Eyal Fruchter

Attention Bias Variability and Symptoms of Posttraumatic Stress Disorder

Cognitive theories implicate information-processing biases in the etiology of anxiety disorders. Results of attention-bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within-subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat-related attention biases, mood and anxiety symptoms, and attention-bias variability following trauma. Experiment 1 included 3 groups in a cross-sectional design: (a) PTSD, (b) trauma-exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention-bias variability was found in the PTSD group compared to the other 2 groups (η(p)2=.23); attention-bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat-exposed and nonexposed soldiers before and during deployment. Attention-bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (ηp2=.16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention-bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.

Attention to Threats and Combat-Related Posttraumatic Stress Symptoms: Prospective Associations and Moderation by the Serotonin Transporter Gene

IMPORTANCE Combat places soldiers at risk for posttraumatic stress disorder (PTSD). The excessive rates of PTSD and other adjustment disorders in soldiers returning home make it imperative to identify risk and resilience factors that could be targeted by novel therapeutic treatments. OBJECTIVE To investigate the interplay among attention to threat, combat exposure, and other risk factors for PTSD symptoms in soldiers deployed to combat. DESIGN AND SETTING Longitudinal prospective study of Israeli Defense Force infantry soldiers carried out in 2008 through 2010. Repeated measurements during a 1-year period included baseline and predeployment data collected in training camps and deployment data collected in the combat theater. PARTICIPANTS Infantry soldiers (1085 men; mean age, 18.8 years). MAIN OUTCOME MEASURES Postcombat PTSD symptoms. RESULTS Soldiers developed threat vigilance during combat deployment, particularly when they were exposed to high-intensity combat, as indicated by faster response times to targets appearing at the location of threat relative to neutral stimuli (P < .001). Threat-related attention bias also interacted with combat exposure to predict risk for PTSD (P < .05). Bias toward threat at recruitment (P < .001) and bias away from threat just before deployment (P < .05) predicted postcombat PTSD symptoms. Moreover, these threat-related attention associations with PTSD were moderated by genetic and environmental factors, including serotonin transporter (5-HTTLPR) genotype. CONCLUSIONS AND RELEVANCE Combat exposure interacts with threat-related attention to place soldiers at risk for PTSD, and interactions with other risk factors account for considerable variance in PTSD vulnerability. Understanding these associations informs research on novel attention bias modification techniques and prevention of PTSD.

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.

Battlefield-like stress following simulated combat and suppression of attention bias to threat

BACKGROUND Acute stress disorder involves prominent symptoms of threat avoidance. Preliminary cross-sectional data suggest that such threat-avoidance symptoms may also manifest cognitively, as attentional threat avoidance. Confirming these findings in a longitudinal study might provide insights on risk prediction and anxiety prevention in traumatic exposures. METHOD Attention-threat bias and post-traumatic symptoms were assessed in soldiers at two points in time: early in basic training and 23 weeks later, during advanced combat training. Based on random assignment, the timing of the repeat assessment occurred in one of two schedules: for a combat simulation group, the repeat assessment occurred immediately following a battlefield simulation exercise, and for a control group, the assessment occurred shortly before this exercise. RESULTS Both groups showed no threat-related attention bias at initial assessments. Following acute stress, the combat simulation group exhibited a shift in attention away from threat whereas the control group showed no change in attention bias. Stronger threat avoidance in the combat simulation group correlated with severity of post-traumatic symptoms. Such an association was not found in the control group. CONCLUSIONS Acute stress may lead some individuals to shift their attention away from threats, perhaps to minimize stress exposure. This acute attention response may come at a psychological cost, given that it correlates with post-traumatic stress disorder (PTSD) symptoms. Further research is needed to determine how these associations relate to full-blown PTSD in soldier and civilian populations.

