Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder

In the rodent forebrain GABAergic neurons are generated from progenitor cells that express the transcription factors Dlx1 and Dlx2. The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons. Expression of both Dlx1/2 and MR-GEF is retained in both adult mouse and human forebrain where, in human, decreased Dlx1 expression has been associated with psychosis. Using in situ hybridization studies we show that MR-GEF expression is significantly down-regulated in the forebrain of Dlx1/2 double mutant mice suggesting that MR-GEF and Dlx1/2 form part of a common signalling pathway during GABAergic neuronal development. We therefore compared MR-GEF expression by in situ hybridization in individuals with major psychiatric disorders (schizophrenia, bipolar disorder, major depression) and control individuals. We observed a significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex (DLPFC) in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder, but not in individuals with schizophrenia, major depressive disorder or in controls. Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission.

Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons

We have performed a screen combining subtractive hybridization with PCR to isolate genes that are regulated when neuroepithelial (NE) cells differentiate into neurons. From this screen, we have isolated a number of known genes that have not previously been associated with neurogenesis, together with several novel genes. Here we report that one of these genes, encoding a guanine nucleotide exchange factor (GEF), is regulated during the differentiation of distinct neuronal populations. We have cloned both rat and mouse GEF genes and shown that they are orthologs of the human gene, MR-GEF, which encodes a GEF that specifically activates the small GTPase, Rap1. We have therefore named the rat gene rat mr-gef (rmr-gef) and the mouse gene mouse mr-gef (mmr-gef). Here, we will collectively refer to these two rodent genes as mr-gef. Expression studies show that mr-gef is expressed by young neurons of the developing rodent CNS but not by progenitor cells in the ventricular zone (VZ). The expression pattern of mr-gef during early telencephalic neurogenesis is strikingly similar to that of GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by GABAergic interneurons generated in the ventral telencephalon, some of which migrate into the cortex during development. These observations suggest that mr-gef encodes a protein that is part of a signaling pathway involved in telencephalic neurogenesis; particularly in the development of GABAergic interneurons.

Mår kvinnliga lärare sämre än manliga?

Stress på jobbet har väckt stor uppmärksamhet de senaste åren. Generellt kan man säga att den psykiska ohälsan ökar. Kvinnor och lärare är överrepresenterade bland de utbrända. Syftet med undersökningen var att genom en enkätstudie ta reda på om det fanns några könsskillnader gällande mäns och kvinnors psykiska ohälsa på två gymnasier i Dalarna. Undersökningen bestod av ett frågeformulär bestående av 18 frågor. Sammanlagt 78 personer valde att delta i studien. Resultatet visade inga signifikanta könsskillnader. Man kan däremot utläsa en tendens till att kvinnorna mår sämre än männen. Då tidigare forskning pekar mot att kvinnor mår sämre än män, kan undersökningens utslag bero på för få deltagare eller på undersökningens låga svarsfrekvens.

Skolsköterskans upplevelse av att arbeta med barn och ungdomar som mår psykiskt dåligt : En intervjustudie med kvalitativ ansats

Syfte: Att beskriva skolsköterskans upplevelse av att arbeta med barn och ungdomar som mår psykiskt dåligt, det preventiva arbetet samt samarbetet med andra vårdgivare.Metod: Studien har en kvalitativ design med fenomenologisk ansats. Deltagare i studien var fem skolsköterskor i en svensk kommun. Utgången i intervjun var tre stora öppna frågor i området "skolsköterskans upplevelse av att arbeta med barn och unga som mår psykiskt dåligt". Analysen genomfördes med hjälp av Kvales metod för analys, så kallad meningskoncentrering, vilket skedde efter transkribering i tre steg. Resultat: Analysen resulterade i följande deskriptiva teman. Viktigt arbete, Tidsbrist, Känslor av otillräcklighet, Barnens företrädare, Att skapa tillit, Tillgänglighet, Betydelsen av preventiva metoder, Betydelsen av samarbete inom skolan, Samarbete med föräldrar - en svår gränsdragning, Socialtjänstens sekretess försvårar arbetet, Utebliven remisshantering försvårar samarbetet med BUP samt "Hål i organisationen".Slutsats: Skolsköterskorna ansåg att det var viktigt att arbeta för psykisk hälsa hos eleverna. De upplevde tidspressen som ett hinder i arbetet med detta, vilket var frustrerande. Alla informanter önskade få möjlighet att arbeta mer preventivt. Samarbetet med lärare, kuratorer och föräldrar var betydelsefullt för att kunna hjälpa barnen. Samarbetet med andra vårdgivare upplevdes skiftande. Samtliga informanter var dock överens om att samarbetet kan förbättras.

Problem-based learning and masculinities : unique opportunities for Mr. Fix It? Well, maybe

I watched a smoker of 30 years being admitted to the Coronary Care unit following an acute Myocardial Infarction (heart attack). The message from the male clinician was simple, accurate, but somewhat behaviourist: " the death of part of your heart muscle is the result of your smoking, if you don’t stop smoking the damage will continue and you will die." A global, proactive and humanistic consultation demonstrating an understanding of the man’s addiction to a legal and accessible drug and illuminating prevention strategies may have been more appropriate. Maybe the interaction was about competing masculinities, the risk taker and the problem solver. The irony? As I left the hospital that night I observed the same clinician strategically positioned in a secluded hospital doorway drawing heavily on a cigarette. Hypocrite? No, invincible late 20’s male? Maybe. Smoking was someone else’s problem – at least today.

In my 16 years as a clinician such scenarios are common. Clinical practice based predominantly on problem solving potentiates hegemonic masculine approaches to treating men in clinical practice, often justified by limited health resources and increasing patient acuity. Ironically, Problem-based Learning (PBL) curriculums commonly used in health sciences higher education encourages, nurtures and rewards such problem solving approaches. As a teaching academic with current clinical practice it occurs to me that health science education and PBL has an opportunity if not obligation to empower clinicians to establish holistic approaches to male health presentations.

This paper explores the interconnections of Problem-based Learning (PBL) curriculums, health promotion, male nurses’ health-related behaviours and the implications and specificities of masculinity. The pilot study offers an insight into the perceptions of three male nurses that completed undergraduate nursing studies in PBL curriculums. The data obtained introduces some connections that could be illuminated by further research.

Sequential 123-I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18-F-FDG-PET imaging)

Purpose Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with ¹²³I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci.
Methods We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation.
Results The 6-h IDEX scan (92%; κappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%;κappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; κappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy.
Conclusion The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.

Dancing with Mr. Penrose and other stories

Stories: Fallen Angel The Inheritance Schlog's Dance The New World Dancing With Mr. Penrose