1999 — 2003 |
Heckers, Stephan |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Neuroimaging of Hippocampal Function in Schizophrenia @ Massachusetts General Hospital
This is a request for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) entitled "Neuroimaging of Hippocampal Function in Schizophrenia". The candidate's interest is the study of hippocampal function in the human brain with a special emphasis on schizophrenia. Several lines of evidence have implicated abnormalities of the hippocampus in schizophrenia. The candidate proposes to test the hypothesis of memory associated hippocampal deficits in schizophrenia with functional neuroimaging experiments. The candidate's previous training was in neuroanatomy and clinical psychiatry, and includes initial training in positron emission tomography (PET) technology. The proposed project will provide more advanced training in PET as well as training in (1) the application of structural and functional magnetic resonance imaging (fMRI), (2) the cognitive neuroscience of memory, (3) the statistical aspects of comparing psychiatric patients and control subjects, and (4) the neurobiology of schizophrenia. The research project designed to achieve these goals integrates four experimental approaches to study hippocampal function in schizophrenia. First, established PET activation paradigms will be used to assess hippocampal function during memory retrieval in schizophrenic patients and control subjects. Second, fMRI will be used to study hippocampal activating during memory processes in schizophrenic patients and control subjects. Third, the pattern of hippocampal activation will be correlated with the structural organization of the brain using morphometric analyses. Fourth, psychological experiments will be developed to study memory and conscious recollection in schizophrenia. This integrated program, providing training in neuroimaging technologies, cognitive neuroscience, and statistical analyses, will foster the candidate's development into an independent investigator in the fields of schizophrenia research and neuropsychiatry. The research conducted will advance our understanding of hippocampal function in the human brain and elucidate the neuropsychology and neurobiology of schizophrenia.
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0.909 |
2005 — 2021 |
Heckers, Stephan |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Imaging Hippocampal Function in Psychosis
DESCRIPTION (provided by applicant): This is a revised proposal to study the structure and function of the hippocampal formation in psychosis. Hippocampal volume deficits are among the most robust brain abnormalities in chronic patients with schizophrenia. More recent studies have now established that hippocampal volume reduction is already present in the early stages of psychosis - in patients who develop schizophrenia as well as those who develop bipolar disorder. It is unclear, however, whether hippocampal pathology can explain the psychotic features or the well-known memory deficits in schizophrenia and bipolar disorder. Here the applicant is proposing to test the hypothesis that hippocampal dysfunction is necessary (but not sufficient) for the production of psychosis. Memory deficits are predicted to be prominent in schizophrenia and bipolar disorder because cortico-hippocampal interactions are perturbed in psychosis. To test this hypothesis, two groups of patients will be studied with novel morphometric and functional imaging approaches. First, two forms of hippocampal-dependent memory (i.e., the ability to remember episodes and the ability to infer relationships among items) will be studied in chronic patients with schizophrenia. This will allow the applicant to test the prediction that hippocampal dysfunction in conjunction with cortical and thalamic abnormalities can explain specific memory deficits in schizophrenia. Second, schizophrenic and bipolar patients will be studied at the time of their first hospitalization. Hippocampal function during episodic and relational memory task performance is predicted to be abnormal in the early stages of psychosis, whereas cortical dysfunction is less prominent compared to chronic patients with schizophrenia. The proposed studies are designed to elucidate the crucial role of hippocampal dysfunction for the production of psychosis and the development of cognitive deficits in schizophrenia and bipolar disorder.
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1 |
2020 — 2021 |
Heckers, Stephan Woodward, Neil D. (co-PI) [⬀] Zald, David H (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The General Factor of Psychopathology in Psychosis and Severe Mental Illness @ Vanderbilt University Medical Center
An increasing body of evidence on the structure of psychopathology indicates the presence of a general factor of psychopathology (GF), also referred to as a P-factor, that explains a significant amount of the common variance in the expression of multiple psychopathological symptoms and disorders. The presence of a GF has substantial implications for understanding psychopathology because it suggests that a comprehensive understanding of mental illness requires an untangling of nonspecific risk factors from more narrow, dimension- specific risk factors or features. Caspi et al., (2014) suggest that schizophrenia symptoms are so highly correlated with the GF, that they are mostly an expression of the GF. However, methodological limitations, such as the use of community and youth samples, limit conclusions from the existing literature. We propose to test the hypothesis that schizophrenia spectrum (SS) symptoms load heavily on both a GF AND a separate higher-order psychosis factor using a sample of 1000 adult psychiatric and medical treatment seeking subjects that includes a substantial group of patients with SS disorders as well as patients with significant externalizing and internalizing symptoms. The potential utility of this hierarchical dimensional approach is that it allows quantification of the extent to which each individual possesses a high GF score (reflected in the overall breadth of symptoms), or symptoms that are more narrowly constrained to a specific 2nd order factor (such as externalizing, internalizing, and psychosis factors) or even more narrow, first-order symptom dimensions. Using this quantitative approach, we will test the extent to which neuropsychological and structural and functional MRI measures that have previously been observed in patients with schizophrenia are more strongly related to the GF versus a psychosis factor. This will allow us to test the hypothesis that some neural correlates, such as the volume of the anterior cingulate area, are nonspecific correlates of the GF, while others, such as temporal cortical sensory processing abnormalities, are specific to the psychosis, and remain even after controlling for the GF. In order to test the prognostic significance of the GF, we will additionally test whether scores on the GF are predictive of course of illness in 50 SS patients experiencing first-episode psychosis. Taken together, the study will provide the most comprehensive test to date of the relevance of GF model to understanding the expression and neural correlates of severe psychopathology,
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1 |