Fronto-limbic-striatal dysfunction in pediatric and adult patients with bipolar disorder: impact of face emotion and attentional demands.

BACKGROUND: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. METHOD: During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. RESULTS: Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. CONCLUSIONS: Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.

Interaction of Ihh and BMP/Noggin signaling during cartilage differentiation.

Bone morphogenetic proteins (BMPs) have been implicated in regulating multiple stages of bone development. Recently it has been shown that constitutive activation of the BMP receptor-IA blocks chondrocyte differentiation in a similar manner as misexpression of Indian hedgehog. In this paper we analyze the role of BMPs as possible mediators of Indian hedgehog signaling and use Noggin misexpression to gain insight into additional roles of BMPs during cartilage differentiation. We show by comparative analysis of BMP and Ihh expression domains that the borders of Indian hedgehog expression in the chondrocytes are reflected in changes of the expression level of several BMP genes in the adjacent perichondrium. We further demonstrate that misexpression of Indian hedgehog appears to directly upregulate BMP2 and BMP4 expression, independent of the differentiation state of the flanking chondrocytes. In contrast, changes in BMP5 and BMP7 expression in the perichondrium correspond to altered differentiation states of the flanking chondrocytes. In addition, Noggin and Chordin, which are both expressed in the developing cartilage elements, also change their expression pattern after Ihh misexpression. Finally, we use retroviral misexpression of Noggin, a potent antagonist of BMP signaling, to gain insight into additional roles of BMP signaling during cartilage differentiation. We find that BMP signaling is necessary for the growth and differentiation of the cartilage elements. In addition, this analysis revealed that the members of the BMP/Noggin signaling pathway are linked in a complex autoregulatory network.

Alveolar bone turnover and tooth movement in male rats after removal of orthodontic appliances.

The purpose of this study was to acquire tooth movement, histomorphometric and biochemical data on oral tissues that had previously been loaded with calibrated orthodontic forces. One hundred and forty-four male Sprague-Dawley rats were randomly divided into two groups: Group I, orthodontic appliances placed for 16 days to mesially move maxillary first molars with an initial force of 40 gm, and group II, sham orthodontic treatment. Seven to twelve rats were killed at each of six times after removal of appliance. Tooth movement was measured cephalometrically, alveolar bone turnover by histomorphometry, and tissue phosphatase levels biochemically. Treated molars moved distally more rapidly than the shams (13.9 vs 5.0 microns/day). The appliance removal group had a persistent 10-fold elevation in root resorption on the mesial (p < 0.0001), as well as early elevations in osteoclasts on the mesial and osteoblasts on the distal (p < 0.001) that returned to control by 3 to 5 days. Acid, alkaline phosphatase, and tartrate-resistant acid phosphatase (TRAP) remained elevated in the tissues until 10 days (p < 0.0001). Changes in the dynamic measures of bone formation were characterized by low rates at days 1 and 3 (p < 0.01), elevating thereafter on the mesial and the converse on the distal. Orthodontic tooth movement relapses, and bone remodeling continues for several days after removal of appliance consistent with the direction of loading, orthodontic treatment stimulates root resorption at sites that were loaded in pressure without detectable recovery, and root resorption does not increase at the tension sites.

Alveolar bone turnover in male rats: site- and age-specific changes.

BACKGROUND: This study compares alveolar bone turnover adjacent to distally drifting maxillary first molar teeth of rapidly and slowly growing rats. METHODS: Two groups of forty male rats (1 and 3 months) were sacrificed. Sera were analyzed for acid (AcP), alkaline (AlkP), and tartrate-resistant acid phosphatase (TRAP). Bone histomophometry was done on parasagittal sections of maxillary molars. Molar drift was quantified cephalometrically. RESULTS: Distal surface contained more osteoclasts and higher osteoclast percents than mesials at both ages (P < 0.001). There were also more osteoclasts on the distals of the older rats as compared to the young (P < 0.001). Osteoblast percents were higher (P < 0.001) in the older rats on both surfaces. Mesials had higher double-labeled surface, MAR and BFR than distals in the younger rats (P < 0.001). The younger rats had higher (P < 0.001) AlkP, AcP, and TRAP. There were no age-specific differences in rate of molar drift. A model of rate of molar drift (P < 0.0015) containing bone formation measures accounts for 54.9% of the variability. CONCLUSIONS: We conclude that the bone turnover dynamics adjacent to maxillary first molars represent predominantly remodeling on the distal in both groups and modeling on the mesial only in the young rats, that distal molar tooth drift reflects alveolar bone turnover, and that alveolar bone manifests the marked reduction in bone cell activity that occurs in the rat skeleton after 8 weeks but that this reduction is compensated by recruitment or maintenance of more bone cells at these sites.