Commentary: Antipsychotic prescribing practices in the Texas prison system.
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Antipsychotic Agents↗
Biomedical subjects
R L Trestman
Publications and source records attributed to R L Trestman.
Behind bars: personality disorders.
Individuals with severe, function-impairing personality disorders comprise a large proportion of the difficult-to-manage inmates. Personality disorders are reliably diagnosable using standardized criteria (DSM-IV), and treatment options are now available. Through careful assessment, differential diagnosis, and differential therapeutic selection, clinicians have the opportunity to help these individuals gain more control over unstable affect, impulsive/ irritable aggression, and paranoid perceptual distortions. Appropriate intervention holds the possibility, if not the promise, of reduced morbidity and recidivism, and may reasonably contribute to the public safety mission of corrections and to the primary mission of clinicians, which is improved health.
Behavior Therapy↗
Serotonin and the prediction of response time to fluoxetine in patients with mild depression.
Serotonin (5-HT) dysregulation has been associated with major depressive disorder (MDD); a blunted prolactin (PRL) response to D,L-fenfluramine (FEN) has been associated with MDD. Pharmacologic manipulation of the serotonin system with a selective serotonin reuptake inhibitor (SSRI) is effective in the treatment of depression. However, the relationship between pre-treatment 5-HT activity and response to SSRIs is not well understood. This study investigated the relationship between 5-HT dysregulation and response to fluoxetine (FLU). Twenty patients with MDD entered a double-blind placebo-controlled trial of fluoxetine preceded by D,L-fenfluramine stimulation. Patients were assigned randomly to either FLU, 20 mg QD, or placebo (PLA) for an 11-week trial. No relationship was found between the PRL response to FEN and response to FLU. Among the seven responding to FLU, there was a significant negative correlation between PRL response and the time until sustained response to FLU (r = -0.93, P < 0.001, n = 7). Although preliminary, this study suggests that low baseline serotonin activity may be associated with a slower response to FLU in depression.
Adult↗
Serum cholesterol and impulsivity in personality disorders.
Decreased serum cholesterol has been associated with impulsive aggressive behaviors. This study was designed to explore the relationship between serum cholesterol levels and measures of impulsive aggression in personality disordered patients. Forty-two personality disordered patients (14 borderline personality disorder, 28 other personality disorders) were included. Fasting serum cholesterol was measured by standard enzymatic assay. An ANOVA was performed with factors of gender and diagnosis, looking at two-way interactions between the factors and serum cholesterol. Patients with borderline personality disorder were found to have significantly lower serum cholesterol than non-borderline personality disorders. A significant interaction effect was also seen between gender and diagnosis with the male patients having lower cholesterol levels. This study suggests there may be a relationship between borderline personality disorder and low serum cholesterol.
Adult↗
Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study.
To assess the relationship between two phenotypes in an extremely well-characterized population of personality disorder patients-impulsive aggression and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype, TPH genotype (at an intronic polymorphic site) and prolactin response to fenfluramine were assessed in 40 Caucasian patients with personality disorder. Impulsive aggression was assessed by using the Buss-Durkee Hostility Inventory (BDHI). Twenty-one male patients with the "LL" genotype had higher BDHI scores than men with the "UL" or the "UU" genotype. No relationship between genotype and prolactin response to fenfluramine was found. It was concluded that impulsive-aggressive behavior in male personality disorder patients may be associated with the TPH genotype.
Adult↗
Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness.
Three central indices of serotonin (5-HT) system activity in human subjects were examined to: (a) estimate intercorrelations among 5-HT indices and (b) compare correlations of these indices with a measure of assaultiveness (Buss-Durkee 'Assault') in personality-disordered individuals. Cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentration and prolactin responses to m-chlorophenylpiperazine (m-CPP) m-CPP (PRL[m-CPP]) and fenfluramine (PRL[FEN]), served as indices of pre-, post- and 'net'-synaptic central 5-HT activity, respectively. PRL[D,L-FEN] responses were inversely related to CSF 5-HIAA concentration and positively correlated with PRL[m-CPP] responses. Both PRL[D,L-FEN] and PRL[m-CPP] response data correlated equally, and inversely, with BD Buss-Durkee Assault when the same subjects were examined. Basal CSF 5-HIAA concentration did not correlate with Buss-Durkee 'Assault'. PRL responses to challenge probes which involve activation of 5-HT post-synaptic receptors may correlate better than a basal measure of pre-synaptic 5-HT function with a tendency to assaultive behavior in non-criminally aggressive personality-disordered individuals.
