Emotional faces processing in major depressive disorder and prediction of antidepressant treatment response: A NeuroPharm study.

BACKGROUND: Major depressive disorder (MDD) is a prevalent neuropsychiatric illness for which it is important to resolve underlying brain mechanisms. Current treatments are often unsuccessful, precipitating a need to identify predictive markers. AIM: We evaluated (1) alterations in brain responses to an emotional faces functional magnetic resonance imaging (fMRI) paradigm in individuals with MDD, compared to controls, (2) whether pretreatment brain responses predicted antidepressant treatment response, and (3) pre-post change in brain responses following treatment. METHODS: Eighty-nine medication-free, depressed individuals and 115 healthy controls completed the fMRI paradigm. Depressed individuals completed a nonrandomized, open-label, 8-week treatment with escitalopram, including the option to switch to duloxetine after 4 weeks. We examined patient-control group differences in regional fMRI responses at baseline, whether baseline fMRI responses predicted treatment response at 8 weeks, including early life stress moderating effects, and change in fMRI responses in 36 depressed individuals rescanned following 8 weeks of treatment. RESULTS: Task reaction time was 5% slower in patients. Multiple brain regions showed significant task-related responses, but we observed no statistically significant patient-control group differences (Cohen's d < 0.35). Patient pretreatment brain responses did not predict antidepressant treatment response (area under the curve of the receiver operator characteristic (AUC-ROC) < 0.6) and brain responses were not statistically significantly changed after treatment (Cohen's d < 0.33). CONCLUSION: This represents the largest prediction study to date examining emotional faces fMRI features as predictors of antidepressant treatment response. Brain response to this fMRI emotional faces paradigm did not distinguish depressed individuals from healthy controls, nor was it predictive of antidepressant treatment response.Clinical Trial Registration: Site: https://clinicaltrials.gov, Trial Number: NCT02869035, Trial Title: Treatment Outcome in Major Depressive Disorder.

Paths to postsecondary education enrollment among adolescents with and without childhood attention-deficit/hyperactivity disorder (ADHD): A longitudinal analysis of symptom and academic trajectories.

We examined developmental trajectories of attention-deficit/hyperactivity disorder (ADHD) symptoms, standardized achievement, and school performance for adolescents with and without ADHD who did and did not enroll in postsecondary education (PSE; N = 749; 79% boys; 63% White, 17% non-Hispanic Black, 10% Hispanic, and 10% other ethnicities). In a multisite study (recruitment based in New York, North Carolina, Pennsylvania, California, and Quebec), participants were originally enrolled between 1994 and 1998 at ages 7 to 9.9 and followed up through 2012 (Mage = 25 at final follow-up). Adolescents who eventually enrolled in PSE had less severe symptoms, but differences were modest and trajectories were similar over time. For all adolescents, standardized achievement trajectories declined up to two thirds of a standard deviation from ages 9 to 17. By the end of high school, the average GPA of adolescents with ADHD was three quarters of a point higher for those who eventually enrolled in PSE compared to those who did not. Overall, school performance mattered more than academic achievement for understanding eventual enrollment of adolescents with ADHD.

Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD.

OBJECTIVE: It is estimated that childhood attention deficit hyperactivity disorder (ADHD) remits by adulthood in approximately 50% of cases; however, this conclusion is typically based on single endpoints, failing to consider longitudinal patterns of ADHD expression. The authors investigated the extent to which children with ADHD experience recovery and variable patterns of remission by adulthood. METHODS: Children with ADHD (N=558) in the Multimodal Treatment Study of ADHD (MTA) underwent eight assessments over follow-ups ranging from 2 years (mean age, 10.44 years) to 16 years (mean age, 25.12 years) after baseline. The authors identified participants with fully remitted, partially remitted, and persistent ADHD at each time point on the basis of parent, teacher, and self-reports of ADHD symptoms and impairment, treatment utilization, and substance use and mental disorders. Longitudinal patterns of remission and persistence were identified that considered context and timing. RESULTS: Approximately 30% of children with ADHD experienced full remission at some point during the follow-up period; however, a majority of them (60%) experienced recurrence of ADHD after the initial period of remission. Only 9.1% of the sample demonstrated recovery (sustained remission) by study endpoint, and only 10.8% demonstrated stable ADHD persistence across study time points. Most participants with ADHD (63.8%) had fluctuating periods of remission and recurrence over time. CONCLUSIONS: The MTA findings challenge the notion that approximately 50% of children with ADHD outgrow the disorder by adulthood. Most cases demonstrated fluctuating symptoms between childhood and young adulthood. Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in MTA continued to experience residual symptoms into young adulthood.

