Search PubMed⌕ Search

Biomedical subjects

A R Doran

Publications and source records attributed to A R Doran.

At least 37 records · Page 2Linked to original sources
PubMed1988

Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical defect.

To replicate earlier findings of central and cortical cerebral structural abnormalities and to further examine specific prefrontal cortical irregularities in schizophrenia, the authors examined computerized tomographic (CT) scans of 71 patients with chronic schizophrenia and 30 normal volunteer control subjects for ventricle-brain ratio (VBR), third ventricle width, and prominence of cortical markings in a generalized (parieto-occipital) distribution compared with the prefrontal area. Patients showed significantly larger VBRs and third ventricle widths than control subjects. Patients also showed significantly greater prefrontal markings in terms of both the number of individuals affected and the degree of difference. The relative differences on measures of VBR and prefrontal atrophy did not appear gender related, but the difference in third ventricle width between schizophrenic and control women was greater than that between schizophrenic and control men.

Adult↗
PubMed1987

Prednisone decreases CSF somatostatin in healthy humans: implications for neuropsychiatric illness.

Several neuropsychiatric illnesses, including depression and Alzheimer's disease, are reported to be characterized by hypercortisolemia and by reduced levels of cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI). To investigate a possible causal linkage between these abnormalities we administered prednisone, 80 mg orally per day for 5 days, to 9 healthy volunteers. We observed significant prednisone-induced reductions in CSF-SLI. Moreover, the magnitude of these reductions was inversely related to the magnitude of prednisone-induced reductions in plasma ACTH levels, suggesting a functional interaction between circulating corticosteroids, central somatostatin and pituitary ACTH release.

Adrenocorticotropic Hormone↗
PubMed1987

Clinical and biochemical effects of verapamil administration to schizophrenic patients.

We administered verapamil hydrochloride, a calcium channel antagonist, to seven chronically ill schizophrenic patients for five weeks under double-blind, placebo-controlled conditions. No therapeutic effect was noted. Worsening in hostile and uncooperative behaviors and a syndrome of heightened emotional tone was observed during verapamil treatment and during the postverapamil placebo period. Verapamil produced significant increases in cerebrospinal fluid (CSF) and plasma levels of homovanillic acid and in plasma levels of prolactin, as well as significant decreases in plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol. Verapamil and its active metabolite, norverapamil, were partitioned into CSF with CSF/plasma ratios of 0.06 and 0.04, respectively. The lack of therapeutic effects of verapamil in schizophrenic patients differs from earlier reports of its usefulness in treating manic patients. The biochemical and clinical data from our study suggest the possibility that verapamil exerts behaviorally relevant central nervous system activity in schizophrenic patients.

Adult↗
PubMed1987

The effects of dexamethasone on plasma homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. Evidence for abnormal corticosteroid-catecholamine interactions in major depression.

We investigated the possible interactions between corticosteroids and catecholamines in depression by studying the effects of the synthetic glucocorticoid dexamethasone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) in a group of depressed patients and normal controls. In comparison with metabolite levels on a control day, normal controls showed a significant dexamethasone-induced increase in the plasma HVA level and a trend toward a decrease in the plasma MHPG level at 4 PM following dexamethasone administration (1 mg orally at 11 PM). Conversely, depressed patients, particularly those with psychotic features, showed a significant dexamethasone-induced increase in the plasma MHPG level and a blunting of the plasma HVA response relative to the normal controls. Dexamethasone-induced increases in the plasma MHPG level were directly correlated with the severity of depressive symptoms and with postdexamethasone cortisol levels in the depressed patients. These data suggest abnormal corticosteroid-catecholamine interactions in depression and, specifically, in depressed patients with psychotic features.

Adult↗
PubMed1987

Pituitary adrenocortical unresponsiveness in lactate-induced panic.

The hypothalamic-pituitary adrenal (HPA) axis responds to a variety of physical and emotional stimuli with increased output of adrenocorticotropic hormone (ACTH) and cortisol, yet there is little known about the activity of this system during episodes of severe anxiety in patients with DSM-III-defined anxiety disorders. To explore further whether alterations of the HPA axis occur during various anxiety states, we measured ACTH and cortisol during lactate infusion in patients with panic disorder and agoraphobia. In eight patients who panicked during lactate infusion, there were no elevations in either ACTH or cortisol. Further, the patterns of hormone secretion did not differ among patients who panicked, nonpanicking patients, or controls. This negative result suggests that the neurobiological mechanisms that mediate panic differ from those responsible for other fear responses.

Adolescent↗
PubMed1987

Structural brain pathology in schizophrenia revisited. Prefrontal cortex pathology is inversely correlated with cerebrospinal fluid levels of homovanillic acid.

Computed tomography scan analysis of 35 schizophrenic patients, 26 medical patients, and 31 normal controls revealed significantly larger ventricular brain ratios and structural changes consistent with cortical atrophy in both schizophrenic and medical patients in comparison with normal controls. The schizophrenic patients, however, differed from both control groups in terms of greater prefrontal cortical markings consistent with prefrontal atrophy, and this finding correlated inversely with levels of cerebrospinal fluid homovanillic acid. Results from this study, in addition to replicating previous findings and addressing methodologic issues concerning controls, provide new evidence implicating abnormality of the prefrontal cortex in schizophrenia and link this abnormality to central nervous system dopaminergic function.

Adult↗
PubMed1987

Cerebrospinal fluid neuropeptide Y in depression and schizophrenia.

