Showing papers in "Psychiatry Research-neuroimaging in 1991"
TL;DR: Evidence for the reliability and construct validity of the Apathy Evaluation Scale is presented and guidelines for the administration of the AES are presented, along with suggestions for potential applications of the scale to clinical and research questions.
Abstract: This article presents evidence for the reliability and construct validity of the Apathy Evaluation Scale (AES). Conceptually, apathy is defined as lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Operationally, the AES treats apathy as a psychological dimension defined by simultaneous deficits in the overt behavioral, cognitive, and emotional concomitants of goal-directed behavior. Three versions of the AES (clinician, informant, and self-rated) were evaluted for 123 subjects, ages 53-85, meeting research criteria for right or left hemisphere stroke, probable Alzheimer's disease, major depression, or well elderly control. Multiple forms of reliability (internal consistency, test-retest, and interrater) were satisfactory. Several types of validity evidence are presented for each version of the scale, including the following: ability of the AES to discriminate between groups according to mean levels of apathy, discriminability of apathy ratings from standard measures of depression and anxiety, convergent validity between the three versions of the scale, and predictive validity measures derived from observing subjects' play with novelty toys and videogames. Guidelines for the administration of the AES are presented, along with suggestions for potential applications of the scale to clinical and research questions.
1,415 citations
TL;DR: A visual analogue scale to evaluate fatigue severity (VAS-F) was developed and tested and demonstrated significant differences between their evening and morning scores, while sleep-disordered patients did not.
Abstract: A visual analogue scale to evaluate fatigue severity (VAS-F) was developed and tested in a sample of 75 healthy individuals and a sample of 57 patients undergoing medical evaluation for sleep disorders. The scale consists of 18 items related to fatigue and energy, has simple instructions, and is completed with minimal time and effort. The VAS-F compares favorably with the Stanford Sleepiness Scale and the Profile of Mood States, and its internal consistency reliabilities are high. Healthy subjects demonstrated significant differences between their evening and morning scores on the VAS-F, while sleep-disordered patients did not.
1,002 citations
TL;DR: There was a consistent trend toward higher psychiatric comorbidity in migraine with aura than in migraine without aura, and persons with migraine had higher rates of suicide attempts than persons without migraine.
Abstract: To determine the prevalence of migraine and the risks for psychiatric disorders and suicide attempts associated with it, we studied a random sample of 1,007 young adults from a large Health Maintenance Organization in the Detroit, MI area. The lifetime prevalence of migraine was 7% in males and 16.3% in females. The rate of migraine was higher in persons with lower education and was equal in whites and blacks. Persons with migraine were at increased risk for affective and anxiety disorders, nicotine dependence, and alcohol or illicit drug abuse or dependence. There was a consistent trend toward higher psychiatric comorbidity in migraine with aura than in migraine without aura. Coexisting anxiety, which generally preceded migraine, was associated with a marked increase in the odds of major depression. Persons with migraine had higher rates of suicide attempts than persons without migraine. The odds ratio for suicide attempts, adjusted for coexisting major depression and other psychiatric and substance use disorders, in migraine with aura was 3.0 (95% confidence interval, 1.4-6.6). The coexistence of migraine with major depression, anxiety disorders, and suicide attempts has important clinical and research implications.
507 citations
TL;DR: "Nonresponse" appears to be extremely rare when both stimulants and a wide range of doses are given, and frequently one drug or the other was superior for an individual child, or adverse effects occurred only on one of the stimulants.
Abstract: The response to stimulant drugs of 48 boys with attention deficit/hyperactivity disorder was measured following dextroamphetamine, methylphenidate, and placebo in a double-blind crossover study. To distinguish lack of behavioral improvement from adverse drug effects, a day hospital setting and a wide dose range were used. Both drugs were highly and equally efficacious for the group as a whole, and frequently one drug or the other was superior for an individual child, or adverse effects occurred only on one of the stimulants. Only one of the 48 boys (2%) was discharged without the recommendation for continued stimulant drug treatment. "Nonresponse" appears to be extremely rare when both stimulants and a wide range of doses are given.
277 citations
TL;DR: These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.
Abstract: The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T2 intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.
264 citations
TL;DR: The standing heart rate variability (R-R variability) was significantly lower in panic disorder patients compared to both normal controls and depressed patients as indicated by the corrected standard deviations, the corrected mean consecutive difference, and the high frequency variability in successive R-R intervals, suggesting an increased vagal withdrawal inpanic disorder patients, especially upon standing.
