Diagnostic specificity of focal white matter abnormalities in bipolar and unipolar mood disorder.
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Adult↗
Biomedical subjects
J C Gillin
Publications and source records attributed to J C Gillin.
No antidepressant effect of biperiden compared with placebo in depression: a double-blind 6-week clinical trial.
Depression may result from an increased ratio of cholinergic to aminergic central neurotransmission. The effect of centrally active anticholinergic agents on depressive ratings in depressed patients, however, has not been well studied. In a previous open label 4-week clinical trial, Kasper et al. (1981) reported that biperiden (Akineton) had antidepressant effects in depressed patients. We compared the effects of placebo and biperiden in a randomized, double-blind, parallel-design 6-week study. All patients received placebo for the first week and then received either biperiden (< or = 12 mg/day) or a peripherally acting anticholinergic agent, glycopyrrolate (Robinul, 1 mg/day) for 4 weeks. All patients received placebo during week 6. Both groups significantly improved, but biperiden did not demonstrate any significant benefit compared with glycopyrrolate. In a subgroup of patients receiving biperiden, the percentage of rapid eye movement sleep was significantly decreased only in the first week of biperiden compared with the initial placebo week, suggesting that tolerance to the central effects of biperiden developed. Further studies would be needed to determine whether anticholinergic agents possess antidepressant properties.
Adult↗
Time course of the corticosteroid-dopaminergic interaction during metyrapone and dexamethasone administration.
Recent studies performed with depressed patients and normal subjects suggest that corticosteroids may alter dopaminergic activity. We measured the time course of the interaction between corticosteroid and plasma homovanillic acid (HVA) levels in 10 young healthy subjects after the administration of 2 mg of dexamethasone in session 1 and after the administration of 4.5 g of metyrapone in session 2. Plasma levels of adrenocorticotropic hormone (ACTH), 11-desoxycortisol, cortisol, HVA, and prolactin (PRL) were measured at 08:00, 09:00, 12:00, 15:00, and 16:00 h on a baseline day and during both drug-administration sessions. Dexamethasone administration resulted in a significant decrease in plasma levels of ACTH, 11-desoxycortisol, and cortisol at all time points and to a significant decrease in PRL secretion in the early morning. Plasma HVA levels were unchanged after dexamethasone administration. Metyrapone administration resulted in a significant decrease in cortisol levels and a significant increase in ACTH and 11-desoxycortisol levels. Plasma HVA levels were significantly increased in the early morning, while PRL levels were unaltered. These results are discussed in relation to the neurochemical and behavioral changes associated with steroid administration and interpreted with regard to a possible association between HVA and PRL in the effects of corticosteroids on dopaminergic activity.
Adrenocorticotropic Hormone↗
The expression of m1-m3 muscarinic receptor mRNAs in rat brain following REM sleep deprivation.
We used in situ hybridization histochemistry to study the effects of REM sleep deprivation on m1-m3 muscarinic receptor mRNA expression in the rat brain. REM sleep deprivation for 72 h did not affect m1 receptor mRNA expression. However, we found significantly increased m3 receptor mRNA expression in the pontine nuclei and nucleus accumbens-bed nucleus of the stria terminalis region of REM sleep-deprived rats compared with controls. Paradoxically, we found significantly decreased m2 receptor mRNA expression in the pontine nuclei of REM sleep-derived rats vs controls. The present findings implicate these structures in the cholinergic effector pathways of REM sleep, although the type and magnitude of the effects of these structures on REM sleep may vary with different receptor subtypes.
Animals↗
Do differences in sleep architecture exist between depressives with comorbid simple phobia as compared with pure depressives?
Sleep records from 19 subjects with major depression and comorbid simple phobia were compared retrospectively with 25 patients with major depression alone and 25 normal controls. Groups were matched for age and gender; depressed subjects were matched for severity of depression. All subjects had been free of psychotropic medications at least 2 weeks when recorded. Sleep variables were analysed using one-way ANOVA. Both depressed groups had significantly longer sleep latency than normal controls. Depressed patients with and without simple phobia showed no differences in sleep architecture.
Depressive Disorder↗
Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities.
