Impact of acute stress, sex, and childhood maltreatment on fear learning and fear generalization in a fear-potentiated startle paradigm

Many researchers approach the etiology of trauma-, stressor-, and anxiety-related mental disorders from the perspective of classical conditioning processes gone awry. According to this view, abnormal associative relationships between conditioned and unconditioned stimuli may underlie pathological anxiety and result in unusually intense fear memories or fear memories that cannot be properly extinguished. Recent work has expanded on this view by showing that many psychological disorders involving pathological anxiety are associated with an exaggerated form of stimulus generalization, leading individuals with such disorders to respond with fear and anxiety to a variety of contexts and cues that should not be threatening. It is well-known that stress, biological sex, childhood maltreatment, and certain dispositional factors can increase one’s susceptibility for pathological anxiety and significantly impact fear learning; thus, it is possible that these factors, alone or in combination, contribute to clinical anxiety by influencing fear generalization processes. In the present study, 478 healthy undergraduate students were exposed to the socially-evaluated cold pressor test immediately or 30 min prior to learning to associate one geometrical shape, but not another, with an aversive stimulus in a fear-potentiated startle paradigm. The next day, participants were tested for fear generalization by measuring their fear responses to a variety of stimuli that were similar to, but different from, the shapes observed on Day 1. Objective and subjective measures of stress were collected on Day 1, and childhood maltreatment was quantified with the Childhood Trauma Questionnaire. The results revealed that, across both stress time points, greater heart rate and greater cortisol levels in response to stress were associated with weaker fear acquisition and a flatter generalization gradient. These effects were influenced by participant sex and trait anxiety. We also found evidence to suggest that greater childhood maltreatment was associated with impaired fear acquisition in males but enhanced fear acquisition in females. These findings reveal a complex interaction between acute stress, biological sex, childhood maltreatment, dispositional anxiety, and fear learning that may lend insight into the etiology of certain stress-related psychological disorders

Tunnel vision, false memories, and intrusive memories following exposure to the Trier Social Stress Test

Most research examining the impact of stress on learning and memory has exposed participants to a stressor and measured how it affects learning and memory for unrelated material (e.g., list of words). Such work has been helpful, but it has not been the most translational to the human condition. When considering phenomena such as intrusive memories in post-traumatic stress disorder (PTSD) or an eyewitness\u27s memory for a crime, it is most useful to know what an individual remembers about the stress experience itself, not unrelated information. In prior work, investigators used a modified version of the Trier Social Stress Test (TSST) to quantify participant memory for the stressor. We aimed to replicate this work by examining participant memory for the TSST and extend on it by quantifying false and intrusive memories that result from TSST exposure. Forty-six undergraduate students from Ohio Northern University were exposed to the TSST or the friendly-TSST (f-TSST). The TSST required participants to deliver a ten-minute speech in front of two lab panel members as part of a mock job interview; the f-TSST required participants to casually converse with the panel members about their interests and hobbies. In both conditions, the panel members interacted with (central) or did not interact with (peripheral) several objects sitting on a desk in front of them. Participants’ anxiety levels were assessed before and after the TSST or f-TSST, and saliva samples were collected to assay for cortisol. The next day, participants’ memory for the objects that were present on Day 1 was assessed with recall and recognition tests. We also quantified participants’ intrusive memories for each task by having them complete an intrusive memory questionnaire on Days 2, 4, 6, and 8. Participants exposed to the TSST exhibited greater recall of central objects than participants exposed to the f-TSST. There were no differences observed for the recall of peripheral objects or for recognition memory. Interestingly, TSST exposure increased false recall in males, but reduced it in females. Females exposed to the TSST also showed greater evidence of intrusive memories than males exposed to the TSST. Consistent with prior work, these findings show that stress enhances memory for the central details of a stressful experience. They also extend on prior work by showing that stressful experiences sex-dependently impact the manifestation of false and intrusive memories. This is the first study of which we are aware to quantify intrusive memory formation with the TSST; the modified TSST paradigm may be useful in understanding differential susceptibility to intrusive memory formation and the development of PTSD

Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya

BACKGROUND: There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management. METHODS AND FINDINGS: A panel of 298, HIV-seronegative individuals aged 13-34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (/=18 years) ratio and the male-to-female ratio was 1ratio1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1-4) which would exclude them from participating in clinical trials. CONCLUSION: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya

Hematological reference values (median and 95^th-percentile) stratified by age and gender from a 13–34 years old cohort in rural western Kenya (2003–2005).

<p>Hematological reference values (median and 95^th-percentile) stratified by age and gender from a 13–34 years old cohort in rural western Kenya (2003–2005).</p

Pre-Learning Stress That Is Temporally Removed from Acquisition Impairs Fear Learning

Few studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS−, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders

Hematological and Biochemistry Laboratory reference ranges derived from rural Western Kenya compared to other sources in Africa.

<p>Hematological and Biochemistry Laboratory reference ranges derived from rural Western Kenya compared to other sources in Africa.</p

Clinical Chemistries Medians and 95% Reference Intervals stratified by age and gender from a 13–34 years cohort study in rural western Kenya (2003–2005).

<p>Clinical Chemistries Medians and 95% Reference Intervals stratified by age and gender from a 13–34 years cohort study in rural western Kenya (2003–2005).</p

Test of difference in hematologic, clinical chemistry and immunologic parameters between gender and age-groups from the 13–34 years old rural western Kenya cohort (2003–2005).

<p>Test of difference in hematologic, clinical chemistry and immunologic parameters between gender and age-groups from the 13–34 years old rural western Kenya cohort (2003–2005).</p