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Biomedical subjects

D L Garver

Publications and source records attributed to D L Garver.

At least 55 records · Page 3Linked to original sources
PubMed1988

Psychosis, lithium-induced antipsychotic response, and seasonality.

Lithium alone has previously been shown to effect antipsychotic response in approximately one-quarter of mood incongruent psychoses. Such lithium-responsive psychoses and/or the antipsychotic effects of lithium appear to be seasonal, with maximal response rates occurring in the 3-month periods surrounding January and July peaks. Within patients, retrials of lithium in formerly lithium-responsive psychotic patients demonstrate a trend toward greater continued antipsychotic effects of lithium during the periods surrounding January and July (80% response rates) vs. the remaining 6 months of the year (33% response rates).

Bipolar Disorder↗
PubMed1988

Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias).

Interaction of therapeutic drugs with a series of different biopathological substrates of psychosis might be expected to generate a series of different response patterns. Herein the authors suggest that multi-modal response patterns following lithium and neuroleptic treatment of psychotic patients may aid in resolving the heterogeneity of psychotic disorders and lead to a new nosology of the psychoses.

Haloperidol↗
PubMed1988

Neuroendocrine findings in the schizophrenias.

A host of abnormalities have been found in responses to neuroendocrine challenges in the schizophrenias. Some, such as dexamethasone suppression, may be associated with pharmacokinetic differences in the handling of agonists or may represent a contamination of a schizophrenic population by patients with affective disorders. Other abnormalities, such as the growth hormone response to thyrotropin-releasing hormone and to luteinizing hormone-releasing hormone in adolescents but not in adults, may reflect developmental changes interacting with disease processes. Still other abnormalities may be more directly reflective of different disease processes: a rapidly neuroleptic-responsive and good-prognosis psychotic disorder appears to be associated with blunted thyrotropin response to thyrotropin-releasing hormone and a blunted growth hormone response to apomorphine; a relatively drug-responsive psychotic disorder whose response requires several weeks of neuroleptic treatment appears to be associated with an excessive growth hormone response to apomorphine. The neuroendocrine windows for viewing brain function in the schizophrenias still permit indistinct images of the processes that modulate their release. Nevertheless, the images may provide important clues to the biopathology underlying these diseases.

Antipsychotic Agents↗
PubMed1988

Neuroendocrine findings in the schizophrenias.

A host of abnormalities have been found in responses to neuroendocrine challenges in the schizophrenias. Some, such as dexamethasone suppression, may be associated with pharmacokinetic differences in the handling of agonists or may represent a contamination of a schizophrenic population by patients with affective disorders. Other abnormalities, such as the growth hormone response to thyrotropin-releasing hormone and to luteinizing hormone-releasing hormone in adolescents but not in adults, may reflect developmental changes interacting with disease processes. Still other abnormalities may be more directly reflective of different disease processes: a rapidly neuroleptic-responsive and good-prognosis psychotic disorder appears to be associated with blunted thyrotropin response to thyrotropin-releasing hormone and a blunted growth hormone response to apomorphine; a relatively drug-responsive psychotic disorder whose response requires several weeks of neuroleptic treatment appears to be associated with an excessive growth hormone response to apomorphine. The neuroendocrine windows for viewing brain function in the schizophrenias still permit indistinct images of the processes that modulate their release. Nevertheless, the images may provide important clues to the biopathology underlying these diseases.

Apomorphine↗
PubMed1987

Growth hormone response to apomorphine and family patterns of illness.

Sixty-five psychotic probands were divided into three groups (low, intermediate, and high) on the basis of the GH response to the dopamine receptor agonist apomorphine. Two hundred and sixty-five first-degree relatives of the probands were diagnosed according to SADS-DSM-III methods, and the relatives of the three groups of probands were compared so as to detect familial differences in the incidence of DSM-III Axis I disorders, schizotypal personality disorder, and antisocial personality. Although the morbid risk of schizophrenic spectrum disorder was only 3.1% in the relatives of the high GH probands, the morbid risk for disorders of the schizophrenic spectrum was 17.0% and 10.7% in the relatives of the intermediate and low GH probands, respectively. These data provide preliminary evidence that there may be a psychotic subtype that is characterized by supersensitivity of the dopamine system that is familially, and perhaps genetically, distinct from the bulk of the schizophrenias.

Adolescent↗
PubMed1987

Changes in urinary catecholamines and their metabolites in depressed patients treated with amitriptyline or imipramine.