Adult↗
Regional cerebral blood flow during the Wisconsin Card Sort Test in schizotypal personality disorder.
Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography in 10 patients with schizotypal personality disorder (SPD) and nine age- and sex-matched normal volunteers. Subjects performed both the Wisconsin Card Sort Test (WCST) and a control task, the Symbol Matching Test (SMT). Four-way analyses of variance were performed to assess relative rCBF of the prefrontal cortex and of the medial temporal region. Normal volunteers showed more marked activation in the precentral gyrus, while SPD patients showed greater activation in the middle frontal gyrus. Relative flow in the left prefrontal cortex was correlated with better WCST performance in normal volunteers. SPD patients, however, showed no such correlations in the left prefrontal cortex, but demonstrated correlations of good and bad performance with CBF in the right middle and inferior frontal gyrus, respectively. Thus, at least some SPD patients demonstrate abnormal patterns of prefrontal activation, perhaps as a compensation for dysfunction in other regions.
Adult↗
Serotonergic function and self-injurious behavior in personality disorder patients.
Self-directed aggression, whether in the form of non-suicidal self-mutilation or suicidal behavior, is a prominent feature of personality disorders. We hypothesized that self-injurious behavior, like suicidal behavior, represents a form of self-directed aggression, and may, like suicidal behavior and impulsive aggression, be associated with a decrease in central serotonin function in personality disorder patients. Ninety-seven patients with DSM-III personality disorder underwent D,L-fenfluramine challenge as an assessment of serotonergic activity. Patients with a history of self-mutilation or suicide had blunted prolactin and cortisol responses to D,L-fenfluramine compared to those with neither, and those with both had the most blunted responses to fenfluramine. These data raise the possibility that the central 5-HT abnormality, previously associated with suicidal behavior, may be associated with self-directed violence and not necessarily specifically with suicidal intent.
Adult↗
Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.
The aim of the present study was to evaluate the pattern of basal cortisol release in PTSD and major depression using a chronobiological analysis. Plasma for cortisol determination was obtained from 15 combat veterans with PTSD, 14 subjects with major depression, and 15 normal men every 30 min during a 24-hour period of bed rest. Raw cortisol data were modeled using standard and multioscillator cosinor models to determine the best fitting functions for circadian, hemicircadian, and ultradian components of cortisol release. PTSD subjects had substantially lower cortisol levels, and displayed a pattern of cortisol release that was better modeled by circadian rhythm. PTSD subjects also showed a greater circadian signal-to-noise ratio than the other groups. In contrast, depressed patients displayed a less-rhythmic, more chaotic pattern of cortisol release. The pattern of cortisol secretion and regulation observed in the PTSD group under baseline conditions may reflect an exaggerated sensitization, whereas the chronobiological alterations in depression may reflect dysregulation, of the hypothalamic-pituitary-adrenal (HPA) axis.
Adult↗
Hormonal responses to meta-chlorophenylpiperazine (m-CPP) are undiminished by acute m-CPP pretreatment.
Two challenges with meta-chlorophenylpiperazine (m-CPP, 0.5 mg/kg, p.o.) were performed in healthy volunteers to test the short-term stability of hormonal responses. Challenges were performed in an identical fashion and were conducted on sequential days. Circulating m-CPP plasma levels, as well as prolactin and cortisol responses to m-CPP, were correspondingly similar in magnitude on the 2 days. These data suggest that both prolactin and cortisol responses to single oral administrations of m-CPP are stable over at least a 24-h period.
Administration, Oral↗
D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder.
The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine-associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge.
Adult↗
Event-related potentials in schizotypal personality disorder.
This study examined whether abnormalities in event-related potentials (ERPs), reported in schizophrenia, extend to patients with schizotypal personality disorder (SPD). Auditory ERPs in an oddball paradigm were obtained in 19 SPD patients, 17 schizophrenic patients, and 20 normal control subjects (NCs). Schizophrenic patients had lower P300 amplitude than NCs; the P300 amplitude of SPD patients was intermediate, showing a linear trend but not a significant group difference. P200 amplitudes showed a similar trend. SPD patients had N100 and N200 amplitudes intermediate to schizophrenic patients and NCs, without significant group differences. Results suggest diminished P300 amplitude may not be as prominent in SPD as in schizophrenia. Studies with larger sample sizes, multiple lead assessment strategies, and more demanding tasks may further characterize ERP deficits in schizophrenia-spectrum disorders such as SPD.
