Biomedical subjects

Shmuel Lissek

Publications and source records attributed to Shmuel Lissek.

12 recordsLinked to original sources

PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗

PubMed2006

The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle.

BACKGROUND: The startle reflex is potentiated by aversive states. It has been proposed that phasic startle potentiation to a threat cue and sustained startle potentiation to contextual stimuli reflect distinct processes mediated by different brain structures. The present study tested the hypothesis that alprazolam would reduce the sustained startle potentiation to contextual threats but not the startle potentiation to a threat cue. METHODS: Sixteen healthy subjects received each of four treatments: placebo, .5 mg of alprazolam, 1 mg of alprazolam, and 50 mg of diphenhydramine (Benadryl) in a crossover design. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which shocks were administered unpredictably, and a third condition in which no shocks were anticipated. Acoustic startle were delivered regularly across conditions. RESULTS: Phasic startle potentiation to the threat cue in the predictable condition was not affected by alprazolam. In contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam. CONCLUSIONS: Startle responses to an explicit threat cue and to an aversive context are psychopharmacologically distinct, suggesting that they may represent functionally dissociable aversive states.

Acoustic Stimulation↗

PubMed2005

The strong situation: a potential impediment to studying the psychobiology and pharmacology of anxiety disorders.

The strong situation, as formulated by social psychologists, refers to an experimental condition offering unambiguous stimuli predicting or constituting hedonically strong events that uniformly guide response sets across individuals. In relation to fear and anxiety, the strong situation results from the unambiguous threat of an imminent and dangerous stimulus that evokes the adaptive fear response among anxiety patients and healthy controls alike. The current paper describes evidence that weakening the experimental situation through reducing the certainty, temporal proximity, and/or potency of the aversive stimulus may facilitate the emergence of patient-control differences in psychobiological measures of anxious arousal. Additionally, weak situations may be useful for testing the clinical utility of anxiolytic agents, given that pharmacological treatments of anxiety disorders are not intended to reduce the adaptive, normative response likely evoked by strong threat situations.

Anti-Anxiety Agents↗

PubMed2005

Airpuff startle probes: an efficacious and less aversive alternative to white-noise.

Fear-potentiated startle (FPS) is an increasingly popular psychophysiological method for the objective assessment of fear and anxiety. Studies applying this method often elicit the startle reflex with loud white-noise stimuli. Such intense stimuli may, however, alter psychological processes of interest by creating unintended emotional or attentional artifacts. Additionally, loud acoustic probes may be unsuitable for use with infants, children, the elderly, and those with hearing damage. Past studies have noted robust and reliable startle reflexes elicited by low intensity airpuffs. The current study compares the aversiveness of white-noise (102 dB) and airpuff (3 psi) probes and examines the sensitivity of each probe for the assessment of fear-potentiated startle. Results point to less physiological arousal and self-reported reactivity to airpuff versus white-noise probes. Additionally, both probes elicited equal startle magnitudes, response probabilities, and levels of fear-potentiated startle. Such results support the use of low intensity airpuffs as efficacious and relatively non-aversive startle probes.

Acoustics↗

PubMed2005

Classical fear conditioning in the anxiety disorders: a meta-analysis.

Fear conditioning represents the process by which a neutral stimulus comes to evoke fear following its repeated pairing with an aversive stimulus. Although fear conditioning has long been considered a central pathogenic mechanism in anxiety disorders, studies employing lab-based conditioning paradigms provide inconsistent support for this idea. A quantitative review of 20 such studies, representing fear-learning scores for 453 anxiety patients and 455 healthy controls, was conducted to verify the aggregated result of this literature and to assess the moderating influences of study characteristics. Results point to modest increases in both acquisition of fear learning and conditioned responding during extinction among anxiety patients. Importantly, these patient-control differences are not apparent when looking at discrimination studies alone and primarily emerge from studies employing simple, single-cue paradigms where only danger cues are presented and no inhibition of fear to safety cues is required.

Anxiety Disorders↗

PubMed2005

Sensation seeking and the aversive motivational system.

Sensation seeking (SS) has traditionally been viewed as a phenomenon of the appetitive motivational system. The limited SS research exploring contributions from the aversive motivational system reveals greater anxious reactivity to dangerous activities among low sensation seekers. The present study extends this line of work by comparing levels of fear and anxiety during anticipation of predictable and unpredictable aversive stimuli across high- and low-SS groups. Low sensation seekers displayed greater fear-potentiated startle (FPS) to predictable aversive stimuli, and only those low on SS showed FPS and skin conductance response effects during experimental contexts in which aversive stimuli were delivered unpredictably. Findings implicate enhanced apprehensive anticipation among those low on SS as a potential deterrent for their participation in intense and threatening stimulus events.

Adult↗

PubMed2005

Major depression predicts an increase in long-term body weight variability in young adults.

