Search

Background: Models of attention-deficit/hyperactivity disorder (ADHD) classically emphasize the relevance of executive processes and, recently, reward circuits. The neural bases of reward processes have barely been explored in relation to this disorder, in contrast to extensive neuroimaging studies that examine executive functions in patients with ADHD. To our knowledge, no previous studies have analyzed the volume of the ventral striatum, a key region for reward processes in ADHD children., Methods: We used a manual region-of-interest approach to examine whether there were volumetric differences in the ventral striatum of ADHD children. Forty-two children/adolescents with ADHD (ages 6-18), and 42 healthy control subjects matched on age, gender, and handedness were selected for the study., Results: The ADHD children presented significant reductions in both right and left ventro-striatal volumes (t = 3.290, p = .001; and t = 3.486, p = .001, respectively). In addition, we found that the volume of the right ventral striatum negatively correlated with maternal ratings of hyperactivity/impulsivity (r = -.503, p = .003)., Conclusions: Our study provides neuroanatomical evidence of alterations in the ventral striatum of ADHD children. These findings coincide with previous explicative models as well as with recent reports in behavioral and functional neuroimaging studies. Furthermore, the negative correlations we observed strongly uphold the relation between the ventral striatum and symptoms of hyperactivity/impulsivity.

Activity-based anorexia (ABA) is considered an animal model for anorexia nervosa (AN). By scheduled feeding and voluntary wheel running, it mimics severe body weight loss and increased physical activity in AN. Pharmacological, genetic and imaging studies implicate dopamine and serotonin in the regulation of feeding behavior, food-anticipatory activity, and food reward. Previous studies propose that the nucleus accumbens (NAc) plays an important role in these food-related processes. Here we determined dopamine and serotonin levels in the NAc upon exposure to the ABA model. Surprisingly, the release of dopamine and serotonin in the NAc were not increased during the initiation of food-anticipatory behavior in ABA rats. Dopamine release in the NAc was increased during feeding behavior in ABA rats. During ABA, levels of serotonin were low and circadian activity is blunted. We conclude that during the early stages of development of food-anticipatory activity, increased dopamine does not trigger hyperactivity.

Asparagus racemosus Linn. (AR) is an Ayurvedic rasayana used as an adaptogen. Adaptogenic drugs are those which are useful as anti-stress agents by promoting non-specific resistance of the body. Although, the adaptogenic effect of AR is well documented, its use in psychological disorders like depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of methanolic extract of roots of AR (MAR) standardized to saponins (62.2% w/w). Rats were given MAR in the doses of 100, 200 and 400 mg/kg daily for 7 days and then subjected to forced swim test (FST) and learned helplessness test (LH). The results show that MAR decreases immobility in FST and increases avoidance response in LH indicating antidepressant activity. In behavioral experiments, MAR increased the number of head twitches produced by 5-HTP and increased clonidine-induced aggressive behavior indicating facilitatory effect on both serotonergic and adrenergic systems respectively. However, MAR had insignificant effect on l-DOPA-induced aggressive behavior indicating absence of activity on dopaminergic system. MAR also reversed changes to the endogenous antioxidant system induced by FST. Thus, MAR has significant antidepressant activity and this effect is probably mediated through the serotonergic and the noradrenergic systems and augmentation of antioxidant defenses.

Background: Motor hyperactivity due to hyper-dopaminergic neurotransmission in the basal ganglia is well characterized; much less is known about the role of the neocortex in controlling motor behavior., Methods: Locomotor behavior and motor, associative, and spatial learning were examined in mice with conditional null mutations of fibroblast growth factor receptor 1 (Fgfr1) restricted to telencephalic neural precursors (Fgfr1(f/f;hGfapCre)). Locomotor responses to a dopamine agonist (Amphetamine 2 mg/kg and Methylphenidate 10 mg/kg) and antagonists (SCH233390 .025 mg/kg and Haloperidol .2 mg/kg) were assessed. Stereological and morphological characterization of various monoaminergic, excitatory, and inhibitory neuronal subtypes was performed., Results: Fgfr1(f/f;hGfapCre) mice have spontaneous locomotor hyperactivity characterized by longer bouts of locomotion and fewer resting points that is significantly reduced by the D1 and D2 receptor antagonists. No differences in dopamine transporter, tyrosine hydroxylase, or serotonin immunostaining were observed in Fgfr1(f/f;hGfapCre) mice. There was no change in cortical pyramidal neurons, but parvalbumin+, somatostatin+, and calbindin+ inhibitory interneurons were reduced in number in the cerebral cortex. The decrease in parvalbumin+ interneurons in cortex correlated with the extent of hyperactivity., Conclusions: Dysfunction in specific inhibitory cortical circuits might account for deficits in behavioral control, providing insights into the neurobiology of psychiatric disorders.