Default mode network functional connectivity negatively associated with trait openness to experience.

Evaluating associations between the five-factor personality domains and resting-state functional connectivity networks (e.g. default mode network, DMN) highlights distributed neurobiological systems linked to behaviorally relevant phenotypes. Establishing these associations can highlight a potential underlying role for these neural pathways in related clinical illness and treatment response. Here, we examined associations between within- and between-network resting-state functional connectivity with functional magnetic resonance imaging and the five-factor personality domains: Openness to experience (Openness), Extraversion, Neuroticism, Agreeableness and Conscientiousness. We included data from 470 resting-state scan sessions and personality assessments in 295 healthy participants. Within- and between-network functional connectivity from 32 a priori defined regions was computed across seven resting-state networks. The association between functional connectivity and personality traits was assessed using generalized least squares. Within-network DMN functional connectivity was significantly negatively associated with trait Openness (regression coefficient = -0.0010; [95% confidence interval] = [-0.0017, -0.0003]; PFWER = 0.033), seemingly driven by association with the Fantasy subfacet. Trait Extraversion was significantly negatively associated with functional connectivity between the visual and dorsal attention networks and positively associated with functional connectivity between the frontoparietal and language networks. Our findings provide evidence that resting-state DMN is associated with trait Openness and gives insight into personality neuroscience.

A high-resolution in vivo atlas of the human brain's benzodiazepine binding site of GABAA receptors.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. For decades, several in vivo and ex vivo techniques have been used to highlight the mechanisms of the GABA system, however, no studies have currently combined the techniques to create a high-resolution multimodal view of the GABA system. Here, we present a quantitative high-resolution in vivo atlas of the human brain benzodiazepine receptor sites (BZR) located on postsynaptic ionotropic GABAA receptors (GABAARs), generated on the basis of in vivo [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on ex vivo autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association between BZR protein density and ex vivo mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.

Editorial: The Vanishing Value of Evidence-based Treatments: Is Our Mental Health Expertise Irrelevant?

The article in this issue of JAACAP by the CAMELS (Child/Adolescent Anxiety Multimodal Extended Long-term Study) study team, Peris et al.1, offers 2 very important contributions. Conveniently, the first contribution is also the stated purpose of this report: to present findings detailing the extent to which children and adolescents who previously participated (averaging 6.5 years previously) in the landmark Child and Adolescent Multimodal Study of Anxiety (CAMS) multisite randomized controlled trial (RCT)2 did or did not receive follow-up services. This is not a good-news story. By and large, over the 6-year follow-up, only 35% of the previous RCT-treated children and youth received "consistent" continuing services, either through medication or cognitive-behavioral therapy (CBT), despite ongoing issues of anxiety and significant impairment.

A Qualitative Analysis of Contextual Factors Relevant to Suspected Late-Onset ADHD.

Objective: Recent studies suggest attention-deficit/hyperactivity disorder (ADHD) may emerge post-childhood. We integrate qualitative methods to systematically characterize contextual factors that may (a) delay identification of ADHD in childhood and (b) inform why ADHD symptoms emerge post-childhood. Method: Suspected late-onset ADHD cases from the local normative comparison group of the Multimodal Treatment Study of ADHD completed a qualitative interview (14 young adults and 7 caregivers). Interviews were qualitatively analyzed. Results: We identified five themes. Three themes may attenuate or delay identification of childhood ADHD: external factors (e.g., supportive adults), internal factors (e.g., strong intellectual functioning), and other factors (e.g., dismissive attitudes toward ADHD). Two themes may accompany an increase in ADHD symptoms post-childhood: external factors (e.g., increased external demands) and internal factors (e.g., perceived stress). Conclusion: Clinicians should probe these factors in suspected late-onset cases to address (a) whether, how, and to what extent ADHD was attenuated in childhood and (b) why symptoms emerge post-childhood.

Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels.

The serotonin 2A receptor (5-HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18 F]altanserin and [11 C]Cimbi-36 positron emission tomography (PET) allow for high-resolution imaging of 5-HT2AR in the living human brain. Cerebral 5-HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5-HT2AR or other serotonin (5-HT) proteins, their effect on human in vivo brain 5-HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5-HTTLPR predict neocortex in vivo 5-HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18 F]altanserin or [11 C]Cimbi-36 PET. Although we observed genotype group differences in 5-HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5-HT2AR binding in what is the largest human in vivo 5-HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5-HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5-HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5-HT2AR binding.

