While pharmacological treatments for psychiatric disorders have offered great promise and have pr... more While pharmacological treatments for psychiatric disorders have offered great promise and have provided clinically meaningful symptom relief these treatments have had less effect on altering the course of these disorders. Research has provided many new insights about the effects of different psychotropic agents on the functions of various brain systems as investigators have embraced the “translational research model.” However, this theoretical approach of deconstructing complex behaviors into smaller measurable behavioral units and targeting brain systems that are hypothesized to underlie these discrete behaviors has offered little of practical clinical relevance to significantly improve the treatment of psychiatric disorders in this century. Radical new treatments have not emerged, and available treatments continue to provide symptom relief without resolution of the underlying conditions. Recent publications on the subject have attempted to identify the barriers to progress and hav...
2 Mike is the CEO of a multinational pharmaceutical company, and he's in trouble. With the pa... more 2 Mike is the CEO of a multinational pharmaceutical company, and he's in trouble. With the patents on several key drugs due to expire soon, his business desperately needs to become more entrepreneurial, par- ticularly in its ability to form internal and external part- nerships to reduce time-to-market. Yet his organization has a silo mentality, with highly competitive teams secretly working against one another. How can Mike change the way thousands of people at his company
Philosophical Transactions of the Royal Society B: Biological Sciences, 2005
Neuropsychological research on the neural basis of behaviour generally posits that brain mechanis... more Neuropsychological research on the neural basis of behaviour generally posits that brain mechanisms will ultimately suffice to explain all psychologically described phenomena. This assumption stems from the idea that the brain is made up entirely of material particles and fields, and that all causal mechanisms relevant to neuroscience can therefore be formulated solely in terms of properties of these elements. Thus, terms having intrinsic mentalistic and/or experiential content (e.g. ‘feeling’, ‘knowing’ and ‘effort’) are not included as primary causal factors. This theoretical restriction is motivated primarily by ideas about the natural world that have been known to be fundamentally incorrect for more than three-quarters of a century. Contemporary basic physical theory differs profoundly from classic physics on the important matter of how the consciousness of human agents enters into the structure of empirical phenomena. The new principles contradict the older idea that local mech...
Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention signifi... more Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention significantly improves obsessive-compulsive disorder (OCD) symptoms in as little as 4 weeks. However, it has been thought that much longer treatment was needed to produce the changes in brain function seen in neuroimaging studies of OCD. We sought to elucidate the brain mediation of response to brief intensive CBT for
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right... more In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response reve...
Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and... more Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non-sex-matched patients with mania. Mean (+/- SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 +/- 0.05; bipolar depression = 1.04 +/- 0.05), and were significantly lower than those in normal controls (1.12 +/- 0.06) or OCD without depression (1.15 +/- 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 +/- 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 +/- 0.03) on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n = 12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem.(ABSTRACT TRUNCATED AT 250 WORDS)
While pharmacological treatments for psychiatric disorders have offered great promise and have pr... more While pharmacological treatments for psychiatric disorders have offered great promise and have provided clinically meaningful symptom relief these treatments have had less effect on altering the course of these disorders. Research has provided many new insights about the effects of different psychotropic agents on the functions of various brain systems as investigators have embraced the “translational research model.” However, this theoretical approach of deconstructing complex behaviors into smaller measurable behavioral units and targeting brain systems that are hypothesized to underlie these discrete behaviors has offered little of practical clinical relevance to significantly improve the treatment of psychiatric disorders in this century. Radical new treatments have not emerged, and available treatments continue to provide symptom relief without resolution of the underlying conditions. Recent publications on the subject have attempted to identify the barriers to progress and have pointed out some of the limitations of the translational approach. It is our position that, given the present limitations of our therapeutic arsenal, both researchers and clinicians would be well-advised to pay closer attention to human specific factors such as the role of language, the creation of personal narratives, and how factors such as these interface with underlying biological diatheses in mental illness. These interactions between pathophysiology and intrapersonal processes may be critical to both the in vivo expression of the underlying biological mechanisms of psychiatric disease states, and to the development of enhancements in therapeutic efficacy. Lastly, we discuss the implications of more coherently integrating neuroscientific research and clinical practice for more effectively addressing the challenges of understanding and treating mental illness.
