Multimodality imaging in a depressed patient with violent behavior and temporal lobe seizures.

Patients suffering from epilepsy commonly experience behavioral symptoms. Behavioral manifestations are especially prevalent in patients with seizures originating in the limbic system. This case report illustrates how an objective, multimodality work-up can guide the clinician in the diagnosis and the treatment of a patient with a complex presentation. After the discontinuation of some medications, the patient underwent a multimodality work-up that consisted of MRI, SPECT, and conventional and quantitative EEG (LORETA). In this case, the functional imaging studies showed a convergence of findings across the three modalities: MRI, SPECT and qEEG. Because of these findings, we supported more aggressive treatment of the seizure disorder. Ultimately this treatment resulted in resolution of the aggression and the depression. In summary, when applied routinely, a comprehensive, systematic, diagnostic approach will minimize treatment false starts and failures, may reduce costs, and also, potentially decrease the severity and the duration of symptoms.

Similar or disparate brain patterns? The intra-personal EEG variability of three women with multiple personality disorder.

Quantitative EEG was used to assess the intra-personal variability of brain electrical activity for 3 women diagnosed with Multiple Personality Disorder (MPD). Two separate control groups (within-subject and between-subject) were used to test the hypothesis that the intra-personal EEG variability between 2 alters would be less than the interpersonal EEG variability between 2 controls, and similar to the intra-personal EEG variability of a single personality. This hypothesis was partially supported. In general, the 2 EEG records of a MPD subject (alter 1 vs. alter 2) were more different from one another than the 2 EEG records of a single control, but less different from one another than the EEG records of 2 separate controls. Most of the EEG variability between alters involved beta activity in the frontal and temporal lobes.

Changes in regional cerebral blood flow after electroconvulsive therapy for depression.

Fifteen patients with major depression and normal results of magnetic resonance imaging or computed tomographic studies were treated by electroconvulsive therapy (ECT). The regional cerebral blood flow (rCBF) of these patients was imaged using Tc-99m hexamethylpropylene amineoxime single-photon emission computed tomography before and after treatment, and their images were compared with a population of 11 healthy volunteers. Before ECT treatment, the patients had hypoperfusion of the frontal region compared with the controls, and they had multiple areas of altered perfusion throughout the brain. Five of the patients had an excellent clinical response to ECT; these patients also showed changes toward normal in rCBF. The remaining patients had minimal to moderate clinical response and showed no significant change in rCBF. These results indicate that improvement in clinical status as a result of ECT is correlated with a change toward normal in rCBF.

Individual differences among cocaine users.

The present study examined whether individual differences in personality could differentiate two types of cocaine users. We hypothesized that self-medicators (SM) use cocaine as a way to alleviate their dysphoric moods, whereas sensation seekers (SS), in contrast, use cocaine primarily to engender positive mood states. Eighteen male cocaine users were classified based on two dimensions of the Tridimensional Personality Questionnaire. SM were defined by having high harm avoidance (>17) and low novelty-seeking scores (<18), and SS by high novelty-seeking (>18) and low harm-avoidance scores (<17). It was predicted that SM would report higher depression and anxiety than would SS, and would also exhibit a brain activity pattern similar to that found in clinical depression. The results showed that SM reported higher anxiety than SS, F(1, 8) = 27.5, p < .001, but did not differ in depression. SM exhibited decreased blood flow within the left frontal lobes, F(1, 10) = 6.78, p < .05, similar to what has been observed in major depressive disorder. These findings suggest the importance of attending to individual differences in the motivation for cocaine use so that treatment can be targeted more effectively.

Platelet cytosolic calcium hyperresponsivity to serotonin in patients with hypertension and depressive symptoms.

BACKGROUND: Data from recent studies indicate that the presence of depression is an independent risk factor for cardiovascular and cerebrovascular events. The mechanism by which depression increases the morbidity and mortality risks in patients with comorbid vascular disease is currently the object of considerable research interest. Platelets may be involved in this pathological process. Although many investigators have extensively evaluated platelet biochemistry in depressed patients, there currently exists very little information regarding how the biochemical alterations might relate to an increased risk of cardiovascular events. In this study, we examined the responsivity of platelet cytosolic calcium concentrations ([Ca++]i) to serotonin stimulation in populations of hypertensive patients with or without comorbid depressive symptoms. METHODS: We utilized Fura-2 loaded platelets to compare changes in intracellular calcium levels (delta [Ca++]i) following serotonin stimulation among 48 patients with hypertension and varying degrees of depressive symptomatology. RESULTS: We found that those patients with higher scores on standardized depression rating scales showed significantly greater [Ca++]i (82.82 +/- 15.88 mmol/L) increase compared with [Ca++]i (60.10 +/- 22.65 mmol/L) patients with lower depression scores. CONCLUSIONS: The results of this study support the hypothesis that the enhanced platelet reactivity seen in patients with depressive symptoms may mediate the deleterious effects of depression on cardiovascular disease.