The effects of treatment with amitriptyline (AMI) or imipramine (IMI) on changes in catecholamines and their metabolites in urine were studied in 95 unipolar and bipolar depressed patients. For the entire group, not separated by drug, substantial reduction in concentrations of all metabolites, but not catecholamines, occurred. Although catecholamine and metabolite change was similar for most substances assayed, there were some specific drug and diagnostic group differences. Vanillylmandelic acid (VMA) reduction was limited to bipolar patients; metanephrine (M) reduction to unipolar patients. Greater M and 3-methoxy-4-hydroxyphenylglycol (MHPG) reduction were associated with response in unipolar, but not bipolar patients. In bipolar, but not unipolar patients, norepinephrine (NE) rose in responders in contrast to reductions among nonresponding bipolar patients. The results suggest that effectiveness of blockade of reuptake of norepinephrine may be relatively more important for recovery in bipolar than in unipolar patients. Study of a battery of amine substances may contribute more information to our understanding of antidepressant drug effects on aminergic systems than analyses of MHPG alone.

Adult↗
PubMed1987

Methodological issues facing the interpretation of high-risk studies: biological heterogeneity.

High-risk studies provide a unique opportunity to examine the interaction of biological vulnerability and psychosocial factors in the development of the major psychiatric illnesses. To parcel out the effects of psychosocial variables, high-risk populations need to be separated into offspring who are and who are not biologically/genetically vulnerable, since psychosocial modifiers will be interactive only in the biologically vulnerable offspring. Criteria are suggested for the use of "biological markers" to detect subjects at genetic/biological risk within high-risk cohorts. Presently, only the d' statistic of the continuous performance test (CPT) appears to satisfy the criteria for identification of such biologically vulnerable offspring.

DNA↗
PubMed1986

Relation of clinical symptoms to apomorphine-stimulated growth hormone release in mood-incongruent psychotic patients.

The relationship between dopamine receptor agonist (apomorphine hydrochloride)-stimulated growth hormone (GH) release and psychotic symptoms was examined in 138 schizophrenic or schizoaffective inpatients (Research Diagnostic Criteria) and ten healthy normal volunteers. Patients were divided into three groups: those demonstrating an abnormally large GH response, an average GH response (mean GH response), or an abnormally low GH response. Abnormally large GH responses were associated with higher total psychosis scores. The increased psychosis scores observed in this group were due primarily to an increased incidence of thought disorder. Further analysis revealed a strong, positive correlation between thought disorder and the GH response. The apomorphine-stimulated GH response was also significantly related to duration of illness, an effect independent of age. Consistent with this last result, patients with a diagnosis of a DSM-III schizophreniform disorder demonstrated an elevated GH response.

Adolescent↗
PubMed1986

Fluphenazine activity and antipsychotic response.

Plasma fluphenazine levels and plasma total neuroleptic activity (as quantitated by the neuroleptic receptor binding assay) were related to therapeutic response in 15 DSM-III schizophrenic patients who received a predetermined, fixed dose of fluphenazine for 14 days. Mean neuroleptic activity of the plasma was 84% greater than can be accounted for by the parent fluphenazine alone, and varied widely between patients. A sigmoidal relationship between total neuroleptic activity of plasma and response was found, with a continued plateau of response at higher total neuroleptic levels. Furthermore, the RBA data suggested (P less than 0.002) that two populations of drug-responsive schizophrenics exist which may be discriminated by the total D2 binding activity of plasma required for response.

Chromatography, Gas↗
PubMed1986

Growth hormone response to apomorphine and diagnosis: a comparison of three diagnostic systems.

Our study takes a further look at the apomorphine test in the psychoses and affective disorders, with special reference to the use of different diagnostic systems. Patients meeting Research Diagnostic Criteria (RDC) for schizophrenia, schizoaffective disorder, or manic disorder were included. In addition to the RDC, diagnosis was also made using the DSM-III and ICD-9. All patients underwent an evaluation of peak GH response to apomorphine administration. The results show that RDC and ICD-9 are similar, in that for both systems, a high GH response correlates with a schizoaffective disorder and distinguishes those patients significantly from manic patients. The DMS-III brings in some new dimensions, in that schizophreniform disorder (6-month cut-off) is distinguished from schizophrenia. In addition, patients with affective symptoms and mood-incongruent psychoses are more closely related to schizophreniform disorder than to classical manic disorder.

