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T D Geracioti

Publications and source records attributed to T D Geracioti.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cerebrospinal fluid and plasma leptin measurements: covariability with dopamine and cortisol in fasting humans.

Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, beta-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.

Adult↗
PubMed1998

Continuous covariability of dopamine and serotonin metabolites in human cerebrospinal fluid.

BACKGROUND: Experiments in lower animals and humans have demonstrated the existence of functional interactions between serotonin and dopamine in neuronal tissue. However, the relationship between parameters of serotonin and dopamine neuronal activity over time within the central nervous system (CNS) of the individual human has not yet been established. METHODS: We used continuous cerebrospinal fluid (CSF) sampling over 6 hours to test the hypothesis that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA) significantly covary in concentration over time. Two groups of normal volunteers (total n = 16) were studied at separate hospitals and CSF was assayed for 5-HIAA and HVA by high-performance liquid chromatography (HPLC). Three subjects underwent repeat CSF-withdrawal procedures after a 6-week interval. RESULTS: Strong and sustained positive covariability in concentrations of HVA and 5-HIAA was observed in the CSF of individual humans. High intraindividual correlation coefficients were +0.897 and +0.871 in the two normal volunteer groups. The HVA to 5-HIAA concentration ratio in CSF was 2.2 +/- 0.7 with very little variability over intervals ranging from minutes to weeks. CONCLUSIONS: The balance between CSF dopamine and serotonin metabolite concentrations remains relatively constant over time in healthy humans. Serial measures of CSF dopamine and serotonin metabolites within the same person could be an effective model in which to explore the interrelationships between these systems in various psychiatric syndromes, in response to drug treatment, and during provactive testing.

Adult↗
PubMed1998

Differences in thyroid function between bipolar manic and mixed states.

BACKGROUND: High rates of thyroid axis abnormalities have been reported in most studies of patients with rapid-cycling bipolar disorder. Mixed states share similarities with rapid-cycling, including close temporal occurrence of manic and depressive symptoms, predominance in women, poor outcome, and less robust response to lithium compared with pure mania; however, thyroid axis abnormalities have not been well studied in mixed mania. METHODS: To test the hypothesis that mixed states are associated with a higher prevalence of hypothyroidism than pure mania, immunoreactive triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) concentrations were determined from serum obtained at the time of admission in 37 consecutive patients with DSM-III-R bipolar disorder, manic or mixed. RESULTS: The mean TSH concentration was significantly higher, and the mean T4 concentration was significantly lower in patients with mixed mania compared with pure mania. There were no significant differences in T3 concentration or in previous lithium exposure. CONCLUSIONS: These findings suggest thyroid axis dysfunction is more common in bipolar mixed than in bipolar manic patients.

Adult↗
PubMed1998

A case of treatment-refractory psychosis responsive to sertindole.

Sertindole is an antipsychotic with atypical in vitro and ex vivo binding profiles and little propensity to cause extrapyramidal symptoms. However, its potential usefulness in the treatment of psychosis resistant to the 'classical' neuroleptics has not been determined. In the present study we used a double blind, placebo-controlled trial of sertindole and observed dramatic, sustained resolution of formerly-chronic positive and negative psychotic symptoms in a schizophrenic patient. This patient had averaged 2.5 inpatient admissions per year for the 8 years preceding initiation of sertindole therapy, but has had no hospitalizations or psychosis in the 3.5 years since. Improved cognitive function has also been documented. This preliminary, but controlled, experience suggests that sertindole may possess a spectrum of clinical activity distinct from that of the typical antipsychotic agent.

Adult↗
PubMed1998

Interpersonal trauma and animal-related experiences in female and male military veterans: implications for program development.

Exposure to trauma is more frequent than was previously recognized. The prevalence and impact of trauma events, including trauma involving animals, was assessed in age-matched male and female veterans. High rates of exposure to at least one trauma event were reported by males (95%) and females (97%). Females were more likely to report sexual and physical abuse by a significant other. Both genders experienced higher trauma rates in the military than in civilian settings. A survey of animal-related experiences showed similar rates of losing a special pet, being frightened or hurt by an animal, witnessing or perpetrating violence toward animals, and having sexual interactions with animals. Almost one-third of the veterans showed evidence of post-traumatic stress disorder symptoms, highlighting the potential benefit of trauma screening to identify veterans in need of further evaluation and treatment.

Animals↗
PubMed1997

Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression.

Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major depression. To test this CRH hypersecretion hypothesis, cerebrospinal fluid (CSF) was continuously withdrawn from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depressed patients, the majority of whom exhibited at least one "atypical" symptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH than nonsmokers. CRH increased acutely in response to lumbar puncture, had a brief half-life, showed rapid variability in concentration over time, and displayed a diurnal concentration rhythm that was preserved in fasting individuals and in most depressed patients. CSF CRH did not correlate with plasma ACTH or cortisol; this and its rapidly fluctuating levels suggest a primarily extrahypothalamic origin of lumbar CSF CRH.

Adrenocorticotropic Hormone↗
PubMed1997

Assessment of diurnal variation of cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in healthy human females.

The role of serotonin (5-HT) in the pathogenesis and treatment of major neuropsychiatric disorders, including mood and anxiety disorders, continues to be the subject of extensive research. Previous studies examining central 5-HT functioning measured cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA) by using single or multiple lumbar punctures. A number of investigators have demonstrated the feasibility of continuous CSF sampling via an indwelling lumbar catheter to study CSF neurochemistry in healthy subjects and patients with neuropsychiatric illness. Four healthy female volunteers, aged 21-34 years, underwent continuous CSF sampling. CSF was collected at a constant rate of 1 ml every 10 minutes over a 30-hour period, with levels of tryptophan (TRP) and 5-HIAA measured every hour. Plasma was also obtained hourly for TRP determination. The results of this study indicate that CSF 5-HIAA, CSF TRP, and plasma TRP levels showed variation over time, but failed to show diurnal fluctuation. Intra-individual coefficients of variation determined for CSF 5-HIAA, CSF TRP, and plasma TRP ranged from 9.2 to 14.9%, 8.8 to 14.6%, and 14.7 to 19.0%, respectively. Continuous CSF sampling is safe and feasible in humans, and may prove useful for studies of central 5-HT neurotransmission in neuropsychiatric illness.

Adult↗
PubMed1997

Cerebrospinal fluid and plasma beta-endorphin in combat veterans with post-traumatic stress disorder.

Opioid-mediated analgesia develops in experimental animals following traumatic stress and increased opioid-mediated analgesia has been observed in combat veterans with post-traumatic stress disorder (PTSD). These observations have led to the hypothesis that increased central nervous system (CNS) opioidergic activity exists in patients with PTSD. However, direct CNS data on opioid peptide concentrations and dynamics in patients with PTSD are lacking. We withdrew cerebrospinal fluid (CSF) via a flexible, indwelling subarachnoid catheter over a 6-h period and determined hourly CSF concentrations of immunoreactive beta-endorphin (ir beta END) in 10 well-characterized combat veterans with PTSD and nine matched normal volunteers. Blood was simultaneously withdrawn to obtain plasma for ir beta END. PTSD symptom clusters, as measured by the CAPS, were correlated with neuroendocrine data. Mean CSF ir beta END was significantly greater in patients with PTSD compared with normals and there was a negative correlation between the ir beta END and PTSD intrusive and avoidant symptoms of PTSD. No intergroup difference between plasma ir beta END was found, nor was there a significant correlation between CSF and plasma ir beta END. Immunoreactive beta-lipotropin (ir beta LPH) and pro-opiomelanocortin (irPOMC), both precursors of beta END, were much more plentiful in human CSF than was beta-endorphin itself, as has been previously reported. It remains to be determined whether the increased CNS opioid concentrations predate traumatic stress, thereby conferring a vulnerability to dissociative states and PTSD itself, or result from the trauma. The negative correlation between CSF ir beta END and avoidant and intrusive symptoms suggests that CNS hypersecretion of opioids might constitute an adaptive response to traumatic experience. Poor correlation between CSF and plasma ir beta END limits use of plasma measures to assess CNS opioid activity.

Adrenocorticotropic Hormone↗
PubMed1997

Regulation of corticotropin-releasing factor (CRF) messenger ribonucleic acid and CRF peptide in the amygdala: studies in primary amygdalar cultures.

