Neuroticism Associates with Cerebral in Vivo Serotonin Transporter Binding Differently in Males and Females

Background: Neuroticism is a major risk factor for affective disorders. This personality trait has been hypothesized to associate with synaptic availability of the serotonin transporter, which critically controls serotonergic tone in the brain. However, earlier studies linking neuroticism and serotonin transporter have failed to produce converging findings. Because sex affects both the serotonergic system and the risk that neuroticism poses to the individual, sex may modify the association between neuroticism and serotonin transporter, but this question has not been investigated by previous studies. Methods: Here, we combined data from 4 different positron emission tomography imaging centers to address whether neuroticism is related to serotonin transporter binding in vivo. The data set included serotonin transporter binding potential values from the thalamus and striatum and personality scores from 91 healthy males and 56 healthy females. We specifically tested if the association between neuroticism and serotonin transporter is different in females and males. Results: We found that neuroticism and thalamic serotonin transporter binding potentials were associated in both males and females, but with opposite directionality. Higher neuroticism associated with higher serotonin transporter binding potential in males (standardized beta 0.292, P = .008), whereas in females, higher neuroticism associated with lower serotonin transporter binding potential (standardized beta -0.288, P = .014). Conclusions: The finding is in agreement with recent studies showing that the serotonergic system is involved in affective disorders differently in males and females and suggests that contribution of thalamic serotonin transporter to the risk of affective disorders depends on sex.Peer reviewe

The Center for Integrated Molecular Brain Imaging (Cimbi) database

AbstractWe here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank

Serotonergic modulation of suicidal behaviour : integrating preclinical data with clinical practice and psychotherapy

Many studies have provided important information regarding the anatomy, development and functional organization of the 5-HT system and the alterations in this system that are present within the brain of the suicidal patient. There is also a growing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits that prove to be long-term predictors of suicidal behaviour. This review will focus on presenting the scientific literature on the role of the serotonergic system in suicidal behaviour as well as dysfunctional attitudes and personality traits associated with the suicidal patient. The association of the serotonin transporter gene, the 5-HT2 receptors and its metabolite 5-hydroxyindoleacetic acid with suicidal behaviour and animal models that may capture the complexity of suicidal behaviour will be discussed. Finally, the relationship between neurobiological models and psychotherapeutic interventions for suicide prevention will be considered with a focus on Schema Therapy (an approach that has shown particular promise in the treatment of suicidal individuals with personality disorders), aiming to invite the reader to integrate some aspects of the neurobiology of human suicidal behaviour into a model of suicide that can be used in a clinical encounter.peer-reviewe

Association of COMT, BDNF and 5-HTT functional polymorphisms with personality characteristics.

Background: The real impact of genetic factors on personality is still unknown, even if in literature about 50% of variance in personality traits are considered genetically determined. The determination of the genetic variance in personality traits could promote psychological well-being and the prevention of psychopathologies, because there are many experimental evidences showing that mental illness is associated to personality. Numerous studies have showed that Catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF) and serotonin transporter (5-HTT) are genes whose variants are associated with personality traits. This aim of this study is the investigation of the association between personality traits and 5-HTTLPR/rs255315-HTT promoter variant, COMT Val158Met and BDNF Val66Met gene polymorphisms. Methods: The sample was composed by 132 healthy female students. Genomic DNA was extracted from buccal swab, while personality was assessed with Cloninger's Temperament and Character Inventory-Revised (TCI-R). Linear discriminant analysis was used to analyze how personality characteristics can differentiate individuals in relation to their genetic polymorphisms. Results: Data showed that the temperament trait Reward Dependence discriminated individuals with different BDNF variants; Novelty Seeking and Harm Avoidance discriminated individuals with different 5HTTLPR variants; Persistence discriminated individuals with different COMT variants. Conclusions: Since these traits are connected to psychological diseases as depression, social anxiety, anorexia and obsessive-compulsive disorders of personality, the study of their genetic component can be used as intermediary issue to better define the connection between genes and predisposition toward maladaptive behavior and mental illness