Platelet cytosolic calcium responses to serotonin in depressed patients and controls: relationship to symptomatology and medication.

BACKGROUND: Serotonin produces an exaggerated rise in platelet cytosolic calcium (delta [Ca++]i) in patients with mood disorders. Studies on patients with bipolar disorder consistently demonstrate calcium abnormalities. By comparison, data on patients with major depression are more variable. METHODS: To determine causes of variability, we utilized Fura-2 loaded platelets to compare changes in platelet intracellular calcium levels (delta [Ca++]i) following serotonin stimulation in 24 patients with major depression and in 20 controls. We also sought relationships between the delta [Ca++]i responses and scores on clinical depression and anxiety scales. RESULTS: We found positive correlations between delta [Ca++]i responses and the clinical scales across all subjects. Furthermore, depressed patients with high anxiety had significantly increased delta [Ca++]i responses compared to depressed patients with low anxiety. In addition, patients receiving selective-serotonin reuptake inhibitors (SSRIs) demonstrated reduced delta [Ca++]i responses compared to patients not on SSRIs. CONCLUSIONS: Since elevations in [Ca++]i mediate platelet aggregation and secretion cascades, the enhanced responsivity observed in depressed, and in particular anxious, depressed patients may contribute to their increased risk for vascular disease.

Pathological gambling in hospitalized substance abusing veterans.

BACKGROUND: Previous studies have suggested that pathological gambling and substance abuse may be more likely to occur together than expected by chance. We examined this possibility as well as explored psychosocial and diagnostic variables that may be associated with this coincidence. METHOD: Of 276 patients who were administered the South Oaks Gambling Screen, 134 subjects were interviewed using a semistructured comprehensive psychiatric questionnaire. Data analysis utilized Student t tests or analysis of variance routines. RESULTS: The rate of comorbid pathological gambling in the sample was 33% (92 of 276). A high rate of comorbid substance abuse and pathological gambling was associated with a positive history of childhood experiences of gambling in the family group (p = .001) and with larger family size (p = .001). In addition, current alcohol consumption was significantly higher (p = .007) in the pathological gambling group. CONCLUSION: Comorbidity of substance abuse and pathological gambling is common in substance abuse patients in a VA hospital. Substance abuse treatment programs should identify patients with pathological gambling and include treatment interventions that address both problems.

Effect of corticosterone on serotonin and catecholamine receptors and uptake sites in rat frontal cortex.

The effects of corticosterone (1 mg/kg per day for 7 days) on serotonin 5-HT1A, 5-HT2A, 5-HT uptake sites, and alpha 2-adrenergic receptor sites were measured. Corticosterone treatment significantly decreased the number of 5-HT1A receptor sites (Bmax = 108 +/- 8.20 fmol/mg protein and 152.31 +/- 13.36 fmol/mg protein in corticosterone- and vehicle-treated rats, respectively). No significant differences were found in other measures. It is possible that corticosteroids exert some of their behavioral effects via regulation of 5-HT1A sites in frontal cortex.

Serotonin-induced increases in platelet cytosolic calcium concentration in depressed, schizophrenic, and substance abuse patients.

Exaggerated intracellular calcium responses to challenges with serotonin (5-HT) have been reported in depression. In our studies, consistent with previous reports, patients with depression exhibited an exaggerated increase in 5-HT-stimulated intracellular calcium concentration ([Ca++]i). Basal cytosolic calcium was elevated in both calcium-free and 1 mM calcium media in depressed patients. the increased responsiveness to 5-HT was seen in both conditions. Patients with schizophrenia and substance abuse did not differ from normal controls. The 5-HT response was correlated with diastolic blood pressure (r = 0.33, p = 0.02): however, this association did not fully account for the exaggerated [Ca++]i responses in the depressed group. These findings suggest that exaggerated increases in [Ca++]i in response to serotonin are a characteristic of depressed patients not shared with schizophrenic and substance abuse patients. The relationship of depression to hypertension, two conditions that share abnormalities of calcium homeostasis, warrants further study.

Cocaine and metabolites in human graying hair: pigmentary relationship.

