Farid F. Youssef

Stress alters personal moral decision making

While early studies of moral decision making highlighted the role of rational, conscious executive processes involving frontal lobe activation more recent work has suggested that emotions and gut reactions have a key part to play in moral reasoning. Given that stress can activate many of the same brain regions that are important for and connected to brain centres involved in emotional processing we sought to evaluate if stress could influence moral decision making. Sixty-five undergraduate volunteers were randomly assigned to control (n=33) and experimental groups (n=32). The latter underwent the Trier Social Stress Test (TSST) and induction of stress was assessed by measurement of salivary cortisol levels. Subjects were then required to provide a response to thirty moral dilemmas via a computer interface that recorded both their decision and reaction time. Three types of dilemmas were used: non-moral, impersonal moral and personal moral. Using a binary logistic model there were no significant predicators of utilitarian response in non-moral and impersonal moral dilemmas. However the stressed group and females were found to predict utilitarian responses to personal moral dilemmas. When comparing percentage utilitarian responses there were no significant differences noted for the non-moral and impersonal moral dilemmas but the stressed group showed significantly less utilitarian responses compared to control subjects. The stress response was significantly negatively correlated with utilitarian responses. Females also showed significantly less utilitarian responses than males. We conclude that activation of the stress response predisposed participants to less utilitarian responses when faced with high conflict personal moral dilemmas and suggest that this offers further support for dual process theory of moral judgment. We also conclude that females tend to make less utilitarian personal moral decisions compared to males, providing further evidence that there are gender differences in moral reasoning.

NMDA-induced preconditioning attenuates synaptic plasticity in the rat hippocampus

It was recently demonstrated that glutamate could precondition hippocampal slices against the damaging effects of hypoxia, and we have now extended this observation by investigating (i) the ability of glutamate receptor agonists to act as preconditioning agents and (ii) the effects of preconditioning on synaptic plasticity. Using rat hippocampal slices, 15 microM NMDA applied for 10 min (chemical insult) caused abolition of the population spike potentials (PS) followed by approximately 33% recovery at 60 min post-insult. In comparison, a 5 min preconditioning exposure of 10 microM NMDA given 30 min prior to the insult significantly improved the recovery to 69%. Preconditioning did not alter paired pulse facilitation; however, it significantly enhanced paired pulse depression and reduced population spike long-term potentiation (PS-LTP) and LTP in field recordings. This effect on PS-LTP appeared to be NMDA receptor dependent and was blocked by the nitric oxide synthase inhibitors nitro-L-arginine methyl ester (L-NAME) and 7-nitro indazole (7-NI) but not by the adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We conclude that preconditioning by NMDA can improve recovery following acute insults but may have deleterious effects on neuronal plasticity.

Knowledge of, attitudes toward, and perceptions of epilepsy among college students in Trinidad and Tobago

Epilepsy is poorly understood by the public and has been associated with numerous myths. This, coupled with its sometimes dramatic clinical manifestations, has often resulted in stigmatization of persons with epilepsy. A questionnaire to measure knowledge of, attitudes toward, and perceptions of epilepsy (KAPE) was adapted from previous studies and administered to students of the University of the West Indies, St. Augustine, Trinidad and Tobago. The response rate was 91% (355 students). Knowledge was limited, especially with respect to epilepsys cause, its incidence, and management of an acute emergency. Attitudes toward epilepsy were generally positive. Students who knew someone with epilepsy scored significantly higher on knowledge and attitude questions. A stigma score was calculated to assess perceived stigmatization. There were no differences between the genders, but persons from rural areas and persons of mixed ethnicity perceived less stigmatization. Hindus perceived greater stigmatization than people of other religions. Overall, students still feel persons with epilepsy are discriminated against and experience stigmatization.

An exploration of changes in cognitive and emotional empathy among medical students in the Caribbean.