Threat-Related Attention Bias Variability and Posttraumatic Stress

OBJECTIVE Threat monitoring facilitates survival by allowing one to efficiently and accurately detect potential threats. Traumatic events can disrupt healthy threat monitoring, inducing biased and unstable threat-related attention deployment. Recent research suggests that greater attention bias variability, that is, attention fluctuations alternating toward and away from threat, occurs in participants with PTSD relative to healthy comparison subjects who were either exposed or not exposed to traumatic events. The current study extends findings on attention bias variability in PTSD. METHOD Previous measurement of attention bias variability was refined by employing a moving average technique. Analyses were conducted across seven independent data sets; in each, data on attention bias variability were collected by using variants of the dot-probe task. Trauma-related and anxiety symptoms were evaluated across samples by using structured psychiatric interviews and widely used self-report questionnaires, as specified for each sample. RESULTS Analyses revealed consistent evidence of greater attention bias variability in patients with PTSD following various types of traumatic events than in healthy participants, participants with social anxiety disorder, and participants with acute stress disorder. Moreover, threat-related, and not positive, attention bias variability was correlated with PTSD severity. CONCLUSIONS These findings carry possibilities for using attention bias variability as a specific cognitive marker of PTSD and for tailoring protocols for attention bias modification for this disorder.

The Relationship Between Risk of Hospitalization for Schizophrenia, SES, and Cognitive Functioning

Although most studies find low socioeconomic status (SES) to be associated with prevalence of schizophrenia, incidence studies do not generally support this, and some even report an inverse association. The objective of the current historical prospective study was to examine the relationship between SES, cognitive functioning, and risk of hospitalization for schizophrenia in a population-based sample of Israeli adolescents. Subjects were 811 487 adolescents, assessed by the Israeli military draft board for socio-demographic factors and cognitive functioning. Data on later hospitalization for schizophrenia were obtained from a population-based hospitalization registry. Findings indicated that when simply examining SES and schizophrenia, lower SES was associated with greater risk of hospitalization for schizophrenia (Hazard Ratio [HR] = 1.193, 95% CI = 1.091-1.303). When dividing the cohort into low, average, and high cognitive functioning, SES did not influence the risk for schizophrenia among individuals with high and average cognitive functioning, whereas among individuals with low cognitive functioning, high SES was found to slightly increase the risk for schizophrenia (HR = 1.21, 95% CI = 1.03-1.42). One possible explanation for this finding might be that among individuals from low socioeconomic backgrounds, low IQ may reflect decreased opportunities related to SES, whereas among individuals from high SES backgrounds, low IQ might reflect risk for later psychopathology.

Borderline intellectual functioning is associated with poor social functioning, increased rates of psychiatric diagnosis and drug use - A cross sectional population based study

Borderline intellectual functioning is defined by the DSM IV as an IQ range that is between one to two standard deviations below the mean (71<IQ<84), and a considerable percentage of the population is included in this definition (approximately 13.5%). The few studies performed on this group indicate that borderline intellectual functioning is associated with various mental disorders, problems in everyday functioning, social disability and poor academic or occupational achievement. Using data from the Israeli military, we retrieved the social and clinical characteristics of 76,962 adolescents with borderline intellectual functioning and compared their social functioning, psychiatric diagnoses and drug abuse with those of 96,580 adolescents with average IQ (± 0.25 SD from population mean). The results demonstrated that the borderline intellectual functioning group had higher rates of poor social functioning compared to the control group (OR=1.9, 95% CI=1.85-1.94). Individuals with borderline intellectual functioning were 2.37 times more likely to have a psychiatric diagnosis (95% CI=2.30-2.45) and 1.2 times more likely to use drugs (95% CI=1.07-0.35) than those with average IQ. These results suggest that adolescents with borderline intellectual functioning are more likely to suffer from psychiatric disorders, poor social functioning and drug abuse than those with average intelligence, and that borderline intellectual functioning is a marker of vulnerability to these poor outcomes.

Neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions

In managing our way through interpersonal conflict, anger might be crucial in determining whether the dispute escalates to aggressive behaviors or resolves cooperatively. The Ultimatum Game (UG) is a social decision-making paradigm that provides a framework for studying interpersonal conflict over division of monetary resources. Unfair monetary UG-offers elicit anger and while accepting them engages regulatory processes, rejecting them is regarded as an aggressive retribution. Ventro-medial prefrontal-cortex (vmPFC) activity has been shown to relate to idiosyncratic tendencies in accepting unfair offers possibly through its role in emotion regulation. Nevertheless, standard UG paradigms lack fundamental aspects of real-life social interactions in which one reacts to other people in a response contingent fashion. To uncover the neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions, we incorporated on-line verbal negotiations with an obnoxious partner in a repeated-UG during fMRI scanning. We hypothesized that vmPFC activity will differentiate between individuals with high or low monetary gains accumulated throughout the game and reflect a divergence in the associated emotional experience. We found that as individuals gained more money, they reported less anger but also more positive feelings and had slower sympathetic response. In addition, high-gain individuals had increased vmPFC activity, but also decreased brainstem activity, which possibly reflected the locus coeruleus. During the more angering unfair offers, these individuals had increased dorsal-posterior Insula (dpI) activity which functionally coupled to the medial-thalamus (mT). Finally, both vmPFC activity and dpI-mT connectivity contributed to increased gain, possibly by modulating the ongoing subjective emotional experience. These ecologically valid findings point towards a neural mechanism that might nurture pro-social interactions by modulating an individuals dynamic emotional experience.

