Family, personal, parental correlates and behavior disturbances in school-aged boys with attention-deficit/hyperactivity disorder (ADHD): a cross-sectional study.

BACKGROUND: To evaluate the relationship among family, personal, parental correlates, and behavioral disturbances in boys with attention-deficit/hyperactivity disorder (ADHD). METHODS: We performed a hospital-based cross-sectional study. School-aged boys who first visited the hospital between 2000 and 2011 with ADHD were identified. Through medical records review, demographic information, family characteristics, personal characteristics, parental characteristics, and the Child Behavior Checklist (CBCL) collected during the first outpatient visit were retrieved. A T-score higher than 63 in the internalizing or externalizing subscale of the CBCL indicated severe behavioral disturbances in each domain. Multivariable logistic regression was used to evaluate the relationship between the correlates and behavioral disturbances. Eligible patients were further classified into groups without behavioral disturbance, with either only severe internalizing or only severe externalizing behaviors, or with both behaviors. Multivariable ordinal logistic regression was used to investigate the association between the correlates and the number of types of behavioral disturbances. RESULTS: A total of 1855 boys with ADHD were included. In the multivariable logistic regression, family factors, including being first-born, living in a family not with both parents, and family history of mental disorder, were associated with severe internalizing and externalizing behaviors. Personal factors, including prenatal complications, perinatal complications, and medical and psychiatric comorbidities, were associated with severe internalizing behaviors, but only prenatal complications and medical comorbidities were associated with severe externalizing behaviors. Parental factors were only associated with severe externalizing behaviors. A higher paternal education level had a protective effect, but younger motherhood increased the risk. In ordinal logistic regression, these factors were also associated with more types of behavioral disturbances. CONCLUSIONS: Multiple factors are related to behavioral disturbances in ADHD. Our study reported the association among family, personal, parental factors, severe internalizing behavior, severe externalizing behavior, and number of behavioral disturbances in boys with ADHD. However, the impacts differed as the behavior phenotypes varied. Further research is needed to better understand the heterogeneity of ADHD behavior.

Family structure, birth order, and aggressive behaviors among school-aged boys with attention deficit hyperactivity disorder (ADHD).

PURPOSE: To evaluate the associations between family structure, birth order, and aggressive behaviors among school-aged boys with attention deficit hyperactivity disorder (ADHD). METHODS: We conducted a matched case-control study. Data were retrieved from medical records at a psychiatry center in northern Taiwan. School-aged boys with ADHD who first visited the outpatient department at the psychiatric center between 2000 and 2011 were identified. The Child Behavior Checklist was used for aggressive behavior assessment. Boys with ADHD with T scores higher than 70 on the aggressive subscale were classified as cases and others with T scores lower than 70 were classified as controls at a 1:4 ratio. After controlling for other familial, personal, and parental factors, a multivariate conditional logistic regression was performed to evaluate the effects of family structure and birth order on aggressive behaviors of boys with ADHD. RESULTS: 277 cases and 1108 controls were included in the final analysis. Compared with living in a traditional family with both parents, living in a non-traditional family in which one or both parents were absent increased the risk of aggressive behaviors by 1.47-fold, with the highest risk for those in single parent families. Being the firstborn increased risk by 1.45-fold and the risk was higher when the firstborn had siblings. CONCLUSIONS: Living in non-traditional families in which one or both parents were absent, and being the firstborn increased risk of aggression in school-aged boys with ADHD. Identification of this high-risk population and development of adequate preventive strategies are warranted.

Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses.

Psychological stress is an important global health problem. It is well documented that stress increases the incidences of various cardiovascular disorders. Regular exercise is known to reduce resting blood pressure (BP) and heart rate (HR). This study was designed to clarify the effects of long-term exercise on stress-evoked cardiovascular responses and to emphasize post-stress recovery effects. Male Wistar rats underwent 8 weeks of moderate treadmill training, with cardiovascular responses, autonomic nervous system activities and local Fos reactivity changes in the cardiovascular regulation center were monitored before, during and after immobilization stress. A spectral analysis of cardiovascular parameters was used to examine autonomic nervous activities. We found that long-term exercise (i) lowered resting BP, HR and sympathetic activity, but increased resting parasympathetic activity and baroreflex sensitivity (BRS); (ii) accelerated post-stress recovery of stress-evoked cardiovascular and sympathetic responses along with increased BRS and (iii) accelerated post-stress recovery of stress-evoked neuron activations in the paraventricular nucleus, but delayed it in the nucleus of the tractus solitarius. We conclude that, in rats, long-term exercise accelerated recovery of stress-evoked cardiovascular responses differentially altering hypothalamic and medullar neuron activities.

Social instability stress differentially affects amygdalar neuron adaptations and memory performance in adolescent and adult rats.

