Biomedical subjects

R E Poland

Publications and source records attributed to R E Poland.

At least 19 recordsLinked to original sources

PubMed1996

In vivo proton magnetic resonance spectroscopy of the normal aging human brain.

The effect of age on brain metabolite concentrations was evaluated using localized proton magnetic resonance spectroscopy. This technique allows in vivo measurements of N-acetyl compounds (NA), total creatine (CR), choline-containing compounds (CHO), myo-inositol (MI), glutamate and glutamine (GLX), as well as the percentage of cerebrospinal fluid (CSF) and the brain water content within the brain region studied. Frontal gray matter and frontal white matter brain regions were examined in 36 normal healthy volunteers (19-78 years of age). Using a rigorous absolute quantitation method, with an external reference and atrophy correction, we found relatively stable concentrations of NA, a neuronal marker. In contrast, CR, CHO, MI, and the percentage of CSF increased in the gray matter with age. However, the brain water content decreased significantly with age (r = -0.72; p < 0.0001). No significant age-related changes in metabolite concentrations, CSF or brain water content were observed in the white matter regions. These findings demonstrate that biochemical alterations are associated with aging in the frontal gray matter. There might be an increase in the brain density as indicated by increased metabolite concentrations and decreased brain water content with aging.

Adult↗

PubMed1996

Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations.

3,4-Methylenedioxymethamphetamine (MDMA) is a phenethylamine with potent effects on serotonergic neurotransmission which has been the object of controversy over its potential as a therapeutic adjunct versus its possible risks for causing neurotoxic injury. This paper discusses the background, methodology and preliminary findings of the first FDA approved Phase I study prospectively evaluating the effects of MDMA administration in humans. Six subjects with prior experience with MDMA were administered two different dosages of MDMA and an inactive placebo utilizing a randomized, double-blind methodologic design. Dosages from 0.25 to 1.0 mg/kg, p.o., were administered. All subjects tolerated the procedures without any overt evidence of physical discomfort or psychological distress. MDMA produced a modest increase in heart rate and blood pressure. The threshold dose for the stimulation of ACTH and prolactin appeared to be between 0.5 and 0.75 mg/kg, with the two higher doses clearly stimulating both ACTH and prolactin. Methodology for assessing MDMA's effects on serotonergic neurotransmission is discussed.

Adult↗

PubMed1996

The evolving science of pharmacogenetics: clinical and ethnic perspectives.

The field of pharmacogenetics has witnessed remarkable progress during the past several decades. Clinical observations of severe toxic reactions and findings of dramatic interindividual as well as cross-ethnic differences in response to therapeutic agents have been instrumental in fostering advances of the field. Research on cytochrome P450 isozymes may be of particular importance to the field of psychiatry, because most psychotropics depend on these enzymes for their biotransformation. This article traces the progress of research in this area and highlights the importance of clinical and cross-ethnic observations in providing the impetus and direction for the field. Knowledge derived from this line of research is likely to make important contributions toward establishment of rational guidelines for psychopharmacotherapy. In addition, research on these enzymes may also have profound implications in regard to the pathogenesis of a number of major disorders, including several types of commonly encountered cancers, as well as neuropsychiatric problems, including Parkinson's disease, tardive dyskinesia, addiction, and drug-induced neurotoxicity.

Cytochrome P-450 Enzyme System↗

PubMed1996

Exposure to threshold doses of nicotine in utero: III. Augmentation of the prolactin and ACTH response to 8-OH DPAT by desipramine treatment is compromised in adult male offspring.

