Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Effects of the antiglucocorticoid RU 38486 on the induction of learned helpless behavior in Sprague-Dawley rats

Learned helplessness (LH) is induced by exposure to an inescapable or uncontrollable stressor which results in an inability to escape or avoid the same stressor when subsequently presented in a different context. In order to understand which central mechanisms may influence the expression of the learned helpless phenotype, we have pursued an experimental approach that seeks to elucidate the behavioral effects of glucocorticoid (GC) hormones in this animal model of depression. We have previously shown that the induction of LH behavior is enhanced by adrenalectomy, an effect that is reversed by corticosterone. In this study, our aim was to attempt to locate CNS sites responsible for the observed effects of glucocorticoids on learned helpless behavior by introducing the type II GC receptor antagonist, RU 38486 to discrete brain regions. We did not observe a significant effect in LH with acute systemic, acute dentate gyrus or intracerebroventricular injection of RU 38486 in contrast to previous studies using the Porsolt swim test, another animal model of depression. However, we were able to observe a significant change upon chronic administration to the dentate gyrus. These findings suggest that glucocorticoids exert a long-term influence on stress-induced behavior, presumably by affecting glucocorticoid responsive genes in the dentate gyrus

Hippocampal neuropeptide Y mRNA is reduced in a strain of learned helpless resistant rats

The learned helpless rat is considered to be one of the better animal models of depression. A genetically inbred strain with a high vulnerability to develop helplessness (LH), as well as a highly resistant strain (NLH) have both been developed. Since the brain peptide neuropeptide Y (NPY) is involved in the regulation of a number of behaviors known to be altered in clinical depression as well as in learned helplessness, we measured the relative level of NPY mRNA in the hippocampus and cortex of control Sprague Dawley (SD), LH and NLH rats. We find that NLH rats have approximately a 30-35% decrease in basal hippocampal NPY mRNA compared with SD and LH rats. By contrast, cortical NPY mRNA and hippocampal pre-proenkephalin and somatostatin mRNA levels were not significantly different in the 3 strains. The data suggest that the regulation of NPY gene expression may be involved in the reduced vulnerability of NLH rats to develop learned helplessness

Alterations in glucocorticoid inducible RNAs in the limbic system of learned helpless rats

Glucocorticoids (GC) have an important effect on mood in humans and influence learned helplessness, an escape avoidance paradigm that is considered one of the best animal models of depression. A strong genetic component underlies the development of learned helplessness as shown by the emergence of a line of highly vulnerable rats (LH strain) through selective inbreeding. In addition, hormonal factors play a role. Adrenalectomy (adx) for example is known to increase the vulnerability to acquire learned helplessness, an effect that is reversed by glucocorticoids (GC). Since GC function primarily by modulating gene expression, hormone mediated alterations in mRNAs expressed in the brain may be important in the development of an adequate escape avoidance response. Conversely, we postulate that the deficit in escape avoidance behavior exhibited by the LH strain may be associated with an alteration in GC-mediated gene expression in the brain. To test this hypothesis, we analyzed GC-responsive mRNAs that are expressed in the hippocampus. Control Sprague-Dawley (SD) rats showed consistent alterations in mRNAs that are modulated by GC, such as type II GC receptor (GR) and metallothionein-1 (MT-1). Under our experimental conditions, both GR and MT-1 mRNA are significantly increased in the hippocampus of hormone-treated SD rats. An increase in hypothalamic GR mRNA was also observed. However, under the same experimental conditions, LH rats showed more selective hormone induced changes since GC had no effect on hypothalamic and hippocampal GR mRNA whereas a significant increase in MT-1 mRNA was observed