Neurobiological Correlates of Personality Traits: A Study on Harm Avoidance and Neuroticism

Harm Avoidance and Neuroticism are traits that predispose to mental illnesses. Studying them provides a unique way to study predisposition of mental illnesses. Understanding the biological mechanisms that mediate vulnerability could lead to improvement in treatment and ultimately to pre-emptive psychiatry. These personality traits describe a tendency to feel negative emotions such as fear, shyness and worry. Previous studies suggest these traits are regulated by serotonin and opiate pathways. The aim of this thesis was to test the following hypotheses using personality trait measures and positron emission tomography (PET): 1) Brain serotonin transporter density in vivo is associated with Harm Avoidance and Neuroticism traits. 2) μ-opioid receptor binding is associated with Harm Avoidance. In addition, we developed a methodology for studying neurotransmitter interactions in the brain using the opiate and serotonin pathways. 32 healthy subjects who were consistently in either the highest or lowest quartile of the Harm Avoidance trait were recruited from a population-based cohort. Each subject underwent two PET scans, serotonin transporter binding was measured with [11C] MADAM and μ-opioid receptor binding with [11C]carfentanil. We found that the serotonin transporter is not associated with anxious personality traits. However, Harm Avoidance positively correlated with μ-opioid receptor availability. Particularly the tendency to feel shy and the inability to cope with stress were associated μ-opioid receptor availability. We also demonstrated that serotonin transporter binding correlates with μ-opioid receptor binding, suggesting interplay between the two systems. These findings shed light on the neurobiological correlates of personality and have an impact on etiological considerations of affective disorders.Persoonallisuuden neurobiologiset taustatekijät Turvallisuushakuisuus ja neuroottisuus ovat persoonallisuuden piirteitä, joihin liittyy ahdistustaipumus ja joiden on osoitettu altistavan mielenterveyshäiriöille. Tutkimalla näitä persoonallisuuspiirteitä on mahdollisuus saada ainutlaatuista tietoa myös alttiudesta sairastua mielenterveyshäiriöön. Tällaista tietoa voitaisiin käyttää hyväksi psykiatrisen hoidon ja sairauksien ennaltaehkäisyn kehittämiseen. Turvallisuushakuisuus ja neuroottisuus kuvaavat taipumusta kokea negatiivisia tunteita kuten pelkoa, ujoutta ja huolta. Aikaisempien tutkimusten perusteella aivojen serotoniini ja opioidijärjestelmien ajatellaan olevan yhteydessä näihin persoonallisuuden piirteisiin. Tässä väitöskirjatyössä käytettiin positroniemissiotomografia (PET) –tekniikkaa aivojen välittäjäainejärjestelmien toiminnan mittaamiseen ja persoonallisuuskyselyjä (TCI, NEO) persoonallisuuspiirteiden määrittelyyn. Tutkimuksessa testattiin seuraavia hypoteeseja: serotoniinin takaisinottajaproteiini on yhteydessä turvallisuushakuisuuteen, serotoniinin takaisinottajaproteiini on yhteydessä neuroottisuuteen ja μ-opioidireseptori on yhteydessä turvallisuushakuisuuteen. Lisäksi tutkimuksessa kehitettiin menetelmä välittäjäaineverkoston tutkimiseen PET menetelmällä. Tutkimukseen värvättiin laajasta väestöpohjaisesta kohorttitutkimuksesta 32 tervettä koehenkilöä, jotka olivat toistettujen mittausten perusteella turvallisuushakuisuuden suhteen joko ylimmässä tai alimmassa kvartiilissa. Kaikille koehenkilöille tehtiin kaksi PET-kuvausta saman päivän aikana. Ensimmäisessä kuvauksessa käytettiin [11C]MADAM–merkkiainetta mittaamaan serotoniinin takaisinottajaproteiinisitoutumista. Toisessa kuvauksessa käytettiin [11C]karfentaniili–merkkiainetta mittaamaan μ-opioidireseptorisitoutumista. Tämän tutkimuksen perusteella serotoniinin takaisinottajaproteiini ei ollut yhteydessä turvallisuushakuisuuteen eikä neuroottisuuteen. Tutkimuksessa havaittiin kuitenkin positiivinen korrelaatio turvallisuushakuisuuden ja μ-opioidireseptorin välillä. Erityisesti ujous ja taipumus tuntea itsensä turvattomaksi vieraiden ihmisten seurassa sekä kyky selvitä stressistä olivat yhteydessä μ-opioidireseptoriin. Lisäksi serotoniinin takaisinottajaproteiinin havaittiin olevan yhteydessä μ-opioidireseptoriin tietyillä aivoalueilla, jotka liittyvät mieliala- ja ahdistuneisuushäiriöihin. Näitä löydöksiä voidaan tulevaisuudessa hyödyntää mielenterveyshäiriöiden etiologisessa ja mahdollisesti ennaltaehkäisevässä tutkimuksessa.Siirretty Doriast

