Therapeutic outcome and long-term naturalistic follow-up of female adolescent outpatients with AN: clinical, personality and psychopathology evolution, process indicators and outcome predictors.

BACKGROUND: Anorexia nervosa (AN) is a serious mental illness of growing prevalence in childhood and adolescence. Despite its severity, there are still no completely satisfactory evidence-based treatments. Follow-up studies represent the most effective attempt to enlighten treatment effectiveness, outcome predictors and process indicators. METHODS: Seventy-three female participants affected with AN were assessed at intake (T0) and at 6 (T1) and 12 (T2) months of an outpatient multimodal treatment program. Nineteen participants were assessed 15 years after discharge (T3). Changes in diagnostic criteria were compared with the chi-square test. Clinical, personality and psychopathology evolution were tested with ANOVA for repeated measures, using the t-test or Wilcoxon test as post-hoc. T0 features among dropout, stable and healed participants were compared. Healed and unhealed groups at long-term follow-up were compared using Mann-Whitney U test. Treatment changes were correlated to each other and with intake features using multivariate regression. RESULTS: The rate of complete remission was 64.4% at T2, and 73.7% at T3. 22% of participants maintained a full diagnosis at T2, and only 15.8% at T3. BMI significantly increased at each time-point. A significant decrease of persistence and increase in self-directedness were evidenced between T0 and T2. Interoceptive awareness, drive to thinness, impulsivity, parent-rated, and adolescent-rated general psychopathology significantly decreased after treatment. Lower reward dependence and lower cooperativeness characterized the dropout group. The healed group displayed lower adolescent-rated aggressive and externalizing symptoms, and lower parent-rated delinquent behaviors. BMI, personality and psychopathology changes were related with each other and with BMI, personality and psychopathology at intake. CONCLUSION: A 12-months outpatient multimodal treatment encompassing psychiatric, nutritional and psychological approaches is an effective approach for the treatment of mild to moderate AN in adolescence. Treatment was associated not only with increased BMI but also with positive personality development, and changes in both eating and general psychopathology. Lower relational abilities may be an obstacle to healing. Approaches to treatment resistance should be personalized according to these finding.

Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.

Epilepsy in a cohort of children with Noonan syndrome and related disorders.

Noonan syndrome (NS) and related disorders encompass a phenotypically heterogeneous group of conditions due to mutations in the Ras/Mitogen-activated protein kinase pathway. The main objective of this study was to assess the presence and characteristics of epilepsy in children and adolescents affected by NS and related disorders. The study included all the patients aged 5-21 years who had been diagnosed with NS or of one of three Noonan-like syndromes (i.e., cardio-facio-cutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan-like syndrome with loose anagen hair) at a university pediatric hospital. Clinical, EEGs, brain MRIs, and genotype data were extracted from the medical records, and follow-up telephone interviews were conducted to obtain updated information about epilepsy and its course. Out of a total of 75 patients (38 [50.7%] males, median age at assessment 12.0 years [q1 9.0-q3 17.0]; 61 [81.3%] with NS; and 14 [18.7%] with a Noonan-like syndrome), 13 (17.3%) had epilepsy, with median age at onset of 4.0 years (q1 2.0-q3 8.0, min 0.1-max 17.0). Epilepsy was more common among Noonan-like patients (50.0%) than in NS (9.8%, p < 0.001), and its presence was associated with neurodevelopmental delay (p < 0.001, OR 14.6 95% CI 3.6-59.4), cognitive impairment (p = 0.002, OR 11.2 95% CI 2.5-51.0), need for educational support (p < 0.001, OR 21.8, 95% CI 2.6-179.1), and lower adaptive functioning (median [q1-q3]: 54.0 [q1 40.0-q3 77.5] vs 97.0 [q1 76.5-q3 107.0] of the non-epileptic subgroup, p = 0.004). In 10 out of 13 cases (76.9%), the epilepsy outcome was good (i.e., seizure-free for more than 12 months with or without anti-seizure medication). CONCLUSION: Epilepsy was more common in NS than reported in the general population, with a significantly higher rate in Noonan-like syndromes. Epilepsy was associated with neurodevelopmental delay, cognitive impairment, and lower adaptive functioning. WHAT IS KNOWN: • Neurological abnormalities have been reported in NS and related disorders. • There is evidence of a phenotype-genotype relationship for neurological abnormalities. WHAT IS NEW: • Epilepsy was found to be more common in NS and related disorders than typically reported in the general population and associated with neurodevelopmental delay, cognitive, and functional impairment. • The Noonan-like phenotype had a higher frequency of epilepsy than typical NS.