Abstract: We have previously reported decreased heart rate variability upon standing in panic disorder patients compared with controls. In this study, we extend our report to include patients with major depression (n = 19). Compared to normal controls (n = 20) and panic disorder patients (n = 30), there was no significant difference in the immediate changes in heart rate upon standing in the depressed group. The standing heart rate variability (R-R variability) was significantly lower in panic disorder patients compared to both normal controls and depressed patients as indicated by the corrected standard deviations, the corrected mean consecutive difference, the corrected standard deviation of the mean consecutive difference of the R-R intervals, and the high frequency variability in successive R-R intervals, suggesting an increased vagal withdrawal in panic disorder patients, especially upon standing. There was no significant difference in any of the heart rate variability measures between depressed patients and normal controls.
209 citations
TL;DR: Correlations in monozygotic and dizygotic twins suggested that genetic factors were important in all four domains of schizotypy, and the results are more consistent with a dimensional than a "disease" model of schzotypy.
Abstract: This report of a pilot study examines 29 pairs of twins from a population-based registry on whom four domains of schizotypy have been measured: personal interview using the Structured Interview for Schizotypy, self-report questionnaire formed from eight published self-report scales, attentional battery of eight individual tests, and root mean square error on smooth pursuit eye tracking. Analyzing the twins as individuals revealed two independent dimensions of clinically rated schizotypy (positive symptom schizotypy and negative symptom schizotypy) and two independent dimensions of self-rated schizotypy (positive trait schizotypy and trait anhedonia). Positive symptom schizotypy was highly correlated with positive trait schizotypy, but not with attentional dysfunction or eye-tracking error. By contrast, negative symptom schizotypy was significantly related to trait anhedonia, attentional dysfunction, and eye-tracking error. Correlations in monozygotic and dizygotic twins suggested that genetic factors were important in all four domains of schizotypy. Except for eye-tracking error, the results are more consistent with a dimensional than a "disease" model of schizotypy. Replication of these results with a larger group of subjects is needed.
199 citations
TL;DR: Only responders showed relative hyperperfusion in parts of the limbic system and a reduction of blood flow in these regions after sleep deprivation.
Abstract: We studied 10 patients with melancholia before and after sleep deprivation and 8 controls with Tc-99m-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT). All depressed subjects showed relative hypoperfusion in the left anterolateral prefrontal cortex under both conditions. Only responders showed relative hyperperfusion in parts of the limbic system and a reduction of blood flow in these regions after sleep deprivation.
192 citations
TL;DR: It is demonstrated that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures, related to the relation of a structure's size and whole brain size.
Abstract: Ratio measures, such as the ventricle-brain ratio (VBR) based on computed tomography or magnetic resonance imaging, are widely used in psychiatric research in studies of brain function and morphology. While imaging techniques have advanced considerably, the form of the index of a structure's size has remained the same—a proportion based on an estimate of the structure's size divided by a like estimate of the whole brain size. We demonstrate that ratio and similar indices can suffer greatly in reliability when compared with simple volume measures. This loss of reliability is related to the relation of a structure's size and whole brain size. We review various methods for measuring the size of structures and discuss their strengths and limitations in terms of reliability and validity. In many instances, other methods of “correcting” for brain size (e.g., regression or covariance) may yield measurements that are more appropriate than ratios.
190 citations
TL;DR: It is suggested that cognitive deficits in schizophrenia are associated with impairments in social skill and that such deficits may limit the rate of skill acquisition and clinical response to social skills training interventions.
Abstract: Memory and symptomatology were examined as predictors of social skill acquisition in psychiatric inpatients participating in a social skills training program. Poor memory was related to pretreatment social skill impairments and slower rates of skill improvement during the intervention for patients with schizophrenia or schizoaffective disorder, but not affective disorder. Symptomatology was not consistently related to pretreatment social skill or changes in skill for either schizophrenic or affective disorder patients. The results suggest that cognitive deficits in schizophrenia are associated with impairments in social skill and that such deficits may limit the rate of skill acquisition and clinical response to social skills training interventions.
190 citations
TL;DR: It is suggested that estradiol might act as a protective modulator in schizophrenia by enhancing the vulnerability threshold for psychosis through the downward regulation of DA neurotransmission.
