Showing papers in "Archives of General Psychiatry in 1988"
TL;DR: In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.
Abstract: • The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics.DSM-IIIschizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 ±14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the doubleblind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included "negative" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients.
3,842 citations
TL;DR: The design and development of the CIDI is described and the current field testing of a slightly reduced "core" version is described, allowing investigators reliably to assess mental disorders according to the most widely accepted nomenclatures in many different populations and cultures.
Abstract: • The Composite International Diagnostic Interview (CIDI), written at the request of the World Health Organization/US Alcohol, Drug Abuse, and Mental Health Administration Task Force on Psychiatric Assessment Instruments, combines questions from the Diagnostic Interview Schedule with questions designed to elicit Present State Examination items. It is fully structured to allow administration by lay interviewers and scoring of diagnoses by computer. A special Substance Abuse Module covers tobacco, alcohol, and other drug abuse in considerable detail, allowing the assessment of the quality and severity of dependence and its course. This article describes the design and development of the CIDI and the current field testing of a slightly reduced "core" version. The field test is being conducted in 19 centers around the world to assess the interviews' reliability and its acceptability to clinicians and the general populace in different cultures and to provide data on which to base revisions that may be found necessary. In addition, questions to assess International Classification of Diseases , ninth revision, and the revised DSM-III diagnoses are being written. If all goes well, the CIDI will allow investigators reliably to assess mental disorders according to the most widely accepted nomenclatures in many different populations and cultures.
2,483 citations
TL;DR: A test-retest reliability study conducted on a series of psychiatric inpatients demonstrated that the use of the SIGH-D results in a substantially improved level of agreement for most of the HDRS items.
Abstract: • The Hamilton Depression Rating Scale (HDRS) is the most widely used scale for patient selection and follow-up in research studies of treatments of depression. Despite extensive study of the reliability and validity of the total scale score, the psychometric characteristics of the individual items have not been well studied. In the only reliability study to report agreement on individual items using a test-retest interview method, most of the items had only fair or poor agreement. Because this is due in part to variability in the way the Information is obtained to make the various rating distinctions, the Structured Interview Guide for the HDRS (SIGH-D) was developed to standardize the manner of administration of the scale. A test-retest reliability study conducted on a series of psychiatric inpatients demonstrated that the use of the SIGH-D results in a substantially improved level of agreement for most of the HDRS items.
1,921 citations
TL;DR: One-month prevalence results were determined from 18571 persons interviewed in the first-wave community samples of all five sites that constituted the National Institute of Mental Health Epidemilogic Catchment Area Program as mentioned in this paper.
Abstract: • One-month prevalence results were determined from 18571 persons interviewed in the first-wave community samples of all five sites that constituted the National Institute of Mental Health Epidemilogic Catchment Area Program. US population estimates, based on combined site data, were that 15.4% of the population 18 years of age and over fulfilled criteria for at least one alcohol, drug abuse, or other mental disorder during the period one month before interview. Higher prevalence rates of most mental disorders were found among younger people (
1,663 citations
TL;DR: The prevalence of obsessive-compulsive disorder was measured in five US communities among more than 18,500 persons in residential settings as part of the National Institute of Mental Health--sponsored Epidemiologic Catchment Area program, finding rates about 25 to 60 times greater than had been estimated on the basis of previous studies of clinical populations.
Abstract: • The prevalence of obsessive-compulsive disorder was measured in five US communities among more than 18500 persons in residential settings as part of the National Institute of Mental Health (Bethesda, Md)—sponsored Epidemiologic Catchment Area program. Lifetime prevalence rates ranged from 1.9% to 3.3% across the five Epidemiologic Catchment Area sites for obsessive-compulsive disorder diagnosed without DSM-III exclusions and 1.2% to 2.4% with such exclusions. These rates are about 25 to 60 times greater than had been estimated on the basis of previous studies of clinical populations.
1,256 citations
TL;DR: It is suggested that it is less the type than the timing of the disturbance during fetal neural development that is critical in determining risk for schizophrenia.