OBJECTIVE: To assess differences in the binding of cocaine, cocaethylene, and benzoylecgonine among pigmented and senile white hairs of the graying human cocaine abuser. DESIGN: A sheath of graying hair in the region around the apex of the head was gathered between the thumb and index finger then cut and removed about 2 mm proximal to the scalp. The graying hair was divided into pigmented and senile white of equal weights and lengths and then analyzed by gas chromatography/mass spectrometry chemical ionization. Twenty-nine such pairs were analyzed. SUBJECTS: Male cocaine abusers, ages 33-55 years hospitalized for substance abuse. Informed consent was obtained and confidentiality assured. MAIN OUTCOME MEASURES: Concentrations of cocaine, cocaethylene and benzoylecgonine in ng were assessed for each of 29 paired hair samples by gas chromatography/mass spectrometry chemical ionization. RESULTS: There were statistically significant differences between pigmented and senile white sections of paired samples. Cocaine (ng/mg hair, mean +/- SD) was 31.5 +/- 30.2 for pigmented hair vs 14.9 +/- 19.8 for senile white portions; (p < 0.0001). Cocaethylene (ng/mg hair, mean +/- SD) 3.22 +/- 5.0 (pigmented) vs 0.52 +/- 0.88 (senile white); (p < 0.0016). Benzoylecgonine (ng/mg hair, mean +/- SD) 5.1 +/- 5.3 (pigmented) vs 3.9 +/- 4.8 (senile white); (p < 0.005). CONCLUSION: Melaninated pigmented hair seems to bind more cocaine, cocaethylene and benzoylecgonine than white hair in the same subject.

Production of nitric oxide and transforming growth factor-beta in developing and adult rat brain.

Nitric oxide (NO) has been suggested to have a neurotoxic role in the brain, while transforming growth factor-beta (TGF-beta) has been considered to be a suppressor of inflammatory cytokine release. The amounts of these modulators that are released by rat brain cultures were measured for tissue obtained from rats of different maturational age groups: weanling (3 weeks), young (3 months), and middle-aged (12 months) rats. Basal levels of brain-derived NO increased with age. This was attributed to brain microglial-derived NO. Culturing of the brain tissue with LPS or PGE2 further increased the amount of NO elaborated from brain cultures of 3-week-old and 3-month-old rats to a level that was similar to the high amounts detected in unstimulated brain cultures from 12-month-old rats. Stimulation of brain cultures from 12-month-old rats did not further enhance NO levels. In contrast to the maturation-associated increase in NO production, levels of brain-derived bioactive TGF-beta declined with age. LPS and PGE2 increased the amount of bioactive TGF-beta released by brain cultures of each rat age group, but there nevertheless remained an age-related reduction in active TGF-beta levels. These results suggest a possible developmental association between an enhancement of brain-derived NO and a concomitant decline in brain TGF-beta.

Hypodensity of platelet serotonin uptake sites in posttraumatic stress disorder: associated clinical features.

We have previously reported that binding to blood platelets of paroxetine, a selective serotonin (5-HT) reuptake inhibitor which binds to 5-HT uptake sites, is decreased in patients with posttraumatic stress disorder (PTSD). Specifically, we found a lower number of platelet 3H-paroxetine binding sites (Bmax) and a lower dissociation constant (Kd) for 3H-paroxetine binding in combat veterans with PTSD compared to normal control subjects. In the current study we assessed the relationship of platelet 3H-paroxetine binding to clinical features in 41 Vietnam combat veterans with SCID-diagnosed PTSD. The results indicated that Bmax of platelet 3H-paroxetine binding was negatively correlated with both state and trait anxiety, as well as with depressive and overall PTSD symptoms. However, there was no evidence that platelet 3H-paroxetine binding differed as a function of comorbid psychiatric diagnoses including major depression, other anxiety disorders, and substance abuse in these patients.

The in vitro differential binding of benzoylecgonine to pigmented human hair samples.

Only fragmentary information on the relationship between hair pigmentation (melanin) and the cocaine/benzoylecgonine content of hair samples is available. The in vitro incorporation of benzoylecgonine into the shafts of black, brown, and blond samples of human hair was accomplished. Post digestion analysis and wash samples demonstrate the relative incorporated ions of benzoylecgonine to be black > brown > blond. Melanin content seems to be important. Lightly pigmented blond hairs may be less appropriate samples for benzoylecgonine and cocaine analysis.

Platelet paroxetine binding and fluoxetine pharmacotherapy in posttraumatic stress disorder: preliminary observations on a possible predictor of clinical treatment response.

