Associations of maternal and cord blood adipokines with offspring adiposity in Project Viva: is there an interaction with child age?

OBJECTIVES: Higher leptin and lower adiponectin correlate with adult and childhood adiposity, but it is unclear how exposure to these adipokines during gestation relates to offspring growth. We aimed to investigate the relationships of maternal and cord adipokines with offspring adiposity across childhood to early adolescence, as well as interactions with child age. METHODS: In mother-child pairs in the Project Viva cohort, we measured adipokines in mothers at second trimester (n=1106) and in cord blood at birth (n=657). We measured offspring adiposity indices at early childhood (mean 3.3±s.d. 0.3 years), mid-childhood (7.9±0.8 years) and early adolescence (13.2±0.9 years). We analyzed associations of maternal and cord adipokines with offspring longitudinal adiposity using a linear mixed model adjusting for pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and other confounders. RESULTS: Mothers with higher BMI and GWG had higher leptin. Offspring born to mothers with the highest vs lowest quartile of leptin had lower BMI z-score (-0.49 units, 95% confidence interval (CI):-0.72,-0.26), waist circumference (-2.6 cm, 95% CI: -3.7,-1.5) and sum of subscapular and triceps skinfolds (-2.8 mm, 95% CI: -4.1,-1.4) in early life. An interaction term between maternal leptin and child age was positive, suggesting that the associations between maternal leptin and child adiposity were not constant over time. Offspring born to mothers with lowest vs highest quartile of maternal adiponectin had lower early life adiposity (BMI z-score -0.27 units, 95% CI: -0.48,-0.05). Results were similar for cord leptin but not cord adiponectin. CONCLUSIONS: Our findings showed higher maternal and cord leptin, and lower maternal adiponectin are associated with lower offspring adiposity from childhood to early adolescence, independent of maternal BMI and GWG. However, the strength of these associations was not constant over time.

Environmental influences on body weight and behavior in developing rats after neonatal 6-hydroxydopamine.

There is less hyperactive motor activity and better avoidance performance in rat pups treated with 6-hydroxydopamine as neonates and reared with vehicle-treated littermates than in pups reared in litters composed solely of other 6-hydroxydopamine-treated animals. Thus, in this experimental model of hyperactivity, an environmental manipulation provides an alternative to pharmacologic agents in reducing activity and improving learning performance.

Platelet monoamine oxidase in early childhood autism.

Platelet monoamine oxidase (MAO) activity was studied in 31 individuals suffering from early childhood autism and was not significantly different from that found in normal children or adults. In the autistic children, MAO activity decreased with age, and there was a trend toward greater platelet MAO activity in prepubertal and pubertal male autistic children relative to normal male children. Total platelet counts were not elevated in autistic children.

Clonidine ameliorates Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (TS) is a severe, familial neuropsychiatric disorder of childhood onset that is characterized by multiform motor, phonic, behavioral, and psychological symptoms. Clonidine hydrochloride, a centrally active alpha-adrenergic agonist, was observed to ameliorate the disorder in the majority of 25 patients who could not tolerate or did not benefit from treatment with haloperidol. Clonidine had a gradual onset of action. Compulsive behavior, frustration intolerance, speech difficulties, behavioral blocking, attentional problems, and tics were responsive to treatment. The noradrenergic system may be involved, primarily or secondarily, in the expression of the genetic predisposition to TS. These observations will require testing by suitably controlled efficacy studies.

Creatine phosphokinase levels in children with severe developmental disturbances.

Serum creatine phosphokinase (CPK) levels were studied in individuals: 40 psychotic children suffering from childhood autism, atypical personality development, and childhood schizophrenia; five children with childhood aphasia; 22 children with severe personality disorders; 29 normal children and normal siblings of psychotic children; and 14 normal parents of psychotic children. Creatine phosphokinase levels from the entire population of adults and children were normally disturbed, and the mean CPK levels for the eight diagnostic groups were within normal limits. Those 22 children with personality disorders had significantly higher CPK levels than the other diagnostic groups. This relatively higher level of CPK may be related to vulnerability to later development of schizophrenic spectrum disorders. There was no apparent relationship between CPK levels and motor activity, nor was there any change in the level of CPK during a trial of psychoactive medication. Creatine phosphokinase levels remained relatively stable on test-retest determination.

Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration.

Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration. The accumulation of 5-HIAA was reduced in patients with multiple tics in contrast with other pediatric patients (N = 27). The degree of reduction in 5-HIAA relative to HVA appeared to be associated with the severity of the tic disorder. With dextroamphetamine, tic symptoms worsened, CSF HVA level decreased, and CSF 5-HIAA concentration increased. These findings suggest an association in Gilles de la Tourette's disease of reduced functioning of inhibitory serotonergic mechanisms and functional dopaminergic overactivity.