Depressiooni ja ärevusega seotud geenivariandid: mõju isiksuseomadustele ja tervistmõjustavale käitumisele

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Varasemate uuringute põhjal on teada, et mõned isiksuseomadused suurendavad depressiooni tekkimise riski. Nii isiksuseomadustel kui ka depressioonil on aga tugev pärilik taust ja osa geneetilisest alusest arvatakse neil olevat ühine. Kummagi fenotüübi geneetilist ülesehitust ei ole veel suudetud tuvastada. Käesoleva väitekirja eesmärgiks oli uurida suurel rahvastiku suhtes representatiivsel valimil, kuidas on seotud neurotransmissiooni mõjustavad depressiooni kandidaatgeenide variandid 5-HTTLPR, BDNF Val66Met, COMT Val158Met ja TPH2 G-703T isiksuseomadustega. Lisaks uurisime ka geenidevahelisi interaktsioone, vanuse ja soo mõju ning seoseid teiste tervise ja heaolu teguritega. Leidsime, et kõik nimetatud kandidaatgeenid tõepoolest mõjutavad isiksuseomadusi rahvastikus. COMT genotüüp avaldab mõju Neurootilisusele, ehk kalduvusele liigselt muretseda ja ärevust tunda. BDNF ja TPH2 mõjutavad aga Meelekindlust, inimese kalduvust olla kohusetundlik, täpne ja distsipliineeritud. Ilmnes ka 5-HTTLPR polümorfismi moduleeriv roll genotüübi ja Meelekindluse seostes. Samuti leidsime, et nii TPH2 kui COMT genotüüpide mõju Neurootilisusele oli sõltuv uuritavate vanusest. Kuigi me ei leidnud nimetatud geenivariantide seoseid ärevus- ja meeleoluhäiretega, peegeldub mõju isiksusele ka teistes inimese tervise ja heaoluga seotud tegurites. Näiteks BDNF polümorfism avaldab mõju söömishäirete sümptomaatika tekkimisel ning COMT mõjutab depressiivsuse taset, haridusteed ja hinnanguid sotsiaalmajanduslikule staatusele. Käitumisgeneetika valdkonna ummikseis isiksuseomaduste geneetiliste aluste tuvastamisel viitab erinevatele moduleerivatele mõjuteguritele geeniefektide avaldumisel. Väitekirjas käsitletud suure rahvastikupõhise uuringu tulemuste põhjal rõhutame soo, vanuse ja geenidevahelise interaktsiooni arvestamise olulisust genotüüpide mõju uurimisel väga mitmetahulistele fenotüüpidele.Previous findings have indicated that some personality traits are increasing the risk for depression. Personality traits and depression are both to a significant extent heritable and are considered to share some of the genetic components. Unraveling the genetic basis of these phenotypes has proven to be difficult. The purpose of this dissertation was to study the effects of several depression-related gene variants, 5-HTTLPR, BDNF Val66Met, COMT Val158Met and TPH2 G-703T, on personality traits in a large population representative sample. In addition, we aimed to study gene × gene interactions, time and sex as possible modulators, and furthermore, to assess if there are any genotype effects on other health-related behaviours. Indeed, we found that all candidate genes under investigation had influence on personality traits. The COMT genotype was affecting Neuroticism, a trait for excessive worrying and anxiety. The main effects of BDNF and TPH2 gene variants were on Conscientiousness, a trait for dutifulness, precision and self-discipline. In addition, these genotype effects on Conscientiousness were modulated by the 5-HTTLPR polymorphism. Also we found the effects of TPH2 and COMT on Neuroticism to be age-dependent. Although we did not find any genotype effects on the history of mood and anxiety disorders, there were associations with health-related behaviour. We found the BDNF polymorphism to affect the emergence of eating disorder symptoms and COMT polymorphism to influence depressiveness, educational attainment, and also socioeconomic status assessment. The difficulties in unraveling the genetic foundations of personality traits suggest a large number of additional factors, which may modulate the emergence of genotype effects. With these results on a large population representative study, we highlight the significance of considering time, sex and gene × gene interactions as possible modulators of genotype effects