OBJECTIVE: To test the hypothesis that major depression predicts an increase in long-term body weight variability (BWV). RESEARCH METHODS AND PROCEDURES: This was a prospective community-based single-age cohort study of young adults (N = 591) followed between the ages of 19 and 40. Following initial screening, information was derived from six subsequent semistructured diagnostic interviews conducted by mental health professionals. Major depression was diagnosed on the basis of DSM criteria. BWV was defined as the root mean square error of a regression line fitted to each individual's BMI values over time. Multiple regression analysis was used to test the association between major depression and BWV while controlling for potentially confounding variables including antidepressant treatment, eating disorder symptoms, and physical activity. We used random effects models to determine the temporal relationship between repeated measures of major depression and body weight change. RESULTS: A highly significant positive association between major depression and BWV was found, whereas major depression was not associated with BMI level or BMI trend. Depression severity showed a dose-response-type relationship with the magnitude of BWV. After controlling for potentially confounding variables including antidepressant use, eating disorder symptoms, smoking, and physical activity, major depression remained a significant predictor of BWV (beta= 0.13, p < 0.001). Longitudinal analysis revealed a unidirectional association between major depression and a later increase in body weight change rate irrespective of antidepressant medication. DISCUSSION: Results from this study implicate depression as an important risk factor for increased BWV. Given increasing evidence for a link between major depression and both diabetes and cardiovascular disease, current results encourage further research on depression, BWV, and negative health outcomes.

Adult↗

PubMed2005

Face-emotion processing in offspring at risk for panic disorder.

OBJECTIVE: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. METHOD: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-presented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. RESULTS: Compared with offspring of parents without PD (n = 79), offspring of PD parents (n = 65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n = 65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. CONCLUSIONS: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing.

Adolescent↗

PubMed2004

Fear conditioning in virtual reality contexts: a new tool for the study of anxiety.

BACKGROUND: Context conditioning has been suggested to model clinical anxiety, but context, as manipulated in animal models, has not been translated to human studies. A virtual environment might prove to be the ideal tool for innovative experimental paradigms to study explicitly cued fear and contextual anxiety in humans. METHODS: Subjects were guided through a virtual environment that consisted of two rooms connected by a street scene. In each of the rooms, a blue and a yellow panel on a wall served as explicit conditioned stimuli (CS). The panels were displayed several times. One of the panels (CS+) was associated with a shock in one of the rooms (shock room). No shock was administered in the other room (safe room). Acoustic startle stimuli were administered in the presence and in the absence of the panels to assess explicit cued conditioning to the CS and context conditioning to the rooms, respectively. RESULTS: Startle was potentiated by the CS+ in both rooms, which suggests generalization of fear across contexts. After acquisition, startle was potentiated in the shock room, compared with the safe room, in the absence of the CS+. CONCLUSIONS: These results support the future use of virtual reality to design new conditioning experiments to study both fear and anxiety.

Adult↗

PubMed2004

Anxious responses to predictable and unpredictable aversive events.

Anxiety induced by 2 types of predictable and unpredictable aversive stimuli, an unpleasant shock or a less aversive airblast to the larynx, were investigated in a between-group design. Participants anticipated predictable (signaled) or unpredictable (not signaled) aversive events, or no aversive event. Unpredictable, relative to predictable, contexts potentiated the startle reflex in the shock group but not in the airblast group. These data suggest that unpredictability can lead to a sustained level of anxiety only when the pending stimulus is sufficiently aversive. Because predictable and unpredictable danger may induce different types of aversive responses, the proposed design can serve as a useful tool for studying the neurobiology and psychopharmacology of fear and anxiety.

Adult↗

PubMed2004

Face-memory and emotion: associations with major depression in children and adolescents.

BACKGROUND: Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. METHODS: Subjects were 152 offspring (ages 9-19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting 'happy,"fearful,' or 'angry' emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. RESULTS: Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n = 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. DISCUSSION: This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with MDD.

Adolescent↗

PubMed2003

Sensation seeking and startle modulation by physically threatening images.

The potential moderating effect of sensation seeking on anxious reactivity to threatening experiences was assessed using the affective modulation of startle-blink paradigm. Startle blinks, as measured by electromyographic (EMG) activity in response to loud (100 dB) white-noise stimuli, were elicited during the presentation of positive, neutral, and threatening visual images. Unlike participants low in sensation seeking who showed blink potentiation during threatening versus neutral images, participants high in sensation seeking showed equal magnitudes of startle to neutral and threatening images. The results suggest that individuals high compared with low on sensation seeking are less anxiously reactive to physically threatening visual stimuli. No attenuation in startle magnitude was elicited by positive images among low or high sensation seekers suggesting that the positive images employed in the current study were not arousing enough to activate the appetitive arousal system.

Adolescent↗