Detecting objective and subjective cognitive effects of electroconvulsive therapy: intensity, duration and test utility in a large clinical sample.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depression but the extent and persistence of cognitive side-effects remain uncertain. It has been reported that there is little evidence that impairments last longer than up to 15 days post-ECT. However, relatively few studies have followed patients for even as long as 1 month post-ECT. Here we report results from a brief cognitive battery given prior to ECT and repeated five times up to 6 months post-ECT. METHOD: In a retrospective case-note study of routinely collected clinical data 126 patients treated with ECT completed two neuropsychological tests [Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination (MMSE)] and two subjective reports of memory function, prior to ECT. Patients were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all patients completed all assessments. RESULTS: Performance relative to pre-ECT baseline was significantly poorer at each post-ECT assessment up to 3 months post-ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score showed improvements relative to baseline from 1 month post-ECT. Mood and subjective memory scores improved following ECT and were correlated with one another, but not with either neuropsychological measure. CONCLUSIONS: The CANTAB SRM task revealed reversible cognitive deficiencies relative to a pre-ECT baseline for at least 3 months following ECT, while MMSE score and patients' subjective reports showed only improvement. Visuospatial memory scores eventually exceeded baseline 6 months post-ECT.

Characterization of dentine structure in three dimensions using FIB-SEM.

All biological tissues are three dimensional and contain structures that span a range of length scales from nanometres through to hundreds of millimetres. These are not ideally suited to current three-dimensional characterization techniques such as X-ray or transmission electron tomography. Such detailed morphological analysis is critical to understanding the structural features relevant to tissue function and designing therapeutic strategies intended to address structural deficiencies encountered in pathological states. We show that use of focused ion beam milling combined with scanning electron microscopy can provide three-dimensional information at nanometre resolution from biologically relevant volumes of material, in this case dentine.

Sex differences in the growth of white matter during adolescence.

The purpose of this study was to examine sex differences in the maturation of white matter during adolescence (12 to 18 years of age). We measured lobular volumes of white matter and white-matter "density" throughout the brain using T1-weighted images, and estimated the myelination index using magnetisation-transfer ratio (MTR). In male adolescents, we observed age-related increases in white-matter lobular volumes accompanied by decreases in the lobular values of white-matter MTR. White-matter density in the putative cortico-spinal tract (pCST) decreased with age. In female adolescents, on the other hand, we found only small age-related increase in white-matter volumes and no age-related changes in white-matter MTR, with the exception of the frontal lobe where MTR increased. White-matter density in the pCST also increased with age. These results suggest that sex-specific mechanisms may underlie the growth of white matter during adolescence. We speculate that these mechanisms involve primarily age-related increases in axonal calibre in males and increased myelination in females.

Glial vascular endothelial growth factor overexpression in rat brainstem under tolerable hypoxia: evidence for a central chemosensitivity.

The ventilatory response to hypoxia is mediated by peripheral inputs arising from the arterial chemoreceptors. In their absence, hypoxic adaptation can be achieved, possibly as a result of central cellular reorganization. To study this reorganization, we used chemodenervated rats to investigate the expression and localization of vascular endothelial growth factor (VEGF) in the brainstem. VEGF is a target gene of hypoxia-inducible factor (HIF) that is responsible for the morphofunctional remodeling induced by hypoxia. Intact and chemodenervated rats were subjected to normoxia or hypoxia for 6 hr (10% O(2) in N(2)). VEGF protein was quantified in micropunches of brainstem tissue. Only chemodenervated animals showed an increased VEGF expression in response to hypoxia, whereas, in normoxia, VEGF expression was not modified by chemodenervation. The same hypoxic condition was repeated for 8 days before immunocytochemical staining with anti-VEGF; antiglial fibrillary acidic protein (GFAP), a marker of astrocytes; and anti-rat endothelial cell antigen-1 (anti-RECA-1) that recognizes endothelial cells. Confocal analysis showed a cellular colocalization of GFAP and VEGF, indicating that VEGF was overexpressed predominantly in astrocytes. Increased RECA-1 immunolabeling indicated an enhanced angiogenesis in chemodenervated rats subjected to hypoxia. These results indicate that glial cells and the vascular network contribute to the brainstem remodeling. The peripheral chemodenervation reveals a central O(2) chemosensitivity involving a cascade of gene expression triggered by hypoxia, which in intact animals may act synergically with peripheral chemosensory inputs.

Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats.

We investigated the involvement of the adrenal glucocorticoid, corticosterone, in the control of the rhythmic expression of the circadian clock protein, Period2, in forebrain nuclei known to be sensitive to glucocorticoids, stressors and drugs of abuse, the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala. We found previously that the daily rhythm of Period2 in these nuclei is uniquely dependent on the integrity of the adrenal glands (Amir S, Lamont EW, Robinson B, Stewart J (2004) A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci 24:781-790; Lamont EW, Robinson B, Stewart J, Amir S (2005) The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci U S A 102:4180-4184). We now show that, in rats, in the absence of the adrenals, corticosterone replacement via the drinking water, which is associated with daily fluctuations in corticosterone levels, restores the rhythm of Period2 in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. Corticosterone replacement via constant-release pellets has no effect. These results underscore the importance of circadian glucocorticoid signaling in Period2 rhythms in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala and suggest a novel mechanism whereby stressors, drugs of abuse, and other abnormal states that affect the patterns of circulating glucocorticoids can alter the functional output of these nuclei.

Practical problems in selection of spina bifida infants for treatment in the USA.

Seventy-five spina bifida infants were studied for results of selectin for treatment. The 31 nonoperated infants had a survival rate of 70% at 18 months, a figure higher than anticipated. Practical difficulties in adhering to the selectin protocol and controlling medical management in a large North American city were noted. Thirty-three surveyed parents of surgically repaired infants reported satisfaction with family function during the 18 months follow-up but discrepant scores increased with time.