Gravid female rats were injected subcutaneously with saline (SAL) or nicotine (3.0 mg/kg and 0.05 mg/kg, bid) from days 14-21 of gestation. Adult 105-day old male offspring from each of the three groups were treated daily with saline or desipramine (DMI) (10 mg/kg, sc) for 14 days. Twenty-four hours after the last injection, animals were challenged with saline or 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH DPAT) (0.1 mg/kg, sc), a serotonin IA(5-HT(IA)) agonist, and plasma prolactin and ACTH concentrations were measured 15 minutes later. DMI treatment augmented both the prolactin and ACTH responses to 8-OH DPAT in the SAL controls. Neither the prolactin nor the ACTH response was augmented significantly in the animals exposed prenatally to either nicotine dosage regimen, although there was a strong trend for the augmentation to occur in the low-dose nicotine exposed animals. The results indicate the capacity of 5-HT systems to adapt normally to DMI administration, as manifested by neuroendocrine responsivity to 8-OH DPAT, was compromised in adult animals exposed to nicotine in utero.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Adult↗

PubMed1995

Prenatal stress prevents the desensitization of the corticosterone response to TFMPP by desmethylimipramine, but not by phenelzine, in adult male offspring.

Gravid female rats were subjected to one hour of restraint stress twice daily or left undisturbed from days 14-21 of gestation. Adult 105-day old male non-stressed (NS) and stressed (S) offspring were treated once daily with saline, desipramine (DMI) (10 mg/kg, sc) or phenelzine (5.0 mg/kg, sc) for 14 days. Twenty-four hours after the last injection, animals were challenged with saline or 1-(m-trifluoromethylphenyl)piperazine (TFMPP) (5.0 mg/kg, sc), a serotonin1B/2C (5-HT1B/2C) agonist, and plasma prolactin and corticosterone concentrations were measured one hour later. As compared to acute saline administration, TFMPP significantly increased prolactin and corticosterone concentrations in all groups. In NS offspring, both DMI and phenelzine treatment augmented the prolactin response, but blunted the corticosterone response, to TFMPP. In S offspring, the prolactin response to TFMPP also was augmented by phenelzine or DMI treatment, whereas the corticosterone response to TFMPP was blunted during phenelzine treatment. However, DMI treatment was not able to desensitize the corticosterone response to TFMPP in the S rats. The results indicate the adaptive capacity of 5-HT systems to DMI administration was compromised in adult animals exposed to stress in utero.

Adaptation, Physiological↗

PubMed1995

Pretreatment with MK-801 inhibits pemoline-induced self-biting behavior in prepubertal rats.

The indirect dopamine agonist, pemoline (120-300 mg/kg s.c.), can induce self-biting behavior in the rat. The present study demonstrates that the non-competitive N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801, 0.2 mg/kg s.c.), significantly attenuates pemoline-induced self-biting behavior, while simultaneously increasing locomotor activity. When animals received a fixed dose of MK-801 with increasing doses of pemoline, a competitive relationship emerged such that high-dose pemoline surmounted the antagonistic effect of MK-801. In contrast to spiperone, delayed administration of MK-801 was ineffective in blocking the subsequent expression of self-biting behavior, suggesting that dizocilpine exerts its protective effect early in the cascade of events which eventually leads to self-biting behavior in this paradigm.

Animals↗

PubMed1995

Ethnicity and psychopharmacology. Bridging the gap.

Taken together, the literature reviewed clearly indicates that the disposition and effect of a large number of psychotropic agents are influenced substantially by ethnicity and culture. Recent advances in the realm of pharmacokinetics, pharmacogenetics, and pharmacodynamics have led to a greater understanding of some of the mechanisms responsible for such differences. In comparison, much less currently is known regarding how various psychosocial factors impinge on drug responses in different cultural settings. Progress in research in this area is important for clinical reasons, as psychiatric clinicians will increasingly be confronted with patients with divergent ethnic and cultural backgrounds. In addition, knowledge derived from such research will contribute significantly to a better understanding of how the effects of psychotropic agents are mediated, and also should be valuable for the drug development industry that will have to take into account the increasingly diversifying domestic and international markets.

Antidepressive Agents, Tricyclic↗

PubMed1994

Exposure to threshold doses of nicotine in utero: II. Neuroendocrine response to nicotine in adult male offspring.