Recent open clinical trials have found the selective serotonin reuptake inhibitor (SSRI) fluoxetine to be beneficial in the treatment of posttraumatic stress disorder (PTSD) symptoms. We have reported previously that the binding of a newer SSRI, paroxetine, to blood platelets is decreased in PTSD patients compared to normal control subjects. In the current study, pretreatment platelet paroxetine binding data were analyzed for ten Vietnam combat veterans who were treated clinically with fluoxetine for PTSD, diagnosed on the basis of the Structured Clinical Interview for DSM-III-R. Specific binding of 3H-paroxetine is reported in terms of the dissociation constant (Kd) and the maximum density of binding sites (Bmax). Based on our previous findings we hypothesized that decreased platelet 3H-paroxetine binding would be associated with positive therapeutic response to subsequent treatment with fluoxetine. Global clinical improvement ratings, conducted blind to the biochemical data, were used to separate patients into five maximal responders and five partial responders. The results indicated that maximal responders had lower pretreatment Kd values (p = .016) and a trend toward lower pretreatment Bmax values (p = .075) than the partial responders. These preliminary findings may warrant further study of platelet SSRI binding as a possible predictor of SSRI treatment response in PTSD patients.

Aging and 3H-paroxetine binding in rat brain: effect of imipramine and tetrahydroacridine.

3H-Paroxetine (PA) binding was studied in the frontal cortex (FC) and hippocampus (H) of 4 mos (young), 15 mos (adult) and 24 mos (aged) old Fischer 344 rats. Bmax (maximum number of binding sites) of PA binding was significantly higher in the H of adult rats compared with either young or old rats. There was no difference in Bmax between young and old rats. No change in Kd was observed in H and Kd or Bmax in FC with age. We also studied the effect of imipramine and tetrahydroacridine (THA) on PA binding in FC and H. Both drugs inhibited PA binding in FC and H but THA was 2000 times less potent than imipramine. There was no effect of age on IC50 values of imipramine and THA. These observations suggest that the number of 5-HT transporter sites in the hippocampus increases with brain maturity but then drops significantly during old age. This finding may have implications for age-related decrements in learning and memory, thought to be mediated by hippocampal structures.

Paroxetine binding in the blood platelets of post-traumatic stress disorder patients.

Platelet serotonin (5-HT) uptake, as determined by 3H-paroxetine (PA) binding, was studied in 20 Post-traumatic Stress Disorder (PTSD) patients and 20 normal controls. Kd (an inverse measure of affinity of 3H-PA binding to uptake sites) and Bmax (maximum number of 3H-PA binding sites) of 3H-PA binding were significantly decreased in PTSD patients as compared to normal controls. However, there was no difference in Kd or Bmax between PTSD patients with and without a diagnosis of major depression. The Bmax of 3H-PA binding was negatively correlated with state dependent anxiety score whereas Kd was positively correlated with the Mississippi Scale for Combat-Related PTSD score. The role of serotonergic processes in the psychobiology of PTSD is discussed.

Current pharmacotherapies for cocaine abuse: a review.

This article attempts to summarize the results of clinical trials on various pharmacotherapies for cocaine abuse described in the literature. A wide variety of drugs have been used for cocaine abuse. They include drugs for the treatment of coexisting psychiatric disorders, cocaine antagonists, dopamimetic agents, L-dopa/carbidopa, the amino acids tyrosine and tryptophan, antidepressants, anticonvulsants, and antabuse-like drugs. Emphasis is placed throughout this review on how extensively each drug has been tested, how successful each drug has proven to be in treating cocaine abuse, and on which drugs require further investigation.

Regulation of murine T-lymphocyte function by spleen cell-derived and exogenous serotonin.

The modulatory effects of serotonin on T-cell activity were investigated. T-cell blastogenesis of normal spleen cells was slightly stimulated by the addition of low doses (1 and 10 ng/ml) of the inducer of serotonin release, fenfluramine. In contrast to the stimulatory effects of low doses of fenfluramine, high doses of fenfluramine (1 and 10 ug/ml) or of exogenously added serotonin (> or = 0.1 ug/ml) inhibited T-cell activation. Both the stimulation by low dose fenfluramine and the inhibition by high dose fenfluramine were accentuated by pretreating mice with tryptophan to heighten intracellular stores of serotonin and then inducing serotonin release. Pretreatment of mice with the serotonin inhibitor p-chlorophenylalanine (PCPA) abolished the fenfluramine inhibition of T-cell activation indicating that the fenfluramine inhibitory effect was mediated via endogenous spleen cell-derived serotonin. However, the PCPA treatment diminished T-cell activation. These results suggest that endogenous serotonin causes a biphasic dose-response effect on T-cell activity with serotonin being required for optimal T-cell function, low doses being immune stimulatory and higher doses being suppressive.