Current Projects

 

Clinical Core, Conte Center for the Neuroscience of Mental Disorgers (CNMD)

The Clinical Services Core of the CCNMD represents a unique resource that is organized around the recruitment and characterization of unmedicated schizophrenic subjects at both early and later phases of the illness. Such subjects represent an extremely limited patient population. The Core integrates and coordinates the recruitment and assessment of subjects for imaging projects in the CCNMD and other currently funded collaborating investigators, which share these subjects efficiently and productively. The Clinical Services Core: 1) screens, recruits and assesses subjects using standardized assessment methods found in the Core Assessment Battery in order to generate a uniform data base shared by all investigators; 2) provides reliable and valid diagnostic evaluation using a well-developed longitudinal methodology and initial clinical follow-up and care; 3) utilizes well developed policies and procedures to coordinate a range of protocols and insure the most efficient use of resources and avoid duplication of effort; and 4) provides clinical and diagnostic expertise for post-mortem diagnostic conferences.

Funded by: NIMH

 

Brain Maturation and Vulnerability to Schizophrenia

Schizophrenia is a highly debilitating disease of great public health importance.  This illness typically begins in adolescence, tends to be lifelong, and is one of the leading causes of disability worldwide.  While the pathophysiological basis of this illness is still poorly understood, accumulating evidence suggests structural and functional brain abnormalities in the early course of schizophrenia.  The view that these abnormalities are related to abnormal brain development is gaining ground; this model suggests that the observed brain abnormalities may be present before illness onset in individuals genetically predisposed to this disorder.  Preliminary and ongoing work by this investigator in this little studied area has shown that young relatives of schizophrenia patients have evidence of attentional, neurological and executive function deficits, and impaired structural and molecular integrity of the heteromodal association cortex (HAC) and subcortical brain structures; these impairments appear to progressively evolve during adolescence.  These observed deficits also appear to be related to schizotypy and other measures of behavioral pathology.  The central hypothesis of this study is that progressive neurodevelopmental dysmaturation of the HAC and subcortical brain regions underlies the vulnerability to schizophrenia.  In this study the investigator will seek to prospectively characterize the nature and longitudinal course of these observations in high-risk non-psychotic young relatives of schizophrenia patients (HR, n=150) and matched and temporally “yoked” healthy control (HC, n=100) subjects.  All the subjects will be evaluated with neurobehavioral and neuroimaging (magnetic resonance imaging and multi-voxel phosphorus and proton magnetic resonance spectroscopy) studies. Additionally, genotyping for schizophrenia related susceptibility genes will be carried out in adult HR and HC subjects and only those minor HR subjects showing evidence of psychopathology. Subjects will be followed up annually for three years to seek evidence of progressive brain dysmaturation and its relation to the emergence of schizophrenia related psychopathology.  These studies will establish a cohort of high-risk subjects for further follow-up studies of developmental vulnerability to schizophrenia.

Funded by: NIMH

 

Systematic Evaluation of Antiviral Medication in Schizophrenia (SEAMS)

Emerging evidence from across the world suggests that certain infectious agents, especially viruses may contribute to the pathogenesis of schizophrenia. Few systematic studies have evaluated the efficacy of antiviral treatment for schizophrenia. Examination of magnetic resonance imaging (MRI) scans in our laboratory revealed reductions in the frontal lobe (more specifically a region called prefrontal cortex) of the brains of schizophrenia patients exposed to herpes simplex virus 1 (HSV1) compared to those who were not. Herpes simplex virus type 1 causes recurrent cold sores that is distributed widely in the general population. Abnormalities in the prefrontal region of the brain among schizophrenia patients have been well documented in the literature. This suggests that HSV1 may contribute to the risk for schizophrenia. Valacyclovir is an effective medication that is widely used in the treatment of herpes virus infections. We are testing whether Valacyclovir-treated schizophrenia/schizoaffective disorder patients would show a decrease in the severity of psychotic symptoms and an improvement in thinking and memory compared to patients treated with placebo (sugar pill). For more information click here.