Adolescence is a time of developmental changes and reorganization in the brain. It has been hypothesized that stress has a greater neurological impact on adolescents than on adults. However, scientific evidence in support of this hypothesis is still limited. We treated adolescent (4-week-old) and adult (8-week-old) rats with social instability stress for 5 weeks and compared the subsequent structural and functional changes to amygdala neurons. In the stress-free control condition, the adolescent group showed higher fear-potentiated startle responses, larger dendritic arborization, more proximal dendritic spine distribution and lower levels of truncated TrkB than the adult rats. Social instability stress exerted opposite effects on fear-potentiated startle responses in these two groups, i.e., the stress period appeared to hamper the performance in adolescents but improved it in adult rats. Furthermore, whilst the chronic social stress applied to adolescent rats reduced their dendritic field and spine density in basal and lateral amygdala neurons, the opposite stress effects on neuron morphology were observed in the adult rats. Moreover, stress in adolescence suppressed the amygdala expression of synaptic proteins, i.e., full-length TrkB and SNAP-25, whereas, in the adult rats, chronic stress enhanced full-length and truncated TrkB expressions in the amygdala. In summary, chronic social instability stress hinders amygdala neuron development in the adolescent brain, while mature neurons in the amygdala are capable of adapting to the stress. The stress induced age-dependent effects on the fear-potentiated memory may occur by altering the brain-derived neurotrophic factor (BDNF)-TrkB signaling and neuroplasticity in the amygdala.

Trends, correlates, and disease patterns of antipsychotic use among children and adolescents in Taiwan.

PURPOSE: We used Taiwan's population-based National Health Insurance database to investigate the trends, correlates, and disease patterns of antipsychotic use among children and adolescents. METHODS: The National Health Research Institutes provided a database of 1,000,000 random subjects for study. We chose subjects who were aged 18 years or younger during 1997-2005. In this sample, subjects who were given at least one antipsychotic prescription, including first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs), were identified. Trends, prevalence, and associated factors of antipsychotic use were determined. The proportion of antipsychotic use for psychiatric and medical disorders was also analyzed. RESULTS: The 1-year prevalence of SGA use increased from 0.00 % in 1997 to 0.09 % in 2005, whereas the 1-year prevalence of FGA use ranged from 2.24 to 3.43 % during this same period, with no significant change. Age and male gender were associated with higher SGA use. Among SGA users, the greatest proportion suffered from psychiatric disorders, including tics, hyperkinetic syndrome of childhood, schizophrenia, affective disorders, and autism. Among FGA users, a larger proportion was for medical conditions, including diseases of the digestive and respiratory systems. CONCLUSION: The prevalence of pediatric SGA use increased greatly from 1997 to 2005. Among pediatric subjects using antipsychotics, SGAs were mostly used for psychiatric disorders, whereas FGAs were mostly prescribed for medical conditions. Future research will focus on indication, dosage, frequency, duration, adverse effects, and off-label use of antipsychotics in the pediatric population.

Trends, correlates, and disease patterns of antidepressant use among children and adolescents in Taiwan.

The authors used a population-based database to investigate antidepressant use among children and adolescents in Taiwan. The National Health Research Institutes provided a database of 1 000 000 random subjects for study. The authors adopted this sample of subjects who were younger than 18 years during 1997 to 2005. Subjects with at least 1 antidepressant prescription were identified. Trends, prevalence, associated factors, and disease patterns of antidepressant use were detected. The 1-year prevalence of pediatric antidepressant use increased from 0.27% in 1997 to 0.47% in 2005. The 1-year prevalence of tricyclic antidepressant, selective serotonin reuptake inhibitor, and other antidepressant use among pediatric population was 0.23%, 0.20%, and 0.08%, respectively, in 2005. The prevalence of pediatric antidepressant use increased from 1997 to 2005. Among pediatric subjects with antidepressant use, selective serotonin reuptake inhibitors, and other antidepressants were used the most for psychiatric disorders, whereas tricyclic antidepressant was used the most for nonpsychiatric disorders.

ACE/ACE2 ratio and MMP-9 activity as potential biomarkers in tuberculous pleural effusions.

OBJECTIVE: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. EXPERIMENTAL DESIGN: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). RESULTS: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. CONCLUSION: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.

Blood pressure variations real-time reflect the conditioned fear learning and memory.

The conditioned fear learning and memory occurs when a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US). This process is critically dependent on the amygdala and inevitably involves blood pressure (BP) alterations. We hypothesized that BP variations could instantaneously reveal individual steps during conditioned fear learning and memory. An implanted telemetric probe was used to monitor the BP real-time in rats during training and testing sessions of the fear-potentiated startle. Our results showed that (i) the conditioned fear learning during the training sessions was reflected by light (CS)-induced rapid BP elevations and by electric shock (US)-evoked sympathetic tone elevations; (ii) these two BP-related parameters were not only negatively correlated with each other but also coupled to each other in the training session trials; (iii) both parameters closely predicted the performance of fear-potentiated startle on the next day; and (iv) although local blocking of one of the two fear-conditioned pathways in the training session partially inhibited fear learning, the fear memory retrieval still used both pathways. Altogether, real-time blood pressure variations faithfully revealed the critical steps involved in conditioned fear learning and memory, and our results supported a coupling between the cued learning and the post-shock calmness.

Chronic treadmill running in normotensive rats resets the resting blood pressure to lower levels by upregulating the hypothalamic GABAergic system.