Abstract: In the context of a Finnish birth cohort, we tested the hypothesis that viral infection during the latter two thirds of fetal development would increase the risk of adult schizophrenic outcome. Psychiatric hospital diagnoses were recorded for all individuals in greater Helsinki who were fetuses during the 1957 type A2 influenza epidemic. Those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia. This was true for both males and females and independently in several psychiatric hospitals. The second-trimester effect was seen in the elevated proportion of schizophrenics among those admitted to a psychiatric hospital and also in higher rates of schizophrenia per 1000 live births in the city of Helsinki. The study has several limitations: (1) We have no direct evidence that the subjects actually suffered a viral infection. (2) The psychiatric data were obtained only for subjects up to the age of 26 years, 56 days. (3) The findings are based on hospital diagnoses. (4) The determination of stage of gestation at time of exposure to the epidemic is based on date of birth. The viral infection might have occurred outside the official epidemic window; the infant may have had a preterm or postterm delivery. These sources of error, however, should not serve to enhance the findings. The observed viral effect is interpreted as being one of many potential perturbations of gestation. We suggest that it is less the type than the timing of the disturbance during fetal neural development that is critical in determining risk for schizophrenia.
1,105 citations
TL;DR: A profile of psychiatric patients at high risk for suicide, and the proper identification and treatment of such patients may prevent suicide in high-risk clinical populations are suggested.
Abstract: • The characteristics of adolescent suicide victims (n = 27) were compared with those of a group at high risk for suicide, suicidal psychiatric inpatients (n = 56) who had either seriously considered (n = 18) or actually attempted (n = 38) suicide. The suicide victims and suicidal inpatients showed similarly high rates of affective disorder and family histories of affective disorder, antisocial disorder, and suicide, suggesting that among adolescents there is a continuum of suicidality from ideation to completion. However, four putative risk factors were more prevalent among the suicide victims: (1) diagnosis of bipolar disorder; (2) affective disorder with comorbidity; (3) lack of previous mental health treatment; and (4) availability of firearms in the homes, which taken together accurately classified 81.9% of cases. In addition, suicide completers showed higher suicidal intent than did suicide attempters. These findings suggest a profile of psychiatric patients at high risk for suicide, and the proper identification and treatment of such patients may prevent suicide in high-risk clinical populations.
814 citations
TL;DR: An intriguing and heuristically rich model of hypothesized interaction between prefrontal cortical and mesolimbic dopamine systems in schizophrenia is presented, consistent with a great deal of evidence that has accumulated with regard to schizophrenia, including the timing of its onset in terms of developmental maturation within the central nervous system.
Abstract: To the Editor.— In his article, published in the July 1987 issue of the Archives, Weinberger1presents an intriguing and heuristically rich model of hypothesized interaction between prefrontal cortical and mesolimbic dopamine systems in schizophrenia. This model is consistent with a great deal of evidence that has accumulated with regard to schizophrenia, including, crucially, the timing of its onset in terms of developmental maturation within the central nervous system. Weinberger's is the latest of a series of structural versions of the "diathesis" in the stress-diathesis model of schizophrenia.2 Weinberger notes that the structural lesion in such a model does not necessarily imply the existence of a distinct, discontinuous biologic subgroup. The "schizophrenia lesion" in such a model could possibly be no more than the extreme end of a developmental spectrum with regard to the organization of a particular central nervous system functional system, such as the hypothesized abnormality
736 citations
TL;DR: A two-stage epidemiologic survey was carried out on a probability sample of the population aged 4 through 16 years in Puerto Rico, and data were provided on the demographic correlates of maladjustment and on the comorbidity of DSM-III diagnostic domains.
Abstract: • A two-stage epidemiologic survey was carried out on a probability sample of the population aged 4 through 16 years in Puerto Rico. The survey used the Child Behavior Checklist as a screening instrument, and prevalence rates were estimated on the basis of clinical diagnoses and other measures provided by child psychiatrists during the second stage. Maladjustment was operationally defined through the use of combined measures, including DSM-III diagnosis and a scale of functional impairment. Data were provided on the demographic correlates of maladjustment and on the comorbidity of DSM-III diagnostic domains. The prevalence rates obtained vis-a-vis the availability of mental health services on the island reflected a major public health problem.
