Subjects: diurnal slope, norepinephrine, animal models, glucocorticoid receptor, catecholamines, fear conditioning, diurnal cortisol profile, prolonged exposure therapy, telomere, perceived stress, life stress, hyperprolactinemia, palatable food, Psychiatry, outpatient, DHEA, early maternal depression, mental development index, prolonged release, serotonin, cell aging, human hair, pregnant woman, animal model, telomere length, early life stress, trauma, alcohol, hypothalamic-pituitary-adrenal axis, lymphocytes, psychosocial stress, vulnerability, mild traumatic brain injury, suicidal behavior, neuronal plasticity, cortisol, Latino, children and adolescents, adolescence, outpatients, 5-HTTLPR, ACTH, chronic stress, adult, lead exposure, gene expression, glutathione peroxidase, treatment, hypothalamus-pituitary-adrenal axis, rhesus amygdale, Trier Social Stress Test (TSST), family conflict, burn-out, sympathetic nerve activity, panicogenic activity, gestational weight gain, sleep, bipolar disorder, stress response, immune function, HPA, psycho-emotional behaviors, life habits, leukocytes, behavior, resilience, foetal programming hypothesis, suicide ideation, RCT, prosocial behavior, autonomic nervous system, testosterone, childhood, parasympathetic nervous system, 2c receptor, orbital frontal cortex, multiple sclerosis, resiliency, metformin, anxiety disorders, amenorrhea, eating behavior, ADHD, high performance liquid chromatography, cardiometabolic syndrome, internalizing problems, postpartum depression, blood sugar, faces, lactate, corticosterone, oxidative stress, ratio, sexuality, mitochondrial DNA, cellular aging, molar cortisol to DHEA ratio, DHEA-S, BclI polymorphism, synthetic glucocorticoids, cortisol levels, school, food consumption, military, FDG-PET, female, immunology, coping, RC435-571, surprise, psychosis patients, HPA axis, emotions, nicotine exposure, military service, sensation seeking, mineralocorticoid receptor, imaging, smoking behavior, stress responses, dexamethasone suppression, metabolic syndrome, anxiety, folate, preschoolers, physiological stress, conditioning, impulsivity, diffusion tensor imaging, longitudinal, CRPS-1, ADHD subtypes, EMG, child, questionnaire, memory, mood, learning, general population, mice, decision making under risk, metabolic health, cognitive control, personality, college students, cortisol reactivity, microRNA, insulin resistance, childhood SES, tricyclic antidepressants, BDNF levels, intranasal oxytocin, disease, Irritable bowel syndrome, startle response, glucose intolerance, meta-analysis, breast cancer, paliperidone palmitate, salivary markers, substance dependence, DNA methylation, α-amylase, cold pressor task, galvanic skin response, dissociation, PTSD-SS, HPA-axis, sexual minority stress, family, disgust, prolactin levels, anxiety sensitivity, DHEA and DHEA-S response, neuroendocrine, mental health, risperidone, salivary cortisol, appetitive hormones, competition, fear/defensive brain circuitry, FKBP5, fMRI, primate, emotion regulation, HPA activity, fatigue, treatment effect, externalizing problems, children, heart rate variability, TSST, orbitofrontal cortex, flow cytometry, BDI scores, cytokines, affective startle eyeblink modulation, Narrative Exposure Therapy, PTSD Checklist, NR3C1, parent-report, fear, social support, diurnal cortisol activity, blood pressure, methylphenidate, oxytocin, risk factors, mood disorders, suicide, leptin, posttraumatic stress disorder, MSCEIT, acute panic inventory, biological markers, self-help books, gonadal steroid hormones, avoidant personality disorder, maternal depression, women, traumatic stress, obsessive-compulsive disorder, telomeres, laparoscopic adjustable gastric banding, primary effects, development quotient, CCK-4, inflammation, postmenopaus, a case series, antidepressant effects, peer, antidepressant treatment, steroid hormones, burnout, amygdale, sleep quality, sex differences, reward, biofeedback, stress, PTSD, cardiovascular disease, disclosure, maternal obesity, exhaustion, health, aggression, attentional bias, body-mass index, birthweight, alpha-amylase, emotion, time-series variance, maternal behavior, brain volume, temperament, allostasis, adolescent development, SNS, rosiglitazone, aripiprazole, stress-related disorders, coronary heart disease, Gulf War, cold pressor test, preterm birth, offspring, cortisol awakening response, LESPW, cortisone, pessimism, hippocampal volume, detrended fluctuation analysis, autonomic activity, longitudinal study, schizophrenia, parent education, emotion recognition, depressive symptoms, psychological distress, daily stress, psychosis, Supplement 1, 2012, longitudinally, sexual functioning, sleep duration, childhood trauma, prognostic modelling, aging-related disorders, HIV, working memory, genetic risk, disease duration, dual task performance, obesity, cytokine, auto-therapy, biomarkers, reduced serum, stress