Groups of gravid female rats were injected subcutaneously with saline (SAL), a low-dose of nicotine (LN) (0.05 mg/kg, bid) or a high-dose of nicotine (HN) (3.0 mg/kg, bid) from day 4 to day 20 of gestation, or were left undisturbed. In adult 120-day-old male offspring, the ACTH and prolactin responses to acute nicotine challenge were evaluated. The experiment was performed on three separate occasions. Based upon dose-response and time-course studies with nicotine in normal animals, the neuroendocrine responses to nicotine (0.75 and 1.0 mg/kg, sc) were measured 7.5 min after nicotine administration, the peak response-time for both hormones. The ACTH response to acute nicotine administration was blunted significantly in the HN rats, but normal in the LN rats, for all three experiments. In two experiments, the prolactin response to acute nicotine administration was blunted significantly in the HN rats, but enhanced significantly in the LN offspring. The results indicate that prenatal nicotine administration can produce long-term neuroendocrine effects involving nicotinic-receptor coupled circuits, with long-term functional sequelae produced by dosages of nicotine considerably smaller than previously shown to be pharmacologically/toxicologically active.

Adrenocorticotropic Hormone↗

PubMed1994

Neuroendocrine responses produced by enantiomeric pairs of drugs that interact with phencyclidine and sigma receptors.

The present study characterized the response of the hypothalamo-pituitary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)-pentazocine produced greater responses than (+)-pentazocine, the two enantiomers of SKF 10,047 did not show stereoselectivity. Although the potency of the enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP receptors, the potency of the enantiomers of pentazocine did not. These results suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis by PCP and drugs with PCP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.

Adrenocorticotropic Hormone↗

PubMed1994

Dissociation between plasma bioactive and immunoactive ACTH concentrations in depressed patients.

Previous studies have reported dissociations between plasma cortisol and immunoactive adrenocorticotropic hormone (ACTH) concentrations in both normal controls and in patients with major depression. In order to investigate this issue further, placebo and dexamethasone (DEX) were administered to normal controls and depressed patients at 11 PM, and plasma cortisol and ACTH were measured the following morning at 7 AM. Plasma ACTH concentrations were quantitated by both immunoassay (I-ACTH) and by bioassay (B-ACTH). In 10 normal controls, DEX (0.25, 0.5, and 1.0 mg, PO, elixir) produced a dose-related suppression of cortisol, I-ACTH and B-ACTH, with all three hormones significantly suppressed by DEX (0.5 and 1.0 mg) (p < or = 0.01). In 20 depressed patients, 7 AM plasma ACTH and cortisol concentrations were assessed following a single dose of DEX (0.5 mg). Fifteen patients were classified as suppressors and five as escapers, as reflected by mean (+/- SEM) cortisol concentration of 19.9 +/- 3.0 ng/ml and 81.2 +/- 7.0 ng/ml, respectively. Mean I-ACTH concentrations were comparable in both the escapers (8.6 +/- 1.6 pg/ml) and in the suppressors (7.0 +/- 1.0 pg/ml). In contrast, the mean B-ACTH concentration was more than two-fold higher in the escapers (4.5 +/- 0.5 pg/ml) than in the suppressors (2.2 +/- 0.3 pg/ml) (p < or = 0.001). Eleven of the 20 patients received both placebo and DEX (0.5 mg) on two separate occasions. Although DEX significantly suppressed both cortisol (p < or = 0.0001) and B-ACTH (p < or = 0.01) concentrations, I-ACTH was not significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers.

