute (cpm) and between-and within-subject hourly activity variability, adjusting for demographics, health characteristics, season, day-of-week, and time-of-day. We tested the significance of a Frailty × Time-of-day interaction and whether adjusting for sleep time altered relationships. Each additional frailty point was associated with a 7.6% (10-0.0343, β = -0.0343; 95% CI: -0.05, -0.02) lower mean hourly cpm in the morning, mid-day, and late afternoon but not evening. Each frailty point was also associated with a 24.5% (e0.219, β = 0.219; 95% CI: 0.09, 0.34) greater between-subject hourly activity variance across the day; a 7% (e0.07, β = 0.07; 95% CI: 0.01¸ 0.13), 6% (e0.06, β = 0.06; 95% CI: 0, 0.12), and 10% (e0.091, β = 0.091; 95% CI: 0.03, 0.15) greater within-subject hourly activity variance in the morning, mid-day, and late afternoon, respectively; and a 6% (e-0.06, β = -0.06; 95% CI: -0.12, -0.003) lower within-subject hourly activity variance in the evening. Adjusting for sleep time did not alter results. Frail adults have more variable hourly activity levels than robust adults, a potential novel marker of vulnerability. These findings suggest a need for more precise activity assessment in older adults.

1056 Perceived Financial Difficulty Predicts Sleep Quality In Participants With Type 2 Diabetes And Obstructive Sleep Apnea

Abstract Introduction People with multiple chronic conditions such as type 2 diabetes (T2D) and obstructive sleep apnea (OSA) are at increased risk for poor sleep quality. It is unclear if social determinants of health (SDoH) such as race, perceived financial difficulty, education, gender, and marital status are associated with sleep quality in this population. The purpose of this cross-sectional secondary analysis of data from the Diabetes Sleep Treatment Trial was to explore SDoH and disease severity as predictors of sleep quality in persons with both OSA and T2D. Methods Disease severity was measured by Apnea-Hypopnea Index [(AHI) ≥ 5] and A1C for glycemic control. SDoH included perceived financial difficulty (none/moderate-severe), race (White/African American), sex (f/m), marital status (no/yes), education (≤ or &amp;gt; 2 years post high school), and age. Sleep quality was measured by Pittsburgh Sleep Quality Index (PSQI). Correlations and linear regression modeling investigated associations between SDoH and disease severity on sleep quality. Post-hoc correlations were explored for significant relations among SDoH. Results The sample (N = 229) was middle-aged (57.6 ± 10.0; 66 % White and 34% African American; and 54 % men vs. 46% women. Participants carried a high burden of disease (mean AHI = 20.7±18.1, mean A1C = 7.9 %±1.7%). Disease severity was not significantly associated with sleep quality (all p &amp;gt;.05). The perception of worse financial difficulty was the only SDoH that predicted worse sleep quality (b=-1.54, p=.015). Characteristics significantly associated with worse financial difficulty were being African American, female, ≤ 2 years post high school, and younger (all p&amp;lt;.01). Conclusion Financial difficulty may be a more important predictor of subjective measures of sleep quality than disease severity in patients with OSA and T2D. Researchers and clinicians should be aware of these characteristics as potential markers of vulnerability to poor sleep quality in this population. Support The National Institute of Diabetes and Digestive and Kidney Diseases (R01DK096028) and through the Clinical +Translational Research Institute grants UL1TR001857 and UL1TR000005.

T133. NEURAL CORRELATES OF EMOTIONAL PROCESSING IN PSYCHOSIS RISK AND ONSET – A SYSTEMATIC REVIEW AND META-ANALYSIS OF FMRI STUDIES