While pharmacological treatments for psychiatric disorders have offered great promise and have pr... more While pharmacological treatments for psychiatric disorders have offered great promise and have provided clinically meaningful symptom relief these treatments have had less effect on altering the course of these disorders. Research has provided many new insights about the effects of different psychotropic agents on the functions of various brain systems as investigators have embraced the “translational research model.” However, this theoretical approach of deconstructing complex behaviors into smaller measurable behavioral units and targeting brain systems that are hypothesized to underlie these discrete behaviors has offered little of practical clinical relevance to significantly improve the treatment of psychiatric disorders in this century. Radical new treatments have not emerged, and available treatments continue to provide symptom relief without resolution of the underlying conditions. Recent publications on the subject have attempted to identify the barriers to progress and hav...
2 Mike is the CEO of a multinational pharmaceutical company, and he's in trouble. With the pa... more 2 Mike is the CEO of a multinational pharmaceutical company, and he's in trouble. With the patents on several key drugs due to expire soon, his business desperately needs to become more entrepreneurial, par- ticularly in its ability to form internal and external part- nerships to reduce time-to-market. Yet his organization has a silo mentality, with highly competitive teams secretly working against one another. How can Mike change the way thousands of people at his company
Philosophical Transactions of the Royal Society B: Biological Sciences, 2005
Neuropsychological research on the neural basis of behaviour generally posits that brain mechanis... more Neuropsychological research on the neural basis of behaviour generally posits that brain mechanisms will ultimately suffice to explain all psychologically described phenomena. This assumption stems from the idea that the brain is made up entirely of material particles and fields, and that all causal mechanisms relevant to neuroscience can therefore be formulated solely in terms of properties of these elements. Thus, terms having intrinsic mentalistic and/or experiential content (e.g. ‘feeling’, ‘knowing’ and ‘effort’) are not included as primary causal factors. This theoretical restriction is motivated primarily by ideas about the natural world that have been known to be fundamentally incorrect for more than three-quarters of a century. Contemporary basic physical theory differs profoundly from classic physics on the important matter of how the consciousness of human agents enters into the structure of empirical phenomena. The new principles contradict the older idea that local mech...
Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention signifi... more Brief intensive cognitive-behavioral therapy (CBT) using exposure and response prevention significantly improves obsessive-compulsive disorder (OCD) symptoms in as little as 4 weeks. However, it has been thought that much longer treatment was needed to produce the changes in brain function seen in neuroimaging studies of OCD. We sought to elucidate the brain mediation of response to brief intensive CBT for
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right... more In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response reve...
Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and... more Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non-sex-matched patients with mania. Mean (+/- SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 +/- 0.05; bipolar depression = 1.04 +/- 0.05), and were significantly lower than those in normal controls (1.12 +/- 0.06) or OCD without depression (1.15 +/- 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 +/- 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 +/- 0.03) on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n = 12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem.(ABSTRACT TRUNCATED AT 250 WORDS)
While pharmacological treatments for psychiatric disorders have offered great promise and have pr... more While pharmacological treatments for psychiatric disorders have offered great promise and have provided clinically meaningful symptom relief these treatments have had less effect on altering the course of these disorders. Research has provided many new insights about the effects of different psychotropic agents on the functions of various brain systems as investigators have embraced the “translational research model.” However, this theoretical approach of deconstructing complex behaviors into smaller measurable behavioral units and targeting brain systems that are hypothesized to underlie these discrete behaviors has offered little of practical clinical relevance to significantly improve the treatment of psychiatric disorders in this century. Radical new treatments have not emerged, and available treatments continue to provide symptom relief without resolution of the underlying conditions. Recent publications on the subject have attempted to identify the barriers to progress and have pointed out some of the limitations of the translational approach. It is our position that, given the present limitations of our therapeutic arsenal, both researchers and clinicians would be well-advised to pay closer attention to human specific factors such as the role of language, the creation of personal narratives, and how factors such as these interface with underlying biological diatheses in mental illness. These interactions between pathophysiology and intrapersonal processes may be critical to both the in vivo expression of the underlying biological mechanisms of psychiatric disease states, and to the development of enhancements in therapeutic efficacy. Lastly, we discuss the implications of more coherently integrating neuroscientific research and clinical practice for more effectively addressing the challenges of understanding and treating mental illness.
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Papers by Jeffrey Schwartz