Adult↗
Impulsivity and serotonergic function in compulsive personality disorder.
This study compared serotonergic function, as assessed by prolactin response to fenfluramine, in males with compulsive personality disorder, males with noncompulsive personality disorders, and normal control subjects. The two patient groups did not differ in age, depression status, suicide history, or comorbid borderline personality disorder. However, compulsive personality disorder patients had significantly greater impulsive aggressive scores than the noncompulsive patients and significantly blunted prolactin responses compared with the non-compulsive patients and normal control subjects. In the combined patient group, total compulsive personality disorder traits correlated positively with impulsive aggression score and inversely with prolactin response. These results support the hypothesis that impulsive and compulsive symptoms do not simply lie at opposite ends of a phenomenological and neurobiological spectrum, but rather have a complex intersection and may both correlate with serotonergic dysfunction.
Adult↗
Cognitive function and biological correlates of cognitive performance in schizotypal personality disorder.
There is evidence that some schizophrenic patients have deficits on tests of cognitive function, particularly tests of executive function, including the Wisconsin Card Sorting Test (WCST) and the Trail-making Test, Part B. This study was conducted to determine the generalizability of these findings across the schizophrenia spectrum to schizotypal personality disorder (SPD). Forty DSM-III SPD patients, 56 nonschizophrenia-related other personality disorder (OPD) patients, and 32 normal volunteers from two medical centers performed tests of executive function such as the WCST, Trail-making Part B, Stroop Word-Color Test, and Verbal Fluency, as well as tests of more general intellectual functioning such as the Wechsler Intelligence Scale-Revised Vocabulary and Block Design subtests, and Trail-making Part A. SPD patients performed more poorly on the WCST and on Trail-making Part B than did OPD patients or normal subjects; the groups did not differ on tests of general intellectual functioning. SPD patients may share some of the cognitive deficits observed in schizophrenia.
Adult↗
Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients.
This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age-range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls. The time course of diurnal heart rate also differed in acutely depressed patients from controls: acutely depressed patients started higher and converged by midday to normal levels. These diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression.
Adult↗
Circadian regulation of basal cortisol levels in posttraumatic stress disorder.
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Activity Cycles↗
The stability of plasma growth hormone and MHPG responses to repeated clonidine challenge in normal males.
Clonidine is a centrally acting alpha 2-adrenergic agonist used in many psychiatric studies to assess adrenergic functioning. The short- and long-term stability of plasma growth hormone (GH) and plasma 3-methoxy-4-hydroxy phenylglycol (MHPG) responses to clonidine (2 micrograms/kg IV) over a 60-min period were assessed in subsets of 13 male normal controls on 2 consecutive days (Study A; n = 11) and on 2 days separated by several months (Study B; n = 11). In Study A, no significant differences between consecutive days were found in either baseline plasma GH or MHPG or their responses to clonidine. The 60 minute plasma GH responses between consecutive days were highly correlated (r = 0.75, n = II, p < .001), while the 60 min plasma MHPG responses were not. In Study B, no significant differences in baseline plasma GH or MHPG, or their responses to clonidine challenge, were found between the 2 test days. However, neither the plasma GH responses nor the plasma MHPG responses to clonidine at 60 min correlated significantly between the 2 study days separated by several months. Both in Study-A and in Study B, 8 of 11 subjects had a stable GH response to clonidine across both study days when defined dichotomously (blunted < 4 ng/ml; otherwise, not blunted). These results suggest that the plasma GH response and plasma MHPG response to clonidine are unaffected by repeat clonidine challenge separated by 24 h, and that the plasma GH response to clonidine may be more stable over time than the plasma MHPG response to clonidine.
Adrenergic alpha-Agonists↗
The cortisol response to clonidine in acute and remitted depressed men.
To assess the relationship between the hypothalamo-pituitary-adrenal (HPA) axis and the noradrenergic system in patients with major depression, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clonidine (2 micrograms/kg) or placebo. Acute, but not remitted, depressed patients had a greater plasma cortisol baseline than did normal controls (t = 2.0, p < 0.03). Only acutely depressed patients had a greater decrease in plasma cortisol in response to clonidine than to placebo (t = 2.5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory disturbance in depressed patients, suggesting that clonidine inhibits the elevated plasma cortisol in acute depression but not the normal concentrations observed in remitted depression or healthy controls.
Adult↗