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.

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.

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.

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.

Defining ADHD symptom persistence in adulthood: optimizing sensitivity and specificity.

OBJECTIVE: Longitudinal studies of children diagnosed with ADHD report widely ranging ADHD persistence rates in adulthood (5-75%). This study documents how information source (parent vs. self-report), method (rating scale vs. interview), and symptom threshold (DSM vs. norm-based) influence reported ADHD persistence rates in adulthood. METHOD: Five hundred seventy-nine children were diagnosed with DSM-IV ADHD-Combined Type at baseline (ages 7.0-9.9 years) 289 classmates served as a local normative comparison group (LNCG), 476 and 241 of whom respectively were evaluated in adulthood (Mean Age = 24.7). Parent and self-reports of symptoms and impairment on rating scales and structured interviews were used to investigate ADHD persistence in adulthood. RESULTS: Persistence rates were higher when using parent rather than self-reports, structured interviews rather than rating scales (for self-report but not parent report), and a norm-based (NB) threshold of 4 symptoms rather than DSM criteria. Receiver-Operating Characteristics (ROC) analyses revealed that sensitivity and specificity were optimized by combining parent and self-reports on a rating scale and applying a NB threshold. CONCLUSION: The interview format optimizes young adult self-reporting when parent reports are not available. However, the combination of parent and self-reports from rating scales, using an 'or' rule and a NB threshold optimized the balance between sensitivity and specificity. With this definition, 60% of the ADHD group demonstrated symptom persistence and 41% met both symptom and impairment criteria in adulthood.

Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression.

BACKGROUND: The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline. METHODS: Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. RESULTS: For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). CONCLUSIONS: In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.

The Center for Integrated Molecular Brain Imaging (Cimbi) database.

We 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.

Treatments and Services Provided to Children Diagnosed with Bipolar Disorder.

To better understand the types and quantity of mental health services and medication usage for youth diagnosed with bipolar disorder (BD) within an integrated healthcare system, medical records were reviewed from 2000 to 2011. Eighty-five youth diagnosed with BD were identified and healthcare services (medication and psychotherapy follow-up appointments, emergency room (ER) visits, admissions, phone contacts) and visit-related details (medication usage) were abstracted for 2 years after initial BD diagnosis. Despite complex medication regimens (91.7 and 81.2 % received mood stabilizers and antipsychotic agents, respectively), medication appointments were infrequent, averaging 1 visit every 2 months. Only 36 (42 %) of 85 youth were noted to receive psychotherapy services following BD diagnosis, also averaging 1 visit every 2 months. Most (58.8 %) patients needed one or more hospitalizations during the follow-up period; nearly half (48.2 %) had psychiatric ER visits. The relative lack of psychotherapy and infrequent follow-up visits suggests need for improvement to optimize healthcare delivery.

Collaboration between Pediatric Primary Care Providers and Child and Adolescent Psychiatrists in Arkansas: Where to Start?.

There is a considerable shortage of child and adolescent psychiatrists (CAPs) in Arkansas. Collaboration between pediatric primary care providers (PCPs) and CPSs is an innovative model of care that may address this shortage. A tiered model of collaboration, ranging from brief speciality consultation to intensive psychiatric services, may help with early treatment and expeansion of available services to a larger population. We describe the current state of collaboration in Arkansas between the two specialties and steps for additional collaboration.

BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels.

Brain-derived neurotrophic factor (BDNF) has been implicated in multiple aspects of brain function including regulation of serotonin signaling. The BDNF val66met polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans but its effects are not well understood. To address this, we evaluated whether BDNF val66met was predictive of a putative marker of brain serotonin levels, serotonin 4 receptor (5-HT4 ) binding assessed with [11C]SB207145 positron emission tomography, which has also been associated with the serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein BDNF val66met significantly predicted a LV reflecting [11C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2-9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative to LL homozygotes (P = 7.3 × 10(-6)). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [11C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5-HTTLPR specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. METHODS: DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. RESULTS: Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). CONCLUSIONS: These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder.

A school-based post-Katrina therapeutic intervention.

