We aimed to examine associations between neuropsychiatric symptoms (NPS) and white matter hyperintensities (WMH) status in older adults without dementia under the hypothesis that WMH increased the odds of having NPS.

Longitudinal analysis of data acquired from the National Alzheimer’s Coordinating Center Uniform Data Set.

Data were derived from 46 National Institute on Aging – funded Alzheimer’s Disease Research Centers.

NACC participants aged ≥50 years with available data on WMH severity with a diagnosis of mild cognitive impairment (MCI) or who were cognitively unimpaired (CU) were studied. Among 4617 CU participants, 376 had moderate and 54 extensive WMH. Among 3170 participants with MCI, 471 had moderate and 88 had extensive WMH.

Using Cardiovascular Health Study (CHS) scores, WMH were coded as no to mild (CHS score: 0–4), moderate (score: 5–6) or extensive (score: 7–8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the odds of reporting each of 12 NPS by WMH status separately for individuals with MCI or who were CU.

Compared to CU individuals with no to mild WMH, the odds of having elation [9.87, (2.63–37.10)], disinhibition [4.42, (1.28–15.32)], agitation [3.51, (1.29–9.54)] or anxiety [2.74, (1.28–5.88)] were higher for the extensive WMH group, whereas the odds of having disinhibition were higher for the moderate WMH group [1.94, (1.05–3.61)]. In the MCI group, he odds of NPS did not vary by WMH status.

Extensive WMH were associated with higher odds of NPS in CU older adults but not in those with MCI.

Inhibitory control impairment is highly prevalent following traumatic brain injury (TBI). There have not been any empirical investigations into whether this could explain social disinhibition following severe TBI, i.e. socially inappropriate behaviour of verbal, physical or sexual nature. Further, social context has proven to be important in studying social disinhibition and using a social version of an established task for the assessment of inhibitory control may provide a new perspective. Therefore, the objectives of this research study were to investigate the role of inhibitory control impairment in social disinhibition following severe TBI, using a social and a non-social task. We hypothesized that people with TBI and clinical levels of social disinhibition would perform worse on both task versions, when compared to those with low disinhibition levels. Further, we hypothesized that participants high on social disinhibition would perform worse on the social, when compared to the non-social version.

We conducted a between-group comparative study. Twenty-six adult participants with severe TBI were matched with 27 adult, healthy controls based on gender, age and education. Frontal Systems Behavior Scale and Social Disinhibition Interview were used to assess social disinhibition. A computerized task based on the cued go/no-go paradigm was used to assess inhibitory control. We included two versions of this task – a coloured (non-social) Go/No-Go with different colored rectangles, and an emotional (social) Go/No-Go with emotional faces serving as ‘go‘ and ‘no-go‘ cues. Two-way mixed ANCOVAs were used to test between-group differences in errors of commission and response speed.

Unexpectedly, the TBI and the control group did not significantly differ on their levels of depression, anxiety, stress, or their level of social disinhibition. Overall, participants were slower (F(1,47) = 15.212, p<.001, ηp2 = .245) and made more errors of commission on no-go trials (F(1,44) = 11.560, p = .001, ηp2 = .208) on the social Go/No-Go task. There was no main effect of participants‘ brain injury status on errors of commission on no-go trials or mean reaction times. When categorized based on disinhibition level (high vs low), participants in the highdisinhibition group made more errors on the social task (F(1,41) = 4.095, p = .050, ηp2 = .091) than those in the low-disinhibition group, and more errors on the social, compared to the non-social task (task-group interaction (F(1,41) = 7.233, p = .010, ηp2 = .150)).

Based on these initial results, social disinhibition is associated with inhibitory control impairment, although this is only evident when a social inhibitory control task is used for assessment. We did not find any relationship between social disinhibition and the speed with which people react to stimuli. The results of this study add to the conceptualization of social disinhibition that is commonly present after severe TBI.

No significant relationships.

Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.

PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.

Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.

PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

Research has demonstrated that chronic stress exposure early in development can lead to detrimental alterations in the orbitofrontal cortex (OFC)–amygdala circuit. However, the majority of this research uses functional neuroimaging methods, and thus the extent to which childhood trauma corresponds to morphometric alterations in this limbic-cortical network has not yet been investigated. This study had two primary objectives: (i) to test whether anatomical associations between OFC–amygdala differed between adults as a function of exposure to chronic childhood assaultive trauma and (ii) to test how these environment-by-neurobiological effects relate to pathological personality traits.

Participants were 137 ethnically diverse adults (48.1% female) recruited from the community who completed a clinical diagnostic interview, a self-report measure of pathological personality traits, and anatomical MRI scans.

Findings revealed that childhood trauma moderated bilateral OFC–amygdala volumetric associations. Specifically, adults with childhood trauma exposure showed a positive association between medial OFC volume and amygdalar volume, whereas adults with no childhood exposure showed the negative OFC–amygdala structural association observed in prior research with healthy samples. Examination of the translational relevance of trauma-related alterations in OFC–amygdala volumetric associations for disordered personality traits revealed that trauma exposure moderated the association of OFC volume with antagonistic and disinhibited phenotypes, traits characteristic of Cluster B personality disorders.