Objectives: This study explored the empathy profile of students across five years of medical training. In addition the study examined whether the Jefferson Scale for Physician Empathy correlated with a measure of cognitive empathy, the Reading the Mind in the Eyes Test and a measure of affective empathy, the Toronto Empathy Questionnaire. Methods: The study was a comparative cross-sectional design at one Caribbean medical school. Students were contacted in class, participation was voluntary and empathy was assessed using all three instruments Descriptive statistics were calculated and differences between groups evaluated using non-parametric tests. Results: Overall 669 students participated (response rate, 67%). There was a significant correlation between the Jefferson Scale of Physician Empathy and the Toronto Empathy Questionnaire (P = 0.48), both scales indicating a decline in medical student empathy scores over time. There was, however, little correlation between scores from the Reading the Mind in the Eyes Test and the Jefferson Scale of Physician Empathy. Female students demonstrated significantly higher scores on all three measures. Conclusions: Medical students’ lower empathy scores during their final years of training appear to be due to a change in the affective component of empathy. These findings may reflect an adaptive neurobiological response to the stressors associated with encountering new clinical situations. Attention should be paid not only to providing empathy training for students but also to teaching strategies for improved cognitive processing capacity when they are encountering new and challenging circumstances.

Long-term potentiation protects rat hippocampal slices from the effects of acute hypoxia

We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (P<0.01; paired t-test). The neuroprotective effects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of hippocampal slices to various models of acute hypoxia. This phenomenon does not appear to involve desensitisation of AMPA receptors or mediation by NO, but may account for the recognised inverse relationship between educational attainment and the development of dementia.

Adult-onset calorie restriction attenuates kainic acid excitotoxicity in the rat hippocampal slice.

Lifelong calorie restriction is the only known intervention that has been shown to consistently increase life span and reduce the effects of aging on the brain. Given the difficulties of replicating lifelong calorie restriction within human populations, we have sought to assess the effects of short-term adult-onset calorie restriction upon acute excitotoxic insults in the rat hippocampus. Adult animals (approximately 6 months of age) underwent calorie restriction (alternate day feeding) for 7-10 weeks. Utilizing both electrophysiological and immunocytochemical techniques, we report that calorie restriction had no effect upon long-term potentiation (LTP), a measure of neuronal function. In control animals, application of kainic acid (20 microM) resulted in only 35% recovery of CA1 population spikes post-insult. However calorie-restricted animals showed significantly improved recovery after kainic acid treatment (64%). This data was supported by immunocytochemical studies which noted widespread loss of microtubule-associated protein (MAP 2) immunoreactivity in control slices following treatment with kainic acid; however MAP 2 staining was preserved in the CA1 and CA3 regions of calorie-restricted animals. Interestingly there was no significant difference in the recovery of population spikes between groups when slices were treated with N-methyl-d-aspartate (15 microM). We conclude that short-term adult-onset calorie restriction does not alter normal neuronal function and serves to protect the hippocampus from acute kainic acid excitotoxicity.

Cannabinoid modulation of neuronal function after oxygen/glucose deprivation in area CA1 of the rat hippocampus

Endocannabinoids released during cerebral ischemia have been implicated as neuroprotective agents. We assessed the role of cannabinoid receptors in modulating the response of neurons to oxygen/glucose deprivation (OGD), a model for in vitro ischemia, in rat hippocampal slices using extracellular recording techniques. Under control conditions, 15 min OGD resulted in only 50% recovery of CA1 field excitatory postsynaptic potentials (fEPSPs) 60 min post-insult. This post-OGD depression of function was primarily NMDA receptor-dependent as the NMDA receptor antagonist MK-801 (50 microM) promoted recovery of synaptic transmission to 76% of the baseline. Treatment with the CB1 receptor antagonist AM251 (1 microM), which prevented the depression of excitatory synaptic transmission caused by WIN55,212-2 (1 microM), also markedly enhanced recovery of function (71% of control). The enhanced recovery after OGD in the presence of AM251 was independent of both GABA(A) receptors and NMDA receptors since co-application of AM251 with either bicuculline (10 microM) or MK-801 (50 microM) did not alter recovery, or further improved recovery, respectively. These results suggest endocannabinoids released during OGD may modulate synaptic transmission and post-OGD neuronal outcome via activation of an AM251-sensitive cannabinoid receptor.