BACKGROUND: There is an extensive literature describing a central serotonin deficit in alcoholic, impulsive, violent offenders and fire setters. In the present study, we investigated biochemical concomitants of impulsivity and aggressiveness, and the physiological consequences of reduced central serotonin turnover. METHODS: Forty-three impulsive and 15 nonimpulsive alcoholic offenders and 21 healthy volunteers were studied in the forensic psychiatry ward of a university psychiatric department. The subjects underwent lumbar punctures and oral glucose and aspartame challenges, and their diurnal activity rhythm was measured with physical activity monitors. Discriminant function analyses were used to investigate psychophysiological and biochemical concomitants of aggressive and impulsive behaviors. RESULTS: Alcoholic, impulsive offenders with antisocial personality disorder had low mean cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and corticotropin levels and high mean CSF testosterone concentrations. Compared with healthy volunteers, they showed increased physical activity during the daytime. Alcoholic, impulsive offenders with intermittent explosive disorder had a low mean CSF 5-HIAA concentration and blood glucose nadir after an oral glucose challenge, and desynchronized diurnal activity rhythm. Healthy volunteers had mean CSF 5-HIAA concentrations that were intermediate between those of alcoholic, impulsive and nonimpulsive offenders. Alcoholic, nonimpulsive offenders had a significantly higher mean CSF 5-HIAA concentration than all the other groups, including healthy volunteers. CONCLUSIONS: In the present sample, a low CSF 5-HIAA concentration was primarily associated with impulsivity and high CSF testosterone concentration, with aggressiveness or interpersonal violence.

Adrenocorticotropic Hormone↗

PubMed1994

Personality profiles and state aggressiveness in Finnish alcoholic, violent offenders, fire setters, and healthy volunteers.

BACKGROUND: Based on clinical observations in a series of studies on Finnish alcoholic, violent offenders, we asserted that the impulsive offenders represented an extreme group of type 2 alcoholics. We also observed that these subjects were vulnerable to hypoglycemia after the administration of oral glucose load. Furthermore, we believe that while being hypoglycemic, the impulsive offenders are particularly irritable and aggressive. In the present study, we addressed these issues by studying psychological trait and state variables in a new group of violent offenders and fire setters, and age- and sex-matched healthy volunteers. METHODS: Fifty-eight alcoholic, violent offenders and impulsive fire setters and 21 healthy volunteers were administered the Karolinska scales of personality and the Rosenzweig picture frustration test after an oral aspartame and glucose challenge. RESULTS: The psychological test results and the criminal histories of the offenders, together with biochemical measurements, suggest that a low 5-hydroxyindoleacetic acid concentration in cerebrospinal fluid in the alcoholic offenders is associated with irritability and impaired impulse control, and a high free testosterone concentration in cerebrospinal fluid is associated with increased aggressiveness, monotony avoidance, sensation seeking, suspiciousness, and reduced socialization. CONCLUSION: Finnish alcoholic, impulsive offenders have personality profiles characteristic of Scandinavian early-onset male alcoholics with antisocial traits, who have been also referred to as type 2 alcoholics.

Adult↗

PubMed1994

Exposure to threshold doses of nicotine in utero: I. Neuroendocrine response to restraint stress in adult male offspring.

Gravid female rats were injected subcutaneously with saline or nicotine (3.0 mg/kg and 0.05 mg/kg, bid) from day 4 to day 20 of gestation or were left undisturbed. In adult 120-day old male offspring, the ACTH, corticosterone and prolactin concentrations before, during (15, 30, 45 and 60 minutes) and after (30, 60, 90 and 120 minutes) one hour of restraint stress were studied. Baseline (non-stress) concentrations of each hormone were comparable among the groups. As compared to saline controls, ACTH concentrations were significantly higher during stress at 30 and 60 minutes in the high-dose nicotine (HN) animals, with the average ACTH concentration during stress also being significantly higher in the HN rats. Neither nicotine regimen affected the corticosterone response to stress at any time-point. The prolactin response to stress was significantly reduced in the HN group at 45 and 60 minutes as compared to saline controls, with the average prolactin concentration also reduced during stress. During recovery, average ACTH concentrations were significantly higher in the HN group, and significantly lower in the LN group, with no differences found for either corticosterone or prolactin. The results indicate that exposure to a high-dose of nicotine during gestation, and to a very low-dose as well, produced functional alterations in adult male offspring as manifested by abnormal neuroendocrine responses to restraint stress. However, the differences between the nicotine and saline controls were sometimes as great as between the non-injected controls and the saline controls. Thus, any conclusions drawn about the long-term effects of prenatal nicotine on neuroendocrine responsivity to stress must be tempered by the influence of the repeated injection procedure.