The OFC–amygdala circuit is a potential anatomical pathway through which early traumatic experiences perpetuate emotional dysregulation into adulthood and confer risk for personality pathology. Results provide novel evidence of divergent neuroanatomical pathways to similar personality phenotypes depending on early trauma exposure.

Individuals diagnosed with borderline personality disorder (BPD) often describe their lives as stressful and unpredictable. However, it is unclear whether the adversity faced by those with BPD is a product of stress reactivity or stress generation. Here, we examined the dynamic, prospective associations between BPD and stressful life events over 3 years. Given the heterogeneity present in BPD, we sought to understand which empirically derived dimensions of this heterogeneous disorder explain stress reactivity v. stress generation.

Participants included 355 individuals diagnosed with BPD and followed longitudinally at three annual assessments. Auto-regressive cross-lagged panel models were used to examine prospective associations between stressful life events and three latent dimensions implicated in BPD: negative affect, disinhibition, and antagonism.

Antagonism and disinhibition, but not negative affect, prospectively predicted dependent stressful life events (events the individual may have some role in). Evidence for decompensation under stress was more tenuous, with independent stressful life events (those presumably outside the individual's control) predicting increases in negative affect.

Our longitudinal study of a well-characterized clinical sample found more evidence for stress generation than for stress-induced decompensation in BPD. Stress generation in BPD is driven by externalizing dimensions: antagonism and disinhibition. These results highlight the utility of empirically derived dimensions for parsing heterogeneity present in BPD, leading to improvements in diagnostic evaluation, clinical prediction, and individualized approaches to treatment planning.

A total of 28 elderly subjects with mild cognitive impairment were recruited and divided into two groups using the Neuropsychiatric Inventory. Fourteen subjects were allocated to the disinhibited group and 14 subjects matched for age, sex and educational level formed a disinhibition-free control group. The neuropsychological battery included the following tests: Mini Mental Score Evaluation, Boston Naming test, Token test, Trail Making and Verbal Fluency. Two tasks were specifically designed to stress the SAS: 1) A specific verbal sentence arrangement task in which subjects had to use sequential reasoning with verbal material. Each test sequence consisted of a series of words shown in jumbled order. The construction of some sequences had to be done by using familiar routine associations (valid conditions). In contrast, other sequences required the overriding selection of familiar routine associations, which were inappropriate within the general context of the task (invalid conditions). 2) Using the Continuous Performance Test, four aspects were evaluated: sustained, selective, preparation and suppressive attention.

The only group differences in neuropsychological test results were the following: 1) the sentence arrangement task. In comparison with the control group, the disinhibited group was impaired in invalid conditions and the calculated difference between the number of correct responses in invalid conditions minus that in valid conditions was significantly higher; and 2) the CPT. Disinhibited subjects had a significantly lower number of hits, exclusively in the ‘suppressive attention’ paradigm.

These results suggest that subjects with disinhibition have impaired supervisory system function.

Impulsivity and compulsivity have been implicated as important transdiagnostic dimensional phenotypes with potential relevance to addiction. We aimed to develop a model that conceptualizes these constructs as overlapping dimensional phenotypes and test whether different components of this model explain the co-occurrence of addictive and related behaviors.

A large sample of adults (N = 487) was recruited through Amazon’s Mechanical Turk and completed self-report questionnaires measuring impulsivity, intolerance of uncertainty, obsessive beliefs, and the severity of 6 addictive and related behaviors. Hierarchical clustering was used to organize addictive behaviors into homogenous groups reflecting their co-occurrence. Structural equation modeling was used to evaluate fit of the hypothesized bifactor model of impulsivity and compulsivity and determine the proportion of variance explained in the co-occurrence of addictive and related behaviors by each component of the model.

Addictive and related behaviors clustered into 2 distinct groups: Impulse-Control Problems, consisting of harmful alcohol use, pathological gambling, and compulsive buying, and Obsessive-Compulsive-Related Problems, consisting of obsessive-compulsive symptoms, binge eating, and internet addiction. The hypothesized bifactor model of impulsivity and compulsivity provided the best empirical fit, with 3 uncorrelated factors corresponding to a general Disinhibition dimension, and specific Impulsivity and Compulsivity dimensions. These dimensional phenotypes uniquely and additively explained 39.9% and 68.7% of the total variance in Impulse-Control Problems and Obsessive-Compulsive-Related Problems.

A model of impulsivity and compulsivity that represents these constructs as overlapping dimensional phenotypes has important implications for understanding addictive and related behaviors in terms of shared etiology, comorbidity, and potential transdiagnostic treatments.

Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.

One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.

A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.

Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.

Trait impulsivity is thought to play a key role in predicting behaviors on the externalizing spectrum, such as drug and alcohol use and aggression. Research suggests that impulsivity may not be a unitary construct, but rather multidimensional in nature with dimensions varying across self-report assessments and laboratory behavioral tasks. Few studies with large samples have included a range of impulsivity-related measures and assessed several externalizing behaviors to clarify the predictive validity of these assessments on important life outcomes.