Development and application of a diagnostic and severity scale to grade post-operative pediatric cerebellar mutism syndrome.

The post-operative pediatric cerebellar mutism syndrome (CMS) affects about one-third of children and adolescents following surgical removal of a posterior fossa tumor (PFT). According to the Posterior Fossa Society consensus working definition, CMS is characterized by delayed-onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children, and is frequently accompanied by additional features such as hypotonia and oropharyngeal dysfunction/dysphagia. The main objective of this work was to develop a diagnostic scale to grade CMS duration and severity. Thirty consecutively referred subjects, aged 1-17 years (median 8 years, IQR 3-10), were evaluated with the proposed Post-Operative Pediatric CMS Survey after surgical resection of a PFT and, in case of CMS, for 30 days after the onset (T0) or until symptom remission. At day 30 (T1), CMS was classified into mild, moderate, or severe according to the proposed scale. CMS occurred in 13 patients (43%, 95% C.I.: 25.5-62.6%), with mild severity in 4 cases (31%), moderate in 4 (31%), and severe in 5 (38%). At T1, longer symptom persistence was associated with greater severity (p = 0.01). Greater severity at T0 predicted greater severity at T1 (p = 0.0001). Children with a midline tumor location and those aged under 5 years at diagnosis were at higher risk of CMS (p = 0.025 and p = 0.008, respectively). In conclusion, the proposed scale is a simple and applicable tool for estimating the severity of CMS at its onset, monitoring its course over time, and providing an early prognostic stratification to guide treatment decisions.

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.

Impact of war and forced displacement on children's mental health-multilevel, needs-oriented, and trauma-informed approaches.

The infliction of war and military aggression upon children must be considered a violation of their basic human rights and can have a persistent impact on their physical and mental health and well-being, with long-term consequences for their development. Given the recent events in Ukraine with millions on the flight, this scoping policy editorial aims to help guide mental health support for young victims of war through an overview of the direct and indirect burden of war on child mental health. We highlight multilevel, need-oriented, and trauma-informed approaches to regaining and sustaining outer and inner security after exposure to the trauma of war. The impact of war on children is tremendous and pervasive, with multiple implications, including immediate stress-responses, increased risk for specific mental disorders, distress from forced separation from parents, and fear for personal and family's safety. Thus, the experiences that children have to endure during and as consequence of war are in harsh contrast to their developmental needs and their right to grow up in a physically and emotionally safe and predictable environment. Mental health and psychosocial interventions for war-affected children should be multileveled, specifically targeted towards the child's needs, trauma-informed, and strength- and resilience-oriented. Immediate supportive interventions should focus on providing basic physical and emotional resources and care to children to help them regain both external safety and inner security. Screening and assessment of the child's mental health burden and resources are indicated to inform targeted interventions. A growing body of research demonstrates the efficacy and effectiveness of evidence-based interventions, from lower-threshold and short-term group-based interventions to individualized evidence-based psychotherapy. Obviously, supporting children also entails enabling and supporting parents in the care for their children, as well as providing post-migration infrastructures and social environments that foster mental health. Health systems in Europe should undertake a concerted effort to meet the increased mental health needs of refugee children directly exposed and traumatized by the recent war in Ukraine as well as to those indirectly affected by these events. The current crisis necessitates political action and collective engagement, together with guidelines by mental health professionals on how to reduce harm in children either directly or indirectly exposed to war and its consequences.

Trends in admissions to a child and adolescent neuropsychiatric inpatient unit in the 2007-2017 decade: how contemporary neuropsychiatry is changing in Northwestern Italy.

PURPOSE: Rising levels of psychopathology in the adolescent population have been evidenced in the last few years throughout the Western world. We aim to examine how contemporary neuropsychiatry is changing in Northwestern Italy and how this impacts inpatient services. METHODS: The present research considered the 1177 admissions to a public neuropsychiatric inpatient service in the 2007-2017 decade. The annual percentual change (APC) was analysed for the total admissions, the number of the neurological vs psychiatric admissions, the length of inpatient stay, and the mean age at admission, also accounting for sex differences. The annual trend was also calculated for each diagnosis. RESULTS: The overall number of inpatient admissions decreased significantly (APC = - 5.91), in particular for children under 12 years of age (APC = - 7.23). The rate of neurologic diagnoses significantly decreased (APC = - 26.44), while the length of the inpatient stay (APC = 6.98) and the mean age at admission (APC = 6.69) increased. Among the psychiatric diagnoses, depression significantly rose (APC = 41.89), in particular among female adolescents (APC = 40.30). CONCLUSIONS: These data document a substantial change in the utilization of inpatient neuropsychiatric services for children and adolescents, with a major increase in psychiatric hospitalizations and a parallel decrease in neurological ones. These trends call for greater attention to early preventive intervention in mental healthcare system.