Amygdalar CRF has been implicated in the mediation of stress behaviors. The signal transduction pathways that regulate amygdalar CRF are not well understood. In this report, we have examined the effect of protein kinase A and C activators, dexamethasone, and interleukin 6 on CRF messenger RNA (mRNA) and CRF peptide expression in dissociated amygdalar cultures. The amygdala from E19 rat pups was dissected out bilaterally and dissociated in 0.25% trypsin for 10-15 min and plated. On day 17 in culture, CRF mRNA and peptide were measured following treatment with the following agents: forskolin, the phorbol ester-phorbol 12 myristate 13-acetate (TPA), dexamethasone, and interleukin-6 (IL6). Both forskolin and IL6, but not TPA, increased CRF mRNA in a time- and dose-dependent manner. Secretion and intracellular content of the CRF peptide also increased with both forskolin and IL6 treatment but not with TPA. Dexamethasone treatment did not alter the expression of CRF message or peptide. Transfection of the primary cultures with a rat CRF promoter-luciferase reporter construct followed by treatment with all four agents produced alterations in luciferase expression that were consistent with changes observed at the level of CRF mRNA and peptide. The results suggest that CRF regulation in the amygdala differs from that known to occur in the hypothalamus, and that elevation of IL6 levels within the central nervous system may directly act to stimulate CRF production and secretion from limbic structures such as the amygdala, to promote subsequent behavioral changes.

Amygdala↗
PubMed1997

Uncoupling of serotonergic and noradrenergic systems in depression: preliminary evidence from continuous cerebrospinal fluid sampling.

We used the technique of continuous cerebrospinal fluid (CSF) sampling to test the following hypotheses regarding CNS monoaminergic systems in depression: (1) absolute concentrations of the informational substances tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) are altered in the CNS of depressed patients (2) abnormal rhythms of tryptophan and/or 5-HIAA, or defective conversion of tryptophan to serotonin (5HT), exist in the CNS of depressed patients, and (3) the relationship between the CNS 5HT and norepinephrine (NE) systems is disrupted in depressed patients. We obtained 6-h concentration time series of tryptophan, 5-HIAA, NE, and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF of 10 patients with major depression and in 10 normal volunteers. No significant differences in CSF tryptophan, 5-HIAA, NE, or MHPG concentrations or rhythms were observed between normal volunteers and depressed patients. Neither were there differences in the mean tryptophan-to-serotonin ratio. However, a negative linear relationship was observed between mean concentrations of 5-HIAA and NE in the CSF of the normal volunteers (r = 0.916 [r2 = 0.839], df = 9, P < 0.001) while, in contrast, depressed patients showed no such relationship (r = +0.094 [r2 = 0.00877], df = 9, n.s.). Furthermore, the correlation coefficients expressing the relationship between CSF MHPG and CSF 5-HIAA within the normal and depressed groups were significantly different. These data support the hypothesis that a disturbance in the interaction between the serotonergic and noradrenergic systems can exist in depressive illness in the absence of any simple 5HT or NE deficit or surplus.

Adult↗
PubMed1995

Fasting and postprandial cerebrospinal fluid glucose concentrations in healthy women and in an obese binge eater.

OBJECTIVE: We hypothesized that abnormal entry of glucose into the central nervous system (CNS) might exist in some chronic binge eaters of carbohydrates, as either a cause or consequence of binge eating. The purpose of this study was thus to determine fasting and postprandial glucose concentrations in the cerebrospinal fluid (CSF) of healthy women, and to obtain similar data in an obese, irritable woman with chronic binge eating of postpartum onset. METHOD: CSF was sampled continuously at 0.1 ml/min from 1100 hr to 1700 hr from the binge eating patient, who consumed 5,000 to 10,000 calories per day (preferentially binging on refined carbohydrates), and 4 healthy women via an indwelling, flexible spinal canal catheter. CSF aliquots were obtained at 10-min intervals for measurement of glucose concentrations. Simultaneously, blood was withdrawn at 30-min intervals to obtain serum for glucose assay. A glucose-rich mixed liquid meal was consumed by participants at 1300 hr. RESULTS: In striking contrast to the normal women, our bulimic patient showed no postprandial rise whatever in CSF glucose concentrations. Fasting CSF glucose concentrations were slightly lower whereas fasting serum glucose levels were normal in the bulimic patient, compared with the normal women. After eating, serum glucose levels increased in all participants, but less so in our patient. DISCUSSION: This is the first description of a lack of postprandial elevation in CSF glucose concentration in a patient with a binge eating disorder. Defective transport of glucose across the blood-brain barrier might account for the observed abnormality. While considering other possibilities, we conjecture that our patient's binge eating was an attempt to compensate for impaired postprandial entry of glucose into her CNS.

Adult↗
PubMed1995

Venlafaxine treatment of panic disorder: a case series.