Trajectories of Growth Associated With Long-Term Stimulant Medication in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To estimate long-term stimulant treatment associations on standardized height, weight, and body mass index trajectories from childhood to adulthood in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: Of 579 children with DSM-IV ADHD-combined type at baseline (aged 7.0-9.9 years) and 289 classmates (local normative comparison group [LNCG]), 568 and 258 respectively, were assessed 8 times over 16 years (final mean age = 24.7). Parent interview data established subgroups with self-selected Consistent (n = 53, 9%), Inconsistent (n = 374, 66%), and Negligible (n = 141, 25%) stimulant medication use, as well as patients starting stimulants prior to MTA entry (n = 211, 39%). Height and weight growth trajectories were calculated for each subgroup. RESULTS: Height z scores trajectories differed among subgroups (F = 2.22, p < .0001) and by stimulant use prior to study entry (F = 2.22, p < .001). The subgroup-by-assessment interaction was significant (F = 2.81, p < .0001). Paired comparisons revealed significant subgroup differences at endpoint: Consistent was shorter than Negligible (-0.66 z units /-4.06 cm /1.6 inches, t = -3.17, p < 0.0016), Consistent shorter than Inconsistent (-0.45 z units /-2.74 cm /-1.08 inches, t = -2.39, p < .0172), and the Consistent shorter than LNCG (-0.54 z units/+3.34 cm/ 1.31 inches, t = -3.30, p < 0.001). Weight z scores initially diverged among subgroups, converged in adolescence, and then diverged again in adulthood when the Consistent outweighed the LNCG (+ 3.561 z units /+7.47 kg /+16.46 lb, p < .0001). CONCLUSION: Compared with those negligibly medicated and the LNCG, 16 years of consistent stimulant treatment of children with ADHD in the MTA was associated with changes in height trajectory, a reduction in adult height, and an increase in weight and body mass index. CLINICAL TRIAL REGISTRATION INFORMATION: Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); https://clinicaltrials.gov/; NCT00000388.

Psychometric Properties and Validation of the EMOTICOM Test Battery in a Healthy Danish Population.

Disruptions in hot cognition, i.e., the processing of emotionally salient information, are prevalent in most neuropsychiatric disorders and constitute a potential treatment target. EMOTICOM is the first comprehensive neuropsychological test battery developed specifically to assess hot cognition. The aim of the study was to validate and establish a Danish language version and reference data for the EMOTICOM test battery. To evaluate the psychometric properties of 11 EMOTICOM tasks, we collected data from 100 healthy Danish participants (50 males, 50 females) including retest data from 49 participants. We assessed test-retest reliability, floor and ceiling effects, task-intercorrelations, and correlations between task performance and relevant demographic and descriptive factors. We found that test-retest reliability varied from poor to excellent while some tasks exhibited floor or ceiling effects. Intercorrelations among EMOTICOM task outcomes were low, indicating that the tasks capture different cognitive constructs. EMOTICOM task performance was largely independent of age, sex, education, and IQ as well as current mood, personality, and self-reported motivation and diligence during task completion. Overall, many of the EMOTICOM tasks were found to be useful and objective measures of hot cognition although select tasks may benefit from modifications to avoid floor and ceiling effects in healthy individuals.

Maladaptive Aggression: With a Focus on Impulsive Aggression in Children and Adolescents.

Objective: Aggressive behavior is among the most common reasons for referral to psychiatric clinics and confers significant burden on individuals. Aggression remains poorly defined; there is currently no consensus on the best ways to recognize, diagnose, and treat aggression in clinical settings. In this review, we synthesize the available literature on aggression in children and adolescents and propose the concept of impulsive aggression (IA) as an important construct associated with diverse and enduring psychopathology. Methods: Articles were identified and screened from online repositories, including PubMed, PsychInfo, the Cochrane Database, EMBase, and relevant book chapters, using combinations of search terms such as "aggression," "aggressive behavio(u)r," "maladaptive aggression," "juvenile," and "developmental trajectory." These were evaluated for quality of research before being incorporated into the article. The final report references 142 sources, published from 1987 to 2019. Results: Aggression can be either adaptive or maladaptive in nature, and the latter may require psychosocial and biomedical interventions when it occurs in the context of central nervous system psychopathology. Aggression can be categorized into various subtypes, including reactive/proactive, overt/covert, relational, and IA. IA in psychiatric or neurological disorders is reviewed along with current treatments, and an algorithm for systematic evaluation of aggression in the clinical setting is proposed. Conclusions: IA is a treatable form of maladaptive aggression that is distinct from other aggression subtypes. It occurs across diverse psychiatric and neurological diagnoses and affects a substantial subpopulation. IA can serve as an important construct in clinical practice and has considerable potential to advance research.

Introduction: Just Say No? New Insights About Change Versus Constancy in Substance Use Behavioral Decisions in Youth With and Without ADHD.