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

Lifetime use of psychedelics is associated with better mental health indicators during the COVID-19 pandemic

Background and aimsThe COVID-19 pandemic and its consequences represent a major challenge to the mental health and well-being of the general population. Building on previous work on the potential long-term benefits of psychedelics, we hypothesized that lifetime use of these drugs could be linked to better mental health indicators in the context of the ongoing pandemic.MethodsTwo anonymous online surveys were conducted between April and June 2020, including questions about lifetime experience with psychedelics and other psychoactive drugs, and psychometric scales designed to measure personality traits, anxiety, negative, and positive affect, well-being, and resilience. Principal component analysis was applied to divide the sample into groups of subjects based on their drug use reports.ResultsFive thousand six hundred eighteen participants (29.15 ± 0.12 years, 71.97% female) completed both surveys and met the inclusion criteria, with 32.43% of the sample reporting at least one use of a psychedelic drug. Preliminary analyses showed that certain psychedelics were linked to improved mental health indicators, while other psychoactive drugs exhibited the opposite behavior. Lifetime psychedelic use was linked to increased openness and decreased conscientiousness, and to higher scores of positive affect. The reported number of past psychedelic experiences predicted higher scores of the secondary personality trait beta factor, which has been interpreted as a measure of plasticity. No significant associations between lifetime use of psychedelics and indicators of impaired mental health were observed.ConclusionWe did not find evidence of an association between lifetime use of psychedelics and poor mental health indicators. Conversely, experience with psychedelic drugs was linked to increased positive affect and to personality traits that favor resilience and stability in the light of the ongoing crisis.Fil: Cavanna, Federico Amadeo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Pallavicini, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Milano, Virginia. No especifíca;Fil: Cuiule, Juan. No especifíca;Fil: Di Tella, Rocco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: González, Pablo. No especifíca;Fil: Tagliazucchi, Enzo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad Adolfo Ibañez; Chil

The neurobiology of openness as a personality trait

Openness is a multifaceted behavioral disposition that encompasses personal, interpersonal, and cultural dimensions. It has been suggested that the interindividual variability in openness as a personality trait is influenced by various environmental and genetic factors, as well as differences in brain functional and structural connectivity patterns along with their various associated cognitive processes. Alterations in degree of openness have been linked to several aspects of health and disease, being impacted by both physical and mental health, substance use, and neurologic conditions. This review aims to explore the current state of knowledge describing the neurobiological basis of openness and how individual differences in openness can manifest in brain health and disease

Acute responsivity of the serotonergic system to S-citalopram and positive emotionality : the moderating role of the 5-HTTLPR

According to the idea that the central serotonergic system has a modulatory function on behavior and personality in general, we aimed to highlight its association to habitual positive emotionality. In a placebo-controlled double-blind and randomized cross-over neuroendocrine challenge design (n = 72 healthy males) we investigated the association of the central serotonergic responsivity, 5-HTTLPR-genotype as well as their combined effects on positive emotionality. Regression analyses revealed an involvement of the serotonergic system in positive emotionality. There was, however, no direct association between positive emotionality and cortisol responses to S-citalopram; rather 5-HTTLPR-genotype showed an association (p < 0.05). That is, positive emotionality scores increased with the number of s-alleles carried by the individuals. Most notable was the moderating role of 5-HTTLPR-genotype (p < 0.05) on the association between acute serotonergic responsivity and positive emotionality. Indeed, this association was only found in ss-homozygotes, in which the acute responsivity of the serotonergic system additionally seems to contribute to the level of positive emotionality (r = 0.70, p < 0.05). The findings correspond to previous research demonstrating that the 5-HTTLPR is not only involved in the negative-emotional aspects of behavior and temperament, but is associated, moreover, with positive affectivity—supporting the assumption of its valence-neutrality. In addition, our data are in line with the idea of possible influences of the 5-HTTLPR-genotype on early neuronal development. They also indicate the need for further studies in order to clearly elucidate the role of the serotonergic system and its subcomponents in the regulation of positive emotionality