Objective: A method is presented here to calculate the delay of BOLD response based on the tempor... more Objective: A method is presented here to calculate the delay of BOLD response based on the temporal center of the BOLD impulse response function (IRF) and can be a useful extension of the deconvolution analysis technique developed by Ward (1) for event-related fMRI studies in AFNI software. Its application is demonstrated through mapping of the modified neural responses associated with prepulse inhibition (PPI), referring to the reduction in sensorimotor activation that occurs when a startling stimulus is immediately preceded by a non-startling stimulus (i.e. prepulse) (2). Methods: The IRF is first estimated based on the deconvolution analysis. Assuming the coefficients of the IRF are sufficient to represent the general shape of the IRF, the temporal center of brain activity (TCA) is calculated through TCA = [Σ((h n -h min) (n + 1) TR)/(Σ(h n -h min)] -TR, where h n = the n th coefficient of IRF from zero to the last one, h min = the minimum of all coefficients of IRF, and TR = tim...
Tolerability and safety considerations play a major role in selecting medications for patients wi... more Tolerability and safety considerations play a major role in selecting medications for patients with schizophrenia. With the exception of clozapine, recent data demonstrate that the efficacy of antipsychotics is similar across and within first and second generation agents. In contrast, there is great variation in the nature and severity of adverse effects among these agents which can markedly influence quality of life and adherence. Adverse effects over the short- and long term may produce permanent disability and at times can be life-threatening. Indeed, they contribute substantially to the diminished life expectancy of our patients. Hence, medication selection requires a thorough understanding of tolerability and safety considerations for each agent, as well as a careful assessment of the patient’s risk factors and preferences.
Individuals with schizophrenia display notable deficits in social functioning. Research indicates... more Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, the authors used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n = 28) and controls (n = 32). The authors also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity an...
... INFLUENCE OF THE HIPPOCAMPUS SUBICULUM ON ANTIDIURETIC HORMONE LEVELS DURING STRESS Morris B.... more ... INFLUENCE OF THE HIPPOCAMPUS SUBICULUM ON ANTIDIURETIC HORMONE LEVELS DURING STRESS Morris B. Goldman and Kendall W. Nettles ... Parrot RF, Thornton SN, Forsling ML, Delaney CE (1987) Endocrine and behavioral factors affecting water balance in ...
To identify the mechanism of unexplained hyponatremia and primary polydipsia in schizophrenia and... more To identify the mechanism of unexplained hyponatremia and primary polydipsia in schizophrenia and its relationship to the underlying psychiatric illness. Briefly review previous studies that led to the conclusion the hyponatremia reflects altered hippocampal inhibition of peripheral neuroendocrine secretion. In greater detail, present the evidence supporting the hypothesis that circuit dysfunction associated with the hyponatremia and the polydipsia contributes to the underlying mental disorder. Polydipsic patients with and without hyponatremia exhibit enhanced neuroendocrine responses to psychological stress in proportion to structural deformations on their anterior hippocampus, amygdala and anterior hypothalamus. Nonpolydipsic patients exhibit blunted responses and deformations on other hippocampal and amygdala surfaces. The deformations in polydipsic patients are also proportional to diminished peripheral oxytocin levels and impaired facial affect recognition that is reversed by i...
Progress in neuro-psychopharmacology & biological psychiatry, 2000
1. Many polydipsic schizophrenics exhibit enhanced antidiuretic hormone (ADH) activity and thus a... more 1. Many polydipsic schizophrenics exhibit enhanced antidiuretic hormone (ADH) activity and thus are hyponatremic and suffer life-threatening water intoxication. Excess cortisol inhibits ADH, while cortisol insufficiency produces impairments in water balance resembling those seen in hyponatremic schizophrenics. Furthermore, hyponatremia normally upregulates cortisol receptors on the neurons which synthesize ADH, which should make them more sensitive to the effects of cortisol. 2. The author treated a hyponatremic schizophrenic, whose water imbalance was unresponsive to standard clinical interventions including clozapine, with a 4-week open trial of 60 mg cortisol daily, followed by a three week taper. 3. Mean serum sodium levels appeared to increase modestly from 114.3 to 118.5 mEq/l while the patient received adjunctive cortisol (P < .06). 4. While a modest effect was seen, the results do not suggest that adjunctive cortisol will reverse hyponatremia, and instead support other da...