Despite enormous social-psychological and economic consequences of substance abuse in youth and young adults, too little is known about effective interventions among substance users, both with and without ADHD. This special issue reports on four linked investigations that employed a novel research strategy when the Multimodal Treatment Children with ADHD Study (MTA) participants were between ages 21.7 and 27.3 years old (14-16 years after initial assessments). Using combination of in-depth qualitative narrative interviews and quantitative analyses ("mixed methods") of 183 participants from four to six original MTA sites, investigators sought to obtain a more complete understanding of factors contributing to youths' substance use (SU) initiation, maintenance, and desistence, (both among youth with ADHD and control participants). The articles in this special issue illuminate important new insights about possible influences contributing to SU, particularly persistent use/abuse. Findings also illustrate the benefits of mixed-methods studies, not only to better understand the linkages between ADHD and SU, but also to understand other areas of child/adult psychopathology.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation, Identification, Assessment, and Initial Management.

OBJECTIVES: To update clinical practice guidelines to assist primary care (PC) clinicians in the management of adolescent depression. This part of the updated guidelines is used to address practice preparation, identification, assessment, and initial management of adolescent depression in PC settings. METHODS: By using a combination of evidence- and consensus-based methodologies, guidelines were developed by an expert steering committee in 2 phases as informed by (1) current scientific evidence (published and unpublished) and (2) draft revision and iteration among the steering committee, which included experts, clinicians, and youth and families with lived experience. RESULTS: Guidelines were updated for youth aged 10 to 21 years and correspond to initial phases of adolescent depression management in PC, including the identification of at-risk youth, assessment and diagnosis, and initial management. The strength of each recommendation and its evidence base are summarized. The practice preparation, identification, assessment, and initial management section of the guidelines include recommendations for (1) the preparation of the PC practice for improved care of adolescents with depression; (2) annual universal screening of youth 12 and over at health maintenance visits; (3) the identification of depression in youth who are at high risk; (4) systematic assessment procedures by using reliable depression scales, patient and caregiver interviews, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria; (5) patient and family psychoeducation; (6) the establishment of relevant links in the community, and (7) the establishment of a safety plan. CONCLUSIONS: This part of the guidelines is intended to assist PC clinicians in the identification and initial management of adolescents with depression in an era of great clinical need and shortage of mental health specialists, but they cannot replace clinical judgment; these guidelines are not meant to be the sole source of guidance for depression management in adolescents. Additional research that addresses the identification and initial management of youth with depression in PC is needed, including empirical testing of these guidelines.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management.

OBJECTIVES: To update clinical practice guidelines to assist primary care (PC) in the screening and assessment of depression. In this second part of the updated guidelines, we address treatment and ongoing management of adolescent depression in the PC setting. METHODS: By using a combination of evidence- and consensus-based methodologies, the guidelines were updated in 2 phases as informed by (1) current scientific evidence (published and unpublished) and (2) revision and iteration among the steering committee, including youth and families with lived experience. RESULTS: These updated guidelines are targeted for youth aged 10 to 21 years and offer recommendations for the management of adolescent depression in PC, including (1) active monitoring of mildly depressed youth, (2) treatment with evidence-based medication and psychotherapeutic approaches in cases of moderate and/or severe depression, (3) close monitoring of side effects, (4) consultation and comanagement of care with mental health specialists, (5) ongoing tracking of outcomes, and (6) specific steps to be taken in instances of partial or no improvement after an initial treatment has begun. The strength of each recommendation and the grade of its evidence base are summarized. CONCLUSIONS: The Guidelines for Adolescent Depression in Primary Care cannot replace clinical judgment, and they should not be the sole source of guidance for adolescent depression management. Nonetheless, the guidelines may assist PC clinicians in the management of depressed adolescents in an era of great clinical need and a shortage of mental health specialists. Additional research concerning the management of depressed youth in PC is needed, including the usability, feasibility, and sustainability of guidelines, and determination of the extent to which the guidelines actually improve outcomes of depressed youth.

Turning Points in the Lives of Youth of With/Without ADHD: Are They Linked to Changes in Substance Use?

OBJECTIVE: This study examines the behavior beliefs, social supports, and turning points in individuals with/without ADHD related to their substance use/abuse (SU/A) decisions. METHOD: The coded interviews from 60 participants with/without ADHD were compared for their SU/A decisions and precipitants with these decisions among abstainers, persisters, and desisters. RESULTS: ADHD participants reported fewer social advantages to avoid SU/A than non-ADHD participants. Desisters and persisters reported more social advantages of using drugs than abstainers. Persisters reported both more negative and positive psychological/physiological effects of SU/A. ADHD participants reported fewer positive role models in their lives. Non-ADHD patients reported more positive turning points than ADHD participants, regardless of SU/A status. CONCLUSION: ADHD individuals face challenges in making healthy decisions about SU/A due to lack of positive role models. Reinforcing accurate behavioral beliefs may be important to change behaviors in individuals with SU/A or to prevent SU/A initiation in ADHD individuals.