Enhanced Expression of Human Endogenous Retroviruses, TRIM28 and SETDB1 in Autism Spectrum Disorder.

Human endogenous retroviruses (HERVs) are relics of ancestral infections and represent 8% of the human genome. They are no longer infectious, but their activation has been associated with several disorders, including neuropsychiatric conditions. Enhanced expression of HERV-K and HERV-H envelope genes has been found in the blood of autism spectrum disorder (ASD) patients, but no information is available on syncytin 1 (SYN1), SYN2, and multiple sclerosis-associated retrovirus (MSRV), which are thought to be implicated in brain development and immune responses. HERV activation is regulated by TRIM28 and SETDB1, which are part of the epigenetic mechanisms that organize the chromatin architecture in response to external stimuli and are involved in neural cell differentiation and brain inflammation. We assessed, through a PCR realtime Taqman amplification assay, the transcription levels of pol genes of HERV-H, -K, and -W families, of env genes of SYN1, SYN2, and MSRV, as well as of TRIM28 and SETDB1 in the blood of 33 ASD children (28 males, median 3.8 years, 25-75% interquartile range 3.0-6.0 y) and healthy controls (HC). Significantly higher expressions of TRIM28 and SETDB1, as well as of all the HERV genes tested, except for HERV-W-pol, were found in ASD, as compared with HC. Positive correlations were observed between the mRNA levels of TRIM28 or SETDB1 and every HERV gene in ASD patients, but not in HC. Overexpression of TRIM28/SETDB1 and several HERVs in children with ASD and the positive correlations between their transcriptional levels suggest that these may be main players in pathogenetic mechanisms leading to ASD.

Obsessive-compulsive symptoms in young women affected with anorexia nervosa, and their relationship with personality, psychopathology, and attachment style.

PURPOSE: Obsessive-compulsive symptoms (OC) are associated with greater morbidity and worse prognosis in anorexia nervosa (AN). We assessed the presence of non-eating OC in participants with AN and related them with their psychopathology, personality, and attachment style features. METHODS: Young women with AN (N = 41, 30 restrictor and 11 binge-purging type) were assessed on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). These participants with AN and 82 healthy controls (HC) completed the Temperament and Character Inventory (TCI), Eating Disorder Inventory-2 (EDI-2), Symptom Checklist-90 (SCL-90), Toronto Alexithymia Scale (TAS-20), and Attachment Style Questionnaire (ASQ). The association between Y-BOCS scores and indexes of psychopathology, personality, and attachment were examined. RESULTS: AN had significantly higher scores than HC on the EDI-2, SCL-90, TAS-20, ASQ-Need for Approval, and TCI-Harm Avoidance and Self-directedness. The Y-BOCS scores were significantly correlated with ASQ-Need for Approval, TAS-20-Difficulty in Describing Feelings, SCL-90-Phobic Anxiety, and Anxiety, EDI-2-Drive to Thinness, and Asceticism. Need for Approval displayed the strongest correlation with OC symptoms. Difficulty in describing feelings displayed the strongest correlation with compulsive OC symptoms. CONCLUSIONS: OC traits in AN were primarily associated with measures of insecure attachment rather than to their eating disorder or general psychopathology. Therapeutic approaches to correcting insecure attachment may be considered as a possible approach to treating AN patients with OC. The study supports a new psychopathological perspective for understanding the meaning of OC symptoms in AN. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Closing the gap: unmet needs of individuals with impulsive aggressive behavior observed in children and adolescents.

Impulsive aggressive (IA, or impulsive aggression) behavior describes an aggregate set of maladaptive, aggressive behaviors occurring across multiple neuropsychiatric disorders. IA is reactive, eruptive, sudden, and unplanned; it provides information about the severity, but not the nature, of its associated primary disorder. IA in children and adolescents is of serious clinical concern for patients, families, and physicians, given the detrimental impact pediatric IA can have on development. Currently, the ability to properly identify, monitor, and treat IA behavior across clinical populations is hindered by two major roadblocks: (1) the lack of an assessment tool designed for and sensitive to the set of behaviors comprising IA, and (2) the absence of a treatment indicated for IA symptomatology. In this review, we discuss the clinical gaps in the approach to monitoring and treating IA behavior, and highlight emerging solutions that may improve clinical outcomes in patients with IA.