BackgroundBehavioural findings suggest that the emotion processing abnormalities typically observed in established schizophrenia are already present in patients with a first episode of psychosis (FEP). Evidence has been less consistent in people at clinical high risk for psychosis (CHRp). While several studies have reported unaltered behavioural performance on emotion identification in people at CHRp compared to healthy controls, some studies have shown poorer negative emotion recognition. A growing number of functional magnetic resonance (fMRI) studies have investigated brain response to emotion processing to elucidate the mechanisms underlying these processes in FEP patients and CHRp individuals. Despite the marked expansion of this field over the last two decades, to date, no systematic review or meta-analysis has attempted to synthesise the evidence on the neural bases of emotion processing in these groups as potential markers of psychosis vulnerability and expression.MethodsThe PubMed and Ovid MEDLINE databases were searched for published English-language articles applying an emotion processing task during fMRI in a FEP and/or a CHRp sample compared to healthy controls. References of included papers were also screened. For CHRp studies, only those including participants by the basic or attenuated symptom presentation criteria were included.Individual study methodology and results were extracted and systematically reviewed. In addition, at present, statistical parametric mapping contrast maps (‘T-maps’) are being collected from study authors and will be meta-analysed using the Seed-based d Mapping method. The contrasts meta-analysed will be the ones most commonly reported in the studies identified, i.e., of all emotion over comparison conditions and of negative emotion over neutral conditions. These will be meta-analysed separately, as behavioural evidence suggests that emotion recognition performance in these populations might be valence specific.ResultsFor the systematic review, 4,389 papers were identified through the search. 19 relevant fMRI papers were identified and their references were screened. 17 articles were included after full-text screening. Six out of twelve fMRI studies in the FEP population reported lower brain activation to emotion processing tasks compared to healthy controls. Four articles reported region-specific hyper- and hypoactivations and two studies found no significant difference. Of the seven studies in the CHRp population, one study reported lower brain response to emotion relative to healthy controls, two studies found hyperactivations, one study found region-specific increases and decreases, and two studies reported no significant difference. The most consistent finding across studies was lower amygdala activation in FEP participants (n=6). Conversely, in the CHRp population one article found an increase in amygdala response to emotion with age, consistently with one other article but contrasting with another study showing activity decreases in this region.DiscussionTo our knowledge, no previous systematic review or meta-analysis has synthesised the fMRI findings of emotion processing in both people at CHRp and a FEP. The present systematic review shows that while more consistent hypoactivations are found in the FEP population, results are less consistent in CHRp studies. The undergoing meta-analysis will quantitatively synthesise these findings. Elucidating the nature of emotion processing aberrances in early psychosis may help understand the functional changes across both vulnerability and symptom emergence phases and inform molecular investigations into its underlying mechanisms.

Aberrant reward prediction errors in young adult at-risk alcohol users.

Previous studies suggest that individuals with substance use disorder have abnormally large responses to unexpected outcomes (reward prediction errors [RPEs]). However, there is much less information on RPE in individuals at risk of alcohol misuse, prior to neurobiological adaptations that might result from sustained alcohol use. Here, participants (mean age 23.77 years, range 18-32 years) performed the electrophysiological monetary incentive delay task. This task involved responding to a target stimulus following reward incentive cues to win, or avoid losing, the cued reward while brain activity was recorded under 64-channel EEG. The Alcohol Use Disorders Identification Test (AUDIT) was used to quantify at-risk alcohol use, with high (n = 22, mean AUDIT score: 13.82) and low (n = 22, mean AUDIT score: 5.77) alcohol use groups. Trial-by-trial RPEs were estimated using a Rescorla-Wagner reinforcement model based on behavioral data. A single-trial analysis revealed that the feedback-related negativity (FRN) and feedback P3 (fb-P3) event-related potential components were significantly modulated by RPEs. There was increased RPE-related fb-P3 amplitude for those in the high alcohol use group. Next, the mean amplitude of ERPs elicited by positive and negative RPEs were compared between groups. We found that high alcohol use participants had attenuated FRN amplitude in contrast with low alcohol use participants for both positive and negative RPEs but enhanced fb-P3 for both positive and negative RPE. These results, with differences in RPE in an at-risk group, suggest that RPE a potential vulnerability marker for alcohol use disorder.

Psychobehavioral risk factors for financial hardship and poor functional outcomes in survivors of multiple primary cancers.

Survivors of multiple primary cancers (MPC) are at increased risk for poor health outcomes compared with survivors of single cancers. Using an adapted psychobehavioral stress-response model, the study purpose was to identify pathways and individual risk factors associated with poor health outcomes in adults with MPC. Adult MPC survivors (N = 211) with first cancers (stages I-III) diagnosed within 1 to 10 years were recruited via tumor registry. Employing a cross-sectional design, established questionnaires were used to operationalize patient characteristics and theoretical constructs including perceived stress, psychological and behavioral responses, financial hardship, social role function, and physical health. Disease and treatment data were obtained via registry and medical records. Structural equation modeling (SEM) was performed to fit, test, and modify the hypothesized psychobehavioral model. Following measurement model refinement, an SEM linking self-management behaviors, distress, financial hardship, and functional health demonstrated a good fit: χ2 (200, N = 206) = 332.06, P < .01; Tucker-Lewis index (TLI) = .95, comparative fit index (CFI) = .96, standardized root mean residual (SRMR) = .06, root-mean-square error of approximation (RMSEA) = .06. Less use of self-management behaviors predicted higher distress which, in turn, predicted higher financial hardship; higher distress and financial hardship predicted poorer functional health. Several sociodemographic and personal factors predicted self-management behaviors and distress. The hypothesized stress-response model was partially supported. Data supported pathways among self-management behaviors, distress, financial hardship, and functional health. Self-management and distress may represent modifiable intervention targets for MPC survivors. High body mass index (BMI), less education, greater neuroticism, and lower social support were associated with less use of self-management behaviors and higher distress and should be further evaluated as potential markers of vulnerability.