BACKGROUND: Recent reports in the literature document an association between focal white matter abnormalities in bipolar as well as unipolar mood disorder. The importance of this finding and other associated anatomic differences is uncertain. METHODS: We examined the volume of abnormal white matter and other brain volumes using quantitative magnetic resonance imaging analysis. We explored the relationship of these variables with diagnosis, cognitive function, and clinical variables in 36 patients with bipolar disorder, 30 patients with unipolar disorder, and 26 control subjects who were free from significant medical and neurologic illness. RESULTS: Younger patients with bipolar disorder (but not similarly aged patients with unipolar disorder or controls) have an increased volume of abnormal white matter. Data also indicate that the total volume of abnormal white matter may be associated with increased cognitive impairment, increased rate of psychiatric illness in the family, and onset after adolescence. CONCLUSION: Patients with bipolar disorder demonstrate a pattern of subcortical brain morphologic abnormalities and cognitive impairment.
Adult↗
Localized and lateralized cerebral glucose metabolism associated with eye movements during REM sleep and wakefulness: a positron emission tomography (PET) study.
In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, we analyzed the positron emission tomography (18Fluorodeoxyglucose positron emission tomography) scan data obtained from normal subjects. Eye movement data were available on nine subjects studied during nighttime REM sleep and six control subjects studied during waking as they periodically moved their eyes. The number of eye movements during REM sleep was positively correlated with glucose metabolic rate in the areas corresponding to (a) the saccadic eye movement system (frontal eye field and dorsolateral prefrontal cortex, statistically significant only on the right side), (b) the midline attentional system (cingulate and medial frontal cortex, precuneus) and (c) the parietal visual spatial attentional system (bilateral superior parietal lobules, right inferior parietal lobule); and negatively correlated with relative metabolic rate in the left inferior parietal lobule. Positive correlations between waking eye movements and metabolic rate were observed in the same areas except inferior parietal lobule. Our results show that the same cortical areas are involved in eye movements in both REM sleep and wakefulness and suggest that REM sleep eye movements are saccadic scans of targets in the dream scene. Our data also suggest right hemispheric specialization in saccadic eye movement control and reciprocal inhibition in the contralateral homologous area during higher cortical functioning.
Attention↗
Cocaine abuse and dependence.
Western countries experienced a widespread cocaine epidemic during the 1980s, and the number of frequent users has not declined in this decade. A key factor in the development of this epidemic has been the introduction of "crack," an affordable form of cocaine that appears to be more addicting than the powder. Epidemiologic studies indicate a high incidence of polysubstance abuse among cocaine abusers and probable gender differences in patterns of abuse and response to treatment. An abstinence syndrome has been documented in outpatients after the acute cessation of cocaine; the symptoms perhaps depend on the presence of cues to evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine is a psychostimulant drug that possesses euphorigenic and reinforcing properties. The fact that various animal species self-administer cocaine through the intravenous route provides a reliable animal model for the study of the molecular mechanism of cocaine action and for the characterization of the anatomical substrates responsible for the rewarding properties of the drug. A multisynaptic, allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to play an important role. This pathway may also be part of the neuronal substrates that mediate the reinforcing properties of other classes of abused drugs and, perhaps, motivated behavior in general. Because of this potent reinforcing nature of cocaine in humans, the problem of designing effective therapy for its addiction has not been simply solved. Clinical treatments, guided by animal studies and designed for specific attack of symptoms of the abstinence syndrome, craving and anhedonia, have been tested. To date, only a few agents have proved effective in controlled trials (amantadine, bromocriptine, carbamazepine, and desipramine) and these have limitations of side effects or delayed onset of action. Agents that interact with specific subcomponents of the dopamine system or its connections offer promise for the development of successful agents to treat cocaine abuse and craving in humans.
Animals↗
Alcoholism and affective disorder: clinical course of depressive symptoms.
