Sex difference in brain CB1 receptor availability in man

none12The endocannabinoid system (ECS) has a widespread neuromodulatory function in the central nervous system and is involved in important aspects of brain function including brain development, cortical rhythms, plasticity, reward, and stress sensitivity. Many of these effects are mediated via the cannabinoid CB1 receptor (CB1R) subtype. Animal studies convincingly show an interaction between the ECS and sex hormones, as well as a sex difference of higher brain CB1R in males. Human in vivo studies of sex difference have yielded discrepant findings. Gender differences in CB1R availability were investigated in vivo in 11 male and 11 female healthy volunteers using a specific CB1R tracer [18F]FMPEP-d2 and positron emission tomography (PET). Regional [18F]FMPEP-d2 distribution volume was used as a proxy for CB1R availability. In addition, we explored whether CB1R availability is linked to neuropsychological functioning. Relative to females, CB1R availability was on average 41% higher in males (p = 0.002) with a regionally specific effect larger in the posterior cingulate and retrosplenial cortices (p = 0.001). Inter-subject variability in CB1R availability was similar in both groups. Voxel-based analyses revealed an inverse association between CB1R availability and visuospatial working memory task performance in both groups (p noneLaurikainen, Heikki; Tuominen, Lauri; Tikka, Maria; Merisaari, Harri; Armio, Reetta-Liina; Sormunen, Elina; Borgan, Faith; Veronese, Mattia; Howes, Oliver; Haaparanta-Solin, Merja; Solin, Olof; Hietala, JarmoLaurikainen, Heikki; Tuominen, Lauri; Tikka, Maria; Merisaari, Harri; Armio, Reetta-Liina; Sormunen, Elina; Borgan, Faith; Veronese, Mattia; Howes, Oliver; Haaparanta-Solin, Merja; Solin, Olof; Hietala, Jarm

Pre-α-pro-GDNF and Pre-β-pro-GDNF Isoforms Are Neuroprotective in the 6-hydroxydopamine Rat Model of Parkinson's Disease

Glial cell line-derived neurotrophic factor (GDNF) is one of the most studied neurotrophic factors. GDNF has two splice isoforms, full-length pre-alpha-pro-GDNF (u-GDNF) and pre-beta-pro-GDNF (beta-GDNF), which has a 26 amino acid deletion in the pro-region. Thus far, studies have focused solely on the u-GDNF isoform, and nothing is known about the in vivo effects of the shorter beta-GDNF variant. Here we compare for the first time the effects of overexpressed cx-GDNF and beta-GDNF in non-lesioned rat striatum and the partial 6-hydroxydopamine lesion model of Parkinson's disease. GDNF isoforms were overexpressed with their native pre-pro-sequences in the striatum using an adeno-associated virus (AAV) vector, and the effects on motor performance and dopaminergic phenotype of the nigrostriatal pathway were assessed. In the non-lesioned striatum, both isoforms increased the density of dopamine transporter-positive fibers at 3 weeks after viral vector delivery. Although both isoforms increased the activity of the animals in cylinder assay, only u-GDNF enhanced the use of contralateral paw. Four weeks later, the striatal tyrosine hydroxylase (TH)-immunoreactivity was decreased in both u-GDNF and 1-GDNF treated animals. In the neuroprotection assay, both GDNF splice isoforms increased the number of TH-immunoreactive cells in the substantia nigra but did not promote behavioral recovery based on amphetamine-induced rotation or cylinder assays. Thus, the shorter GDNF isoform, beta-GDNF, and the full-length alpha-isoform have comparable neuroprotective efficacy on dopamine neurons of the nigrostriatal circuitry.Peer reviewe

Amygdala subnucleus volumes in psychosis high-risk state and first-episode psychosis

Structural and functional abnormalities of the amygdala in schizophrenia have been well documented. Post-mortem studies suggest that the lateral nucleus is particularly affected in schizophrenia. It is not known whether the amygdala subnuclei are differently affected at the time of the first-episode psychosis or already at high-risk state.75 first-episode psychosis patients (FEP), 45 clinical high-risk patients (CHR) and 76 population controls participated in this cross-sectional case-control study. Participants underwent T1-weighted 3T MRI scans, from which the amygdala was segmented using a newly developed automated algorithm. Because early adverse events increase risk for psychosis and affect the amygdala, we also tested whether experiences of childhood maltreatment associate with the putative amygdala subnuclei abnormalities.Compared to the population controls, FEP had smaller volumes of the lateral, and basal nuclei. In CHR, only the lateral nucleus was significantly smaller compared to the control subjects. Experience of childhood maltreatment was inversely associated with lateral nucleus volumes in FEP but not in CHR.These results show that the lateral and basal nuclei of the amygdala are already affected in FEP. These volumetric changes may reflect specific cellular abnormalities that have been observed in post-mortem studies in schizophrenia in the same subnuclei. Decreased volume of the lateral nucleus in CHR suggest that a smaller lateral nucleus could serve as a potential biomarker for psychosis risk. Finally, we found that the lateral nucleus volumes in FEP may be sensitive to the effects of childhood maltreatment.</p

Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson's disease

Cerebral dopamine neurotrophic factor (CDNF) protein has been shown to protect the nigrostriatal dopaminergic pathway when given as intrastriatal infusions in rat and mouse models of Parkinson's disease (PD). In this study, we assessed the neuroprotective effect of CDNF delivered with a recombinant adeno-associated viral (AAV) serotype 2 vector in a rat 6-hydroxydopamine (6-OHDA) model of PD. AAV2 vectors encoding CDNF, glial cell line-derived neurotrophic factor (GDNF), or green fluorescent protein were injected into the rat striatum. Protein expression analysis showed that our AAV2 vector efficiently delivered the neurotrophic factor genes into the brain and gave rise to a long-lasting expression of the proteins. Two weeks after AAV2 vector injection, 6-OHDA was injected into the rat striatum, creating a progressive degeneration of the nigrostriatal dopaminergic system. Treatment with AAV2-CDNF resulted in a marked decrease in amphetamine-induced ipsilateral rotations while it provided only partial protection of tyrosine hydroxylase (TH)-immunoreactive cells in the rat substantia nigra pars compacta and TH-reactive fibers in the striatum. Results from this study provide additional evidence that CDNF can be considered a potential treatment of Parkinson's disease.Peer reviewe

Short-term functional outcome in psychotic patients: results of the Turku early psychosis study (TEPS)

Background Functional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N). Methods Altogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA. Results During follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning. Conclusions In patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis.</p

Psykoosipotilaiden toimintakyvyn ennuste ja sitä ennustavat tekijät

TAUSTA. Tavoitteenamme oli tutkia luonnollisessa tutkimusasetelmassa psykoosin ja psykoosiriskin vuoksi ensi kertaa hoitoon tulleiden potilaiden toimintakyvyn ennustetta ja siihen vaikuttavia tekijöitä.AINEISTO JA MENETELMÄT. Tutkimusaineisto koostui 130 psykoosi- ja 107 psykoosiriskipotilaasta, joille tehtiin alkuhaastattelun jälkeen seurantahaastattelu yhdeksän ja 18 kuukauden kuluttua. Seurannan perusteella muodostettiin hyvän ja huonon ennusteen ryhmät, joita selitettiin logistisella regressioanalyysillä.TULOKSET JA PÄÄTELMÄT. Psykoosi- ja riskipotilaiden toimintakyvyn ennusteissa ei ollut eroa. Hyvä ennuste yhdistyi naissukupuoleen, lapsuuden sosiaalisuuteen, koulumenestykseen ja vähäisiin traumakokemuksiin sekä hyvään koulutustasoon ja työtilanteeseen. Oireista tunneköyhyys ja ajattelun hajanaisuus liittyvät huonoon ennusteeseen. Monimuuttuja-analyysissä naimattomuus, lapsuuden traumakokemukset ja heikko koulumenestys, huono työtilanne sekä tunneköyhyys ja ajattelun hajanaisuus ennustivat huonoa toimintakykyä. Koulutuksen ja työteon tukemiseen liittyvät kuntoutustoimenpiteet ovat keskeisiä pyrittäessä parantamaan psykoosipotilaiden ja psykoosiriskissä olevien potilaiden toimintakykyä.</p