Analysis of association between temperament and psychological symptoms using the Affective and Emotional Composite Temperament (AFECT) model: An internet-based survey

BackgroundTemperamental characteristics have been suggested as potential vulnerability markers or could help differential diagnosis among psychiatric disorders. The current study aimed to explore whether there are specific temperament profiles related to different psychological symptoms, according to the Affective and Emotional Composite Temperament (AFECT) model. MethodsWe used a cross-sectional web-based survey collected from the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). The sample consisted of 16,495 self-selected volunteers assessed with the Affective and Emotional Composite Temperament Scale (AFECTS), Adult Self-Report Inventory (ASRI), and Adult Self-Report Scale (ASRS). ResultsAll unstable affective temperaments (cyclothymic, dysphoric, and volatile) correlated, in different intensities, with all psychiatric symptoms assessed. Cyclothymic temperament was mainly related to borderline personality symptoms. Dysphoric and volatile temperament showed an association with attention deficit hyperactivity symptoms. Melancholic temperament was associated with major depressive symptoms, and euphoric temperament showed a positive correlation with maniac symptoms. Euthymic and hyperthymic temperaments were negatively correlated with all psychiatric symptoms. In addition, the assessment of the emotional traits of temperament showed that high volition, low anger, low sensitivity, and high control are characteristics that are not related to psychopathology. LimitationsThis study had a cross-sectional design, which does not allow an exact inference of cause and consequence. ConclusionsOur results suggest that temperament assessment using AFECT model may be relevant to assess the risk of developing psychological symptoms over the time. These results strengthen the theoretical framework that psychiatric disorders may be manifestations of the extremes of affective temperaments.

Source-based morphometry reveals gray matter differences related to suicidal behavior in criminal offenders.

Relative to the general population, criminal offenders have a higher risk of suicide. Neurobiological deficits related to suicidal behavior have been identified in the general population, but unexamined in offenders to date. We examined the association between brain morphology and suicidal behavior in adult male criminal offenders. Brain morphology was examined using voxel-based morphometry (VBM) and source-based morphometry (SBM), a multivariate alternative to VBM which analyzes brain volume in between-subject spatially independent networks. Results showed that offenders with past suicide attempts (n = 19), relative to offenders without past suicide attempts (n = 19) and non-offenders (n = 26), had reduced gray matter in an SBM component that comprised the posterior cingulate, dorsal prefrontal cortex, and amygdala. The SBM source weights were significantly associated with suicide attempts independent of other suicide risk variables (e.g., depression). VBM results were similar to the SBM results but less robust. The results reveal a potential neurobiological marker of vulnerability to suicidal behavior among criminal offenders and illustrate the utility of multivariate methods of gray matter analyses.

DUCHENNE MUSCULAR DYSTROPHY – CLINICAL: P.25Circadian rhythms in young boys with Duchenne muscular dystrophy

Research has determined that the circadian timing system exerts temporal control over physiology, and its alteration has been associated with several systemic symptoms, including fatigue, appetite loss and poor sleep. However, the clinical impact of circadian disruption in young boys with DMD has not been empirically studied. In fact, there is little to no clinical data on sleep disturbances in very young boys with DMD, although such disturbances have been observed in typically developing children and older boys with DMD. Moreover, current research suggests children with hereditary disorders are rarely evaluated for sleep quality, hence rarely provided with sleep interventions or strategies. We have enrolled 35 boys with DMD and their caregivers throughout the U.S. to explore sleep and daily activity over a 30-day period. We have observed low levels of sleep efficiency, high levels of sleep fragmentation, and erratic behavior in the young boys' circadian rest-activity rhythms. Circadian rhythm disturbances may represent a potential vulnerability marker for emergence of numerous bio-behavioral problems, and thus, rest/activity rhythm stabilization has promise to inform early-identification and prevention/ intervention strategies for young boys with DMD. Through longitudinally and objectively measuring and monitoring daytime activity and nighttime sleep patterns in young boys with DMD, we have determined the need to explore family-based interventions tailored for children to achieve optimum sleep. We are also studying known relationships between cognition, physical function, and other bio-behavioral outcomes in our young boys with DMD. It is highly likely that results from this study will inform sleep interventions in other young populations with disability.

Structural and functional alterations in the brain during working memory in medication-naïve patients at clinical high-risk for psychosis.

Several previous studies suggest that clinical high risk for psychosis (CHR) is associated with prefrontal functional abnormalities and more widespread reduced grey matter in prefrontal, temporal and parietal areas. We investigated neural correlates to CHR in medication-naïve patients. 41 CHR patients and 37 healthy controls were examined with 1.5 Tesla MRI, yielding functional scans while performing an N-back task and structural T1-weighted brain images. Functional and structural data underwent automated preprocessing steps in SPM and Freesurfer, correspondingly. The groups were compared employing mass-univariate strategy within the generalized linear modelling framework. CHR demonstrated reduced suppression of the medial temporal lobe (MTL) regions during n-back task. We also found that, consistent with previous findings, CHR subjects demonstrated thinning in prefrontal, cingulate, insular and inferior temporal areas, as well as reduced hippocampal volumes. The present findings add to the growing evidence of specific structural and functional abnormalities in the brain as potential neuroimaging markers of psychosis vulnerability.