BACKGROUND: Venlafaxine inhibits the neuronal reuptake of both serotonin and norepinephrine and has been shown to be an effective antidepressant; however, its potential efficacy in treating panic disorder has not yet been evaluated. METHOD: Four consecutive patients with panic disorder were administered low doses of venlafaxine in an open-label, nonblinded trial. Outcome data were obtained at regular intervals via detailed clinical exploration and patient self-report. In no case was any depth psychotherapy or attempt at conflict resolution provided. RESULTS: Panic attacks were completely eliminated in the first four patients with panic disorder that I treated with low doses of venlafaxine. Three of these patients experienced no further panic attacks after the institution of venlafaxine therapy. The total daily maintenance doses used were between 50 and 75 mg/day, and the effective starting doses were even lower. CONCLUSION: The resolution of panic disorder in all four patients treated with low doses of venlafaxine suggests that venlafaxine might be an effective treatment for panic disorder. Moreover, the rapid, apparently immediate, disappearance of panic attacks after the initiation of venlafaxine in three of four patients raises the possibility that this agent may have an unusually fast onset of action. The efficacy of low doses of venlafaxine or the need to start treatment with very low doses in patients with panic disorder was predicted by experience with other monoamine reuptake inhibitors in this patient population. Double-blind, placebo-controlled studies of venlafaxine in panic disorder are indicated.

Adult↗
PubMed1994

Concentrations of corticotropin-releasing hormone, norepinephrine, MHPG, 5-hydroxyindoleacetic acid, and tryptophan in the cerebrospinal fluid of alcoholic patients: serial sampling studies.

Abnormalities in corticotropin-releasing hormone (CRH) secretion, noradrenergic neurotransmission, and serotonergic activity in the central nervous system (CNS) have all been hypothesized to exist in alcoholic patients, as have abnormalities in hypothalamic-pituitary adrenal function. To test these hypotheses, we continuously sampled cerebrospinal fluid (CSF) from alcoholic patients after 38-124 days of abstinence and from normal volunteers via a flexible, indwelling lumbar subarachnoid catheter and measured CRH, norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), tryptophan, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations at 10-min intervals, from 11:00 through 17:00 h. The spinal canal catheter was inserted at approximately 08:00 h. Serial plasma ACTH, cortisol, and NE concentrations were also measured. A mixed liquid meal was consumed at 13:00 h. CSF CRH concentrations were lower in alcoholic patients than in normal volunteers (26 +/- 15 vs. 60 +/- 30 pg/ml, respectively, p < 0.05 by ANOVA), as were CSF NE levels (0.33 +/- 0.09 vs. 1.15 +/- 0.51 pmol/ml, respectively, p < 0.01). Plasma NE and CSF MHPG levels were normal in the alcoholic patients. CSF tryptophan and 5-HIAA and plasma ACTH and cortisol concentrations did not differ between the groups. These studies extend our finding of reduced spinal canal CSF CRH concentrations in depressed patients to abstinent chronic alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Diurnal variation of cerebrospinal fluid immunoreactive corticotropin-releasing hormone levels in healthy volunteers.

CRH is not only secreted into hypophyseal protal blood where it is believed to regulate the circadian rhythm of pituitary-adrenal activity, but is also measurable in cerebrospinal fluid (CSF). Altered CSF immunoreactive CRH (IR-CRH) levels have been found in patients with a number of neuropsychiatric disorders and have been implicated in some of the symptoms of these disorders. To further study the potential functional relevance of CRH in human CSF, we examined whether a nonuniform temporal pattern of IR-CRH levels existed in CSF using hourly sampling over a 30-h period in six healthy volunteers. CSF was withdrawn continuously at 6 mL/h through a catheter placed in the lumbar subarachnoid space and connected to a miniroller pump and fraction collector. A significant diurnal variation in CSF IR-CRH levels was observed (P < 0.001), with highest levels between 1830-2330 h and lowest levels around 0730 h. This pattern was nearly opposite that of plasma cortisol levels, which showed the expected peak around 0800 h and nadir around 2000-2200 h. In addition, CSF IR-CRH levels in three of the six volunteers showed significant negative correlations with simultaneous plasma cortisol levels. These data suggest that CSF IR-CRH concentrations are negatively modulated by peripheral cortisol secretion, which may be one factor involved in the entrainment of this rhythm. Although the functional significance of this diurnal variation in CSF IR-CRH levels is unknown, the presence of a distinct temporal organization of CRH release into the CSF in humans is compatible with the idea that CSF may play a functional role in or otherwise reflect nonsynaptic information processing in the central nervous system. Diurnal factors should be taken into account in future studies of CRH concentrations in human CSF.

Adult↗
PubMed1994

Effects of electroconvulsive therapy on the CRH-ACTH-cortisol system in melancholic depression: preliminary findings.