Interactions of glutamate receptor agonists with long-term potentiation in the rat hippocampal slice.

Previous work has described the apparent desensitisation of neuronal networks in the rat neocortex to amino acid agonists, following prior exposure several minutes earlier. Since long-term potentiation is believed to involve activation of amino acid receptors, we have now sought to determine whether long-term potentiation can modify the sensitivity of neurones to glutamate receptor agonists in rat hippocampal slices. Responses were measured as the change in population spike or postsynaptic potential (e.p.s.p.) size. Two applications of N-methyl-D-aspartate (NMDA), quinolinic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainate, 45 min apart, did not exhibit any apparent desensitisation. However, the induction of long-term potentiation produced a marked loss of sensitivity to quinolinic acid, with smaller effects on NMDA, AMPA and kainate responses. No marked changes were obtained of e.p. s.p. size. In order to localise the cellular sites of these changes, agonists were also applied by microiontophoresis to the cell bodies or dendritic regions of CA1 neurones. Responses to quinolinic acid showed apparent desensitisation at both sites, whereas no decrease was observed in responses to NMDA or AMPA application. The induction of long-term potentiation again produced a decrease in the size of responses to NMDA and AMPA. Inhibition of nitric oxide (NO) synthase prevented the long-term potentiation-induced loss of responsiveness to NMDA, but not AMPA, implying a role for NO in the loss of NMDA sensitivity. Recordings of single cell activity during the iontophoretic application of agonists and induction of long-term potentiation showed that responses to NMDA were often suppressed to a greater extent than to quinolinic acid. The results indicate that long-term potentiation can modify the sensitivity of hippocampal neurones to glutamate receptor agonists, and that differences exist in the pharmacology of NMDA and quinolinic acid.

AMPA receptor activation reduces epileptiform activity in the rat neocortex

We have previously reported that topical application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects of a subsequent application of N-methyl-d-aspartic acid (NMDA). Activation of NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore, we examined if topically applied AMPA could affect changes in the somatosensory evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by bicuculline. AMPA (50 microM) prevented the epileptiform activity to a level that was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100 mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. In the hippocampal slice, bicuculline-induced changes in the population spike potentials recorded from the CA1 cells were not affected by AMPA. We conclude that in the complex neuronal network of the rat neocortex, epileptiform activity can be suppressed in a variety of strategies that target the AMPA receptors: (1) blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA receptors (possibly on the pyramidal neurons) or (3) reducing an apparent desensitization of AMPA receptors (possibly on the inhibitory GABA-ergic interneurons).

Knowledge and attitudes towards mental illness among college students: Insights into the wider English-speaking Caribbean population

Background: Mental illness is a significant contributor to global disease burden and this is expected to increase over the coming decades. Traditionally mental illness has not been well understood by the general public, resulting in poor attitudes towards persons with mental illness and stigmatization. Such conditions are common in the Caribbean where less than 5% of the health budget is allocated to mental illness. Aims: To assess knowledge and attitudes towards mental illness among college students within the English-speaking Caribbean. Methods: A self-report questionnaire was adapted from previous studies designed to measure knowledge and attitudes of mental illness. Students were sampled from the University of the West Indies campuses in Jamaica, Barbados and Trinidad & Tobago. Results: Responses were collected from 673 persons with a response rate of 84%. While participants were agreed that particular diseases were mental illnesses, overall knowledge scores were low. Knowledge was higher among those persons who knew someone with a mental illness. Attitude scores were suggestive of stigmatization, with drug abuse and schizophrenia seen in a particularly poor light. Conclusions: These results suggest that widespread educational campaigns need to be implemented across the region, designed to both increase knowledge about mental illness and reduce discrimination towards persons suffering with mental illness.