OBJECTIVE: The cardiovascular integration center not only sends out signals to offset the stimulus-induced responses but also resets the resting blood pressure. We hypothesize that GABAergic adaptations in the hypothalamus participate in the chronic exercise-induced cardiovascular resetting effects in conscious normotensive animals. METHODS: Male Wistar rats were subjected to chronic moderate exercise (CME, 8-week treadmill running at moderate intensity). A biotelemetry system was used to measure blood pressure, heart rate, autonomic nervous activities, baroreflex sensitivity and endogenous GABAergic activities in the paraventricular nucleus and the posterior hypothalamic area. Hypothalamic specimens were collected for quantifying GABA-related proteins and GABAergic neurons. RESULTS: CME reduced resting blood pressure, heart rate, sympathetic activity and enhanced parasympathetic activity and baroreflex sensitivity. Additionally, CME elevated the resting level of hypothalamic GABAergic activities, increased the percentage of GABAergic neurons in the hypothalamus and upregulated the hypothalamic protein levels of neuronal nitric oxide synthase, GAD67 and gephyrin, but not GABAA receptor. Moreover, a single bout of moderate exercise transiently elevated blood pressure and heart rate with prolonged high levels of neural controls (sympathetic activity, baroreflex sensitivity and hypothalamic GABAergic activities). CME accelerated the postexercise recovery in cardiovascular parameters and neural control alterations. CONCLUSION: Chronic treadmill running in normotensive rats augmented the GABAergic system in both paraventricular nucleus and posterior hypothalamic area, resulting in lower resting blood pressure, heart rate and sympathetic tone under conscious unrestraint conditions. This study provides insight into mechanisms important for explaining how chronic exercise resets the resting blood pressure.

The anti-cancer effects of (-)-epigallocatechin-3-gallate on the signaling pathways associated with membrane receptors in MCF-7 cells.

(-)-Epigallocatechin-3-gallate (EGCg) has been implicated in cancer chemo-prevention in studies using many different kinds of cancer cells. The present study measured cell viability, osteopontin (OPN) secretion, fatty acid synthase (FAS) expression, and cytosolic Ca(2+) and verified the anti-cancer activities of EGCg in MCF-7 human breast cancer cells. EGCg-induced apoptosis was evidenced by nuclear condensation, increased protein levels of activated caspase-3, down-regulation of gelsolin and tropomyosin-4 (Tm-4), and up-regulation of tropomyosin-1(Tm-1). By disrupting adherens junction formation, EGCg caused accumulation of extra-nuclear ß-catenin aggregates in the cytosol and alterations of the protein content and mRNA expression of E-cadherin and ß-catenin, but not N-cadherin, in MCF-7 cells. To identify the putative mechanisms underlying the EGCg signaling pathways, EGFP (enhanced green fluorescence protein) was ectopically expressed in MCF-7 cells. This allowed us to monitor the EGCg-induced fluorescence changes associated with the effects of Triton X-100 (to remove plasma membrane) or the addition of laminin, anti-laminin receptor (LR) antibody, epidermal growth factor (EGF), and genistein on the cells. Our results indicated that EGCg acts via the signaling pathways associated with cell membrane to suppress cell proliferation, provoke apoptosis, and disturb cell-cell adhesion in MCF-7 cells. The altered events include the EGFR, LR, FAS, intracellular Ca(2+) , OPN secretion, caspace-3, gelsolin, Tm-4, Tm-1, and adherens junction proteins, E-cadherin and ß-catenin.

Thermal effects on the activity and structural conformation of catechol 2,3-dioxygenase from Pseudomonas putida SH1.

A bacterium, Pseudomonas putida SH1, which can catabolize phenol, naphthalene, or cresol as the sole carbon and energy source, was isolated from a petroleum-contaminated site in Taiwan. The catechol 2,3-dioxygenase (C23O) was purified from this bacterial strain when grown on naphthalene as the sole carbon and energy source. The enzyme is composed of four identical subunits with a native molecular weight of 128 +/- 5 kD. Small-angle neutron scattering (SANS) techniques were employed to study the thermal effects on the structural conformation of this enzyme in solution. The SANS measurements revealed distinct changes in the size of the enzyme between 50 and 80 degrees C, and the size was not restored during the subsequent cooling. The enzyme started to denature at 55 degrees C, and the structure was destroyed by the time the temperature reached 80 degrees C, at which the enzyme had become more than twice the original size. The optimal catalytic temperature of the enzyme was at 50 degrees C. The half-life of the activity at this temperature was 45 min. The enzyme activity increases starting from 25 degrees C and reaches its maximum at 50 degrees C, below which no obvious change in the size of the enzyme is found. Noticeable enlargement of the enzyme is revealed when the enzymatic activity starts to fall. By combination of SANS measurement and biochemical properties of the enzyme, this study demonstrates the correlation of enzyme size in solution and catalytic activity upon a heat treatment. In addition, for a protein composed of multiple subunits, the shape of the enzyme and the dissociation of the enzyme subunits in a thermal cycle were also demonstrated by SANS methodology.