OBJECTIVE: This study compared the severity of and the change in depressive symptoms among men with alcohol dependence, affective disorder, or both disorders during 4 weeks of inpatient treatment. METHOD: After their primary and secondary psychiatric disorders were defined with the use of criteria based on chronology of symptoms, 54 unmedicated men entering treatment for alcohol dependence or affective disorder were assessed for 4 consecutive weeks with the Hamilton Depression Rating Scale. RESULTS: The findings indicate that the rate of remission of depressive symptoms was consistent with the primary diagnosis. Depressive symptoms remitted more rapidly among the men with primary alcoholism than among those with primary affective disorder. However, a minimum of 3 weeks of abstinence from alcohol appeared to be necessary to consistently differentiate the groups with dual diagnoses on the basis of their current depressive symptoms. Alcohol dependence occurring in conjunction with primary affective disorder did not intensify presenting depressive symptoms or retard the resolution of such symptoms. CONCLUSIONS: Diagnoses of alcohol dependence and affective disorder based on symptom chronology appear to have prognostic significance with respect to remission of depressive symptoms in men with both diagnoses. Depressive symptoms of dysphoric mood, dysfunctional cognitions, vegetative symptoms, and anxiety/agitation showed different rates and levels of remission across the primary diagnostic groups.
Adult↗
Early versus late partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects.
OBJECTIVE: The aim of this study was to compare the clinical effects of early-night and late-night partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects. METHOD: In the premenstrual phase of two menstrual cycles, 23 subjects with DSM-IV premenstrual dysphoric disorder and 18 normal comparison subjects underwent a randomized crossover trial of 1) early-night sleep deprivation, in which subjects slept from 3:00 a.m. to 7:00 a.m., followed by a night of recovery sleep (11:00 p.m. to 7:00 a.m.), and 2) late-night sleep deprivation, in which subjects slept from 9:00 p.m. to 1:00 a.m., followed by a night of recovery sleep. RESULTS: For the subjects with premenstrual dysphoric disorder, in both partial sleep deprivation conditions the Hamilton and Beck depression ratings were significantly lower after recovery sleep than at baseline. Ratings on the day after early or late partial sleep deprivation tended to be lower than at baseline but were not statistically different. The normal comparison subjects showed no clinically important mood changes. A factor analytic approach used with the Hamilton depression scores showed that depressive retardation symptoms were the most responsive to sleep deprivation in the premenstrual dysphoric disorder subjects. CONCLUSIONS: These results are consistent with the reported efficacy of sleep deprivation for major depressive disorder. However, the premenstrual dysphoric disorder subjects improved after the recovery sleep rather than directly after partial sleep deprivation. That late-night sleep deprivation did not have greater benefit than did the hypothesized sham treatment, early-night sleep deprivation, also suggests that placebo effects cannot be ruled out.
Adult↗
Gender differences in outpatient research subjects with affective disorders: a comparison of descriptive variables.
BACKGROUND: Gender may play an important role in the etiopathophysiology of psychiatric illness and has become a subject of increasing interest because of its possible effects on biological markers, treatment outcome, and prognosis. Intrigued by this issue and as part of our attempt to further characterize research subjects in San Diego, we evaluated male and female research subjects from our affective disorders clinical research center on a variety of measures. Based on epidemiologic data, we postulated that female and male subjects would be similar to epidemiologic samples and would differ in terms of comorbid diagnoses and that female subjects would be more likely to have had a history of previous treatment. METHOD: The demographic characteristics; coffee, tobacco, and alcohol consumption patterns; symptom patterns; and current and lifetime comorbid DSM-III-R Axis I diagnoses of 124 female and 69 male outpatient research subjects were contrasted. RESULTS: Female research subjects had more comorbid problems with anxiety disorders, were more likely to have been previously treated, and were more likely to have a family history of psychiatric illness. CONCLUSION: Male and female research subjects were remarkably similar with respect to most characteristics assessed but, as postulated, differed in terms of their comorbid diagnoses and prior treatment history.
Adult↗
Neuroendocrine effects of light therapy in late luteal phase dysphoric disorder.
In 20 late luteal phase dysphoric disorder (LLPDD) and in 11 normal control (NC) subjects, circadian profiles of cortisol, prolactin, thyrotropin-stimulating hormone (TSH), and core body temperature were measured during midfollicular (MF) and late luteal (LL) menstrual cycle phases and after 1 week of light therapy either with (1) bright (tau 2500 lux) white morning (6:30 AM to 8:30 AM), (2) bright white evening (7 PM to 9 PM) or (3) dim (< 10 lux) red evening light, randomly administered in three separate luteal phases. In NC but not PMDD subjects, the cortisol peak significantly delayed in the LL compared with the MF phase. In PMDD, prolactin peak and amplitude were higher, prolactin acrophase earlier, and temperature amplitude higher during both the MF and LL phases. After light treatment, prolactin amplitude remained higher in LLPDD than in controls. In both groups, bright light shifted the cortisol acrophase, and AM light increased the prolactin nadir. Bright PM light increased the TSH nadir in LLPDD, but decreased it in controls. Thus, menstrual cycle phase, diagnosis, and light therapy may differentially affect neuroendocrine systems.