Abstract: Schizophrenic women have been consistently found to have a later age of onset and a less severe clinical course of illness as compared with schizophrenic men. Because these differences are not explained by diagnostic artifacts or sociocultural factors, we tested the hypothesis that they are determined by the influence of the gonadal hormones testosterone and estradiol on dopaminergic (DA) neurotransmission. We used animal models in which the effects of the hormones on behavioral changes induced by the DA antagonist haloperidol (catalepsy) and by the DA agonist apomorphine (oral stereotypies, grooming and sitting behavior) were investigated in neonatal and in adult treated rats. No consistent effects of testosterone were observed. Estradiol significantly reduced the behavioral changes induced by both haloperidol and apomorphine, and this effect was more pronounced in neonatally treated animals. These results suggest a downward regulation of DA neurotransmission by estradiol, which is supported by the results of 3H-sulpiride binding determinations in brain homogenates from the same animals: estradiol caused a 2.8-fold reduction of DA receptor affinity to sulpiride. Our findings suggest that estradiol might act as a protective modulator in schizophrenia by enhancing the vulnerability threshold for psychosis through the downward regulation of DA neurotransmission. Such mechanism could explain, at least in part, the later onset and the more favorable course of schizophrenia in female patients.
TL;DR: The combined dexamethasone/h-CRH challenge test may be of particular value in the detection of state-dependent changes of pituitary-adrenocortical neuroregulation in patients with major depression.
Abstract: Human corticotropin releasing hormone (h-CRH) was administered to 14 patients with major depression, after premedication with an overnight dose of 1.5 mg dexamethasone. Cortisol response, expressed as area under the time course curve (AUC), was significantly higher in the 14 patients than in a group of 13 age-matched control subjects (9.4 ± 7.6 ng × min × 1,000/ml vs. 3.1 ± 3.6 ng × min × 1,000/ml). Corresponding AUC values for plasma adrenocorticotropic hormone (ACTH) were also significantly higher in patients than in control subjects (4.9 ± 1.4 pg × min × 1,000/ml vs. 2.6 ± 0.9 pg × min × 1,000/ml). After patients were treated with trimipramine (200 mg/day) for 6 weeks, the combined dexamethasone/h-CRH test was repeated. At that time, depression scores were significantly improved and the patients' cortisol response pattern became indistinguishable from that of controls. While plasma cortisol output normalized during treatment with trimipramine, ACTH release remained exaggerated. The combined dexamethasone/h-CRH challenge test may be of particular value in the detection of state-dependent changes of pituitary-adrenocortical neuroregulation.
TL;DR: It is indicated that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring, however, parental MDD does not appear to place children at risk for anxiety disorders.
Abstract: Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders.
TL;DR: A "Social Rhythm Metric" of daily rhythmic behavior was given to 20 treated depressives and 15 day-working control subjects for a continuous 12-week period, and there were significant differences in intersubject vs. intrasubject variability between the two groups.
Abstract: A "Social Rhythm Metric" (SRM) of daily rhythmic behavior (developed previously) was given to 20 treated depressives (in remission) and 15 day-working control subjects for a continuous 12-week period. Long-term use of the SRM appeared feasible with no evidence of a deterioration in scores over the 12 weeks. Comparisons were made between intersubject and intrasubject variability, as well as a study of overall trends in SRM during the 12 weeks. Two further measures from the instrument--the Activity Level Index (ALI) and Other Person Involvement--were developed and shown to be useful adjuncts to the SRM. Although no simple differences in absolute SRM score emerged between patients and controls, there were significant differences in intersubject vs. intrasubject variability between the two groups. The patients showed more intrasubject variability and required more weeks of sampling to achieve a stable "trait" measure. Patients' social rhythms also appeared to be more "other person" prompted than those of controls.
TL;DR: A mathematical model developed is suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers, and suggests that the P50 defect is familially associated with schizophrenia.
Abstract: Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.
TL;DR: Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to m CPP in patients with OCD, suggesting adaptive homeostatic effects may reflect fluoxettine's antiobsessional mechanism.
Abstract: To investigate the effect of fluoxetine on serotonergic sensitivity in obsessive-compulsive disorder (COD), the partial serotonin agonist metachlorophenylpiperazine (mCPP) was compared to placebo under double-blind conditions in six patients with OCD before and during treatment with fluoxetine. Readministration of oral mCPP (0.5 mg/kg) after at least 12 weeks of fluoxetine treatment did not increase obsessive-compulsive (OC) symptoms, in contrast to exacerbation of OC symptoms produced by mCPP before treatment. Chronic fluoxetine treatment resulted in a significant increase in prolactin and cortisol response to mCPP. This may be accounted for, however, by substantially increased plasma mCPP levels during fluoxetine treatment. Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to mCPP in patients with OCD. These adaptive homeostatic effects may reflect fluoxetine's antiobsessional mechanism.