The Journal of neuropsychiatry and clinical neurosciences, 1999
Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant s... more Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI: 5.5-25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia.
Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic polydipsic patients... more Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic polydipsic patients with schizophrenia. Mean dose fell from 1980 +/- 1289 to 631 +/- 135 chlorpromazine equivalents/day over a mean of 12.2 weeks until behavioral relapse occurred. During this time, serum sodium did not vary from baseline levels (132.9 +/- 4.9 mEq/1), suggesting that minimizing neuroleptic dose does not alter the severity of hyponatremia in these patients.
An effective, practical, and inexpensive method of preventing water intoxication in inpatients is... more An effective, practical, and inexpensive method of preventing water intoxication in inpatients is described. The procedure uses the relationship between acute changes in body water and body weight to predict body weights associated with severe hyponatremia.
Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-... more Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-induced disorders of water balance, which include excessive water intake, excessive water excretion, and impaired water excretion. Patients with these disorders manifest polydipsia and polyuria with or without symptomatic hyponatremia (low serum sodium concentration). Other serious sequelae include life-threatening water intoxication. The author reviews the physiology of normal water balance and the mechanism, causes, clinical presentation, and diagnosis of disorders of water balance. Interventions must first focus on identifying reversible factors. Medication-induced water imbalance can usually be reversed without compromising treatment of the underlying psychiatric disorder. A fully effective treatment for idiopathic polydipsia has not been found, although providing optimal treatment for the underlying psychiatric disorder often helps. Monitoring changes in body weight, in conjunction ...
Objective: A method is presented here to calculate the delay of BOLD response based on the tempor... more Objective: A method is presented here to calculate the delay of BOLD response based on the temporal center of the BOLD impulse response function (IRF) and can be a useful extension of the deconvolution analysis technique developed by Ward (1) for event-related fMRI studies in AFNI software. Its application is demonstrated through mapping of the modified neural responses associated with prepulse inhibition (PPI), referring to the reduction in sensorimotor activation that occurs when a startling stimulus is immediately preceded by a non-startling stimulus (i.e. prepulse) (2). Methods: The IRF is first estimated based on the deconvolution analysis. Assuming the coefficients of the IRF are sufficient to represent the general shape of the IRF, the temporal center of brain activity (TCA) is calculated through TCA = [Σ((h n -h min) (n + 1) TR)/(Σ(h n -h min)] -TR, where h n = the n th coefficient of IRF from zero to the last one, h min = the minimum of all coefficients of IRF, and TR = tim...
Tolerability and safety considerations play a major role in selecting medications for patients wi... more Tolerability and safety considerations play a major role in selecting medications for patients with schizophrenia. With the exception of clozapine, recent data demonstrate that the efficacy of antipsychotics is similar across and within first and second generation agents. In contrast, there is great variation in the nature and severity of adverse effects among these agents which can markedly influence quality of life and adherence. Adverse effects over the short- and long term may produce permanent disability and at times can be life-threatening. Indeed, they contribute substantially to the diminished life expectancy of our patients. Hence, medication selection requires a thorough understanding of tolerability and safety considerations for each agent, as well as a careful assessment of the patient’s risk factors and preferences.
Individuals with schizophrenia display notable deficits in social functioning. Research indicates... more Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, the authors used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n = 28) and controls (n = 32). The authors also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity an...
... INFLUENCE OF THE HIPPOCAMPUS SUBICULUM ON ANTIDIURETIC HORMONE LEVELS DURING STRESS Morris B.... more ... INFLUENCE OF THE HIPPOCAMPUS SUBICULUM ON ANTIDIURETIC HORMONE LEVELS DURING STRESS Morris B. Goldman and Kendall W. Nettles ... Parrot RF, Thornton SN, Forsling ML, Delaney CE (1987) Endocrine and behavioral factors affecting water balance in ...