Arousal↗
A linkage study of distal chromosome 5q and bipolar disorder.
There are well-established abnormalities of hypothalamic-pituitary-adrenal (HPA) axis and beta 2 adrenergic receptor function in affective disorders. The genes for the glucocorticoid receptor (GRL) and the beta 2 adrenergic receptor (ADRB2) have been cloned and mapped to distal chromosome 5q. In this study, we have examined polymorphisms of these two candidate genes and other nearby markers for linkage to bipolar disorder in Amish pedigree 110 and three large Icelandic pedigrees. These loci were tested for linkage in two-point and multipoint analyses using a model of autosomal dominant transmission with age-dependent reduced penetrance. Two-point analyses revealed a maximum LOD score of 1.14 at theta = 0.20 from GRL. Linkage could be excluded to ADRB2, as well as to three nearby anonymous markers, D5S207, D5S70, and D5S119. Analyses of another anonymous marker, D5S36, were inconclusive. Multipoint analyses excluded linkage to a 55 cM region including the interval between D5S207 and D5S36 and flanking regions, with the exception of a 7 cM interval between GRL and ADRB2. Despite the intriguing positive LOD score obtained with GRL, linkage to bipolar disorder could not be demonstrated in the region examined.
Adolescent↗
The effects of lisuride on mood and sleep during acute withdrawal in stimulant abusers: a preliminary report.
Psychostimulant abusers often experience anhedonia, depression, fatigue, craving, and hypersomnia and increased propensity for rapid eye movement (REM) sleep during periods of acute and subacute withdrawal from cocaine and amphetamine. These signs and symptoms may reflect a state of relative functional dopamine depletion in the brain during abstinence. Lisuride, which has dopaminergic agonist effects, has been reported to reduce signs of psychostimulant withdrawal in rodent models of stimulant abuse. These observations prompted us to test the effects of oral administration of lisuride for 3 weeks (up to 4.0 mg daily) on mood and craving ratings in a double-blind, parallel design, controlled study in hospitalized stimulant abusers during acute withdrawal from cocaine or amphetamine. Although administration of lisuride significantly prolonged REM latency and reduced REM time, amelioration of other signs of withdrawal was not significantly greater in lisuride as compared with placebo treated patients. Self-rated craving ratings, however, were low in both groups throughout the hospital stay. Further studies, perhaps in patients with more severe symptoms during withdrawal, are needed to fully test the efficacy of lisuride in the treatment of stimulant withdrawal.
Administration, Oral↗
Increased pressure for rapid eye movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary alcoholism at 3-month follow-up.
