Search PubMed⌕ Search

Biomedical subjects

D Pickar

Publications and source records attributed to D Pickar.

At least 181 records · Page 10Linked to original sources
PubMed1986

Relative activity of metabolic pathways for norepinephrine in endogenous depression.

Thirteen patients with endogenous depression, compared to 25 normal controls, had a significantly greater ratio of the urinary excretion of norepinephrine plus its metabolite normetanephrine to either the sum of the two urinary norepinephrine metabolites 3-methoxy-4-hydroxyphenylglycol plus vanillylmandelic acid or to the sum of urinary norepinephrine and all of its metabolites. As urinary levels of norepinephrine and normetanephrine are derived from an extraneuronal metabolic pathway, while levels of 3-methoxy-4-hydroxyphenylglycol and vanillylmandelic acid are more representative of total norepinephrine metabolism, these results suggest that there is a shift in endogenous depression to extraneuronal metabolic pathways for norepinephrine and its metabolites.

Adult↗
PubMed1986

Suicide and aggression in schizophrenia. Neurobiologic correlates.

In this study of schizophrenic patients, we were unable to find an association between past history of suicide attempt and levels of CSF amine metabolites, response to DST, and ventricular size by CT scan, neurobiologic variables each of which have been reported to be associated with attempted suicide in some patient groups. Our data, however, demonstrate the marked responsiveness of measures of aggressive behavior to neuroleptic treatment, suggesting a dopaminergic involvement in these behaviors when observed in the presence of overt psychotic symptoms. Some support for an association between decreased CNS serotonin function and aggressive behavior was found in drug-free schizophrenics, although difficulty in separating illness from trait factors is an important confounding variable. The need for clinical interventions required to treat severely disturbed and aggressive behavior in the schizophrenic patients studied could not be predicted by any of the neurobiologic variables.

Aggression↗
PubMed1986

Topographic differences between normals and schizophrenics: the N120 evoked potential component.

Topographic differences in evoked potentials were measured in 20 off-medication chronic schizophrenics and 24 normal controls. Four intensities of brief electrical shocks were administered to the subject's right forearm in a random order at 1-second intervals. Evoked potentials (EPs) were recorded from the scalp over the left hemisphere. The EP data from 16 left hemisphere leads were used to generate EP maps of brain response for individual subjects. The maps were normalized by z transformation. Group mean maps of EP activity and unpaired t tests were then computed. Normals showed strongly localized activity in the pre- and postcentral gyri, with increasing intensity resulting in the attenuation of parietal response. Schizophrenics showed more diffuse EP activity which did not vary with intensity. Significant differences between normals and schizophrenics were found for all four intensities in posterior frontal and anterior parietal cortex. This is consistent with the findings of small EPs reported by others in the somatosensory, visual and auditory modalities.

Adult↗
PubMed1986

The corticotropin-releasing hormone stimulation test in chronic schizophrenia.

During a drug-free period a group of schizophrenic subjects (N = 9) showed normal mean basal plasma ACTH and cortisol levels in association with normal plasma ACTH and cortisol responses to an infusion of corticotropin-releasing hormone (CRH). Administration of fluphenazine had no effect on basal ACTH and cortisol levels or their responses to CRH (N = 8). These data differ from those previously reported in depressed patients, who showed elevated basal cortisol values in association with a blunted ACTH response to CRH, and add to a growing body of literature which suggests that hypothalamic-pituitary-adrenal regulation is less disturbed in schizophrenia than in depression.

Adrenocorticotropic Hormone↗
PubMed1986

Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression.

Depressed patients who had attempted suicide (N = 19) had significantly lower CSF homovanillic acid (HVA) levels than patients who had not attempted suicide (N = 8) and control subjects (N = 41). Intergroup levels of 5-hydroxyindoleacetic acid (5-HIAA) were not significantly different. The ratio of CSF HVA to CSF 5-HIAA was significantly lower in both patient groups than in control subjects, and patients who had attempted suicide had CSF HVA/5-HIAA ratios that were nearly 50% those of the control subjects. The combinations of nonsuppression on the dexamethasone suppression test and either a low CSF HVA level or a low CSF HVA/5-HIAA ratio were significantly more common among patients who had attempted suicide than among those who had not.

