Is risk-taking propensity a familial vulnerability factor for alcohol use? An examination in two independent samples

Research indicates that increased risk-taking propensity (RTP) is associated with higher alcohol use. There is also some evidence to suggest that it is not just a state factor or ‘scar,’ but instead a vulnerability factor. If this is the case, increased RTP should be evident in healthy individuals that are at risk for alcohol use. To date, few studies have examined whether RTP is a familial vulnerability factor and thus, the aim of the current study was to test whether RTP aggregates within families and if increased RTP is evident in biological family members at risk for alcohol use. Sample 1 included 87 biological, adult sibling pairs and Sample 2 included 111 biological mother and adolescent dyads (total N=396). All participants completed a behavioral measure of RTP and were assessed for alcohol use. Results in both samples were strikingly consistent. In Sample 1, RTP was correlated among siblings and greater frequency of proband alcohol use predicted greater sibling RTP, over and above sibling alcohol use. In Sample 2, RTP was correlated among mothers and their offspring and greater maternal alcohol use problems predicted greater adolescent RTP over and above adolescent substance use. Together, these findings suggest that RTP may be a familial vulnerability factor for alcohol use as it aggregates within families and is increased in relatives of individuals with higher levels of alcohol use

The predictive power of depression screening procedures for veterans with coronary artery disease

Depression leads to a worse outcome for patients with coronary artery disease (CAD). Thus, accurately identifying depression in CAD patients is imperative. In many veterans affairs (VA) hospitals, patients are screened for depression once a year using the patient health questionnaire (PHQ-9). Although the PHQ-9 is generally considered a specific and sensitive measure of depression, there is reason to believe that these screening procedures may miss a large number of cases of depression within CAD patients and cardiology patients more generally. The goal of this study was to provide data as to the predictive power of this depression screening procedure by (a) comparing the prevalence rate of depression identified by the PHQ-9 to known prevalence rates and (b) examining whether patients identified as “depressed” also had conditions that consistently co-occur with depression (eg, post-traumatic stress disorder [PTSD], other medical issues). Participants were 813 consecutive patients who received an angiogram in the cardiac catheterization laboratory at a large VA Medical Center. Prevalence of depression was 6.9% in the overall sample and less than 6% when the sample was restricted to CAD patients with significant stenosis. Depression was significantly associated with PTSD, smoking, and alcohol problems. However, depression was not associated with other medical problems such as diabetes, renal failure, peripheral vascular disease, or anemia. In conclusion, the low prevalence rate of depression and lack of associations with comorbid medical problems may suggest that the VA’s depression screening procedures have low sensitivity for identifying depression in CAD patients. It is recommended that clinicians treating CAD regularly screen for depression and do not rely on archival depression screens

Motor abnormalities, depression risk, and clinical course in adolescence.

Background Motor abnormalities, such as psychomotor agitation and retardation, are widely recognized as core features of depression. However, it is not currently known if motor abnormalities connote risk for depression. Methods Using data from the Adolescent Brain Cognitive Development (ABCD) Study, a nationally representative sample of youth (n=10,835, 9-11 years old), the present paper examines whether motor abnormalities are associated with (a) depression symptoms in early adolescence, (b) familial risk for depression (familial risk loading), and (c) future depression symptoms. Motor abnormalities measures included traditional (DSM) motor signs such as psychomotor agitation and retardation as well as other motor domains such as developmental motor delays and dyscoordination. Results Traditional motor abnormalities were less prevalent (agitation=3.2%, retardation=0.3%) than non-traditional domains (delays=13.79%, coordination=35.5%) among adolescents. Motor dysfunction was associated with depression symptoms (Cohen's ds=0.02 to 0.12). Familial risk for depression was related to motor abnormalities (Cohen's ds=0.08 to 0.27), with the exception of motor retardation. Family vulnerability varied in sensitivity to depression risk (e.g., retardation: .53%; dyscoordination: 32.05%). Baseline endorsement of motor abnormalities predicted future depression symptoms at one-year follow-up. Conclusions These findings suggest that motor signs reflect a novel, promising future direction for examining vulnerability to depression risk in early adolescence

Hand gesture performance is impaired in major depressive disorder: A matter of working memory performance?

OBJECTIVE Individuals with depression exhibit numerous interpersonal deficits. As effective use of gestures is critical for social communication, it is possible that depressed individuals' interpersonal deficits may be due to deficits in gesture performance. The present study thus compared gesture performance of depressed patients and controls and examined whether these deficits relate to cognitive and other domains of dysfunction. METHODS Gesture performance was evaluated in 30 depressed patients and 30 controls using the Test of Upper Limb Apraxia (TULIA). Clinical rating scales were assessed to determine if gesture deficits were associated with motor, cognitive or functional outcomes. RESULTS Compared to controls, depressed patients exhibited impaired gesture performance with 2/3 of the patients demonstrating gesture deficits. Within depressed patients, gesture performance was highly correlated with working memory abilities. In contrast, no association between gesture performance and gestural knowledge, psychomotor retardation, depression severity, or frontal dysfunction was observed in patients. LIMITATIONS This is a cross-sectional study and a larger size would have allowed for confident detection of more subtle, but potentially relevant effects. CONCLUSION Gesture performance is impaired in depressed patients, and appears to be related to poor working memory abilities, suggesting a disruption in the retrieval of gestural cues indicative of a distinct clinical phenomenon that might be related to social functioning

The neural signature of psychomotor disturbance in depression.

Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation

An Examination of Psychomotor Disturbance in Current and Remitted MDD: An RDoC Study.

Major depressive disorder (MDD) is a serious public health problem that has, at best, modest treatment response-potentially due to its heterogeneous clinical presentation. One way to parse the heterogeneity is to investigate the role of particular features of MDD, an endeavor that can also help identify novel and focal targets for treatment and prevention efforts. Our R01 focuses on the feature of psychomotor disturbance (e.g., psychomotor agitation (PmA) and retardation (PmR)), a particularly pernicious feature of MDD, that has not been examined extensively in MDD. Aim 1 is comparing three groups of individuals-those with current MDD (n = 100), remitted MDD (n = 100), and controls (n = 50)-on multiple measures of PmR and PmA (assessed both in the lab and in the subjects' natural environment). Aim 2 is examining the structural (diffusion MRI) and functional (resting state fMRI) connectivity of motor circuitry of the three groups as well as the relation between motor circuitry and the proposed indicators of PmR and PmA. Aim 3 is following up with subjects three times over 18 months to evaluate whether motor symptoms change in tandem with overall depressive symptoms and functioning over time and/or whether baseline PmR/PmA predicts course of depression and functioning. Aim 3 is particularly clinically significant. Finding that motor functioning and overall depression severity co-vary over time, or that motor variables predict subsequent change in overall depression severity, would support the potential clinical utility of these novel, reliable, and easily administered motor assessments

Psychomotor Slowing in Schizophrenia: Implications for Endophenotype and Biomarker Development.

Motor abnormalities (e.g., dyskinesia, psychomotor slowing, neurological soft signs) are core features of schizophrenia that occur independent of drug treatment and are associated with the genetic vulnerability and pathophysiology for the illness. Among this list, psychomotor slowing in particular is one of the most consistently observed and robust findings in the field. Critically, psychomotor slowing may serve as a uniquely promising endophenotype and/or biomarker for schizophrenia considering it is frequently observed in those with genetic vulnerability for the illness, predicts transition in subjects at high-risk for the disorder, and is associated with symptoms and recovery in patients. The purpose of the present review is to provide an overview of the history of psychomotor slowing in psychosis, discuss its possible neural underpinnings, and review the current literature supporting slowing as a putative endophenotype and/or biomarker for the illness. This review summarizes substantial evidence from a diverse array of methodologies and research designs that supports the notion that psychomotor slowing not only reflects genetic vulnerability, but is also sensitive to disease processes and the pathophysiology of the illness. Furthermore, there are unique deficits across the cognitive (prefix "psycho") and motor execution (root word "motor") aspects of slowing, with cognitive processes such as planning and response selection being particularly affected. These findings suggest that psychomotor slowing may serve as a promising endophenotype and biomarker for schizophrenia that may prove useful for identifying individuals at greatest risk and tracking the course of the illness and recovery

Conducting Psychopathology Prevention Research in the RDoC Era.

The Research Domain Criteria (RDoC) initiative promoted by the National Institute of Mental Health emphasizes a dimensional approach to psychopathology that is agnostic to DSM diagnosis. The RDoC project offers exciting possibilities for advancing research aimed at preventing psychopathology. However, prevention has historically been defined using diagnostic status, requiring the field to redefine what constitutes prevention using an RDoC approach. This article outlines new criteria for prevention in the RDoC context and provides guidance for implementing these criteria. We also describe the role of prevention-mechanism trials that examine whether preventive interventions change proximal etiological mechanisms known to be associated with psychopathology. We hope that these modified criteria and recommendations will stimulate new possibilities for prevention research that will advance the field

Does Intolerance of Uncertainty Predict Anticipatory Startle Responses to Uncertain Threat?

Intolerance of uncertainty (IU) has been proposed to be an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. While IU has been shown to predict subjective ratings and decision-making during uncertain/ambiguous situations, few studies have examined whether IU also predicts emotional responding to uncertain threat. The present study examined whether IU predicted aversive responding (startle and subjective ratings) during the anticipation of temporally uncertain shocks. Sixty-nine participants completed three experimental conditions during which they received: no shocks, temporally certain/predictable shocks, and temporally uncertain shocks. Results indicated that IU was negatively associated with startle during the uncertain threat condition in that those with higher IU had a smaller startle response. IU was also only related to startle during the uncertain (and not the certain/predictable) threat condition, suggesting that it was not predictive of general aversive responding, but specific to responses to uncertain aversiveness. Perceived control over anxiety-related events mediated the relation between IU and startle to uncertain threat, such that high IU led to lowered perceived control, which in turn led to a smaller startle response. We discuss several potential explanations for these findings, including the inhibitory qualities of IU. Overall, our results suggest IU is associated with attenuated aversive responding to uncertain threat