Affectionless control: A parenting style associated with obesity and binge eating disorder in adulthood.

OBJECTIVE: Obesity is rising globally with a heavy health and economic burden. Early attachment experiences are relevant to the development of obesity. The purpose of this study was to investigate if parental care and attachment style experienced in childhood is associated with obesity, with or without binge eating disorder (BED), in adulthood. METHOD: Parental style, personality traits, and psychopathology were assessed in 810 clinically referred adults with obesity, of whom 357 with BED and 453 without BED (non-BED), and 463 healthy subjects (HS). Assessments included the Parental Bonding Instrument, Temperament and Character Inventory, Eating Disorder Inventory-2, Symptom Checklist-90 and Beck Depression Inventory-II. RESULTS: Both BED and non-BED reported lower maternal and paternal care and higher overprotection than HS. BED reported worse levels of parental care than non-BED and HS. 'Affectionless control' parenting style was more frequently reported by both BED and non-BED than HS. No significant differences in parenting style emerged between BED and non-BED. CONCLUSIONS: Perception of parental 'affectionless control' was associated with obesity in adults, and lower quality of parental care was more frequently reported by participants with BED. Parental style may constitute an important target for early interventions to prevent obesity.

The song of Anorexia Nervosa: a specific evoked potential response to musical stimuli in affected participants.

PURPOSE: Research applying electroencephalography (EEG) to Anorexia Nervosa (AN) is still limited, even though in other psychiatric disorders EEG has permitted to find out the hallmarks of the disorder. The aim of the study was to explore whether EEG basal activity and reactivity to musical stimulation differ in participants with AN as compared to healthy subjects (HS). METHODS: Twenty female participants (respectively 10 with AN and 10 healthy controls) were administered a battery of psychometric tests and underwent EEG under three different conditions: (1) at baseline; (2) after a generic music stimulation; and (3) after a favorite musical stimulation. RESULTS: In participants with AN, basal EEG showed the higher absolute amplitude of cortical slow waves (theta) in the parieto-occipital and temporal derivations, with a deficit in the beta band. In AN, there was a higher N100 latency and a reduced P300 latency compared to HS. While the N100 and P300 latencies were sensitive to the musical stimulus in HS, there was no difference after music stimulation in AN. CONCLUSION: These data suggest that AN is accompanied by a state of brain hyperarousal with abnormal reactivity to environmental stimuli, similar to the state of HS after musical stimulation. If confirmed, this finding may have treatment implications. LEVEL OF EVIDENCE: III, Evidence obtained from well-designed cohort or case-control analytic studies.

Cigarette Smoking Progression Among Young Adults Diagnosed With ADHD in Childhood: A 16-year Longitudinal Study of Children With and Without ADHD.

INTRODUCTION: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for smoking cigarettes, but there is little longitudinal research on the array of smoking characteristics known to be prognostic of long-term smoking outcomes into adulthood. These variables were studied into early adulthood in a multisite sample diagnosed with ADHD combined type at ages 7-9.9 and followed prospectively alongside an age- and sex-matched local normative comparison group (LNCG). METHODS: Cigarette smoking quantity, quit attempts, dependence, and other characteristics were assessed in the longitudinal Multimodal Treatment Study of Children with ADHD (MTA) eight times to a mean age of 24.9 years: ADHD n = 469; LNCG n = 240. RESULTS: In adulthood, the ADHD group had higher rates of daily cigarette smoking, one or more quit attempts, shorter time to first cigarette of the day, and more severe withdrawal than the LNCG. The ADHD group did not appear to have better smoking cessation rates despite a higher proportion quitting at least once. Smoking quantity and nicotine dependence did not differ between groups. The ADHD group reported younger daily smoking onset and faster progression from smoking initiation to daily smoking across assessments. Finally, ADHD symptom severity in later adolescence and adulthood was associated with higher risk for daily smoking across assessments in the ADHD sample. CONCLUSIONS: This study shows that ADHD-related smoking risk begins at a young age, progresses rapidly, and becomes resistant to cessation attempts by adulthood. Prevention efforts should acknowledge the speed of uptake; treatments should target the higher relapse risk in this vulnerable population. IMPLICATIONS: Although childhood ADHD predicts later smoking, longitudinal studies of this population have yet to fully characterize smoking behaviors into adulthood that are known to be prognostic of long-term smoking outcome. The current study demonstrates earlier and faster progression to daily smoking among those with a childhood ADHD diagnosis, as well as greater risk for failed quit attempts. Prevention efforts should address speed of smoking uptake, while treatments are needed that address smoking relapse risk. The current study also demonstrates ADHD symptom severity over development increases daily smoking risk, implicating the need for continuous ADHD symptom management.