TL;DR: It is concluded that alterations of the immunological system which are, as has been demonstrated, not due to treatment with neuroleptics might play a role in schizophrenia.
Abstract: A possible connection between immunological alterations and schizophrenia has been discussed for many years. We studied 55 schizophrenic patients in an acute stage of illness before they began neuroleptic treatment. 35 patients who showed clinical improvement on neuroleptics, and 51 healthy controls. Our interest was focused on parameters of cellular immunity. We found an increased lymphocyte response to stimulation with pokeweed mitogen (PWM) and phytohemagglutinin (PHA) in patients before neuroleptic therapy and also an increased response to stimulation with PWM and PHA during treatment compared to controls. Stimulation with antigens generally showed a lower lymphocyte response in patients than in controls, but the difference was only significant after stimulation with tuberculin before neuroleptic treatment and after stimulation with varidase, diphteria-toxoid, tuberculin, vaccinia, and rubella during neuroleptic treatment. The number of CD3+ and CD4+ cells, but not the number of CD8+ cells, was increased before and during treatment in comparison to controls. Suppressor-cell activity was reduced in three different suppressor cell assays before and during neuroleptic medication compared to controls. We therefore conclude that alterations of the immunological system which are, as has been demonstrated, not due to treatment with neuroleptics might play a role in schizophrenia.
TL;DR: It is indicated that considerable improvement in neuropsychological functioning can occur in schizophrenic patients over the months following an acute episode of illness, and that recovery of cognitive function can occur after substantial clinical recovery from an acuteepisode of illness has already been achieved.
Abstract: Few studies have evaluated the longitudinal stability of neuropsychological deficits in schizophrenia. In the present study, 39 inpatients with DSM-III-R schizophrenia were administered a comprehensive battery of neuropsychological tests after achieving sufficient clinical recovery to warrant discharge, and again 1 year after the first assessment during a nonacute period. Significant improvement in neuropsychological functioning from the first to the second assessment was observed on several tasks, including the following: Trails A and B, Digit Symbol, Judgment of Line Orientation, recognition memory on the Rey Auditory Verbal Learning Test, the Wisconsin Card Sort, and Finger Tapping. These improvements were unrelated to treatment history, and were similar in first episode and chronic cases. For many patients, the improvement in functioning brought test performance into line with normative scores from test standardization samples. These results indicate that considerable improvement in neuropsychological functioning can occur in schizophrenic patients over the months following an acute episode of illness, and that recovery of cognitive functioning can occur after substantial clinical recovery from an acute episode of illness has already been achieved.
TL;DR: A heterogeneous sample of chronically psychotic patients were subgrouped according to the presence or absence of a self-reported history of childhood abuse, finding that patients reporting childhood abuse had an earlier age of onset, scored higher on the Dissociative Experiences Scale, reported more amnesia, and relapsed more frequently than patients not reporting abuse histories.
Abstract: A heterogeneous sample of 61 chronically psychotic patients were subgrouped according to the presence or absence of a self-reported history of childhood abuse. Patients reporting childhood abuse (n = 27) had an earlier age of onset, scored higher on the Dissociative Experiences Scale, reported more amnesia, and relapsed more frequently than patients not reporting abuse histories. Histories of childhood abuse and of past stimulant abuse predicted the score on the Dissociative Experiences Scale. A history of childhood abuse may thus contribute to the symptomatology and course of illness in some chronically psychotic patients.
TL;DR: MRI scans do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder and further studies using other anatomic measurements and other brain structural imaging techniques are warranted.
Abstract: Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted.
TL;DR: In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC, which suggests that some of the deficits observed may be based on faulty neurodevelopment.
Abstract: Post-mortem brain tissue was obtained from four patients with schizophrenia and five controls to study cell groups in the brain stem reticular formation. Cholinergic neurons in the pedunculopontine nucleus (PPN) and lateral dorsal tegmental nucleus (LDT) were labeled using nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry, while catecholaminergic neurons of the locus ceruleus (LC) were labeled immunocytochemically using an antibody to tyrosine hydroxylase. In schizophrenic patients, there were increased numbers of neurons in the PPN labeled by NADPH-diaphorase and reduced cell size in the LC. These results implicate the reticular formation as a possible pathophysiological site for at least some patients with schizophrenia. This also suggests that some of the deficits observed may be based on faulty neurodevelopment.