Adult↗
PubMed1986

Serum antibodies to Epstein-Barr virus in patients with major depressive disorder.

To determine whether major depressive disorder might be associated with serologic evidence for a chronic active Epstein-Barr virus infection, viral-specific antibodies were measured in two separate groups of depressed patients (N=43) and in 46 appropriately matched healthy volunteers. No evidence that depression affects cellular immunity to the point that a persistent Epstein-Barr virus carrier state becomes activated was found. There was also no evidence that depression results from an unrecognized chronic active Epstein-Barr virus infection. The authors conclude that the routine clinical determination of expensive commercial Epstein-Barr virus antibody profiles is not indicated in most patients with major depressive disorder in the absence of other signs of chronic active Epstein-Barr viral infection.

Adult↗
PubMed1986

Plasma MHPG in depressive disorders and relationship to the dexamethasone suppression test.

Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in 51 depressed patients and 43 normal control subjects. There were significantly higher plasma MHPG levels in the combined patient group with current or past melancholia (N = 28) than in nonmelancholic (N = 12) or dysthymic (N = 11) patients, in unipolar melancholic (N = 16) versus bipolar melancholic (N = 4) patients, and in patients with a major depressive episode who failed to suppress cortisol after the dexamethasone suppression test (N = 24) versus patients with normal suppression (N = 16). Anxiety symptoms correlated significantly with plasma MHPG levels. These results substantiate previous evidence that dysregulation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system occur together in a subgroup of depressed patients.

Adult↗
PubMed1986

Suicidal behavior in chronic schizophrenic patients: a follow-up study.

A follow-up study was carried out of suicidal behavior among 127 chronic schizophrenic patients. We were able to obtain follow-up information for 100 of the 127 patients (78.7%). Over the mean follow-up time of 4 1/2 years, 6 of these 100 patients (6%) had committed suicide and 16 other patients (16%) had attempted suicide. Chronic schizophrenic patients who attempted suicide during the follow-up period, compared with those who did not, had had significantly more psychiatric admissions. Using the data obtained at the time of the index admission we were unable to accurately predict the 6 schizophrenic patients who were known to have subsequently committed suicide.

Adult↗
PubMed1986

Pre-menopausal and post-menopausal depressed women.

In a consecutive series of 28 depressed women, pre-menopausal (n = 13) and post-menopausal (n = 15) patients were compared. Post-menopausal women had significantly higher levels of plasma norepinephrine, plasma 3-methoxy-4-hydroxyphenylglycol, post-dexamethasone plasma cortisol, cerebrospinal fluid 3-methoxy-4-hydroxyphenylglycol and corticotropin-releasing hormone. However, when biologic measures were adjusted for age by analyses of covariance there were no significant differences. Pre-menopausal women had had significantly more life events before the onset of depression than post-menopausal women. The implications of these findings are discussed.

Adult↗
PubMed1986

Neuroleptics, dopamine, and schizophrenia.

Neuroleptic drugs have provided not only the most efficacious form of treatment for schizophrenia but also a unique pharmacologic probe for discerning its pathophysiology. The link between the antipsychotic effects of neuroleptics and dopamine systems continues to be supported by current research. Recent preclinical and clinical studies suggest that time-delayed changes in DA neuronal function may more closely relate to the therapeutic effects of neuroleptics than does their relatively immediate effect of DA receptor blockade. The use of levels of plasma HVA as a noninvasive reflector of DA function provides a research strategy for longitudinal studies of neuroleptic effects in schizophrenia. Preliminary evidence suggests that neuroleptic-induced changes in levels of plasma HVA may be of value as an in vivo marker for neuroleptic antipsychotic effects. The recent identification and characterization of the mesocortical DA system, which links the midbrain to frontal areas of the cerebral cortex, represents a significant development in the neurobiology of CNS DA systems. The behavioral implications of the functional neuroanatomy of the mesocortical system, its relative unresponsiveness to neuroleptic agents, and the possibility of modulatory effects on the mesolimbic DA system render the mesocortical system a particularly important area of research with etiologic and pharmacotherapeutic implications for schizophrenia. The accumulating evidence indicating structural brain abnormalities in a significant number of schizophrenic patients has renewed interest in classical neuropathologic approaches to understanding its etiology. Although current evidence does not uniformly support the hypothesis of two schizophrenia types reflecting DA and non-DA forms of the illness, the postulate is useful as an attempt to integrate recent findings into a conceptual framework. Better understanding of the biochemical basis for heterogeneity of neuroleptic response and systematic data relating this responsivity to morphologic brain changes constitute an important direction for schizophrenia research.