Beyond Screen Time : Multidimensionality of Socio-Digital Participation and Relations to Academic Well-Being in Three Educational Phases

This study contributes to the research on the differences in young peoples' approaches to socio-digital participation (SDP). We first investigated the differences in SDP between three samples of Finnish students (i.e., elementary school 6th grade, n = 741; high school 1st year, n = 1317; higher education 1st year, n = 1232) and then looked at how these differences are associated with academic well-being. We used exploratory structural equation modeling to investigate the factor structure of SDP and further structural relations to study engagement and study burnout. Despite some differences between the three student cohorts regarding the factor structure of SDP, the same five dimensions of participation were identified in all of them: social networking oriented participation, knowledge-oriented participation, media-oriented participation, action gaming, and social gaming. In the high school sample also a sixth factor, blogging-oriented participation, differentiated from the knowledgeoriented dimension. Taken together, using digital technologies to communicate and maintain social networks (social networking), was consistently either related to lower study engagement or to higher study burnout. Playing of action and sports games (action gaming) was related in all samples either to lower engagement or higher cynicism. Using digital tools to gain and share knowledge (knowledge-oriented) was, in contrast, related to higher study engagement. The results demonstrate that students' digital activities reflect multiple dimensions that are differently related to academic well-being. This study sheds light on the complexity of young peoples' SDP orientations and their related outcomes such as socio-emotional and motivational functioning.Peer reviewe

Is Student Motivation Related to Socio-digital Participation? : A Person-oriented Approach

5th ICEEPSY International Conference on Education & Educational Psychology in Kyrenia Cyprus (Oct 22-25, 2014)/ guest editors: Zafer Bekirogullari, Melis Minas.There is a hypothesized gap between the technology-mediated practices of adolescents and school, hindering student motivation and well-being. This study examined how students’ school motivation is associated with ICT-use. Previous research has shown that achievement goal orientations are related to students’ academic and emotional functioning. Simultaneously, adolescents engage in various socio-digital activities on a daily basis. Our aim is to integrate these two approaches to examine whether students with different motivational profiles display different patterns of socio-digital participation. The participants were Finnish high school students (N=1342) who filled in a self-report questionnaire assessing school motivation and ICT-use both in and out of school. We examined the structural validity of the measurement model by confirmatory factor analyses, classified the students by latent profile analyses and examined group and gender differences by ANOVAs. Four groups were identified: indifferent, success-oriented, mastery-oriented, and avoidance-oriented. The groups differed in their generalized motivational beliefs and there were meaningful differences in terms of their orientations to socio-digital participation: e.g. indifferent students were more likely to engage in hanging-out and gaming, avoidance-oriented students were the least engaged in academic activities. Also, there were some interesting group × gender interaction effects. We found that students’ indifference towards school is associated with ICT-engagement outside of school (gaming and hanging-out). We conclude that there appears to be evidence of discontinuities between today's schools and their students, raising a question of whether the indifference is the cause or the outcome. Furthermore, the findings raise new insights on achievement goal and gender interaction effects.Peer reviewe

Preoperative brain μ-opioid receptor availability predicts weight development following bariatric surgery in women

Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors leading to postoperative weight loss or weight regain remain elusive. Alterations in the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) systems are associated with obesity and appetite control, and the magnitude of initial brain receptor system perturbation may predict long-term surgical weight loss outcomes. We tested this hypothesis by studying 19 morbidly obese women (mean BMI 40) scheduled to undergo bariatric surgery. We measured their preoperative MOR and D2R availabilities using positron emission tomography with [11C]carfentanil and [11C]raclopride, respectively, and then assessed their weight development association with regional MOR and D2R availabilities at 24-month follow-up. MOR availability in the amygdala consistently predicted weight development throughout the follow-up period, but no associations were found for D2R. This is the first study to our knowledge to demonstrate that neuroreceptor markers prior to bariatric surgery are associated with postoperative weight development. Postoperative weight regain may derive from dysfunction in the opioid system, and weight loss outcomes after bariatric surgery may be partially predicted based on preoperative brain receptor availability, opening up new potential for treatment possibilities

Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery

Obesity is a growing burden to health and the economy worldwide. Obesity is associated with central mu-opioid receptor (MOR) downregulation and disruption of the interaction between MOR and dopamine D-2 receptor (D2R) system in the ventral striatum. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying 20 healthy non-obese and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability were measured using positron emission tomography (PET) with [C-11]carfentanil and [C-11]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed on obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. In the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but the unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss. Bariatric surgery and concomitant weight loss recover the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioral interventions for treating obesity

Impairment in acquisition of conditioned fear in schizophrenia

Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. To address this issue, we pooled data from four independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) to stimuli that were paired (the CS + ) or not paired (CS−) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS + vs. CS− SCRs) and responses to CS + and CS− separately were assessed. We found that acquisition of differential conditioned fear responses was significantly lower in individuals with schizophrenia than in healthy controls (Cohen’s d = 0.53). This effect was primarily related to a significantly higher response to the CS− stimulus in the schizophrenia compared to the control group. Moreover, the magnitude of this response to the CS− in the schizophrenia group was correlated with the severity of delusional ideation (p = 0.006). Other symptoms or antipsychotic dose were not associated with fear conditioning measures. In conclusion, individuals with schizophrenia who endorse delusional beliefs may be over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of abnormal associative learning in psychosis

Opioid Release after High-Intensity Interval Training in Healthy Human Subjects

Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant effective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [11C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest. Mood was measured repeatedly throughout the experiment. HIIT significantly decreased MOR binding selectively in the frontolimbic regions involved in pain, reward, and emotional processing (thalamus, insula, orbitofrontal cortex, hippocampus, and anterior cingulate cortex). Decreased binding correlated with increased negative emotionality. Moderate-intensity exercise did not change MOR binding, although increased euphoria correlated with decreased receptor binding. These observations, consistent with endogenous opioid release, highlight the role of the μ-opioid system in mediating affective responses to high-intensity training as opposed to recreational moderate physical exercise

Segmentation of Striatal Brain Structures from High Resolution PET Images

We propose and evaluate an automatic segmentation method for extracting striatal brain structures (caudate, putamen, and ventral striatum) from parametric 11C-raclopride positron emission tomography (PET) brain images. We focus on the images acquired using a novel brain dedicated high-resolution (HRRT) PET scanner. The segmentation method first extracts the striatum using a deformable surface model and then divides the striatum into its substructures based on a graph partitioning algorithm. The weighted kernel k-means algorithm is used to partition the graph describing the voxel affinities within the striatum into the desired number of clusters. The method was experimentally validated with synthetic and real image data. The experiments showed that our method was able to automatically extract caudate, ventral striatum, and putamen from the images. Moreover, the putamen could be subdivided into anterior and posterior parts. An automatic method for the extraction of striatal structures from high-resolution PET images allows for inexpensive and reproducible extraction of the quantitative information from these images necessary in brain research and drug development

Aerobic exercise modulates anticipatory reward processing via the mu-opioid receptor system

Physical exercise modulates food reward and helps control body weight. The endogenous mu-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [C-11]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control

Cerebral grey matter density is associated with neuroreceptor and neurotransporter availability: A combined PET and MRI study

Positron emission tomography (PET) can be used for in vivo measurement of specific neuroreceptors and transporters using radioligands, while voxel-based morphometric analysis of magnetic resonance images allows automated estimation of local grey matter densities. However, it is not known how regional neuroreceptor or transporter densities are reflected in grey matter densities. Here, we analyzed brain scans retrospectively from 328 subjects and compared grey matter density estimates with neuroreceptor and transporter availabilities. µ-opioid receptors (MORs) were measured with [11C]carfentanil (162 scans), dopamine D2 receptors with [11C]raclopride (92 scans) and serotonin transporters (SERT) with [11C]MADAM (74 scans). The PET data were modelled with simplified reference tissue model. Voxel-wise correlations between binding potential and grey matter density images were computed. Regional binding of all the used radiotracers was associated with grey matter density in region and ligand-specific manner independently of subjects’ age or sex. These data show that grey matter density and MOR and D2R neuroreceptor / SERT availability are correlated, with effect sizes (r2) ranging from 0.04 to 0.69. This suggests that future studies comparing PET outcome measure different groups (such as patients and controls) should also analyze interactive effects of grey matter density and PET outcome measures