How Substance Users With ADHD Perceive the Relationship Between Substance Use and Emotional Functioning.

OBJECTIVE: Although substance use (SU) is elevated in ADHD and both are associated with disrupted emotional functioning, little is known about how emotions and SU interact in ADHD. We used a mixed qualitative-quantitative approach to explore this relationship. METHOD: Narrative comments were coded for 67 persistent (50 ADHD, 17 local normative comparison group [LNCG]) and 25 desistent (20 ADHD, 5 LNCG) substance users from the Multimodal Treatment Study of Children with ADHD (MTA) adult follow-up (21.7-26.7 years-old). RESULTS: SU persisters perceived SU positively affects emotional states and positive emotional effects outweigh negative effects. No ADHD group effects emerged. Qualitative analysis identified perceptions that cannabis enhanced positive mood for ADHD and LNCG SU persisters, and improved negative mood and ADHD for ADHD SU persisters. CONCLUSION: Perceptions about SU broadly and mood do not differentiate ADHD and non-ADHD SU persisters. However, perceptions that cannabis is therapeutic may inform ADHD-related risk for cannabis use.

Maternal ADHD Symptoms, Personality, and Parenting Stress: Differences Between Mothers of Children With ADHD and Mothers of Comparison Children.

OBJECTIVE: Mothers raising a child with ADHD can experience high parenting stress. We evaluated if mothers' personality traits and own ADHD symptoms could also affect parenting stress. METHOD: 430 biological mothers from the Multimodal Treatment Study of Children with ADHD (MTA mothers) and 237 of a local normative comparison group (LNCG mothers) were evaluated at baseline. Interactions were tested between mothers' group and maternal personality/ADHD symptoms related to parenting stress. RESULTS: Compared to LNCG, MTA mothers had higher parenting stress, self-reported ADHD, neuroticism, and lower conscientiousness and agreeableness. When personality and ADHD were evaluated together, ADHD symptoms interacted with mothers' group: high maternal ADHD was positively associated with parenting stress for LNCG but not MTA mothers. CONCLUSION: Personality traits or ADHD characteristics do not appear operative for the high parenting stress of mothers of a child with ADHD. However, high maternal ADHD or low conscientiousness are associated with stress levels similar to raising a child with ADHD.

Follow-Up of Young Adults With ADHD in the MTA: Design and Methods for Qualitative Interviews.

OBJECTIVE: Qualitative interviews with 183 young adults (YA) in the follow-up of the Multimodal Treatment Study of Children With and Without ADHD (MTA) provide rich information on beliefs and expectations regarding ADHD, life's turning points, medication use, and substance use (SU). METHOD: Participants from four MTA sites were sampled to include those with persistent and atypically high SU, and a local normative comparison group (LNCG). Respondents were encouraged to "tell their story" about their lives, using a semistructured conversational interview format. RESULTS: Interviews were reliably coded for interview topics. ADHD youth more often desisted from SU because of seeing others going down wrong paths due to SU. Narratives revealed very diverse accounts and explanations for SU-ADHD influences. CONCLUSION: Qualitative methods captured the perspectives of YAs regarding using substances. This information is essential for improving resilience models in drug prevention and treatment programs and for treatment development for this at-risk population.

The Qualitative Interview Study of Persistent and Nonpersistent Substance Use in the MTA: Sample Characteristics, Frequent Use, and Reasons for Use.

OBJECTIVE: To evaluate participants' perceptions about frequent use and reasons for substance use (SU) in the qualitative interview study, an add-on to the multimodal treatment study of ADHD (MTA). METHOD: Using the longitudinal MTA database, 39 ADHD cases and 19 peers with Persistent SU, and 86 ADHD cases and 39 peers without Persistent SU were identified and recruited. In adulthood, an open-ended interview was administered, and SU excerpts were indexed and classified to create subtopics (frequent use and reasons for use of alcohol, marijuana, and other drugs). RESULTS: For marijuana, the Persistent compared with Nonpersistent SU group had a significantly higher percentage of participants describing frequent use and giving reasons for use, and the ADHD group compared with the group of peers had a significantly higher percentage giving "stability" as a reason for use. CONCLUSION: Motivations for persistent marijuana use may differ for adults with and without a history of ADHD.

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.