Clinical outcomes of mild isolated cerebral ventriculomegaly in the presence of other neurodevelopmental risk factors.

OBJECTIVES: The purpose of this study was to evaluate neuropsychological test data in school-aged children whose fetal sonograms revealed mild isolated cerebral ventriculomegaly without asymmetry of the lateral ventricles. METHODS: Nine of 52 children 6 years and older with sonographic evidence of mild isolated cerebral ventriculomegaly without asymmetry of the lateral ventricles were able to be recruited for follow-up school-aged neuropsychological testing. The children received a half-day battery of neuropsychological tests, including the Wechsler Abbreviated Scales of Intelligence; Beery-Buktenica Developmental Test of Visual Motor Integration, Fifth Edition; Wide Range Achievement Test, Fourth Edition; and Integrated Visual and Auditory Continuous Performance Test. Parents completed the Conners 3 Parent Short Form and the Personality Inventory for Children, Second Edition. RESULTS: In this small group, other risk factors for neurodevelopmental disorders were often present, including preterm birth, perinatal hypoxia, and a family history of psychiatric disease or substance abuse. Within this sample, the proportion of children with a pattern of test results showing poorer nonverbal intelligence than verbal intelligence scores and poorer math than reading performance, as well as meeting criteria for a diagnosis of attention deficit/hyperactivity disorder, was higher than the basal rates of these problems among children in general. CONCLUSIONS: Particularly given the complexity of various factors affecting neurodevelopment, follow-up neuropsychological evaluation is warranted in children with sonographic evidence of mild isolated cerebral ventriculomegaly without asymmetry of the lateral ventricle (eg, in the context of poor school performance).

Does subtle disturbance of neuronal migration contribute to schizophrenia and other neurodevelopmental disorders? Potential genetic mechanisms with possible treatment implications.

Pathways associated with genes that regulate neuronal migration by influencing the function of microtubules in the developing fetal brain may be interfered with as part of the "first-hit" of schizophrenia. In the fully-developed brain, these same pathways that impact microtubule function mediate at least some aspects of experience-dependent plasticity, which may also be impaired in schizophrenia. Whereas severe presentations of "lissencephaly" are associated with mutations and deletions of DISC1, LIS1 and the gene for the very low-density lipoprotein receptor, genetic variations of these loci are good candidate schizophrenia genes. Importantly, in the fully-developed brain, there is a possibility that at least some of the consequences of these disturbed genetic pathways that adversely affect microtubule function may be "bypassed" or mitigated.

Cholinergic abnormalities in autism: is there a rationale for selective nicotinic agonist interventions?

The core dysfunctions of autism spectrum disorders, which include autistic disorder, Asperger disorder, and pervasive developmental disorder not otherwise specified, include deficits in socialization and communication and a need for the preservation of "sameness;" intellectual impairment and epilepsy are common comorbidities. Data suggest that pathological involvement of cholinergic nuclei and altered expression of acetylcholine receptors, particularly nicotinic acetylcholine receptors, occur in brain of persons with autistic disorder. However, many of these studies involved postmortem tissue from small samples of primarily adult persons. Thus, the findings may reflect compensatory changes and may relate more closely to intellectual impairment and the confounding effects of seizures and medications, as opposed to the core dysfunctions of autism. Nonetheless, because of the roles played by acetylcholine receptors in general, and nicotinic acetylcholine receptors in particular, in normal processes of attention, cognition, and memory, selective cholinergic interventions should be explored for possible therapeutic effects. Additionally, there are electrophysiological data that complement the clinical observations of frequent comorbid seizure disorders in these patients, suggesting a disturbance in the balance of excitatory and inhibitory tone in the brains of persons with autistic disorders. Conceivably, because the alpha7 nicotinic acetylcholine receptor is located on the surface of gamma-aminobutyric acid inhibitory neurons, selective stimulation of this receptor would promote gamma-aminobutyric acid's release and restore diminished inhibitory tone. The development of agonists and partial agonists for nicotinic acetylcholine receptors and positive allosteric modulators that enhance the efficiency of coupling between the binding of agonist and channel opening should facilitate consideration of clinical trials.

NMDA NR2B subtype-selective receptor antagonists fail to antagonize electrically-precipitated seizures and elicit popping in mice.

NR2B-subtype-selective antagonists differ from MK-801, a nonselective NMDA receptor antagonist. MK-801 antagonizes electrical seizures at doses as low as 0.1 to 0.18mg/kg and elicits popping at doses as low as 0.5mg/kg, whereas ifenprodil and Ro 8-4304 were unable to do so at the doses tested. Ro 25-6981, however, was able to antagonize electrically-precipitated tonic hindlimb extension at 100mg/kg, but was not able to elicit popping behavior at this dose.