TL;DR: Patients who had higher (rather than lower) pretreatment HRSD, BDI, or DAS scores and were single ( rather than married) showed a poorer response to cognitive therapy, and effects were stronger when response was assessed according to clinician-rated severity measures rather than patient self-reports.
Abstract: This preliminary study evaluated prognostic indicators or predictors of response to cognitive therapy. The sample included 37 unipolar outpatients with moderate to severe major nonpsychotic depressive disorder, according to Research Diagnostic Criteria. Demographic characteristics (sex, age, marital status, and education), pretreatment severity measures (Hamilton Rating Scale for Depression [HRSD] and Beck Depression Inventory [BDI]), pretreatment cognitive measures (Dysfunctional Attitudes Scale [DAS] and Attributional Style Questionnaire Failure Composite [ASQ-F]), and historical features (length of illness, length of current episode, number of episodes, and age of onset) were used in multiple regression models to predict response. In accord with previous findings, patients who had higher (rather than lower) pretreatment HRSD, BDI, or DAS scores and were single (rather than married) showed a poorer response to cognitive therapy, according to the HRSD. Furthermore, married outpatients with high DAS scores or single patients with low DAS scores showed an intermediate response to cognitive therapy, while single patients with high DAS scores responded the least. Generally, effects were stronger when response was assessed according to clinician-rated severity measures rather than patient self-reports.
TL;DR: Compared with controls, patients with the onset of manic symptoms after the age of 50 years demonstrated a significantly greater number of large subcortical hyperintensities, particularly in the middle third of the brain parenchyma.
Abstract: In a retrospective study, brain magnetic resonance images of 12 patients with the onset of manic symptoms after the age of 50 years were compared to age- and sex-matched control subjects for the incidence, size, and location of subcortical hyperintensities. Compared with controls, the patients demonstrated a significantly greater number of large subcortical hyperintensities, particularly in the middle third of the brain parenchyma. The lesions occurred with equal frequency in the right and left hemisphere. There were no differences between the two groups in the size of the ventricles or the presence of periventricular hyperintensities.
TL;DR: Patients with suicide attempts had altered intranight temporal distribution of phasic REM activity, with increased REM activity in REM sleep period 2 (significant group x period interaction), which may be more traitlike or persistent than state-related.
Abstract: In a retrospective study of the electroencephalographic (EEG) sleep of major depressives with and without a history of suicide attempts, suicide attempters had longer sleep latency, lower sleep efficiency, and fewer late-night delta wave counts than normal controls. Nonattempters, compared to attempters, had less rapid eye movement (REM) time and activity in period 2, but more delta wave counts in non-REM period 4. Although both attempters and nonattempters were like controls in regard to REM period 2, patients with suicide attempts had altered intranight temporal distribution of phasic REM activity, with increased REM activity (by both visual and automated scoring) in REM sleep period 2 (significant group x period interaction). These findings, which may be more traitlike or persistent than state-related, are discussed in the context of current theories on the role of serotonin in the regulation of sleep and in suicidal behavior.
TL;DR: The increase in metabolic activity in the cerebellum was correlated with the subjective sense of THC intoxication and with plasma THC concentration, and corresponds well with the high density of cannabinoid receptors known to be in this area.
Abstract: We investigated the effects of acute i.v. administration of 2 mg of delta 9-tetrahydrocannabinol (THC) on regional brain glucose metabolism using 18F-2-fluoro-2-deoxyglucose and positron emission tomography (PET) in eight normal subjects. Subjects were tested twice: during baseline conditions and 30-40 min after THC administration. Changes in global cerebral glucose metabolism in response to THC were variable: three subjects showed an increase, three showed a decrease, and two showed no change. In contrast, all subjects showed an increase in normalized metabolism in the cerebellum following THC administration. Cerebellar changes were the only significant regional metabolic changes due to THC administration. The increase in metabolic activity in the cerebellum was correlated with the subjective sense of THC intoxication and with plasma THC concentration. Cerebellar localization of metabolic effects due to THC administration corresponds well with the high density of cannabinoid receptors known to be in this area.
TL;DR: A role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans is suggested, and premedication with ritanserin attenuated the MCPp-induced increases in self-rated anxiety and prolactin, and completely antagonized M CPP cortisol elevations.
Abstract: Ten healthy male subjects were administered i.v. meta-chlorophenyl-piperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5–10 mg), a putative 5HT 1c /5HT 2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT 1c /5-HT 2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.
