Using Cognitive Bias Modification to Deflate Responsibility in Compulsive Checkers

Cognitive-behavioural models of compulsive checking posit a dominant role for beliefs regarding one’s responsibility to prevent harm. In the current study we employed a computerised cognitive bias modification of interpretation (CBM-I) paradigm to target and modify responsibility biases in a sample of undergraduate students with high levels of checking symptoms (N = 100). Participants were randomly assigned to either a positive (decrease responsibility bias) or negative (increase responsibility bias) CBM-I training condition. Relative to participants in the negative training condition, participants in the positive training condition demonstrated reduced responsibility bias in a subsequent interpretive bias test. Positive training also resulted in more adaptive physiological responding during a responsibility stressor task. There were no differential effects of CBM-I training, however, on observed or self-reported checking or self-reported responsibility beliefs. In light of these mixed findings, we outline future avenues for improving the efficacy of CBM-I training targeting responsibility biases.     

The Heartsink Patient: A Preliminary Study

Eight GPs identified 78 heartsink patients; in an open-endedinterview they were asked to explain why they regarded themin this way. A GP's definition of a heartsink patient was influencedby GP sex, practice location, and time of surgery, althoughthe number of participating GPs was too low to make any definiteassertions. Practitioners' anticipations of heartsink consultationswere generally over-exaggerated, with most of the encountersgoing better than expected. GPs expressed the view that thesepatients raised serious professional issues for them, whilstthere was also a dislike for these patients' personalities andbehaviour. Two levels of the heartsink state are hypothesized:one, a state of inertia, is when the heartsink patient has beena chronic high user of the primary health care system, and aGP has exhausted all avenues. The other is an acute situationwith those heartsink patients who have been low users of thesystem in the past. Recent, new events in these patients' liveshave raised an issue that is just as much to do with patientand doctor reaction to these events, as it is about findinga diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussionand research.     

Evoked potential maps in learning disabled children

Some childhood learning disabilities are associated with altered synchrony patterns of brain evoked potentials. Scalp recorded electrical synchrony between selected brain regions was measured in response to visual, auditory and somatosensory stimuli and compared between a group of learning disabled children and a group of normal children. Statistically significant inter-group differences revealed stimulus dependent greater inter-regional EP synchrony in the learning disabled group. These findings support the notion that some childhood learning disabilities reflect, in part, altered connections between selected brain regions.     

Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B- cell precursors

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen- activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non- c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low- expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.     

Tetanus toxin alters 5-hydroxytryptamine, dopamine, and their metabolites in rat hippocampus measured by in vivo microdialysis.

Tetanus toxin is a potent neurotoxin, the mode of action of which is unknown, although it is widely considered to be mediated by loss of inhibitory neurotransmission. In the present study we have investigated the effect of a single unilateral injection of tetanus toxin in the hippocampus on extracellular concentrations of 5-hydroxytryptamine (5-HT), dopamine and their metabolites in freely moving rats. Tetanus toxin treatment caused a progressive decline in hippocampal dialysate 5-hydroxytryptamine over the 3-day period following the injection. After 3 days the level of 5-HT on the injected side was only 20% of the control side. On the second day of observation the level of dopamine was found to be elevated by more than 2-fold but this was not the case for either of the other 2 days studied. The 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid declined in a manner similar to that of the parent transmitter, but to a lesser extent. Of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid was decreased on the second and third days of observation, whilst homovanillic acid was not significantly altered during the period of observation.     

Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI.

We sought to identify magnetic resonance imaging (MRI) parameters that can identify as well as predict disruption of the blood-brain barrier (BBB) after embolic stroke in the rat. Rats subjected to embolic stroke with (n=13) and without (n=13) rt-PA treatment were followed with MRI using quantitative permeability-related parameters, consisting of: transfer constant (K(i)) of Gd- DTPA, the distribution volume (V(p)) of the mobile protons, and the inverse of the apparent forward transfer rate for magnetization transfer (k(inv)), as well as the apparent diffusion coefficient of water (ADC(w)), T2, and cerebral cerebral blood flow (CBF). Tissue progressing to fibrin leakage resulting from BBB disruption and adjacent tissue were then analyzed to identify MRI markers that characterize BBB disruption. Animals were killed after final MRI measurements at 24 h after induction of embolic stroke and cerebral tissues were perfused and stained to detect fibrin leakage. K(i), V(p), and k(inv) were the most sensitive early (2 to 3 h) indices of the cerebral tissue that progresses to fibrin leakage. Cerebral blood flow was not significantly different between ischemic tissue with a compromised and an intact BBB. Our data indicate that compromise of the BBB can be sensitively predicted using a select set of MR parameters.     

The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal dialysates in vivo

Tianeptine is a novel tricyclic antidepressant which, in marked contrast to other antidepressants, increases the uptake of 5-HT in brain tissue and blood platelet preparations ex vivo. In the present study it was shown, by microdialysis, that tianeptine (10 mg/kg i.p.), whether given as a single dose or as daily doses for 14 days, attenuated the K(+)-evoked rise of extracellular 5-HT in the hippocampus in vivo. Tianeptine (10 mg/kg i.p.), given acutely, did not reduce basal levels of 5-HT in hippocampal dialysates in the presence of the 5-HT reuptake inhibitor, citalopram. These results suggest mutually opposing effects of tianeptine and citalopram on neuronal uptake of 5-HT. Their significance in relation to the role of 5-HT in the action of antidepressants is discussed.