Faculty Bibliography

The functional decline and onset of psychosis that individuals with schizophrenia experience suggests that schizophrenia has a neurodegenerational origin. However, current research favors a neurodevelopmental model in which individuals with schizophrenia develop abnormalities during brain development. The abnormality that leads to psychosis and deterioration remains latent as the brain develops but emerges concurrently with the brain's normal development or after an outside event that leads to changes in brain function. Prenatal adversity may underlie the neurodevelopmental process and neurodegeneration of schizophrenia. Because psychosis may be a clinically identifiable marker of an underlying neuropathologic process associated with deterioration, the best way to treat the illness is to reduce the duration of untreated psychosis, aim for full remission of psychosis, and combine medication with other therapies

OBJECTIVE: To evaluate the influence of paternal age upon spontaneous abortion. METHODS: This case-control study of 13,865 women draws on data from women's antenatal or postpartum interviews in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in 1964-1976. Case women (n=1,506) reported spontaneous abortion in the pregnancy preceding the interview; they were compared with women reporting live births in their previous pregnancy (n=12,359). Logistic regression was used to adjust for maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions before the index pregnancy, parity at interview, and interval between the index pregnancy and the interview. RESULTS: The adjusted odds ratio for spontaneous abortion was 0.59 (95% confidence interval 0.45-0.76, P< .0001) for pregnancies conceived from fathers aged younger than 25 years compared with those from fathers aged 25-29 years. For fathers age 40 years or older the odds ratio for spontaneous abortion was 1.6 (95% confidence interval 1.2-2.0, P=.0003) when compared with the same reference group. CONCLUSION: Increasing paternal age is significantly associated with spontaneous abortion, independent of maternal age and multiple other factors.

Although the hippocampus plays a crucial role in the formation of spatial memories, as these memories mature they may become additionally (or even exclusively) dependent on extrahippocampal structures. However, the identity of these extrahippocampal structures that support remote spatial memory is currently not known. Using a Morris water-maze task, we show that the anterior cingulate cortex (ACC) plays a key role in the expression of remote spatial memories in mice. To first evaluate whether the ACC is activated after the recall of spatial memory, we examined the expression of the immediate early gene, c-fos, in the ACC. Fos expression was elevated after expression of a remote (1 month old), but not recent (1 d old), water-maze memory, suggesting that ACC plays an increasingly important role as a function of time. Consistent with the gene expression data, targeted pharmacological inactivation of the ACC with the sodium channel blocker lidocaine blocked expression of remote, but spared recent, spatial memory. In contrast, inactivation of the dorsal hippocampus disrupted expression of spatial memory, regardless of its age. We further showed that inactivation of the ACC blocked expression of remote spatial memory in two different mouse strains, after training with either a hidden or visible platform in a constant location, and using the AMPA receptor antagonist CNQX. Together, our data provide evidence that circuits supporting spatial memory are reorganized in a time-dependent manner, and establish that activity in neurons intrinsic to the ACC is critical for processing remote spatial memories.

Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.

Emerging evidence suggests that individuals who receive morphine while hospitalized demonstrate a decrease in symptoms of posttraumatic stress disorder (PTSD). However, the mechanisms of effects are not yet well understood. The goal of the current study was to examine three possible mediators for this effect. Sixty-one injured (burns, motor vehicle accidents, falls, and assaults) children were assessed during hospitalization and again 3 months post discharge. Assessment included acute and follow-up child report measures of pain, PTSD, and anxiety symptoms, as well as a medical record review for medication administration and pulse during hospitalization. Pathway analyses were conducted to test the potential mediating roles of pain reduction, noradrenergic attenuation, and separation anxiety on the association between morphine and PTSD. Results suggest that a reduction in separation anxiety may mediate the association between morphine administration and PTSD symptom reduction at 3 months. These findings have implications for our understanding of morphine's effects on psychological functioning following an acute injury and for direct clinical care

OBJECTIVE: This study examined whether outcomes in housing, clinical status, and well-being of persons with severe mental illness and a history of homelessness differ between those in supported housing and those in community residences, two housing arrangements that substantially differ in the level of independence that is offered to its tenants. METHODS: A quasi-experimental 18-month follow-up study was conducted with 157 persons newly entering supported housing and community residences. The housing models accepted persons with similar illness characteristics and homelessness histories, so that the inability to randomly assign tenants to housing types could be compensated for by propensity scoring methods. Tenure in housing was examined by using survival models. Analyses of other outcomes used hierarchical linear and regression models in both intent-to-treat (N=139) and true-stayer (N=80) analyses. RESULTS: Tenure in housing did not differ by housing type. Substantial proportions of tenants in both models remained housed during the follow-up period. Tenants in supported housing reported greater housing satisfaction in terms of autonomy and economic viability. Over time some tenants in supported housing reported greater feelings of isolation. Independent of housing type, symptoms of depression or anxiety at housing entry increased the risk of poorer outcomes. CONCLUSIONS: The models of supported housing were viable portals of entry into community housing for homeless persons, even for consumers with characteristics indicating that they would have been more likely to be placed in community residences. The results suggest that greater clinical attention should be paid to persons who exhibit depression or anxiety when entering housing