The current study presents the implementation of a set of school based interventions in a greater New Orleans school district one year following Hurricane Katrina. The interventions included adaptation and implementation of evidence based treatments in a crisis situation with at-risk youth which involved training and clinical challenges. 386 students found to have significant depressive and/or disruptive disorder symptoms received treatment from the School Therapeutic Enhancement Program (STEP). Further, a district-wide mental health needs assessment of middle and high school students (N = 11,861) screened for behavioral and emotional difficulties at the beginning and end of the school year provided a benchmark for community youth's emotional and behavioral distress. High-need intervention students demonstrated clinically significant lower levels of emotional and behavioral problems, depression and inattention in comparison to pre-treatment levels as indicated by multiple informants (i.e., self, parent, teacher). Self-reported distress levels were also lower than screening group students at post-test. These findings support the efficacy of a school-based intervention for youth struggling with the aftereffects of a highly disruptive natural disaster. Implications for utilizing a flexible adaptation of an evidence-based training model involving coaching and consultation are discussed.

Comparison of discrimination and prognostic value of two US Doppler scoring systems in rheumatoid arthritis patients: a prospective cohort study.

OBJECTIVES: The aim of this paper is to investigate sensitivity to change (SRM), predictive validity and discriminative ability of a quantitative (QS) and a semi-quantitative (SQS) Doppler ultrasound scoring systems in patients with rheumatoid arthritis (RA) treated with anti-TNF-α therapy. METHODS: RA patients with wrist joint affection treated with TNF-α inhibitor were followed for one year. The wrist was examined with Doppler before initiating therapy and after one year. DAS28 was determined at both visits. One person trained in the SQS system and one in the QS system evaluated the anonymised images. The SRM, predictive validity and discriminative ability for both systems were calculated using DAS28 as the measure of disease improvement. RESULTS: Fourty-six patients with RA (80% females) were included. The mean Doppler activity at baseline was QS:24.4% (SD=17.7%) and SQS:2.0 (SD=0.6). A decrease in Doppler activity was seen for both systems after anti-TNF-α therapy. Sensitivity to change was seen, SRM=-0.52 (95%CI; -0.83 to -0.21; QS) and -0.24 (-0.53 to -0.05; SQS). Predictive value was poor (QS rs=-0.24; SQS rs=-0.05). Construct validity was; QS: rs=0.29, SQS: rs=0.23. CONCLUSIONS: Both systems were to some extent sensitive to change. Predictive validity and discriminate capacity of both systems showed only a weak association to DAS 28 in the study population. The QS was a little superior to the SQS. The results do not necessarily reflect Doppler evaluation as being ineffective, but may be caused by DAS28 not being a perfect marker of inflammation.

Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family.

Retinoblastoma is the most common eye cancer in children. It is caused by pathogenic alterations of both alleles of the tumor suppressor gene RB1. In heritable retinoblastoma, a constitutional RB1 variant predisposes the cells to tumor formation, and loss of the other allele is a prerequisite for the development of retinoblastoma. Heritable retinoblastoma is inherited in an autosomal dominant manner; however, the majority of cases are the result of a de novo pathogenic RB1 variant. Penetrance is usually high (>90%), but with marked inter-familial variability. In some families, penetrance is incomplete and family members who develop tumors tend to remain unilaterally affected. Moreover, some families with low penetrance also show a parent-of-origin effect. We describe a patient with unilateral retinoblastoma caused by a previously unreported likely pathogenic RB1 variant (c.1199T>C) that disrupts a highly conserved amino acid residue within the A-box functional domain. Segregation analysis showed that the variant had unusually low penetrance as nine non-affected family members carried the same variant. We emphasize the use of genetic analysis on tumor DNA for classifying the RB1 variant, and underline the challenges in clinical management and counseling of families carrying the specific RB1 variant.

Does a one-day educational training session influence primary care pediatricians' mental health practice procedures in response to a community disaster? Results from the reaching children initiative (RCI).

Although many children and adolescents need assessment and treatment for psychological problems, few get such treatment from mental health specialists after a community disaster Research suggests that a very large proportion of children are seen in pediatric primary care settings and that pediatricians can provide appropriate care for many social and emotional problems in children. However few pediatricians have received training in providing this help. The focus of this study was to assess whether brief training to increase the capacity of primary care pediatricians (PCPs) to respond to the social or emotional problems of children after the World Trade Center terrorist attacks improved the quality of services to disaster-affected children. Pediatricians (N = 137) attended a one-day training workshop covering best practice treatments for mental health problems with an emphasis on trauma, bereavement, and medication use. We surveyed attendees prior to training, immediately post-intervention, and 1- and 6-months later. At 6-months post-intervention, 64% of the primary care clinicians reported instituting practice changes recommended during training. Reported use of formal mental health screening instruments increased, but greater use of medications was more limited. Although participants in the immediate post-intervention survey indicated strong agreement with the desirability to implement specific practice changes, the perceived desirability of such changes declined substantially at the 6-month follow-up. Changes in PCPs 'mental health related practice procedures can be facilitated by brief educational interventions, but continued training and support may be needed. We discuss these results relative to preparedness for community disasters.

