Modulatory effects of ayahuasca on personality structure in a traditional framework.

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth. RATIONALE: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration. OBJECTIVES: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists. METHOD: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca). RESULTS: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism. CONCLUSIONS: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Spatiotemporal brain activation pattern following acute citalopram challenge is dose dependent and associated with neuroticism: A human phMRI study.

BACKGROUND: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram. METHODS: During the study, 7.5 mg i.v. citalopram was administered to 32 healthy subjects. In addition, 11.25 mg citalopram was administered to a subset of 9 subjects to investigate the dose-response. Associations with neuroticism (assessed by the NEO PI-R) of the emerging brain activation to citalopram was also investigated. RESULTS: Citalopram challenge evoked significant activation in brain regions that are part of the default mode network, the visual network and the sensorimotor network, extending to the thalamus, and midbrain. Most effects appeared to be dose-dependent and this was statistically significant in the middle cingulate gyrus. Individual citalopram-induced brain responses were positively correlated with neuroticism scores and its subscales in specific brain areas; anxiety subscale scores in thalamus and midbrain and self-consciousness scores in middle cingulate gyrus. There were no sex differences. LIMITATIONS: We investigated only healthy subjects and we used a relatively low sample size in the 11.25 mg citalopram analysis. DISCUSSION: Our results suggest that SSRIs acutely induce an increased arousal-like state of distributed cortical and subcortical systems that is mediated by enhanced serotonin neurotransmission according to levels of neuroticism and underpins trait sensitivity to environmental stimuli and stressors. Studies in depression are needed to determine how therapeutic effects eventually emerge. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.

Human anxiety-specific "theta" occurs with selective stopping and localizes to right inferior frontal gyrus.

Anxiety disorders have high prevalence and generate major disability. But they have poor treatment targeting because psychiatry lacks diagnostic biomarkers. Right frontal goal-conflict-specific-rhythmicity (GCSR) in the simple stop signal task appears homologous to hippocampal "theta" as an anxiety-process biomarker but is weak and transient. An anticipatory response inhibition task (ARIT) elicits strong subjective conflict and so might generate stronger GCSR. Healthy participants provided EEG during an ARIT, which allowed direct comparison of selective (left, SG; right, GS), and nonselective (both, SS) handed stopping. We assessed GCSR as intermediate versus the average of short and long delay stop-specific power. SG produced right frontal 5-12 Hz GCSR that, as in the SST: significantly correlated with trait anxiety and neuroticism; and was sensitive to pregabalin (75 mg), buspirone (10 mg), and perhaps triazolam (0.25 mg). GS and SS produced faster stopping and only 9-10Hz GCSR, which did not correlate significantly with trait anxiety or neuroticism and was sensitive to pregabalin and buspirone but not triazolam. Source localization suggested that GCSR, like stopping, involves multiple right frontal circuits that depend on response speed. Anxiolytic-sensitive GCSR generalizes from the speeded stop signal task to fixed-time anticipatory response inhibition tasks. GCSR, and the circuits engaged, vary with stop signal RTs conditions. Tasks with longer stop times may be optimal to generate GCSR homologous with rodent hippocampal theta as (a) the first direct anchor of a specific neural form of trait anxiety; (b) a single-dose screen in normal humans for novel anxiolytics; and (c) a potential clinical anxiety biomarker. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Personality as a Predictor of Treatment Response to Escitalopram in Adults With Body Dysmorphic Disorder.

OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the first-line pharmacotherapy for body dysmorphic disorder (BDD), a common and severe disorder. However, predictors and correlates of treatment response are not well understood. A closer examination of baseline personality dimensions and disorders and of changes in personality during SRI treatment is needed to advance knowledge of this clinically important issue. METHOD: We conducted a secondary analysis of data from a pharmacotherapy relapse prevention trial of the SRI escitalopram in adults with BDD to examine personality dimensions and traits, as well as whether these variables predict and correlate with treatment response. A total of 65 participants with BDD completed the Revised NEO Personality Inventory (NEO PI-R) before starting open-label treatment with escitalopram and 42 participants completed the NEO PI-R after treatment. RESULTS: At baseline, participants with BDD displayed higher levels of neuroticism and lower levels of extraversion than a normed reference group. Higher baseline neuroticism was a significant predictor of nonresponse to escitalopram treatment, even when baseline depression severity was controlled for. Changes in neuroticism were not associated with treatment response. CONCLUSION: Our findings underscore the relationship between BDD and neuroticism, and they suggest a link between neuroticism and SRI treatment response.

