Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system

AbstractRecent research shows that the effects of oxytocin are more diverse than initially thought and that in some cases oxytocin can directly influence the response to drugs and alcohol. Large individual differences in basal oxytocin levels and reactivity of the oxytocin system exist. This paper will review the literature to explore how individual differences in the oxytocin system arise and examine the hypothesis that this may mediate some of the individual differences in susceptibility to addiction and relapse.Differences in the oxytocin system can be based on individual factors, e.g. genetic variation especially in the oxytocin receptor, age or gender, or be the result of early environmental influences such as social experiences, stress or trauma. The paper addresses the factors that cause individual differences in the oxytocin system and the environmental factors that have been identified to induce long-term changes in the developing oxytocin system during different life phases.Individual differences in the oxytocin system can influence effects of drugs and alcohol directly or indirectly. The oxytocin system has bidirectional interactions with the stress-axis, autonomic nervous system, neurotransmitter systems (e.g. dopamine, serotonin and GABA/glutamate) and the immune system. These systems are all important, even vital, in different phases of addiction.It is suggested that early life adversity can change the development of the oxytocin system and the way it modulates other systems. This in turn could minimise the negative feedback loops that would normally exist. Individuals may show only minor differences in behaviour and function unless subsequent stressors or drug use challenges the system. It is postulated that at that time individual differences in oxytocin levels, reactivity of the system or interactions with other systems can influence general resilience, drug effects and the susceptibility to develop problematic drug and alcohol use

Perceptual Sensitivity and Response to Strong Stimuli Are Related

To shed new light on the long-standing debate about the (in)dependence of sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the relation between these tendencies within the neurobehavioral framework of the Predictive and Reactive Control Systems (PARCS) theory (Tops et al., 2010, 2014). Whereas previous studies only considered overreactivity in terms of the individual tendency to experience unpleasant affect (punishment reactivity) resulting from strong sensory stimulation, we also took the individual tendency to experience pleasant affect (reward reactivity) resulting from strong sensory stimulation into account. According to PARCS theory, these temperamental tendencies overlap in terms of high reactivity toward stimulation, but oppose each other in terms of the response orientation (approach or avoid). PARCS theory predicts that both types of reactivity to strong stimuli relate to sensitivity to weak stimuli, but that these relationships are suppressed due to the opposing relationship between reward and punishment reactivity. We measured punishment and reward reactivity to strong stimuli and sensitivity to weak stimuli using scales from the Adult Temperament Questionnaire (Evans and Rothbart, 2007). Sensitivity was also measured more objectively using the masked auditory threshold. We found that sensitivity to weak stimuli (both self-reported and objectively assessed) was positively associated with self-reported punishment and reward reactivity to strong stimuli, but only when these reactivity measures were controlled for each other, implicating a mutual suppression effect. These results are in line with PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are dependent, but this dependency is likely to be obscured if punishment and reward reactivity are not both taken into account

Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers

Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5. The area under the operator receiving characteristic curve (AU

The Study of Education Effect on Knowledge of, and Attitudes Toward Electroconvulsive Therapy Among Iranian Nurses and Patients’ Relatives in a Psychiatric Hospital, 2009-2010

AbstractElectroconvulsive therapy (ECT) is a cost effective method in the treatment of some psychiatric disorders. Although, service users such as health providers and nurses, also patients and their relatives may refuse ECT when indicated, due to the myths and little or lack of knowledge about the procedure. The knowledge of and attitudes toward ECT among nurses, may reflect on patients and influence treatment choice. For doing this procedure relatives informed consent is necessary, so their knowledge of and attitude toward ECT is important for getting informed consent and following treatment sessions. Objective: This research was conducted as a quasi-experimental study to measure knowledge of and attitudes toward ECT in 2 groups: relatives and nursing. Also, to study the effect of education on knowledge of and attitudes toward ECT in 2 groups. Methods: In this research the pre and post test self – administered questionnaires were completed by 46 relatives and 46 nurses before and after education about ECT. Results: Nurses in this research received a mean score of X=34.97 knowledge before education and X=39.78 after education (t=2.02, p<0.05), and a mean score of X=33.41 attitude before education and, X=42.82 after education (t=-14.25, p<0.001). Relatives received a mean score of X=23.41 knowledge before education and X=30.15 after education (t=-12.44, p<0.001), and a mean score of X=33.39 attitude before education and, X=41.13 after education (t=-9.10, p<0.001). The differences between the 2 means among two groups were found to be statistically significant. Conclusion: Education given to nurses and relatives about ECT increased their knowledge of, and improved their attitudes toward ECT. For this reason it is recommended that continuing education about ECT process should be planned and given at regular intervals

Uptake of prenatal diagnostic testing for retinoblastoma compared to other hereditary cancer syndromes in the Netherlands