Päihdehoitotyö suomalaisessa hoitotieteessä

Opinnäytetyö kuvaa suomalaisia hoitotieteellisiä päihdehoitotyötä käsitteleviä tutkimuksia. Opinnäytetyön tarkoituksena oli koota yhteen suomalaisia hoitotieteellisiä päihdehoitotyöhön liittyviä tutkimuksia ja kuvata, miten päihdehoitotyötä on tutkittu suomalaisessa hoitotieteessä ja mihin päihdehoitotyötä koskeviin ongelmiin ja kysymyksiin hoitotiede on vastannut. Lisäksi tutkimuksen tarkoituksena oli koota päihdehoitotyötä käsittelevien tutkimuksien tuottamat jatkotutkimushaasteet. Opinnäytetyö toteutettiin kuvailevana kirjallisuuskatsauksena, jonka aineisto kerättiin sähköisistä tietokannoista sekä manuaalisella haulla. Aineisto koostui suomalaisista hoitotieteellisistä tutkimusartikkeleista (n=6), väitöskirjoista (n=4) ja pro gradu -tutkielmista (n=17). Opinnäytetyön tulokset saatiin käyttämällä aineiston analyysimenetelmänä teemoittelua. Tuloksista kävi ilmi, että suomalaisissa hoitotieteellisissä tutkimuksissa päihdehoitotyötä kuvaavat tutkimukset muodostivat seitsemän teemaa. Suurimmaksi tutkituksi teemaksi nousi päihdehoitotyön sisältöjä ja menetelmiä käsittelevät tutkimukset. Myös hoitotyöntekijää päihdehoitotyön toteuttajana käsitteleviä tutkimuksia ja päihde-ehtoista asiakkuutta kuvaavia tutkimuksia on tehty runsaasti. Lisäksi koulu- ja opiskeluterveydenhuollossa tapahtuvaa päihdehoitotyötä tarkastelevien tutkimuksien osuus on huomattava. Omiksi teemoikseen erottuivat päihdehoitotyötä äitiyshuollon yhteydessä käsittelevät tutkimukset sekä päihdehoitotyötä huumeidenkäyttäjien hoidossa käsittelevät tutkimukset. Hoitotyön opiskelijoiden päihdehoitotyön osaamista käsiteltiin kahdessa tutkimuksessa. Osa opinnäytetyön aineistossa olleista tutkimuksista kuuluu aihepiiriltään useampaan teemaan. Laaja-alainen kuvaileva kirjallisuuskatsaus soveltui erinomaisesti kartoittamaan jo olemassa olevaa tutkimustietoa. Kirjallisuuskatsaus ilmensi, että päihdehoito-työtä on tutkittu suomalaisessa hoitotieteessä varsin monipuolisesti, mutta jatkotutkittavaa on edelleen runsaasti. Opinnäytetyön tulokset tarjoavat jo itsessään useita jatkotutkimushaasteita. Lisäksi aihetta voisi tarkastella eri mittakaavassa, kuten esimerkiksi, miten päihdehoitotyötä on tutkittu ulkomaalaisissa tutkimuksissa. Samaa tutkimusmenetelmää voisi myös hyödyntää tarkastelemalla muita hoitotyön osa-alueita koskevia tutkimuksia.The purpose of the thesis was to describe how Finnish nursing science has researched substance abuse nursing. The aim of this research was to aggregate Finnish dissertations and describe how substance abuse nursing has been restudied in Finnish nursing science and examine which research problems nursing science has been able to find an answer for. In addition, the aim of the research was aggregate already existing dissertations further research issues. The thesis was conducted as a descriptive literature review. The material consisted of articles, doctoral dissertations and master's theses that were collected from electronic databases and manual search. According to the results, seven themes were found in the studies of substance abuse nursing. The most studied theme was the study of the content and methods. There were also a number of studies on employees and clients and their experiences about substance abuse nursing. The proportion of studies on substance abuse nursing on school and student health care was also notable. Furthermore, there were other themes such as the studies on substance abuse nursing in maternity care and substance abuse nursing for drug users. Nursing students’ skills in substance abuse nursing were discussed in two studies. Some of the studies were simultaneously related to several themes. A wide literature review was a suitable method to map already existing research data. This literature review disclosed that substance abuse nursing has been studied quite widely in Finnish nursing science but there are still many research topics left to be studied. The results of the thesis offer topics for further research. In addition, the topic could be viewed on a larger scale, for example, how substance abuse nursing has been studied in international studies. The same research method could also be utilized by examining other studies in the areas of nursing

