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

Getting lost in a story: how narrative engagement emerges from narrative perspective and individual differences in alexithymia

The present research examines how narrative engagement, or the extent to which people immerse themselves into the world of a story, varies as a function of narrative perspective and individual differences in alexithymia. The authors hypothesised that narrative engagement would be higher when people assume a first-person (rather than third-person) perspective and for people lower (rather than higher) on alexithymia. In an online study (N = 541) and a lab study (N = 55), participants with varying levels of alexithymia read first- and/or third-person narrated texts and then rated their narrative engagement. As expected, first-person stories evoked more narrative engagement than third-person stories, and global alexithymia was negatively correlated with narrative engagement. Narrative perspective did not interact with cognitive facets of alexithymia (i.e. difficulties identifying, verbalising, and understanding feelings). However, narrative perspective did interact with affective facets of alexithymia (i.e. emotionalising and fantasising): First-person (rather than third-person) stories elicited more narrative engagement at lower levels of affective alexithymia, but not at higher levels of affective alexithymia. The interaction effect was significant in Study 1; the interaction was significant in Study 2 after controlling for trait absorption. Together, these findings suggest that alexithymia is linked to difficulties in mentally simulating narrative worlds.Pathways through Adolescenc

Quality in the feed grain Market

Diffuse gliomas comprise a group of primary brain tumors that originate from glial (precursor) cells and present as a variety of malignancy grades which have in common that they grow by diffuse infiltration. This phenotype complicates treatment enormously as it precludes curative surgery and radiotherapy. Furthermore, diffusely infiltrating glioma cells often hide behind a functional blood-brain barrier, hampering delivery of systemically administered therapeutic and diagnostic compounds to the tumor cells. The present review addresses the biological mechanisms that underlie the diffuse infiltrative phenotype, knowledge of which may improve treatment strategies for this disastrous tumor type. The invasive phenotype is specific for glioma: most other brain tumor types, both primary and metastatic, grow as delineated lesions. Differences between the genetic make-up of glioma and that of other tumor types may therefore help to unravel molecular pathways, involved in diffuse infiltrative growth. One such difference concerns mutations in the NADP+-dependent isocitrate dehydrogenase (IDH1 and IDH2) genes, which occur in >80% of cases of low grade glioma and secondary glioblastoma. In this review we present a novel hypothesis which links IDH1 and IDH2 mutations to glutamate metabolism, possibly explaining the specific biological behavior of diffuse glioma

The impact of oxytocin administration on charitable donating is moderated by experiences of parental love-withdrawal

Oxytocin has been implicated in a variety of prosocial processes but most of this work has used laboratory tasks (such as the ultimatum game or the dictator game) to evaluate oxytocin's prosocial effects. In a double blind randomized trial we examined the influence of intranasal administration of oxytocin on real, high-cost donating money to a charity with-out any expectation for reciprocation. Participants in the current study were 57 female undergraduate students, aged 18-30 years, who received a nasal spray containing either 24 IU of oxytocin or a placebo, and were then given the opportunity to make a charita-ble donation. The participants reported how often their parents used love-withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. Oxytocin appeared to increase the participants' willingness to donate money to a charity but only in participants who experienced low levels of parental love-withdrawal. In contrast, oxytocin administration was ineffective in enhancing donating behavior in individuals who experienced high levels of parental love-withdrawal. We conclude that the positive effect of oxytocin administration on prosocial behavior may be limited to individuals with supportive backgrounds

Spelling in adolescents with dyslexia: errors and modes of assessment

In this study we focused on the spelling of high-functioning students with dyslexia. We made a detailed classification of the errors in a word and sentence dictation task made by 100 students with dyslexia and 100 matched control students. All participants were in the first year of their bachelor’s studies and had Dutch as mother tongue. Three main error categories were distinguished: phonological, orthographic, and grammatical errors (on the basis of morphology and language-specific spelling rules). The results indicated that higher-education students with dyslexia made on average twice as many spelling errors as the controls, with effect sizes of d ≥ 2. When the errors were classified as phonological, orthographic, or grammatical, we found a slight dominance of phonological errors in students with dyslexia. Sentence dictation did not provide more information than word dictation in the correct classification of students with and without dyslexia

Noninvasive Evaluation of the Aortic Root With Multislice Computed Tomography Implications for Transcatheter Aortic Valve Replacement

ObjectivesIn the present study, the anatomy of the aortic root was assessed noninvasively with multislice computed tomography (MSCT).BackgroundTranscatheter aortic valve replacement has been proposed as an alternative to surgery in high-risk patients with severe aortic stenosis. For this procedure, detailed knowledge of aortic annulus diameters and the relation between the annulus and the coronary arteries is needed.MethodsIn 169 patients (111 men, age 54 ± 11 years), a 64-slice MSCT scan was performed for evaluation of coronary artery disease. Of these, 150 patients had no or mild aortic stenosis, and 19 patients had moderate to severe aortic stenosis. Reconstructed coronal and sagittal views were used for assessment of the aortic annulus diameter in 2 directions. In addition, the distance between the annulus and the ostium of the right and left coronary arteries and the length of the coronary leaflets were assessed. The LV outflow tract and interventricular septum were analyzed on the single oblique sagittal view at end-diastole.ResultsThe diameter of the aortic annulus was 26.3 ± 2.8 mm on the coronal view, and 23.5 ± 2.7 mm on the sagittal view. Mean difference between the 2 diameters was 2.9 ± 1.8 mm, indicating an oval shape of the aortic annulus. Mean distance between the aortic annulus and the ostium of the right coronary artery was 17.2 ± 3.3 mm, and mean distance between the annulus and the ostium of the left coronary artery was 14.4 ± 2.9 mm. In 82 patients (49%), the length of the left coronary leaflet exceeded the distance between the annulus and the ostium of the left coronary artery. There were no significant differences in the diameter of annulus, diameter of sinus of Valsalva, or the distance between the annulus, left coronary leaflet, and the ostium of the left coronary artery, between the patient with and without severe aortic stenosis.ConclusionsThe MSCT can provide detailed information on the shape of the aortic annulus and the relation between the annulus and the ostia of the coronary arteries. Thereby, MSCT may be helpful for avoiding paravalvular leakage and coronary occlusion and may facilitate the selection of candidates for transcatheter aortic valve replacement

Role of computed tomography imaging for transcatheter valvular repair/insertion

During the last decade, the development of transcatheter based therapies has provided feasible therapeutic options for patients with symptomatic severe valvular heart disease who are deemed inoperable. The promising results of many nonrandomized series and recent landmark trials have increased the number of percutaneous transcatheter valve procedures in high operative risk patients. Pre-procedural imaging of the anatomy of the aortic or mitral valve and their spatial relationships is crucial to select the most appropriate device or prosthesis and to plan the percutaneous procedure. Multidetector row computed tomography provides 3-dimensional volumetric data sets allowing unlimited plane reconstructions and plays an important role in pre-procedural screening and procedural planning. This review will describe the evolving role of multidetector row computed tomography in patient selection and strategy planning of transcatheter aortic and mitral valve procedures

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are—at least to some extent—nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline

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