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [(11)C]SB207145 PET in humans.

Serotonin (5-HT) is a neuromodulator affecting myriad aspects of personality and behavior and has been implicated in the pathophysiology of affective disorders including depression and anxiety. The 5-HTTLPR is a common genetic polymorphism within the promoter region of the gene coding for the serotonin transporter such that the S allele is associated with reduced transcriptional efficacy compared to the L allele, potentially contributing to increased serotonin levels. In humans, this genetic variant has been linked to inter-individual variability in risk for affective disorders, related aspects of personality and brain function including response to threat. However, its effects on aspects of serotonin signaling in humans are not fully understood. Studies in animals suggest that the 5-HT 4 receptor (5-HT(4)) shows a monotonic inverse association with long-term changes in serotonin levels indicating that it may be a useful measure for identifying differences in serotonergic neurotransmission. In 47 healthy adults we evaluated the association between 5-HTTLPR status and in vivo 5-HT(4) receptor binding assessed with [(11)C]SB207145 positron emission tomography (PET). We observed a significant association within the neocortex where [(11)C]SB207145 binding was 9% lower in S carriers compared to LL homozygotes. We did not find evidence for an effect of season or a season-by-5-HTTLPR interaction effect on regional [(11)C]SB207145 binding. Our findings are consistent with a model wherein the 5-HTTLPR S allele is associated with relatively increased serotonin levels. These findings provide novel evidence supporting an effect of 5-HTTLPR status on serotonergic neurotransmission in adult humans. There were no indications of seasonal effects on serotonergic neurotransmission.

Head-to-head comparison of quantitative and semi-quantitative ultrasound scoring systems for rheumatoid arthritis: reliability, agreement and construct validity.

OBJECTIVE: To evaluate the reliability and agreement of semi-quantitative scoring (SQS) and quantitative scoring (QS) systems. To compare the two types of scoring system and investigate the construct validity for both scoring systems. METHODS: A total of 46 RA patients (median disease duration of 6.5 years) were enrolled in the study. They were investigated with colour Doppler ultrasound using the central position of the wrist. Disease activity score based on 28 joints (DAS-28) was determined for all patients using CRP. Two participants trained in the SQS system and two in the QS system evaluated the 46 anonymized images. All images were scored twice by each of the two assessors in order to assess both intra- and inter-reader reliability. RESULTS: The reliability for the two systems were 0.964 for the QS, and 0.817 for the SQS, with a comparable inter-reader agreement for both scoring systems; 95% limits of agreement for the QS being between -7.7% and +6.7% on the colour fraction scale (0-100%), whereas SQS was between -0.8 and +0.8 on the ordinal scale from 0 to 3. There was a direct but non-linear relationship between the two modalities (Spearman's r = 0.73) and critical conceptual issues in the agreement between the scoring systems were revealed. The construct validity was poor for both systems with only a weak correlation to CRP. CONCLUSION: High reliability and good agreement of both scoring systems were found when applied to the same patient cohort. Different scoring systems appear to be highly correlated.

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.

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.

Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in patients with rheumatoid arthritis: a prospective cohort study.

OBJECTIVE: To investigate the predictive ability of core outcomes applied in RA trials, including ultrasound (US) Doppler (USD) measurements differentiating patients who remain on anti-TNF-α therapy following 1 year. METHODS: Patients with RA in anti-TNF-α therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-α therapy after 1 year was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. RESULTS: The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure predicting which patients would stay on the initial anti-TNF-α therapy for 1 year, evaluated using the square-root of CF (P = 0.024). The other disease markers could not significantly differentiate between the two groups of patients, with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively, 0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION: There is now evidence to support that baseline USD, in contrast to clinical measures, can predict which patients will remain on anti-TNF-α 1 year after initiating therapy.