A randomized placebo-controlled trial examining the effects of escitalopram on neuroticism and state anxiety in a nonclinical sample.

OBJECTIVE: This study reanalyzed data from a randomized placebo-controlled trial that failed to find an effect of the selective serotonin reuptake inhibitor escitalopram on neuroticism and state anxiety in a nonclinical sample. The purpose was to test for unique effects on two neuroticism factors, trait anxiety and mood instability, and to explore whether neuroticism moderated the effect of escitalopram on state anxiety. METHODS: The sample included 80 adults who had a first-degree relative with major depression but without any psychiatric disorders themselves. Participants were randomized to escitalopram 10 mg/day or placebo for 4 weeks. Neuroticism was assessed with the Eysenck Personality Questionnaire (EPQ) and state anxiety with the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The main effects on the neuroticism factors were not statistically significant, although there was a significant interaction such that the effect of escitalopram compared with placebo on HAM-A scores was statistically significant in participants with higher levels of EPQ trait anxiety, even after controlling for baseline HAM-A scores. A similar interaction with EPQ mood instability was nonsignificant. CONCLUSION: A potential beneficial effect of escitalopram on neuroticism may be driven by reductions in anxiety.

The effect of testosterone therapy on personality traits of trans men: a controlled prospective study in Germany and Switzerland.

Gender dysphoria in transgender men is generally treated with exogenous testosterone administration aiming to suppress secondary female sex characteristics and achieve masculinization. However, the effect of testosterone on the personality of transgender men remains largely unknown. Therefore, we conducted a controlled study with 23 trans men (M = 27.2 years, Range = 18-51 years), recruited from internet-groups, medical and psychiatric services in Switzerland and Germany versus 27 cisgender women matched by age as control group. Data were collected prior to hormone therapy (HT), three and six months after the first treatment. Non-pathological personality traits (Big Five) were measured with the revised NEO-Personality-Inventory (NEO-PI-R). The greatest changes in the Big Five and its subdimensions occurred within the first three months. Interaction effects showed a significant decrease in the dimension Neuroticism (p < 0.01) - with the most relevant decline in its facet Depression - conversely, Extraversion (p < 0.001) increased, in particular, within its facets of Assertiveness (p < 0.01) and Warmth (p < 0.01). Expectedly, personality traits were stable in the control group. An overall decrease in interpersonal stress-related traits and a substantial increase in enhanced social-interaction traits and personal well-being occurred. These results enable medical services to ensure that informed-consent prior to HT is evidence-based with respect to potential changes in personality and may reduce concerns of trans men and their significant others regarding increased aggressiveness.

Neuroticism predicts the impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex.

The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroticism scores influence the neural response to negative emotional faces and their sensitivity to serotonergic tone. Twenty healthy participants performed an emotional face task under functional MRI on three occasions: increased serotonin tone following infusion of a selective serotonin reuptake inhibitor (SSRI), decreased serotonin tone following acute tryptophan depletion (ATD) protocol, and no serotonin challenge (control). During the task, participants performed a gender-discrimination task of neutral, fearful or angry facial expressions. Individual variations in neuroticism scores were associated with neural response of subgenual anterior cingulate cortex to fearful facial expressions. The association was however opposite under the two serotoninergic challenges. The fear-related response in this region and individual neuroticism scores correlated negatively during citalopram challenge and positively during ATD. Thus, neuroticism scores were associated with the relative impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex. This finding may link to a neural mechanism for the variable therapeutic effect of SSRI treatment observed in clinical populations.

Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts.

There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, ß = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, ß = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.

Effects of psilocybin therapy on personality structure.

OBJECTIVE: To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment-resistant depression (TRD). METHOD: Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3-month follow-up using the Revised NEO Personality Inventory (NEO-PI-R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS-SR16. RESULTS: Neuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO-PI-R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend-level increases, and Agreeableness did not change. CONCLUSION: Our observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.