Adrenocorticotropic Hormone↗

PubMed1993

Effects of low-dose dexamethasone on sleep EEG patterns, plasma cortisol, and the TSH response to TRH in major depression.

Dexamethasone (DEX) (0.5 mg, P.O.) and placebo were administered at 2300 h in randomized design to 19 patients with major depression and the effects on the sleep electroencephalogram (EEG) were studied. In addition, the thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) and basal plasma cortisol concentrations were assessed the following morning. DEX did not affect sleep architecture or continuity variables, including rapid eye movement (REM) latency, REM activity and REM density. Similarly, DEX did not significantly influence the TSH response to TRH (delta max TSH). In contrast, plasma cortisol concentrations were significantly suppressed by DEX. The results indicate that, as opposed to higher dosages of glucocorticoids, 0.5 mg DEX had minimal effects on the sleep EEG or delta max TSH in depressed patients.

Adult↗

PubMed1992

Haloperidol plasma levels and clinical response: a therapeutic window relationship.

OBJECTIVE: The purpose of the study was to assess the relationship between plasma haloperidol and clinical response. METHOD: Sixty-nine newly admitted drug-free schizophrenic men were randomly assigned to receive haloperidol, 5, 10, or 20 mg daily for 4 weeks, and clinical response was measured at the end of the fixed-dose period. Haloperidol was assayed by a sensitive and specific radioimmunoassay. RESULTS: The authors found a curvilinear relationship between clinical response and plasma haloperidol during fixed-dose treatment, with an apparent optimum between 5 and 12 ng/ml. When plasma levels above 12 ng/ml were lowered to the 5-12 ng/ml range, all patients improved to varying degrees and no patient deteriorated. When plasma levels of nonresponders within this therapeutic window were raised above 12 ng/ml (as in routine practice), they, on balance, deteriorated in that they became more dysphoric. With the 20-mg dose, half the patients had plasma levels above 12 ng/ml. CONCLUSIONS: In this sample of newly admitted schizophrenic men, optimal clinical response occurred with a plasma haloperidol range of 5-12 ng/ml.

Adult↗

PubMed1991

Ethnicity and family involvement in the treatment of schizophrenic patients.

In a cross-ethnic study of neuroleptic response, the level of family involvement with the treatment of 26 Asian and 26 Caucasian patients was evaluated. Asian family members were intimately involved, Caucasians much less so. These results quantitatively demonstrated the relatively greater importance of working with family members when treating Asian patients. They also indicate that relatively more effort is needed to increase involvement of Caucasian families in the treatment process.

Asia↗

PubMed1991

Corticosterone and prolactin response to TFMPP in rats during repeated antidepressant administration.

The corticosterone and prolactin response to acute administration of the 5-HT agonist 1-(m-trifluoromethylphenyl) piperazine (TFMPP) (10 mg kg-1) was assessed in rats treated for 10 days with either saline, amitriptyline (20 mg kg-1 day-1) or nialamide (40 mg kg-1 day-1). For all groups, TFMPP significantly increased both serum corticosterone and prolactin concentrations compared with control animals challenged with saline. However, the corticosterone response to TFMPP was attenuated significantly by nialamide pretreatment, while the prolactin response to TFMPP was enhanced significantly by amitriptyline pretreatment. These results support previous reports that antidepressants differentially affect 5-HT-ergic systems involved in the regulation of corticosterone and prolactin secretion.

Amitriptyline↗