Neuropeptide Y (a recently discovered brain peptide that is colocalized with norepinephrine within some adrenergic central nervous system neurons) was measured in the cerebrospinal fluid (CSF) from patients with major affective disorder, chronic schizophrenia, and in normal volunteers. No differences between diagnostic groups were found, suggesting that if this neuropeptide is involved in the pathogenesis of these disorders, an abnormality is not detectable in the CSF.

Biomarkers↗
PubMed1987

Neuroleptic responsivity of negative and positive symptoms in schizophrenia.

The authors prospectively examined the effects of double-blind, placebo-controlled neuroleptic withdrawal and administration on ratings of negative and positive symptoms in 19 young patients with chronic schizophrenia. Negative symptoms were significantly reduced by neuroleptic treatment, and negative and positive symptoms demonstrated similar patterns of reduction and exacerbation during neuroleptic treatment and withdrawal, respectively. The changes in negative and positive symptoms induced by neuroleptic treatment and withdrawal were not significantly correlated, however. The negative and positive symptom profiles of individual patients were significantly altered by neuroleptic treatment, indicating limitations to the cross-sectional classification of patients on the basis of predominance of one or the other symptom group. The authors discuss implications for the neurobiological underpinnings of negative and positive symptoms.

Adult↗
PubMed1986

Cerebrospinal fluid monoamine and monoamine metabolite levels and the dexamethasone suppression test in depression. Relationship to life events.

The cerebrospinal fluid levels of norepinephrine and six monoamine metabolites were measured in 23 patients meeting DSM-III criteria for major depressive episode, 15 of whom also met criteria for melancholia. Life events during the six-month period before the onset of depression were recorded using Paykel's method. There was no difference in Hamilton depression ratings between patients with life events and those without. However, depressed patients who did not have a life event in the six months before the onset of depression had significantly lower levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid than those with life events. The incidence of nonsuppression on the dexamethasone suppression test was also greater in patients with a major depressive episode who did not have an undesirable life event than in those who did. Thus, the presence or absence of life events led to a separation into biologically distinct groups.

Adult↗
PubMed1986

CSF somatostatin and abnormal response to dexamethasone administration in schizophrenic and depressed patients.

Low levels of cerebrospinal fluid (CSF) somatostatin and abnormal response to dexamethasone are two neuroendocrine disturbances reported to appear in depression and other neuropsychiatric disorders. We measured the levels of CSF somatostatin in patients with schizophrenia (n = 44) and depression (n = 19). In view of in vitro and animal evidence of the ability of somatostatin to inhibit stimulated corticotropin secretion, we also administered the dexamethasone suppression test to a subgroup of the patients with schizophrenia (n = 16) and the total depressed group. Lower levels of CSF somatostatin were found in dexamethasone nonsuppressors regardless of diagnosis and were negatively correlated with maximum postdexamethasone cortisol level in the total and depressed patient groups. These data suggest a functional relationship between hypothalamic-pituitary-adrenal axis hyperactivity and reduced CSF somatostatin level.

Adult↗
PubMed1986

Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients. Correlation with psychosis and response to neuroleptic treatment.

The plasma levels of homovanillic acid (HVA), a major circulating dopamine (DA) metabolite, were measured in schizophrenic patients during five weeks each of double-blind placebo-controlled neuroleptic treatment (N = 16) and withdrawal (N = 11). Both neuroleptic treatment and withdrawal were associated with time-dependent changes in the plasma levels of HVA; treatment was associated with decreases and withdrawal with increases. The levels of plasma HVA measured longitudinally during both conditions were highly correlated with psychosis ratings. Moreover, changes in individual mean weekly levels of plasma HVA were predictive of treatment response, including changes in both positive and negative symptoms of schizophrenia. These data are consistent with the suggestion that the mechanisms of action of antipsychotic drugs involve, in addition to short-term DA receptor blockade, a slowly developing decrease in presynaptic DA activity.

Adult↗
PubMed1986

Endogenous opioid regulation of hypothalamo-pituitary-adrenal axis activity in schizophrenia.

We utilized a naloxone challenge strategy to investigate the functioning of the endogenous opioid system (EOS) in schizophrenia. Patients with schizophrenia, who were on neuroleptic medication or drug-free, demonstrated a significantly larger serum cortisol response to opioid blockade by naloxone than did age- and sex-matched normal controls. Patients, but not normal controls, also demonstrated an inverse relationship between baseline cortisol and the magnitude of the response. This enhanced cortisol response is consistent with tonic hyperactivity of the EOS in schizophrenia.

Adult↗
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

Differential diagnosis and diagnostic systems in schizophrenia.

Diagnosis and prognosis are critical issues confronting psychiatry. In order to answer the fundamental questions concerning the origin and development of schizophrenia, we must first be clear about what it is. We must be able to separate the illness of schizophrenia from other disorders (see Fig. 1). We have attempted in this article to examine some of the illnesses that may resemble schizophrenia and make its discrimination difficult. We hope that by discussing these disorders and their similarities to schizophrenia the important issues and dilemmas have become clearer and more readily understood by the clinician. Future studies assessing the validity of diagnostic systems for schizophrenia may have to rely on features other than cross-sectional symptoms and longitudinal course. Such characteristics as pharmacologic responsivity and genetic transmission and the development of biologic markers may be the prospective cornerstones for validating the diagnosis of schizophrenia.

Bipolar Disorder↗