reduction, basal concentration, earthquake, nucleus accumbens, acute exercise, biomarker, rumination, prolonged stress, deep brain stimulation, neuroimaging, autoregressive latent trajectory model, cognitive intervention, hydrocortisone, methylation, decision making, anhedonia, adolescent, biomatrices, Trier Social Stress Test, panic disorder, medication condition, veterans, magnetic resonance imaging, sociodemographic variables, glyburide, economic tournament, coping resources, prefrontal cortex, EEG, salivary alpha-amylase, maternal mood, DNA damage, emotion dysregulation, emotional reactivity, amylase, hormonal contraception, olanzapine, positive psychology, hyperglycemia, hair, elders, genetics, telomerase, CAR, cortisol response, neuroinflammation, array, acute stress, DTI, appraisal, mass spectrometry, personality disorders, heart rate, glucocorticoid, DHEAS, predictors of treatment, hippocampus, takotsubo cardiomyopathy, cognition, allostatic load, sympathetic nervous system, inpatient, mitochondria, immune activation, psychoneuroimmunology, stress hormones, emotional stress, physical activity, neonatal maternal separation, saliva, stress reactivity, regulation, autonomic response, attention, antenatal, challenge, psychophysiology, depression, threat, body esteem, exhaustion disorder, response of BDNF
Statement of the problem Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophic receptors, appears to intervene in the pathogenesis and treatment response in Attention deficit hyperactivity disorder (ADHD), hypothesis based on the conceptualization of ADHD as a neurodevelopmental disorder and the importance of the BDNF for normal neural development. In addition, in experimental models, psychostimulants and antidepressants increase the brain concentration of BDNF. Genetic polymorphisms related with the activity of the BDNF seem to correlate with the incidence, clinical manifestations, endophenotypes or the treatment response in ADHD. We aim to define if the response to prolonged release methylphenidate treatment is different in the main ADHD subtypes, in an open, quasi-experimental and controlled study. Methods A total of 148 (115 males, 33 females) patients, of 9.77 (2.56) years old, were subdivided in two group. (1) Control group (n=37; 27 males, 10 females); healthy siblings of the ADHD patients. (2) ADHD group (n=111; 88 males, 23 females), without epilepsy and with a normal value in an abbreviated intelligence test (KBIT). In all subjects, after written informed consent, we performed identical clinical, psychometric and biochemical study, before and after (only ADHD group) treatment. ADHD group were diagnosed according Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and sub-classified in the primary ADHD subtypes by EDAH scale (). Measurement: BDNF by ELISA (IBL International, ref. RB59041), in serum samples obtained at 09:00 and 20:00 h, before and after 4.63 (2.3) months of the daily morning ingestion of PRMPH. Statistic: factorial analyses using statistical package STATA 12.0. Funding: Grant of Spanish government, FIS-PI07-0603. Results In the control group serum BDNF concentration in the morning (36.36±11.62 ng/ml) was very similar to the value seen in the predominantly inattentive subgroup of ADHD children, although evening concentration was higher (31.78±11.92 ng/ml). The treatment with prolonged release methyphenidate do not modify the daily fluctuation of BDNF in the children with hyperactive/impulsive/conduct disorder children, whereas in children with predominantly inattentive disorder PRMPH induces a significant decrease (χ2=6.62, p=0.010). ADHD subtypeSerum BDNF (ng/ml) in ADHD childrenPre-MPHPost-MPHDayNightDayNightPHI/CD30.76±12.3429.09±12.8230.29±12.527.25±12.93PDA35.31±12.8526.41±11.5526.97±10.325.05±10.21 PDA: Day vs. Night, pre: χ2=11.63, p=0.0019. ADHD pre- vs. post-treatment, day: χ2=6.62, p = 0.010. All statistical values for comparisons not shown were non-significant. Our results show both similar morning concentrations and daily fluctuation of BDNF, between predominantly inattentive ADHD children and healthy sibling controls. The PRMPH treatment does not modify the reduced BDNF concentration (vs. controls) in hyperactive/conduct disorder children, nor the absence of daily fluctuation; but contrary to expectation reduces the concentration in the predominantly inattentive patients to values similar to that observed at night, disappearing the highly significant basal day/night fluctuation also noted in the control group. Conclusion Besides our data in hyperactive/conduct disorder children has been reported that the major depression is also associated with a decrease in BDNF concentration. As serum BDNF seem parallel with intra-cerebral concentration, especially in messencephalic areas, this neurotrophin could be the link between ADHD and major depression, and provide a new pathway for the development of drugs for ADHD.