Benefits and limitations of drug studies in temperament research: biochemical responses as indicators of temperament.

This paper presents a discussion of principles and problems of neurotransmitter challenge tests using examples of experiments, most of which were performed in the author's laboratory. Drugs targeting synthesis, release, receptors or reuptake of dopamine, serotonin and noradrenergic transmitter (TM) systems were used for characterizing or discriminating certain temperament or personality traits and their sub-factors. Any personality or temperament trait is characterized by multiple TM responses, thus constellations of hormone responses to drugs acting on different TM systems or on different sources of TM activity were investigated within individuals in crossover designs. The major conclusions are: (i) intra-individual patterns of hormone responses to different TM-related drugs, or to agonists and antagonists, can help to discriminate subtypes of temperament dimensions, and (ii) the latency and shape of response curves may help specify processes of biological responses related to psychological dimensions and reveal common TM sensitivities in clusters of traits. TM sensitivity, defined by hormone responses, does not always correspond to accompanying behavioural indicators, but may provide more specific information on underlying mechanisms. Additional consideration of drug doses and experimental induction of stressors may serve to identify temperament-related susceptibilities to certain drugs. Limitations of the challenge approach and recommendations for future research are discussed.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy.

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.

Psychological symptomatology and impaired prepulse inhibition of the startle reflex are associated with cannabis-induced psychosis.

BACKGROUND: Cannabis-induced psychotic disorder (CIPD) is a psychiatric disorder induced by cannabis consumption. The psychological and psychophysiological features of this disorder are still unknown. We aimed to examine the psychological, personality and psychophysiological features of patients with CIPD. This study is an analytical extension of our previously published data, which previously found prepulse inhibition (PPI) deficits in the CIPD group used in this current paper. METHODS: We used a sample of 45 patients with CIPD. After 9 months of follow up, these patients were assessed with a Symptom Checklist-90-R (SCL-90-R) questionnaire of psychopathology, with the Eysenck Personality Questionnaire, and with a psychophysiological paradigm of inhibition of the startle reflex (PPI). These results were compared with a group of patients with schizophrenia and cannabis abuse (SCHZ) ( n = 54); patients with cannabis dependence (CD) ( n = 21); and healthy controls ( n = 50). RESULTS: CIPD patients obtained significant higher scores in the SCL-90-R subscale of neuroticism. These patients showed PPI percentages similar to SCHZ patients within early attentional levels (30 ms). The variables with greater correlation, and that appeared in the CIPD group were interpersonal sensitivity, depression and phobia. CONCLUSIONS: Neurotic symptomatology and difficulties in inhibition of the startle reflex might be risk factors for developing CIPD.

Clinical characteristics of latent classes of CO2 hypersensitivity in adolescents and young adults.

Although breathing CO2-enriched air reliably increases anxiety, there is debate concerning the nature and specificity of CO2 hypersensitivity to panic risk and panic disorder versus anxiety disorders and related traits broadly, particularly among adolescents and emerging adults. The present study sought to clarify the association of CO2 hypersensitivity with internalizing conditions and symptoms among adolescents and young adults. Participants (N = 628) self-reported anxiety levels every 2 min while breathing air enriched to 7.5% CO2 for 8 min. Growth mixture models were used to examine the structure of anxiety trajectories during the task and the association of each trajectory with dimensional and diagnostic assessments of internalizing disorders. Three distinct trajectories emerged: overall low (low), overall high (high), and acutely increased anxiety (acute). Compared to the low class, the acute class reported elevated neuroticism, anxiety sensitivity, and stress whereas the high class reported elevated anxiety symptoms, depression symptoms, neuroticism, anxiety sensitivity, and increased likelihood of an anxiety disorder diagnosis. Moreover, the acute and high classes reported experiencing a panic-like event at a higher rate than the low class while participants in the high class terminated the task prematurely at a higher rate. The present study clarifies the nature of response to CO2 challenge. Three distinct response profiles emerged, which clarifies the manifestation of CO2 hypersensitivity in anxiety disorders with strong, though not unique, associations with panic-relevant traits.