A study of the personal radiation dose received by nuclear medicine technologists working in a dedicated PET center.

The use of dedicated PET scanners is becoming more widespread throughout Australia and the world. PET imaging utilizes short-lived (approximately 108 min), high-energy (511 keV) gamma-ray emitters that could result in a high radiation dose being received by staff. As part of a larger staff and area monitoring project, this paper discusses the personal dose equivalent, H(p)(10), received by PET staff working in a dedicated PET center. The typical H(p)(10) received by staff was approximately 1 microSv per minute of close contact with patients, which resulted in an average daily dose for nuclear medicine technologists of approximately 31 microSv. The average daily administered activity to patients at Austin Health was 1,280 MBq.

A literature review of the effects of computer input device design on biomechanical loading and musculoskeletal outcomes during computer work.

BACKGROUND: Extended use of conventional computer input devices is associated with negative musculoskeletal outcomes. While many alternative designs have been proposed, it is unclear whether these devices reduce biomechanical loading and musculoskeletal outcomes. OBJECTIVE: To review studies describing and evaluating the biomechanical loading and musculoskeletal outcomes associated with conventional and alternative input devices. METHODS: Included studies evaluated biomechanical loading and/or musculoskeletal outcomes of users' distal or proximal upper extremity regions associated with the operation of alternative input devices (pointing devices, mice, other devices) that could be used in a desktop personal computing environment during typical office work. RESULTS: Some alternative pointing device designs (e.g. rollerbar) were consistently associated with decreased biomechanical loading while other designs had inconsistent results across studies. Most alternative keyboards evaluated in the literature reduce biomechanical loading and musculoskeletal outcomes. Studies of other input devices (e.g. touchscreen and gestural controls) were rare, however, those reported to date indicate that these devices are currently unsuitable as replacements for traditional devices. CONCLUSIONS: Alternative input devices that reduce biomechanical loading may make better choices for preventing or alleviating musculoskeletal outcomes during computer use, however, it is unclear whether many existing designs are effective.

Decreased 24-hour urinary MHPG in childhood autism.

The authors compared a group of boys with childhood autism and a group of normal boys of similar age and found a decrease in urinary 3-methoxy-4-hydroxyphenethylene glycol (MHPG) in the autistic group. They hypothesize that autistic children might have an alteration in central and peripheral noradrenergic function, which might be related to impaired regulation of attention, arousal, and anxiety.

Guns and suicide: possible effects of some specific legislation.

The authors describe suicide rates in Toronto and Ontario and methods used for suicide in Toronto for 5 years before and after enactment of Canadian gun control legislation in 1978. They also present data from San Diego, Calif., where state laws attempt to limit access to guns by certain psychiatric patients. Both sets of data indicate that gun control legislation may have led to decreased use of guns by suicidal men, but the difference was apparently offset by an increase in suicide by leaping. In the case of men using guns for suicide, these data support a hypothesis of substitution of suicide method.

Poor outcome and low platelet MAO activity in chronic schizophrenia.

Platelet monoamine oxidase (MAO) activity was significantly lower among 21 chronic schizophrenic patients, 19 of whom were receiving stable doses of antipsychotic medication, than among 16 control subjects. Poor ego functioning and poor outcome were significantly correlated with low MAO activity; current dose of major tranquilizer was negatively but not significantly correlated. The degree of psychopathology, rather than presence or absence of specific symptom constellations, was the significant characteristic of patients with low enzyme levels. This finding is in accordance with those of earlier studies of schizophrenic patients as well as with recent findings in nonschizophrenic samples.

CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls.

A total of 114 subjects (41 depressed, 20 schizophrenic, 15 manic, and 38 normal controls) underwent lumbar puncture and their CSF was analyzed for levels of tyrosine, tryptophan, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), choline, gamma-aminobutyric acid (GABA), and calcium. Results showed that depressed patients, particularly those over 40 years of age, had lower levels of GABA than did controls, and that their level of HVA increased with age, while controls' decreased. Schizophrenic subjects tended to have higher levels of 5-HIAA and manic subjects tended to have higher levels of HVA and MHPG. Age-associated changes were found in HVA, 5-HIAA, MHPG, GABA, and choline concentrations.

CSF neurochemistry of women with anorexia nervosa and normal women.

CSF tyrosine, tryptophan, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), gamma-aminobutyric acid, choline, and calcium were compared in 33 anorexic and 14 normal women. The only significant difference between groups was a lower tyrosine level in the anorexic patients; their MHPG level was nonsignificantly higher. No significant group differences in body weight or depressive subgroup were found. HVA levels were positively related to body weight, and choline was negatively correlated with anorexia severity. The role of tyrosine requires further research, but these findings do suggest that HVA and choline increase with some recovery measures and MHPG is increased with this illness.

Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation.

In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.

Dopaminergic but not noradrenergic mediation of hyperactivity and performance deficits in the developing rat pup.

The relative contribution of dopamine (DA) and norepinephrine (NE) in behavioral arousal was examined in developing rat pups using intracisternal 6-hydroxydopamine (6-OHDA) either alone or following pretreatment with desmethylimipramine (DMI). Such treatments were designed to examine the effects of preferential reduction of DA (DA depletion), NE (NE depletion), or both catecholamines (CA depletion) in the development of motor activity and escape performance. General motor activity increased with age and, over all ages, DA-depleted pups tended to exhibit greater activity. This was most apparent at 15 days of age, where DA-depleted pups were significantly more active than controls, NE-depleted, or CA-depleted pups. DA-depleted pups failed to exhibit the steep decline in activity over time (habituation of activity) demonstrated by the control and NE-depleted pups, while pups depleted of both CA fell into an intermediate position in habituation. Escape latency in a T-maze at 20 days and shuttle box at 26 days of age indicated comparable performance to controls for NE-depleted pups, while those animals in DA-depleted and CA-depleted groups appeared unable to perform the task. Brain CA concentrations (determined by a radioenzymatic assay) indicated preferential reduction of DA in the DA-depleted group to concentrations 25% of controls, reduction of NE to 62% of controls in the NE-depleted group, and reductions of DA to 42% and NE to 60% in the CA-depleted group. These results suggest that preferential reduction of brain DA in the developing rat pup increases motor activity and impairs habituation of activity during the stage of behavioral arousal in week 3 of postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)

Are ADDH and ADHD the same or different?

To assess the relationship between the DSM-III criteria for attention deficit disorder with hyperactivity (ADDH) and the DSM-III-R criteria for attention-deficit hyperactivity disorder (ADHD), children from an inner city parochial school were evaluated using a 30-item teacher questionnaire consisting of the DMS-III and DSM-III-R criteria for these disorders, the revised Conners Parent and Teacher Questionnaires, and a continuous performance test. Diagnostic groups were established based on teacher ratings of the DSM items and evaluated in relation to the rating scale data and continuous performance test. While children who were identified by teachers as having ADDH almost always satisfied the criteria for ADHD, a new group of children who were hyperactive and impulsive but less clearly inattentive also met the criteria for ADHD. Implications of the change in diagnostic criteria are discussed.

Thyroid function in developmental disorders.

The relationships between catecholamines and thyroid state are considered from clinical and molecular perspectives. The effects of thyroid hormone on adrenergic systems are mediated by altered receptor and post-receptor function. Clinical symptoms of major childhood neuropsychiatric disorders, as well as related biological measures, may be influenced by thyroid hormone regulation.

Platelet monoamine oxidase activity in children and adolescents with psychiatric disorders.

Platelet monoamine oxidase (MAO) activity was studied in 108 children and adolescents with psychiatric illness and 67 control subjects. Platelet MAO activity was higher in male children with a psychiatric disturbance than in male control subjects. There was a gradual decline in platelet MAO activity during childhood and adolescence. Associations were demonstrated between MAO activity and hemoglobin, hematocrit, and platelet count, and should be considered in biological studies of vulnerability to psychiatric illness.

Catecholamine-thyroid hormone interactions: II. Thyroid hormone and platelet MAO activity in patients with thyroid disorders.

Platelet monoamine oxidase (MAO) activity and serum thyroxine indices were determined in 62 children and adolescents currently undergoing medical treatment for various thyroid disorders. The platelet MAO activity of these patients was similar to that of control and contrast groups previously reported, and there were no differences when patients were grouped according to specific thyroid disorders. Estimated free thyroxine and total thyroxine levels were generally in the upper normal or slightly elevated range and were not significantly related to MAO activity.

Assessment of brain function in clinical pediatric research: behavioral and biological strategies.

Psychobiological research in child psychiatry requires rigorous assessment of behavior and multiple perspectives on brain function through neurochemical, neuroendocrine, psychophysiological, and other advanced methods. The serious neuropsychiatric disorders of childhood, such as autism, attention deficit disorder, and language disorders, can be studied in complementary clinical protocols aimed at explicating patterns of behavioral and metabolic dysfunction which characterize various clinical syndromes. Clinical research with children raises sensitive ethical issues; the ethical problems can be addressed when children and families are active collaborators with the investigators and a long-term relationship is established. In this setting, participation in research can facilitate better treatment for a child. The use of novel biological strategies, such as pharmacological challenge tests, permits evaluation of the relation of specific neuronal systems to behavioral dimensions in clinical disorders. The development of a new treatment for Tourette's syndrome illustrates the integration of basic and clinical research methods.