Adult↗
PubMed1986

Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine.

The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity.

Adolescent↗
PubMed1986

Lithium ratio in vitro: familial patterns of illness.

Psychiatric illness in first-degree relatives of psychotic patients with low, intermediate, and high red blood cell (RBC) in vitro lithium ratio (LR) was investigated using the Schedule for Affective Disorders and Schizophrenia and DSM-III. Fewer schizophrenic spectrum disorders were found in the first-degree relatives of high and low LR probands as compared to intermediate LR probands; high LR psychotic probands had families with an increased frequency of depressive spectrum disorder. Alcohol dependence and abuse was particularly prominent in the first-degree relatives of the higher LR probands. High LR may identify a disease that does not belong to the familial-genetic disorders of the schizophrenic spectrum; this illness may bear a closer relationship to disorders of the depressive spectrum.

Adult↗
PubMed1985

Down-regulation of central dopamine receptors in schizophrenia.

CSF homovanillic acid (HVA) levels reflecting central dopamine release and apomorphine-stimulated human growth hormone (HGH) secretion reflecting central dopamine receptor activity were concomitantly determined in 20 schizophrenic patients. There was a strong negative correlation between HVA and HGH levels: high dopamine release was associated with lower HGH responses to dopamine receptor activation by apomorphine. Studies are reviewed which suggest that the presently observed relationship reflects release-mediated down-regulation of central D2 receptors, the dopamine receptor subtype associated with the antipsychotic properties of neuroleptic medication.

Adolescent↗
PubMed1984

Lithium ratio in vitro. Diagnosis and lithium carbonate response in psychotic patients.

The distribution of RBC lithium ratios in vitro in a recently hospitalized psychiatric population was found to be multimodal. Psychotic patients who had an antipsychotic response during open trials of lithium carbonate alone were identified with high sensitivity (89%), but low specificity (51%) before drug treatment, by lithium ratios that were in the extreme modes of the distribution (less than 0.30 or greater than 0.38). Diagnostic efficiency of the test was 61%. The DSM-III diagnosis of schizophreniform disorder demonstrated 90% diagnostic efficiency in predicting response/nonresponse during treatment with lithium carbonate alone. A subgroup of the psychotic disorders was similar to affective disorders with respect to course of illness, biological characteristics, and response to lithium carbonate.

Clinical Trials as Topic↗
PubMed1984

Combined thioridazine and desipramine: early antidepressant response.

The authors examined the effect of combined thioridazine (THI) and desipramine (DMI) for an early antidepressant response in 14 patients with a DSM III diagnosis of major depressive disorder with melancholia. All 14 patients received a constant dose of 200 mg DMI/day for 21 days while 7 patients received 100 mg THI/day for only the first 7 days. A significantly greater improvement from baseline Hamilton Depression Scale (HDS) scores occurred during the first 7 days in patients receiving both drugs. Possible mechanisms for this early antidepressant action are discussed.

Adult↗
PubMed1984

Dopamine and non-dopamine psychoses.

The time course of antipsychotic response following the initiation of an antipsychotic drug and functional dopamine receptor sensitivity were explored in a cohort of recently admitted psychotic (mood-incongruent) patients. The distribution of the latencies of antipsychotic response suggested at least two populations. Rapid responders (RRs) had 60% reduction of baseline psychotic symptoms by a mean of 5.5 days of drug treatment. Delayed/nonresponders required 2-7 weeks for a similar reduction of psychotic symptoms. The sensitivity of postsynaptic dopamine receptors was explored using a neuroendocrine probe: growth hormone response to the dopamine agonist, apomorphine (AP). RRs had an exaggerated growth hormone response to AP in comparison to delayed/nonresponders (P less than 0.05). Exaggerated sensitivity of postsynaptic dopamine receptors and rapid antipsychotic response following dopamine receptor blockade in RRs suggest a true functional dopamine hypersensitivity disorder in the RR group. In contrast, lower postsynaptic receptor sensitivity (as reflected by lower growth hormone response to AP) and failure of early response following dopamine receptor blockade focus attention away from dopamine hyperactivity as a relevant etiologic mechanism in delayed/nonresponders. Response rates to neuroleptic drugs and neuroendocrine probes of receptor sensitivity may separate two or more etiologically distinct diseases with schizophrenic-like symptoms.

Antipsychotic Agents↗