Painetut bioaktiiviset materiaalit diagnostiikassa

The aim of the work was to study printing technology methods in diagnostics. The goal was to print bacteriolytic reagents onto nonwoven fabrics and compare their effectiveness to same reagents in solutions. Another goal was to detect visually as small bacteria amount as possible on fabrics. The literature part discusses the use of printing technology in the production of bioactive materials for diagnostics, concentrating on printing bio molecules. Research activity of printed bio molecules has been very high. However, there are relatively few commercial applications available. In the experimental part different bacteriolytic reagents were gravure printed. Bacteriolytic effectiveness of the fabrics was studied by using enzymatic method in which the result was detected visually as a colour change. Most of the printed reagents performed as well as in solutions. Lysis of bacteria was most effective when done with fabrics containing detergents in these experimental conditions. The lowest bacteria amount detected was 7.5.102 CFU. This was detected after three hours test reaction incubation. The colorization of the fabrics was typically uneven because of the diffusion of the reagents and detected analyte. The easiest way to detect colour differences between fabrics was scanning the fabrics to photos. If using the described method as a diagnostic rapid test it would be recommended to scan the fabrics for result reading. Using printed bacteriolytic enzyme A fabric to replace multi-phased acid cell extraction of the commercial immunological Strep A rapid test was also studied in the experimental part. Printed enzyme A fabric was observed to perform well with the test. Therefore, using printed enzyme A fabric it could be possible to develop a simpler and faster Strep A rapid test than there is commercially available at the moment.Työn tarkoituksena oli tutkia painotekniikan hyödyntämistä diagnostisten tuotteiden valmistuksessa. Työn tavoitteena oli perinteisiä painomenetelmiä käyttäen painaa bakteerisoluja hajottavia reagensseja kankaalle ja vertailla painettujen reagenssien toimivuutta vastaaviin reagensseihin liuoksina. Lisäksi tavoitteena oli kehittää pikamenetelmä, jolla voitaisiin todeta mahdollisimman pieni bakteerimäärä visuaalisesti kankaalta. Kirjallisuusosiossa on tarkasteltu painoteknologian käyttöä bioaktiivisten materiaalien valmistuksessa diagnostisiin sovelluksiin, keskittyen biomolekyylien painamiseen. Havaittiin, että biomolekyylien painamisesta on olemassa melko paljon tutkimustietoa, mutta sovelluksia on vain vähän markkinoilla. Tutkimusosassa painettiin erilaisia bakteerisoluja hajottavia reagensseja syväpainokoneella ja niiden toimivuutta tutkittiin visuaalisesti värinmuutoksena kankaalla havaittavalla entsymaattisella menetelmällä. Suurin osa painetuista reagensseista toimi samalla tavalla liuoksena. Bakteerien hajotuksessa käytetyissä koeolosuhteissa parhaiten toimivat detergenttejä sisältävät kankaat. Pienin havaittava bakteerimäärä oli 7,5.102 PMY ja se pystyttiin havaitsemaan jopa kolmen tunnin testireaktioinkuboinnin jälkeen. Värin muodostuminen kankaille oli epätasaista reagenssien ja detektoitavan analyytin diffuusiosta johtuen. Skannaamalla kankaat kuviksi pystyttiin havaitsemaan parhaiten värieroja eri kankaiden välillä. Tuloksen lukeminen kankailta kuvantamislaitteella olisikin järkevää sovellettaessa menetelmää diagnostiseksi pikatestiksi. Tutkimusosiossa tutkittiin lisäksi kaupallisen immunologisen Strep A -pikatestin monivaiheisen bakteereja hajottavan happouuton korvaamista painetulla bakteriolyyttisellä entsyymi A -kankaalla. Koska entsyymi A -kankaan todettiin soveltuvan Strep A -pikatestiin, voidaan havaintoa hyödyntämällä mahdollisesti kehittää yksinkertaisempi ja nopeampi Strep A -pikatesti kuin mitä tällä hetkellä on markkinoilla

Adult Attachment System Links With Brain Mu Opioid Receptor Availability In Vivo

BACKGROUND: Secure attachment is important in maintaining an individual's health and well-being. Attachment disturbances increase the risk for developing psychiatric disorders such as affective disorders. Yet, the neurobiological correlates of human attachment are poorly understood at the neurotransmitter level. We investigated whether adult attachment style is linked to functioning of the opioid and serotonergic systems in the human brain. METHODS: We used positron emission tomography with radioligands [C-11]carfentanil and [C-11]MADAM to quantify mu opioid receptor (n = 39) and serotonin transporter (n = 37) availability in volunteers with no current psychiatric disorders. Attachment style was determined according to the Dynamic-Maturational Model of Attachment and Adaptation with the structured Adult Attachment Interview. RESULTS: Secure attachment was associated with higher mu opioid receptor availability in the hippocampus, amygdala, thalamus, and prefrontal cortex when compared with insecure (i.e., avoidant or ambivalent groups combined) attachment. In contrast, attachment style was not associated with serotonin transporter availability. CONCLUSIONS: Our results provide preliminary in vivo evidence that the opioid system may be involved in the neurocircuits associated with individual differences in adult attachment behavior. The results suggest that variation in mu opioid receptor availability may be linked with the individuals' social relationships and psychosocial well-being and thus contributes to risk for psychiatric morbidity.Peer reviewe