TL;DR: Serotonin (5-hydroxytryptamine; 5HT) uptake sites have been measured using the selective high affinity uptake inhibitor 3H-citalopram in post-mortem frontal cortex from depressed and matched control subjects and no difference in the binding capacity was noted between hemispheres of normal brains.
Abstract: Serotonin (5-hydroxytryptamine; 5HT) uptake sites have been measured using the selective high affinity uptake inhibitor 3H-citalopram in post-mortem frontal cortex from depressed and matched control subjects. The lateralization of these sites was assessed in neurologically normal brain. A lower concentration of 3H-citalopram binding was found in brains from depressed subjects. A nonsignificant trend toward a greater attenuation of 5HT uptake sites was observed in brains of bipolar cases in the depressed state. No effect of antidepressant treatment or of the age at onset of illness was noted. No difference in the binding capacity of the 5HT uptake site was noted between hemispheres of normal brains.
TL;DR: Among the not depressed, those whose divorces remained incomplete at the followup had lower delta, higher REM percent, and shorter REM latency than did thosewhose divorces were finalized, suggesting that prolonged emotional stress may put these subjects at some risk for a mood disorder.
Abstract: Seventy volunteers had 3 nights of sleep recordings during a period of marital separation, and 61 returned for repeat studies 1 year later. At that time, the divorce was final for 42. Forty of the volunteers were depressed when first screened, and 30 were not. Initially all those undergoing marital separation had less delta sleep than an age-matched married comparison sample. Delta increased at followup for those whose divorce was completed. Rapid eye movement (REM) latency was reduced and REM percent was elevated only in the depressed. Among the not depressed, those whose divorces remained incomplete at the followup had lower delta, higher REM percent, and shorter REM latency than did those whose divorces were finalized. This suggests that prolonged emotional stress may put these subjects at some risk for a mood disorder.
TL;DR: Delayed development of reading skills suggests that precursers of illness may appear early in life before psychosis is evident, and an association of the inheritance of thyroid disorders with schizophrenia is suggested.
Abstract: One hundred consecutive first admission patients with a DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder were compared with 100 randomly selected community controls. Childhood histories of physical, medical, and perinatal trauma, as well as physical and cognitive development, were examined by structured interviews with all available mothers of patients and controls. The prevalence of specific psychiatric disorders and several medical illnesses among first degree and more distant relatives was determined by family history questionnaires. The patient group did not have an excess of childhood head injuries, serious infections, or perinatal/birth complications compared with controls. With social class level taken into account, it was found that the acquisition of reading skills occurred significantly later in patients than controls. Family histories of schizophrenia and thyroid disorders were significantly more frequent among patients than controls. These data fail to indicate any childhood physical or medical environmental trauma that could lead to an increased risk for schizophrenia, although patients were substance abusers to a greater extent than controls. This study also confirms the already known contribution of familial factors and suggests an association of the inheritance of thyroid disorders with schizophrenia. Delayed development of reading skills suggests that precursers of illness may appear early in life before psychosis is evident.
TL;DR: The S1 amplitude as measured in this study (with 120 averages) appears to be a reliable psychophysiologic measurement, but the S2/S1 attenuation measure is more variable, perhaps reflecting a greater sensitivity of the S3/S2 to uncontrolled variables inThis study.
Abstract: Attenuation in mid-latency auditory evoked responses (MLAERs) can be used to study sensory gating. If paired-click stimuli (S 1 and S 2 ) are used, lower amplitude in response to S 2 vs. S 1 (attenuation) is considered evidence for intact sensory gating. However, the need for reliable measurements of MLAER amplitude and attenuation is a recognized problem. Ten normal volunteers were studied six times each. An S 1 amplitude test-retest reliability coefficient ( r ) of 0.585 was obtained when means of two recordings were used vs. reliability coefficients as high as 0.809 for means of six recordings. Averaging a higher number of runs (120 vs. 60) resulted in a reliability of 0.677/recording. Similar values were obtained for S 1 and S 2 latencies. Reliability coefficients for S 2 attenuation (S 2 /S 1 ) were not nearly as high (a value of 0.138 when means of all six recordings were used). The S 1 amplitude as measured in this study (with 120 averages) appears to be a reliable psychophysiologic measurement, but the S 2 /S 1 attenuation measure is more variable, perhaps reflecting a greater sensitivity of the S 2 /S 1 to uncontrolled variables in this study. Further research to identify such variables is necessary.