To identify the mechanism of unexplained hyponatremia and primary polydipsia in schizophrenia and... more To identify the mechanism of unexplained hyponatremia and primary polydipsia in schizophrenia and its relationship to the underlying psychiatric illness. Briefly review previous studies that led to the conclusion the hyponatremia reflects altered hippocampal inhibition of peripheral neuroendocrine secretion. In greater detail, present the evidence supporting the hypothesis that circuit dysfunction associated with the hyponatremia and the polydipsia contributes to the underlying mental disorder. Polydipsic patients with and without hyponatremia exhibit enhanced neuroendocrine responses to psychological stress in proportion to structural deformations on their anterior hippocampus, amygdala and anterior hypothalamus. Nonpolydipsic patients exhibit blunted responses and deformations on other hippocampal and amygdala surfaces. The deformations in polydipsic patients are also proportional to diminished peripheral oxytocin levels and impaired facial affect recognition that is reversed by i...
Progress in neuro-psychopharmacology & biological psychiatry, 2000
1. Many polydipsic schizophrenics exhibit enhanced antidiuretic hormone (ADH) activity and thus a... more 1. Many polydipsic schizophrenics exhibit enhanced antidiuretic hormone (ADH) activity and thus are hyponatremic and suffer life-threatening water intoxication. Excess cortisol inhibits ADH, while cortisol insufficiency produces impairments in water balance resembling those seen in hyponatremic schizophrenics. Furthermore, hyponatremia normally upregulates cortisol receptors on the neurons which synthesize ADH, which should make them more sensitive to the effects of cortisol. 2. The author treated a hyponatremic schizophrenic, whose water imbalance was unresponsive to standard clinical interventions including clozapine, with a 4-week open trial of 60 mg cortisol daily, followed by a three week taper. 3. Mean serum sodium levels appeared to increase modestly from 114.3 to 118.5 mEq/l while the patient received adjunctive cortisol (P < .06). 4. While a modest effect was seen, the results do not suggest that adjunctive cortisol will reverse hyponatremia, and instead support other da...
The Journal of neuropsychiatry and clinical neurosciences, 1999
Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant s... more Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI: 5.5-25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia.
Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic polydipsic patients... more Neuroleptic dosage was reduced by 10% every 2 weeks in five male hyponatremic polydipsic patients with schizophrenia. Mean dose fell from 1980 +/- 1289 to 631 +/- 135 chlorpromazine equivalents/day over a mean of 12.2 weeks until behavioral relapse occurred. During this time, serum sodium did not vary from baseline levels (132.9 +/- 4.9 mEq/1), suggesting that minimizing neuroleptic dose does not alter the severity of hyponatremia in these patients.
An effective, practical, and inexpensive method of preventing water intoxication in inpatients is... more An effective, practical, and inexpensive method of preventing water intoxication in inpatients is described. The procedure uses the relationship between acute changes in body water and body weight to predict body weights associated with severe hyponatremia.
Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-... more Many mentally ill patients, particularly those with schizophrenia, have idiopathic or medication-induced disorders of water balance, which include excessive water intake, excessive water excretion, and impaired water excretion. Patients with these disorders manifest polydipsia and polyuria with or without symptomatic hyponatremia (low serum sodium concentration). Other serious sequelae include life-threatening water intoxication. The author reviews the physiology of normal water balance and the mechanism, causes, clinical presentation, and diagnosis of disorders of water balance. Interventions must first focus on identifying reversible factors. Medication-induced water imbalance can usually be reversed without compromising treatment of the underlying psychiatric disorder. A fully effective treatment for idiopathic polydipsia has not been found, although providing optimal treatment for the underlying psychiatric disorder often helps. Monitoring changes in body weight, in conjunction ...
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