OBJECTIVE: To determine whether polygraphic sleep recordings, obtained at the time of admission to an inpatient alcohol treatment program, predict abstinence and relapse 3 months following hospital discharge in nondepressed patients with primary alcoholism. DESIGN: Two independent, consecutive cohorts of patients (group 1, n = 28; group 2, n = 17) underwent all-night polygraphic sleep recordings and other clinical evaluations during the first and fourth weeks of a 1-month inpatient treatment program within a Veteran Affairs Medical Center. They were reevaluated 3 months following discharge to the community. None were treated with disulfiram or other medications during or after hospitalization. PATIENTS: All subjects were male veterans with primary alcoholism and without significant preexisting, secondary, or comorbid diagnoses such as major medical problems, depression, antisocial personality, or drug addiction. OUTCOME MEASURES: Relapse was defined as any alcohol consumption between discharge from the hospital and 3-month follow-up. RESULTS: Ten (36%) of 28 patients in group 1 were Relapsers at 3-month follow-up. Relapsers in group 1 showed significantly shorter Rapid Eye Movement (REM) latency, increased Rapid Eye Movement percent (REM%), and increased REM Density during their admission sleep studies compared with Abstainers. To replicate these observations, group 2 was then studied as a validation sample. Six (35%) of 17 patients relapsed. As in group 1, Relapsers had significantly shorter REM latency and increased REM% compared with Abstainers; REM Density was not significantly different in the Relapsers as compared with Abstainers in group 2. Using a principal components analysis based on these three REM sleep measures to determine "REM pressure," three separate discriminant function analyses (DFAs) were calculated: one for each group and one for all patients (n = 45) together. The DFA from group 1 correctly classified 22 (78.6%) of the 28 patients in group 1 and 13 (76.5%) of the 17 patients in group 2 as Relapsers or Abstainers. The DFA from group 2 correctly classified 13 (76.5%) of the 17 patients in group 2 and 23 (82.1%) of the 28 patients in group 1. The DFA formed from both groups together correctly classified 36 (80%) of the 45 patients. When the REM sleep measures at hospital admission and discharge were compared, no statistically significant effect of time was observed. Abstinence and relapse were not consistently related to other clinical measures at the time of hospital admission such as age, duration and severity of alcoholism, marital status, employment, hepatic enzyme levels, cognitive performance, or depression ratings. CONCLUSION: Short REM latency, increased REM%, and, possibly, increased REM Density at the time of admission to a 1-month inpatient alcohol treatment program predict relapse in nondepressed patients with primary alcoholism by 3 months following hospital discharge.
Alcohol Drinking↗
Inhibition of REM sleep by ipsapirone, a 5HT1A agonist, in normal volunteers.
In order to test the hypothesis that serotonergic mechanisms inhibit REM sleep via a 5HT1A receptor, we administered placebo and ipsapirone (10 and 20 mg by mouth 15 min before bedtime) to ten normal volunteers in a double blind fashion. Ipsapirone is a relatively selective 5HT1A receptor agonist. As predicted, ipsapirone prolonged REM latency and Mean Latency to Eye Movements (M-LEM), a measure of time between onset of REM sleep and the first eye movement of the REM period, and REM% at both doses compared with placebo. It also reduced sleep efficiency and total REM sleep time at the highest dose. These results support the hypothesis that systemic stimulation of 5HT1A receptors prolong REM latency and inhibit REM sleep.
Adult↗
Sleep in non-institutionalized Alzheimer's disease patients.
The sleep of Alzheimer's disease (AD) patients is often disturbed by medications, depression, circadian rhythm changes and sleep disorders. Institutionalization is often precipitated by the effect of the patient's sleep and wakefulness on the caregiver. We examined reports of sleep disturbance in mild AD patients. The study cohort consisted of 246 AD patients and 94 controls. Self-reports of sleep disturbance in mild AD patients were examined as was the relationship of sleep and medication use. Results were compared to those of normal controls, and the patients' responses to the reports of their caregivers. Dementia was assessed with the Mini Mental Status Exam, the Blessed Dementia Scale, the Mattis Dementia Rating Scale, and the Pfeiffer Outpatient Disability Test. The more demented the patients, the more time they spent in bed, the more fragmented their sleep, and the more naps they took. Caregivers reports of increased wandering at night and more aggressive behavior during the day were associated with increased use of sedative-hypnotics and with going to bed early. Lengthy sleep was associated with disruptive behavior. We conclude that increased sleep may be associated with dementia and with more disruptive behavior.
Aged↗
Latency to rapid eye movement sleep as a predictor of treatment response to fluoxetine and placebo in nonpsychotic depressed outpatients.
Fluoxetine and placebo were compared in 89 outpatients with major depression with (n = 45) or without (n = 44) a reduced or shortened rapid eye movement latency (SREML) (< or = 65 minutes) to determine whether rapid eye movement latency (REML) predicted placebo and/or antidepressant response. Men and women were stratified based on polysomnographic recordings and then randomly assigned to receive double-blind fluoxetine (20 mg/day) or placebo for 8 weeks after a 2-week, single-blind, placebo lead-in period. Fluoxetine-treated patients demonstrated a significantly greater reduction in the Hamilton Rating Scale for Depression total score and a significantly greater response rate than placebo-treated patients in both the SREML and the combined strata. Treatment differences in the non-SREML stratum were not statistically significant. Results supported REML as a predictor of placebo nonresponse but did not predict a differential fluoxetine response in patients with SREML compared with patients without SREML.
Adolescent↗