Adult↗
PubMed1985

Atrophy limited to the third ventricle in chronic schizophrenic patients. Report of a controlled series.

Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy.

Adult↗
PubMed1985

Plasma norepinephrine level in affective disorders. Relationship to melancholia.

The plasma norepinephrine (NE) level was measured in 45 depressed patients and in 41 normal control subjects. Patients who met DSM-III criteria for a major depressive episode with melancholia (MDE-MEL; N = 16), and those with MDE but with melancholia in a previous episode (MDE-PMEL; N = 8), had significantly higher levels of plasma NE than normal control subjects while lying and standing and a greater change in the levels; whereas, patients with MDE alone (N = 10) and patients with dysthymic disorder (N = 11) had levels of NE comparable with control levels. Bipolar patients (N = 7), all with current melancholia or a history of it, had significantly lower levels of NE while lying down or standing than depressed unipolar patients with similar histories of melancholia. Among unipolar patients with melancholia, nonsuppressors on the dexamethasone suppression test had significantly higher lying-down NE values than did suppressors, suggesting that dysregulation of both the hypothalamic-pituitary-adrenal axis and the peripheral sympathetic nervous system occur together in this subgroup of depressed patients.

Adult↗
PubMed1985

Tyramine pressor sensitivity changes during deprenyl treatment.

Deprenyl has previously been reported to be a selective monoamine oxidase (MAO) type B inhibitor, which is associated with little or no enhancement of the pressor effects of tyramine. Employing an intravenous steady-state tyramine infusion technique, the effects of different doses of deprenyl and, for comparison, the mixed inhibitor tranylcypromine on the pressor response to tyramine were studied in 11 depressed patients. After 3 weeks of treatment, deprenyl produced dose-proportionate increases in tyramine sensitivity at all three doses (10, 30, and 60 mg/day) when compared to placebo baseline tyramine responses. While only a modest (3.7-fold) increase in tyramine sensitivity was found with the 10 mg/day deprenyl dose, the increase in tyramine sensitivity at the 60 mg/day dose of deprenyl (22-fold) approached that found with tranylcypromine. Reductions in plasma 3-methoxy,4-hydroxyphenylglycol (MHPG), used as a possible index of in vivo MAO-A inhibition, were highly correlated with increases in tyramine pressor sensitivity (r = 0.82). The data suggest that deprenyl acts as a relatively selective MAO-B inhibitor at low doses, but that this selectivity is lost at higher doses, resulting in a significant "crossover" inhibition of MAO-A and increased tyramine pressor sensitivity.

Blood Pressure↗
PubMed1985

Chronic clorgyline and pargyline increase apomorphine-induced stereotypy in the rat.

The effects of monoamine oxidase inhibiting antidepressant drugs on behavioral and biochemical measures of dopamine receptor status were measured in the rat. Male Wistar rats received clorgyline (1 mg/kg/day for 21-28 days), pargyline (1 mg/kg/day for 21-28 days) or a combination of these regimens. They were then either tested for stereotypy induced by 1 mg/kg SC injection of apomorphine or were sacrificed and their striata used to measure specific [3H]spiroperidol binding. All three chronic treatment regimens produced statistically significant increases in apomorphine induced stereotypy: there was, however, no significant difference between the three drug regimens. None of the antidepressant drug treatments significantly affected [3H]spiroperidol binding in the corpus striatum. This study demonstrates that behavioral and biochemical measures of dopamine function may not always be closely correlated. It is proposed that the behavioral changes may be related to alterations in other monoaminergic systems, which are known to have fibres running into the nigrostriatal pathway.

Animals↗