Discontinuity in the genetic and environmental causes of the intellectual disability spectrum

Significance Intellectual disability (ID) is present in almost 3% of children and fundamentally characterized by IQ scores below 70. Genetic research has shown that it is among the most heritable traits, and it has been accepted that ID is the extreme low of the normal IQ distribution. However, we show that, while the genetic and environmental factors influencing mild ID (lowest 3% of IQ distribution) are similar to those influencing IQ in the normal range, factors influencing severe ID (lowest 0.5%) differ from those influencing mild ID or IQ scores in the normal range. Therefore, severe ID is a distinct disorder, qualitatively different from the majority of ID, which in turn represents the low extreme of the normal distribution of intelligence. Intellectual disability (ID) occurs in almost 3% of newborns. Despite substantial research, a fundamental question about its origin and links to intelligence (IQ) still remains. ID has been shown to be inherited and has been accepted as the extreme low of the normal IQ distribution. However, ID displays a complex pattern of inheritance. Previously, noninherited rare mutations were shown to contribute to severe ID risk in individual families, but in the majority of cases causes remain unknown. Common variants associated with ID risk in the population have not been systematically established. Here we evaluate the hypothesis, originally proposed almost 1 century ago, that most ID is caused by the same genetic and environmental influences responsible for the normal distribution of IQ, but that severe ID is not. We studied more than 1,000,000 sibling pairs and 9,000 twin pairs assessed for IQ and for the presence of ID. We evaluated whether genetic and environmental influences at the extremes of the distribution are different from those operating in the normal range. Here we show that factors influencing mild ID (lowest 3% of IQ distribution) were similar to those influencing IQ in the normal range. In contrast, the factors influencing severe ID (lowest 0.5% of IQ distribution) differ from those influencing mild ID or IQ scores in the normal range. Taken together, our results suggest that most severe ID is a distinct condition, qualitatively different from the preponderance of ID, which, in turn, represents the low extreme of the normal distribution of intelligence.

Cognitive Function and the Risk for Diabetes Among Young Men

OBJECTIVE Diabetes is a risk factor for an accelerated rate of cognitive decline and dementia. However, the relationship between cognitive function and the subsequent development of diabetes is unclear. RESEARCH DESIGN AND METHODS We conducted a historical-prospective cohort study merging data collected at premilitary recruitment assessment with information collected at the Staff Periodic Examination Center of the Israeli Army Medical Corps. Included were men aged 25 years or older without a history of diabetes at the beginning of follow-up with available data regarding their general intelligence score (GIS), a comprehensive measure of cognitive function, at age 17 years. RESULTS Among 35,500 men followed for a median of 5.5 years, 770 new cases of diabetes were diagnosed. After adjustment for age, participants in the lowest GIS category had a 2.6-fold greater risk for developing diabetes compared with those in the highest GIS category. In multivariable analysis adjusted for age, BMI, fasting plasma glucose, sociogenetic variables, and lifestyle risk factors, those in the lowest GIS category had a twofold greater risk for incident diabetes when compared with the highest GIS category (hazard ratio 2.1 [95% CI 1.5–3.1]; P < 0.001). Additionally, participants in the lowest GIS category developed diabetes at a mean age of 39.5 ± 4.7 years and those in the highest GIS group at a mean age of 41.5 ± 5.1 years (P for comparison 0.042). CONCLUSIONS This study demonstrates that in addition to a potential causal link between diabetes and enhanced cognitive decline, lower cognitive function at late adolescence is independently associated with an elevated risk for future diabetes.