Community adults (N = 1295) between the ages of 30 and 54 completed a multidimensional assessment of impulsivity-related traits (including 54 self-report scales of personality traits implicated in impulsive behaviors, and four behavioral tasks purporting to assess a construct similar to impulsivity) and reported on five externalizing behavioral outcomes (i.e. drug, alcohol, and cigarette use, and physical and verbal aggression). We ran an exploratory factor analysis on the trait scales, and then a structural equation model predicting the externalizing behaviors from the three higher-order personality factors (i.e. Disinhibition v. Constraint/Conscientiousness, Neuroticism/Negative Emotionality, and Extraversion/Positive Emotionality) and the four behavioral tasks.

Relations between the self-report factors and behavioral tasks were small or nonexistent. Associations between the self-report factors and the externalizing outcomes were generally medium to large, but relationships between the behavioral tasks and externalizing outcomes were either nonexistent or small.

These results partially replicate and extend recent meta-analytic findings reported by Sharma et al. (2014) to further clarify the predictive validity of impulsivity-related trait scales and laboratory behavioral tasks on externalizing behaviors.

The Triarchic Psychopathy Measure (TriPM) provides Disinhibition, Boldness, and Meanness scales for assessing the three trait domains of the triarchic model. Here we examined the genetic and environmental etiology of these three domains, including evaluation of potential sex differences.

A total of 1016 men and women ages 19–20 years were drawn from the University of Southern California Risk Factors for Antisocial Behavior twin study.

Scores for the three TriPM scales were correlated to differing degrees, with the strongest phenotypic correlation between Disinhibition and Meanness. No sex differences were found in the genetic and environmental influences underlying these three domains, suggesting that the same genes and life experiences contribute to these traits in young men and women. For TriPM Disinhibition and Boldness, genetic factors explained about half or less of the variance, with the rest of the variance being explained by non-shared environmental factors. For TriPM Meanness, on the other hand, genetic, shared environmental, and non-shared environmental factors accounted for the variance. The phenotypic correlation between Disinhibition and Meanness was explained in part by common genes (26%), with the remainder attributable about equally to common shared (39%), and non-shared environmental influences (35%).

These findings contribute to our understanding of psychopathic personality traits by demonstrating the importance of heritable factors for disinhibition and boldness facets of psychopathy, and the importance of shared environmental influences for the meanness facet.

Can core genetic liabilities for suicidal behavior be indexed using psychological and neural indicators combined? The current work addressed this question by examining phenotypic and genetic associations of two biobehavioral traits, threat sensitivity (THT) and disinhibition (DIS) – operationalized as psychoneurometric variables (i.e., composites of psychological-scale and neurophysiological measures) – with suicidal behaviors in a sample of adult twins.

Participants were 444 identical and fraternal twins recruited from an urban community. THT was assessed using a psychological-scale measure of fear/fearlessness combined with physiological indicators of reactivity to aversive pictures, and DIS was assessed using scale measures of disinhibitory tendencies combined with indicators of brain response from lab performance tasks. Suicidality was assessed using items from structured interview and questionnaire protocols.

THT and DIS each contributed uniquely to prediction of suicidality when assessed psychoneurometrically (i.e., as composites of scale and neurophysiological indicators). In addition, these traits predicted suicidality interactively, with participants high on both reporting the greatest degree of suicidal behaviors. Biometric (twin-modeling) analyses revealed that a high percentage of the predictive association for each psychoneurometric trait (83% for THT, 68% for DIS) was attributable to genetic variance in common with suicidality.

Findings indicate that psychoneurometric assessments of biobehavioral traits index genetic liability for suicidal behavior, and as such, can serve as innovative targets for research on core biological processes contributing to severe psychopathology, including suicidal proclivities and actions.

The triarchic model of psychopathy characterizes the disorder in terms of three distinguishable phenotypic facets: disinhibition, meanness and boldness. The present study sought to (1) inform current debates regarding the role of boldness in the definition of psychopathy and (2) clarify boundaries between psychopathy and antisocial personality disorder (ASPD).

This study evaluated the degree to which facets of the triarchic model are represented in the most widely used clinical inventory for psychopathy, the Psychopathy Checklist – Revised (PCL-R), in comparison with ASPD as defined by DSM-IV criteria. Adult male offenders from two distinct correctional settings (n = 157 and 169) were investigated to ensure replicability of findings across samples exhibiting high base rates of psychopathy and antisocial behavior.

We found evidence for convergent and discriminant validity of the three triarchic facets in predicting symptomatic components of psychopathy as assessed by the PCL-R. Additionally, and crucially vis-à-vis current debates in the field, we found that boldness contributed incrementally (over and above disinhibition and meanness) to prediction of PCL-R psychopathy, in particular its interpersonal style component, but not ASPD.

The three distinct facets of the triarchic model of psychopathy are represented clearly and distinctly in the PCL-R, with boldness through its interpersonal facet, but not in DSM-defined ASPD. Our findings suggest that boldness is central to diagnostic conceptions of psychopathy and distinguishes psychopathy from the more prevalent diagnosis of ASPD.