Funded by: Stanley Medical Research Institute

 

 

Genetic Variations and Neurobiology of Schizophrenia

Our goals in this study are to understand the association of schizophrenia risk genes with brain structure, function and chemicals. We are recruiting patients diagnosed with schizophrenia or schizoaffective disorder, offspring of patients with schizophrenia or schizoaffective disorder and healthy subjects. We will collect blood samples, conduct a detailed psychiatric evaluation, tests for memory and thinking, and MRI scans from eligible subjects.

Funded by: NIMH, NARSAD, APIRE, Lilly

 

Neuroimaging Studies in Children at Risk for Bipolar Disorders and Schizophrenia

Bipolar disorder (BPD) and schizophrenia (SCZ) are severely debilitating psychiatric disorders of considerable personal and societal cost.  Despite a century of research it is only recent technological advances that have begun to elucidate the neurobiological bases of these illnesses.  Accumulating data from brain imaging studies suggest neurobiological alterations in both BPD and SCZ. In this study, we propose to explore whether HR-BPD subjects with attentional and executive function impairments will like HR-SCZ subjects have similar alterations in structural (decreased volume) and metabolic integrity (decreased PME, increased phosphodiesters (PDE) of the HAC compared to matched healthy controls. The existence of ongoing studies of adolescent relatives of both BPD and SCZ in schizophrenia gives us the opportunity to elucidate this question.  Modern techniques of non-invasive neuroimaging such as Magnetic Resonance Imaging (MRI), and Magnetic Resonance Spectroscopy (MRS) enable investigation of the high-risk offspring of BPD and SCZ patients.

Funded by: NARSAD

 

Completed Projects

 

Rehabilitation, Brain Function and Early Schizophrenia

In this study, investigators collaboratively seek to determine the efficacy of Cognitive Enhancement Therapy (CET) in ameliorating specific cognitive, structural and functional brain abnormalities in early course schizophrenia. We predict that CET will be more effective than enriched supportive psychotherapy (EST) in differentially improving behavioral and neurobiological dysfunctions in schizophrenia that compromise "executive" cognitive functions, specifically, the structural and functional integrity of the prefrontal cortex (PFC). We also predict that a relatively preserved PFC integrity will be associated with a better response to CET. A series of early course schizophrenia patients, stabilized on an atypical antipsychotic, will be randomized to CET or EST. Cognitive and functional outcomes will be assessed before, and following 1 and 2 years of psychosocial treatment and maintenance antipsychotic treatment. In a subset of these patients, an integrated neuroimaging study (MRI, MRS and fMRI) will be conducted before and after one year of CET or EST. If successful, the study will provide the first evidence of neurobiological remediation, and possible mechanism and site(s) of action for cognitive rehabilitation in early schizophrenia. An understanding of the cerebral correlates of improvement (or lack thereof) in cognition and behavior might guide development of future cognitive rehabilitation strategies in schizophrenia.

Funded by: NIMH

 

EEG Sleep and Neurodevelopment in Schizophrenia

The investigator’s data indicate that reductions in slow-wave sleep (SWS) in schizophrenia are present early in the disorder and persist during later phases of illness. It was also found that decreased SWS in schizophrenia correlates with negative symptoms, attentional impairment, relatively poor outcome and abnormal brain metabolism as evidenced by ³¹Phosphorous MRS (³¹P MRS) studies. Magnetic resonance studies have also revealed significant volume deficits in cortical gray matter, as well as altered membrane and energy metabolism in the prefrontal cortex in these patients. The presence of the observed alterations early in illness, the lack of a relationship with illness duration and their persistence suggest that they may be related to neurodevelopmental abnormalities. It is therefore hypothesized that abnormal SWS in schizophrenia is related to developmentally mediated pathophysiology of the association cortex and the thalamus. This project’s overall goal is to examine EEG sleep parameters (specifically SWS), in conjunction with brain structural and metabolic data, to address the pathophysiological heterogeneity in schizophrenia.

Funded by: NIMH