Since the 1980s the genetic cause of many hereditary tumor syndromes has been elucidated. As a consequence, carriers of a deleterious mutation in these genes may opt for prenatal diagnoses (PND). We studied the uptake of prenatal diagnosis for five hereditary cancer syndromes in the Netherlands. Uptake for retinoblastoma (Rb) was compared with uptake for Von Hippel–Lindau disease (VHL), Li–Fraumeni syndrome (LFS), familial adenomatous polyposis (FAP), and hereditary breast ovarian cancer (HBOC). A questionnaire was completed by all nine DNA-diagnostic laboratories assessing the number of independent mutation-positive families identified from the start of diagnostic testing until May 2013, and the number of PNDs performed for these syndromes within these families. Of 187 families with a known Rb-gene mutation, 22 had performed PND (11.8%), this was significantly higher than uptake for FAP (1.6%) and HBOC (<0.2%). For VHL (6.5%) and LFS (4.9%) the difference was not statistically significant. PND for Rb started 3 years after introduction of diagnostic DNA testing and remained stable over the years. For the other cancer syndromes PND started 10–15 years after the introduction and uptake for PND showed an increase after 2009. We conclude that uptake of PND for Rb was significantly higher than for FAP and HBOC, but not different from VHL and LFS. Early onset, high penetrance, lack of preventive surgery and perceived burden of disease may explain these differences

Grammar disruption in a patient with Neuro-Sweet syndrome

This paper for the first time reports detailed neurolinguistic findings in a patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of central nervous system (CNS) involvement primarily consisted of a selective grammar deficit restricted to spontaneous speech. On MRI a left prefrontal ischemic stroke (superior part BA 6) and two small subcortical left parietal infarctions were found. Neurolinguistic analyses, however, did not reveal a profile consistent with any observations of agrammatism caused by structural damage to the language areas critically involved in grammatical processing. It is hypothesized that selectively distorted grammar might reflect disruption of the frontosubcortical network involved in language processing. Prefrontal neurobehavioral abnormalities associated with functional disruption of the inferior medial frontal regions as demonstrated by SPECT, additionally suggest that agrammatic symptoms may be linked to a higher-level cognitive disorder following encephalopathic CNS involvement

Acute left ventricular dysfunction secondary to right ventricular septal pacing in a woman with initial preserved contractility: a case report

<p>Abstract</p> <p>Introduction</p> <p>Right ventricular apical pacing-related heart failure is reported in some patients after long-term pacing. The exact mechanism is not yet clear but may be related to left ventricular dyssynchrony induced by right ventricular apical pacing. Right ventricular septal pacing is thought to deteriorate left ventricular function less frequently because of a more normal left ventricular activation pattern.</p> <p>Case presentation</p> <p>We report the case of a 55-year-old Tunisian woman with preserved ventricular function, implanted with a dual-chamber pacemaker for complete atrioventricular block. Right ventricular septal pacing induced a major ventricular dyssynchrony, severe left ventricular ejection fraction deterioration and symptoms of congestive heart failure. Upgrading to a biventricular device was associated with a decrease in the symptoms and the ventricular dyssynchrony, and an increase of left ventricular ejection fraction.</p> <p>Conclusion</p> <p>Right ventricular septal pacing can induce reversible left ventricular dysfunction and heart failure secondary to left ventricular dyssynchrony. This complication remains an unpredictable complication of right ventricular septal pacing.</p

Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>There is strong evidence that left atrial (LA) size is a prognostic marker in a variety of heart diseases. Recently, real-time three-dimensional echocardiography (RT3DE) has been reported as a useful tool for studying the phasic changes of the left atrial volumes. The aim of this study was to investigate the performance of the left atrium in beta-thalassemic patients with preserved left ventricular ejection fraction (EF) and no iron overload, using RT3DE.</p> <p>Methods</p> <p>Twenty-eight asymptomatic b-thalassemic patients (32.2 ± 4.3 years old, 17 men) who were on iron chelating therapy, as well as 20 age- and sex-matched healthy controls underwent transthoracic RT3DE. The patient group had normal echocardiographic systolic and diastolic indices, while there was no myocardial iron disposition according to MRI. Apical full volume data sets were obtained and LA volumes were measured at 3 time points of the cardiac cycle: (1) maximum volume (LAmax) at end-systole, just before mitral valve opening; (2) minimum volume (LAmin) at end-diastole, just before mitral valve closure; and (3) volume before atrial active contraction (LApreA) obtained from the last frame before mitral valve reopening or at time of the P wave on the surface electrocardiogram. From the derived values, left atrial active and passive emptying volumes, as well as the respective emptying fractions were calculated.</p> <p>Results</p> <p>Left ventricular EF (59.2 ± 2.5% patients vs. 60.1 ± 2.1% controls), E/A, E/E' were similar between the two groups. Differences in the LAmax, LAmin and LApreA between b-thalassemic patients and controls were non-significant, LAmax:(35.5 ± 13.4 vs 31.8 ± 9.8)cm³, LAmin:(16.0 ± 6.0 vs. 13.5 ±4.2)cm³, and LApreA:(25.4 ± 9.8 vs. 24.3 ± 7.2)cm³. However, left atrial active emptying fraction was reduced in the patient group as compared to the healthy population (34.3 ± 16.4% vs. 43.2 ± 11.4%, p < 0.05).</p> <p>Conclusion</p> <p>RT3DE may be a novel technique for the evaluation of LA function in asymptomatic patients with b-Thalassemia Major. Among three-dimensional volumes and indices, left atrial active emptying fraction may be an early index of LA dysfunction in the specific patient population.</p