Since an emerging body of evidence is accumulating that endocrine disruptors exert their effects on the central nervous system, their neuronal risk assessment is now required. A previous study showed that a single intracisternal administration of bisphenol A, an endocrine disruptor, into neonatal rats caused hyperactivity. To evaluate the neural risk assessment of bisphenol A, it is very important to test the potential of the chemical via an environmental exposure route. In this study, we tested the hypothesis that oral exposure to bisphenol A would exhibit effects observed previously with direct instillation. Oral administration of 600mug/pup/day bisphenol A into male Wistar rats aged 5 days-3 weeks caused significant hyperactivity at 4-5 weeks of age. Treated rats were about 1.3 times as active in the nocturnal phase as were vehicle-treated control rats (p<0.005). The long-term effects of the chemical resulted in a large reduction of immunoreactivity for tyrosine hydroxylase in the midbrain at 7 weeks of age, where terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were detected. Furthermore, bisphenol A decreased gene expression levels of dopamine transporter in adult rats.

Purpose: To describe repetitive movements of the right arm possibly originating from the ipsilateral SMA area in two drug-resistant epileptic patients., Methods: Two epileptic patients (one female, one male, 35 and 36 years old, respectively) were submitted to pre-surgical evaluation including history, neurological examination, long-term video-EEG monitoring, interictal and ictal SPET, MRI and fMRI, neuropsychological assessment. Invasive recordings (stereoelectroencephalography) were also performed., Results: In both patients ictal semiology was characterized by very stereotyped repetitive right arm movements, i.e. tapping towards the thorax (movement rate of 6-7 Hz and 3-4 Hz for the two subjects, respectively). Seizures in the first patient, whose epilepsy was cryptogenetic, originated from the right pre-SMA area, which was surgically removed. She is seizure free 2 years after the operation. In the second patient, in whom a right pre-frontal post-abscess porencephaly was disclosed, the epileptogenic zone included the lesion and surrounding areas, while the SMA area was involved less consistently., Conclusions: Even if, according to literature, SMA epilepsy is predominantly characterized by postural manifestations, ipsilateral repetitive movements could be a relevant sign in this kind of epilepsy, as showed in our first patient. The presence of similar semiology in the second patient, might suggest that the symptomatogenic zone involved SMA area.

Background: Several studies have associated preterm birth with impaired behavioral functioning and attention problems. In addition, preterm individuals have an increased risk of brain injury in the neonatal period. Such early lesions have the potential to disrupt subsequent neurodevelopment. This study explored behavioral functioning, particularly externalizing behavior, in a group of adolescents who were born very preterm and its relationship with volume of the caudate, a brain region particularly vulnerable to damage in the preterm neonate., Methods: We studied 72 adolescents born before 33 weeks and 50 age- and gender-matched full-term control subjects. Behavioral assessment included the Rutter Behavioural Scale and a social adjustment scale. Bilateral caudate volumes were quantified by stereologic methods., Results: Preterm adolescents scored significantly higher than control subjects on the Rutter hyperactivity score, and boys scored higher than girls. In preterm boys only, left caudate volume was negatively correlated with hyperactivity score (r = -.43, p = .018) and social adjustment score in childhood (r = -.40, p = .028)., Conclusions: Our data suggest that boys born very preterm are more likely to experience nonclinical behavioral problems in adolescence compared with full-term control subjects. Our results indicate that behavioral problems in this group might be associated with reductions in volume of the left caudate nucleus.

We report a boy with 4-hydroxybutyric aciduria resulting from a deficiency of succinic semialdehyde dehydrogenase (SSADH). A boy, 1 year 5 months, showed delayed walk with hypotonia and could not speak meaningful words. The blood levels of lactate, pyruvate and amino acids were not elevated. Head magnetic resonance imaging (MRI) and electroenchephalography (EEG) were normal. Urinary organic acid analysis with gas chromatography-mass spectrometry (GCMS) revealed increased levels of 4-hydroxybutyric acid, glutaric acid, adipic acid and suberic acid. The concentrations of 4-hydroxybutyric acid and gamma-aminobutyric acid (GABA) were elevated in the serum and cerebrospinal fluid (CSF). SSADH activity in cultured lymphoblasts was 4.5% of the normal level. So far as we know this is the first Japanese patient diagnosed as 4-hydroxybutyric acid. Urinary organic acid analysis is necessary for the diagnosis of patients with unexplained psychomotor retardation.