Faculty Bibliography

BACKGROUND: A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions. METHODS: DTI and structural MRI scans were obtained from 32 chronic schizophrenic subjects and 42 controls. Corpus callosum cross sectional area and its probabilistic subdivisions were determined automatically from structural MRI scans using a model based deformable contour segmentation. These subdivisions employ a previously generated probabilistic subdivision atlas, based on fiber tractography and anatomical lobe subdivision. The structural scan was then co-registered with the DTI scan and the anatomical corpus callosum subdivisions were propagated to the associated FA map. RESULTS: Results revealed decreased FA within parts of the corpus interconnecting frontal regions in schizophrenia compared with controls, but no significant changes for callosal fibers interconnecting parietal and temporo-occipital brain regions. In addition, integrity of the anterior corpus was statistically significantly correlated with negative as well as positive symptoms, while posterior measures correlated with positive symptoms only. CONCLUSIONS: This study provides quantitative evidence for a reduction of interhemispheric brain connectivity in schizophrenia, involving corpus callosum, and further points to frontal connections as possibly disrupted in schizophrenia.

OBJECTIVE: Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome, but it has been difficult to dissociate the effects of epilepsy from the role of antiepileptic drugs. To distinguish the effects of chronic seizures from medication, we used the laboratory rat, because an epileptic condition can be induced without concomitant anticonvulsant drug treatment. METHODS: Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus, which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed epileptic. Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop status epilepticus. Ovarian cyclicity and weight gain were evaluated for 2 to 3 months. Serum hormone levels were assayed from trunk blood, which was collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS: Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if status epilepticus did not occur. Ovarian cysts and weight gain were significantly greater in epileptic than control rats, whether rats maintained cyclicity or not. Serum testosterone was increased in epileptic rats, but estradiol, progesterone, and prolactin were not. INTERPRETATIONS: The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries, and increased testosterone levels. Although caution is required when comparing female rats with women, the data suggest that recurrent seizures have adverse effects, independent of antiepileptic drugs

Affordances--possibilities for action--are constrained by the match between actors and their environments. For motor decisions to be adaptive, affordances must be detected accurately. Three experiments examined the correspondence between motor decisions and affordances as participants reached through apertures of varying size. A psychophysical procedure was used to estimate an affordance threshold for each participant (smallest aperture they could fit their hand through on 50% of trials), and motor decisions were assessed relative to affordance thresholds. Experiment 1 showed that participants scale motor decisions to hand size, and motor decisions and affordance thresholds are reliable over two blocked protocols. Experiment 2 examined the effects of habitual practice: Motor decisions were equally accurate when reaching with the more practiced dominant hand and less practiced nondominant hand. Experiment 3 showed that participants recalibrate motor decisions to take changing body dimensions into account: Motor decisions while wearing a hand-enlarging prosthesis were similar to motor decisions without the prosthesis when data were normalized to affordance thresholds. Across experiments, errors in decisions to reach through too-small apertures were likely due to low penalty for error.

The objective of this study was to determine the effects and mechanisms of serum amyloid A (SAA) on coronary endothelial function. Porcine coronary arteries and human coronary arterial endothelial cells (HCAECs) were treated with SAA (0, 1, 10, or 25 microg/ml). Vasomotor reactivity was studied using a myograph tension system. SAA significantly reduced endothelium-dependent vasorelaxation of porcine coronary arteries in response to bradykinin in a concentration-dependent manner. SAA significantly decreased endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein levels as well as NO bioavailability, whereas it increased ROS in both artery rings and HCAECs. In addition, the activities of internal antioxidant enzymes catalase and SOD were decreased in SAA-treated HCAECs. Bio-plex immunoassay analysis showed the activation of JNK, ERK2, and IkappaB-alpha after SAA treatment. Consequently, the antioxidants seleno-l-methionine and Mn(III) tetrakis-(4-benzoic acid)porphyrin and specific inhibitors for JNK and ERK1/2 effectively blocked the SAA-induced eNOS mRNA decrease and SAA-induced decrease in endothelium-dependent vasorelaxation in porcine coronary arteries. Thus, SAA at clinically relevant concentrations causes endothelial dysfunction in both porcine coronary arteries and HCAECs through molecular mechanisms involving eNOS downregulation, oxidative stress, and activation of JNK and ERK1/2 as well as NF-kappaB. These findings suggest that SAA may contribute to the progress of coronary artery disease.

Generalized social phobia (GSP) is characterized by a marked fear of most social situations. It is associated with an anomalous neural response to emotional stimuli, and individuals with the disorder frequently show interpretation bias in social situations. From this it might be suggested that GSP involves difficulty in accurately perceiving, using, understanding and managing emotions. Here we applied the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) to medication-free GSP (n=28) and no pathology (n=21) individuals. Patients with GSP performed within the normal range on the measure however severity of social anxiety significantly correlated with emotional intelligence (EI). Specifically, there was a negative correlation between social anxiety severity and Experiential (basic-level emotional processing) EI. In contrast, there was no significant correlation between social anxiety severity and Strategic (higher-level conscious emotional processing) EI. These results suggest that EI may index emotional processing systems that mitigate the impact of systems causally implicated in GSP.

We have shown previously that auditory experience regulates the maturation of excitatory synapses in the auditory cortex (ACx). In this study, we used electron microscopic immunocytochemistry to determine whether the heightened excitability of the ACx following neonatal sensorineural hearing loss (SNHL) also involves pre- or postsynaptic alterations of GABAergic synapses. SNHL was induced in gerbils just prior to the onset of hearing (postnatal day 10). At P17, the gamma-aminobutyri acid type A (GABA(A)) receptor's beta2/3-subunit (GABA(A)beta2/3) clusters residing at plasma membranes in layers 2/3 of ACx was reduced significantly in size (P < 0.05) and number (P < 0.005), whereas the overall number of immunoreactive puncta (intracellular + plasmalemmal) remained unchanged. The reduction of GABA(A)beta2/3 was observed along perikaryal plasma membranes of excitatory neurons but not of GABAergic interneurons. This cell-specific change can contribute to the enhanced excitability of SNHL ACx. Presynaptically, GABAergic axon terminals were significantly larger but less numerous and contained 47% greater density of glutamic acid decarboxylase immunoreactivity (P < 0.05). This suggests that GABA synthesis may be upregulated by a retrograde signal arising from lowered levels of postsynaptic GABA(A)R. Thus, both, the pre- and postsynaptic sides of inhibitory synapses that form upon pyramidal neurons of the ACx are regulated by neonatal auditory experience

Reviews the book, Child and Adolescent Psychiatric Clinics of North America: Neuropsychiatric genetic syndromes, edited by Doron Gothelf. The overall goal of the volume appears to be to provide the reader with a small and succinct book to reach for when looking for a description of these, thankfully, infrequently diagnosed disorders. This particular volume is well organized; the division of the volume into a series of articles concerning the general aspects of neuropsychiatry syndromes, covering approaches to diagnosis, (including the new field of imaging genetics), is interesting and informative. There is a comprehensive index, and each chapter has its own bibliography. The graphics, brain imaging, and pictures are of excellent quality (many are in full color) and are clearly explained. On a slightly less positive note, each chapter has different authors, so the writing style varies; as a result, some articles are easier to read than others. This volume of the Child and Adolescent Psychiatry Clinics of North America is a much appreciated reference and review for any clinician desiring to refresh their memory about these disorders.