Hypercortisolism is one of the most consistent biological abnormalities seen in patients with major depression, particularly the melancholic subtype. We present preliminary data regarding the effects of electroconvulsive therapy (ECT) on urinary-free cortisol (UFC) excretion and on the secretion of its principal regulatory hormone, corticotropin-releasing hormone (CRH), into the cerebrospinal fluid (CSF) of patients with major depression. Our preliminary results indicate that, while acute elevations in UFC may occur with the initiation of ECT or other antidepressant treatments, successful treatment with ECT is associated with a reduction in both UFC excretion and the diurnal pattern of CSF immunoreactive CRH levels. These findings are compatible with data in experimental animals that show reductions in hypothalamic CRH expression and pituitary-adrenal function with long-term antidepressant treatments.

Adrenocorticotropic Hormone↗
PubMed1993

Cholecystokinin in human cerebrospinal fluid: concentrations, dynamics, molecular forms and relationship to fasting and feeding in health, depression and alcoholism.

Very little is known about the physiologic significance of the gut-brain hormone cholecystokinin (CCK) in the human central nervous system, although the hormone has been hypothesized to be involved in the regulation of both appetite and anxiety. We continuously collected lumbar cerebrospinal fluid (CSF) via indwelling subarachnoid catheters in ten normal volunteers, ten patients with major depression and five abstinent alcoholic humans, while fasting and after eating. Five other healthy subjects were fasted throughout the experiment. We quantified CSF immunoreactive cholecystokinin (IR-CCK) and glucose concentrations at 10-min intervals from 11.00 to 17.00 h. No difference in CSF IR-CCK concentration, half-life or rhythm was observed between normal volunteers and either depressed or alcoholic patients. Fasting CSF IR-CCK concentrations were 1.3 +/- 0.18, 1.3 +/- 0.21 and 1.2 +/- 0.21 fmol/ml (mean +/- S.E.M.) in normal volunteers, depressed patients and alcoholic patients, respectively. After eating, CSF IR-CCK concentrations rose to 1.5 +/- 0.21, 1.5 +/- 0.24 and 1.4 +/- 0.26 fmol/ml, respectively. Normal volunteers who did not eat had similar basal CSF IR-CCK concentrations (1.1 +/- 0.1 fmol/ml) which similarly rose to 1.4 +/- 0.13 fmol/ml during the sampling interval. In contrast, CSF glucose concentrations rose only in the subjects who ate, beginning to rise after about 1 h and remaining elevated for at least 3 h after eating. These data suggest the existence of a diurnal rhythm of IR-CCK release into CSF, as opposed to a response to feeding. The disappearance half-time of CCK in human CSF is less than 13 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Thyroid and adrenal dysfunction in abstinent alcoholic men: locus of disturbance.

Certain neuroendocrine abnormalities (e.g., blunted plasma adrenocorticotropic hormone [ACTH] response to corticotropin-releasing hormone [CRH] administration and blunted serum TSH response to thyrotropin-releasing hormone [TRH] administration) are common in alcoholic patients. It was the objective of this study to evaluate whether they are centrally mediated: that is, whether they are secondary to increased activity of CRH and/or TRH neurons. We evaluated the nocturnal secretion (2200 hours to 1000 hours, q 15 min) of plasma ACTH, serum cortisol, and serum TSH, and their responses to the combined administration of CRH and TRH, in 28 acutely abstinent alcoholic (age range: 32 to 57 years; mean: 42.4 years) and 19 normal men (age range: 21 to 52 years; mean: 32.1 years). To assess the validity of administering CRH and TRH simultaneously, we gave 10 additional abstinent alcoholic men (age range: 36 to 53 years; mean: 45.8 years), in random order and at least 4 days apart, either CRH, TRH, placebo, or CRH plus TRH. Nocturnal ACTH, cortisol, and TSH secretion, as well as cortisol and TSH responses after CRH plus TRH administration, were similar in alcoholic and normal men. However, ACTH peak responses to CRH plus TRH were reduced in the alcoholic men (p < 0.05). The ACTH, but not cortisol, response was greater after combined CRH plus TRH administration than after CRH alone (p < .002). The blunted ACTH response does not appear to be the result of increased endogenous CRH activity, because all parameters of nocturnal ACTH pulsatility were normal in the alcoholics. It rather appears to be secondary to an intrinsic defect in the CRH responsiveness of the pituitary corticotroph, possibly due to genetic vulnerability or to the toxic effects of prolonged alcohol abuse.

Adrenal Cortex Hormones↗