Clinical and personality characteristics of adolescents with anorexia nervosa with or without non-suicidal self-injurious behavior.

PURPOSE: About one-fifth of patients with anorexia nervosa (AN) engage in non-suicidal self-injury (NSSI). This study examined clinical and temperament profile of female adolescents with both disorders (AN+NSSI) as compared with peers with AN only. METHODS: A consecutive sample of 73 female adolescents with AN (mean age: 13.77 years), who had been admitted to inpatient or day-hospital services, received clinical, cognitive, and temperament/character evaluations. Of them, 32 met DSM-5 criteria also for NSSI. Assessments included demographics, standard nutrition parameters, Youth Self-Report (YSR), Wechsler Intelligence Scale for Children IV (WISC-IV), Temperament and Character Inventory (TCI), and Global Assessment of Functioning (GAF). RESULTS: No differences were detected between AN+NSSI and AN in demographics, body mass index, or age at onset of AN. AN+NSSI had higher rate of binging and purging, higher YSR scores for both internalizing and externalizing psychopathology, lower total IQ, and lower Self-directedness and Cooperativeness scores. CONCLUSIONS: These data suggest that adolescents with AN+NSSI have psychopathological, cognitive and overall character features that differ from patients with AN only. These characteristics may have implications for treatment and outcome.

An exploration of concomitant psychiatric disorders in children with autism spectrum disorder.

OBJECTIVE: We explored patterns of concomitant psychiatric disorders in a large sample of treatment-seeking children and adolescents with autism spectrum disorder (ASD). METHODS: Participants were 658 children with ASD (age 3-17 years; mean = 7.2 years) in one of six federally-funded multisite randomized clinical trials (RCT) between 1999 and 2014. All children were referred for hyperactivity or irritability. Study designs varied, but all used the Child and Adolescent Symptom Inventory or Early Childhood Inventory to assess Attention Deficit Hyperactivity Disorder (ADHD), Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), Anxiety Disorders, and Mood Disorders. In addition, several measures in common were used to assess demographic and clinical characteristics. RESULTS: Of the 658 children, 73% were Caucasian and 59% had an IQ >70. The rates of concomitant disorders across studies were: ADHD 81%, ODD 46%, CD 12%, any anxiety disorder 42%, and any mood disorder 8%. Two or more psychiatric disorders were identified in 66% of the sample. Of those who met criteria for ADHD, 50% also met criteria for ODD and 46% for any anxiety disorder. Associations between types of concomitant disorders and a number of demographic and clinical characteristics are presented. CONCLUSION: In this well-characterized sample of treatment-seeking children with ASD, rates of concomitant psychiatric disorders were high and the presence of two or more co-occurring disorders was common. Findings highlight the importance of improving diagnostic practice in ASD and understanding possible mechanisms of comorbidity.

Substance use through adolescence into early adulthood after childhood-diagnosed ADHD: findings from the MTA longitudinal study.

BACKGROUND: Inconsistent findings exist regarding long-term substance use (SU) risk for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The observational follow-up of the Multimodal Treatment Study of Children with ADHD (MTA) provides an opportunity to assess long-term outcomes in a large, diverse sample. METHODS: Five hundred forty-seven children, mean age 8.5, diagnosed with DSM-IV combined-type ADHD and 258 classmates without ADHD (local normative comparison group; LNCG) completed the Substance Use Questionnaire up to eight times from mean age 10 to mean age 25. RESULTS: In adulthood, weekly marijuana use (32.8% ADHD vs. 21.3% LNCG) and daily cigarette smoking (35.9% vs. 17.5%) were more prevalent in the ADHD group than the LNCG. The cumulative record also revealed more early substance users in adolescence for ADHD (57.9%) than LNCG (41.9%), including younger first use of alcohol, cigarettes, marijuana, and illicit drugs. Alcohol and nonmarijuana illicit drug use escalated slightly faster in the ADHD group in early adolescence. Early SU predicted quicker SU escalation and more SU in adulthood for both groups. CONCLUSIONS: Frequent SU for young adults with childhood ADHD is accompanied by greater initial exposure at a young age and slightly faster progression. Early SU prevention and screening is critical before escalation to intractable levels.

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 Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors.

Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.