Obesity is associated with high serotonin 4 receptor availability in the brain reward circuitry.

The neurobiology underlying obesity is not fully understood. The neurotransmitter serotonin (5-HT) is established as a satiety-generating signal, but its rewarding role in feeding is less well elucidated. From animal experiments there is now evidence that the 5-HT(4) receptor (5-HT(4)R) is involved in food intake, and that pharmacological or genetic manipulation of the receptor in reward-related brain areas alters food intake. Here, we used positron emission tomography in humans to examine the association between cerebral 5-HT(4)Rs and common obesity. We found in humans a strong positive association between body mass index and the 5-HT(4)R density bilaterally in the two reward 'hot spots' nucleus accumbens and ventral pallidum, and additionally in the left hippocampal region and orbitofrontal cortex. These findings suggest that the 5-HT(4)R is critically involved in reward circuits that regulate people's food intake. They also suggest that pharmacological stimulation of the cerebral 5-HT(4)R may reduce reward-related overeating in humans.

Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation.

Many psychiatric disorders are characterized by cognitive and emotional alterations that are related to abnormal function of the frontal cortex (FC). FC is involved in working memory and decision making and is activated following exposure to a novel environment. The serotonin 2A receptor (5-HT(2A)R) is highly expressed in the FC where its activation induces hallucinations, while blockade of 5-HT(2A)Rs contributes to the therapeutic effects of atypical antipsychotic drugs. The purpose of the present study was to investigate the involvement of 5-HT(2A)R in FC activation following exposure to a novel environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A)R antagonists ketanserin and MDL100907, but not with the selective 5-HT(2C)R antagonist SB242084. Novelty-exposure also induced Arc mRNA expression in hippocampus (∼150%), but not in cerebellum or brainstem. Pretreatment with 5-HT(2A)R antagonist ketanserin did not repress the Arc induction in hippocampus, indicating that the involvement of 5-HT(2A)R in this response is restricted to the FC. Similarly, the novelty-induced stress as determined by increasing levels of plasma corticosterone, was not influenced by 5-HT(2A)R antagonism suggesting that Arc mRNA and stress are activated via distinct mechanisms. Taken together, our results demonstrate that the induction of Arc in the FC following exposure to a novel environment is dependent on the 5-HT(2A)R, and that the simultaneous release of corticosterone is regulated via another system independent of 5-HT(2A)R activation.

Ecologically relevant stimuli and color memory.

Ecologically relevant stimuli were developed as an alternative to Munsell color chips. Colored pictures of familiar objects were used to study color memory. We investigated the typicality of color to particular objects. Contextually typical colors were remembered more accurately than atypical colors were. Moreover, this variable had a stronger effect on memory than focality did. We concluded that memory for ecologically relevant material is more impressed by a color's relation to experience than by its intrinsic properties.

Subfoveal neovascularization in the ocular histoplasmosis syndrome. A natural history study.

The visual outcome of 74 eyes with the ocular histoplasmosis syndrome and active subfoveal subretinal neovascular membranes was studied retrospectively. Follow-up time ranged from 12 to 109 months (median, 36.5 months). Ten eyes (14%) retained visual acuity of 20/40 or better. Fifty-seven eyes (77%) suffered visual loss of 20/100 or worse and 36 eyes (49%) suffered visual loss of 20/400 or worse. Factors significantly associated with retaining vision of 20/40 or better were: age less than 30 years (P = 0.008); smaller membrane size (P = 0.0002); and absence of visual loss secondary to ocular histoplasmosis in the fellow eye (P = 0.053). Factors significantly associated with vision decreasing by four or more lines were: older patient age (P = 0.006); better initial visual acuity (P = 0.090); and more than 50% involvement of the foveal avascular zone (P = 0.059). These results were confirmed by multiple logistic regression. Final vision of 20/40 or better was associated with better initial visual acuity using univariate analysis, but this result was not confirmed by multiple logistic regression.

The impact of a change in commitment procedures on the character of involuntary psychiatric patients.

The statutory requirements for involuntary civil psychiatric confinement have become increasingly restrictive. In the jurisdiction under investigation, patients were originally admitted under an Order to Apprehend (OTA) procedure simply on the petition of two affiants who indicated the patient was in need of care. A newly elected judge instituted changes requiring affiants to claim the subject was "dangerous" to self or others and asking for a clinical assessment and recommendation before signing the petitioned request for involuntary confinement. It might be expected that the more restrictive procedures would have produced a population of more assaultive patients. A study of petitions signed under in the earlier (N = 133) and later, more restrictive (N = 218) procedures indicated that the proportion of assaultive or dangerous patients was virtually identical. Further investigation, using hospital data an OTA patients from this area in both time periods, suggested that while patients were not more assaultive, they appeared to be more seriously ill or psychiatrically impaired. Apparently, movement to a dangerousness standard that allows clinical discretion in interpreting its presence may result in involuntary commitments for more seriously ill, although not necessarily more assaultive, patients.

Pars plana vitrectomy for complicated retinal detachments.

The authors used vitreous surgery to treat 514 cases with retinal detachment. Three hundred sixty-five (71%) of the 514 eyes had retinal detachment associated with proliferative diabetic retinopathy. A successful anatomic result was achieved in 245 (67%) of these 365 cases and 227 (62%) obtained final vision of 5/200 or better. Five factors were associated with a successful visual result in diabetic eyes: (1) preoperative visual acuity of 5/200 or better, (2) retaining the crystalline lens, (3) an attached macula preoperatively, (4) preoperative retinal detachment limited to the posterior pole or less than one quarter the fundus area, and (5) absence of iatrogenic retinal breaks. Of those cases without diabetic retinopathy, a successful anatomic result was achieved in (1) 27 (84%) of 32 eyes with nondiabetic traction detachment, (2) 13 (65%) of 20 giant retinal tears, (3) 21 (50%) of 42 eyes with opaque media complicating retinal detachment, (4) 9 (90%) of 10 eyes with posterior retinal breaks, (5) 29 (42%) of 69 eyes with advanced proliferative vitreoretinopathy (PVR), and (6) 29 (64%) of 45 eyes with retinal detachment complicating prior ocular trauma.