732 citations
TL;DR: The lifetime and current prevalence of mental disorders in 501 patients seeking assistance with alcohol and other drug problems at an addiction research and treatment facility and computer diagnoses were generated according to DSM-III criteria.
Abstract: A survey evaluated the lifetime and current prevalence of mental disorders in 501 patients seeking assistance with alcohol and other drug problems at an addiction research and treatment facility. Information was gathered using the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and computer diagnoses were generated according to DSM-III criteria. Four fifths (78%) of the sample had a DIS lifetime psychiatric disorder in addition to substance use, and two thirds (65%) had a current DIS mental disorder. Excluding the unreliably diagnosed generalized anxiety disorder, the most common lifetime disorders were antisocial personality disorder, phobias, psychosexual dysfunctions, major depression, and dysthymia. Patients who abused both alcohol and other drugs were the most psychiatrically impaired. Patients with DIS psychiatric disorders had more severe alcohol and other drug problems. Barbiturate/sedative/hypnotic, amphetamine, and alcohol abusers were the most likely to have a DIS mental disorder.
722 citations
TL;DR: Clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans, and this effect appears to be selective for the antipsychotics.
Abstract: • Using positron emission tomography and the carbon 11—labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11—raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.
TL;DR: A new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies and showed that behavior-specific hypofunction of DLPFC in schizophrenia is reproducible, and they implicate a monoaminergic mechanism.
Abstract: We previously reported that compared with normals, patients with chronic schizophrenia have reduced regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) during performance of the Wisconsin Card Sort Test (WCS), a DLPFC-related cognitive task, but not during nonprefrontal tasks, such as a simple number-matching (NM) test. We also found that unlike normals, patients failed to activate DLPFC during the WCS over their own baseline (NM) level. To explore the reproducibility of these findings, a new cohort of 16 medication-free patients underwent a series of xenon 133 inhalation rCBF studies under the following conditions: at rest, while performing the WCS, and while performing NM. The results confirmed our earlier findings. In addition, the concentrations in cerebrospinal fluid of homovanillic acid and 5-hydroxyindoleacetic acid correlated with prefrontal rCBF during the WCS but not during the NM test or at rest. The results show that behavior-specific hypofunction of DLPFC in schizophrenia is reproducible, and they implicate a monoaminergic mechanism.
TL;DR: It is suggested that a disruption of social rhythms, which may result in instability in biological rhythms, could be responsible for triggering the onset of a major depressive episode in vulnerable individuals.
Abstract: • Results of biological and psychosocial studies of depression completed in the last decade have stimulated the need for new hypotheses that synthesize these findings in a unified etiologic theory. The importance of disruption of biological rhythms on the one hand, and psychosocial losses on the other, in the causation of depressive episodes suggest one possible unifying hypothesis. The concept of loss of "social zeitgebers," ie, persons, social demands, or tasks that set the biological clock, may provide the link between biological and psychosocial theories of etiology. We suggest that a disruption of social rhythms, which may result in instability in biological rhythms, could be responsible for triggering the onset of a major depressive episode in vulnerable individuals.
TL;DR: Levels of intrafamilial EE and AS were found to predict likelihood of patient relapse at follow-up, especially when used as conjoint predictors of patient outcome status.
Abstract: • Measures of family attitudes (expressed emotion [EE]) and interactional behaviors (affective style [AS]), both of which have been found to predict relapse in schizophrenia, were obtained from key relatives of 23 hospitalized recently manic bipolar patients. Patients were then followed up for a period of nine months after hospital discharge and rated on measures of clinical course, social adjustment, and medication compliance. Levels of intrafamilial EE and AS were found to predict likelihood of patient relapse at follow-up, especially when used as conjoint predictors of patient outcome status. Levels of AS also predicted degree of social adjustment at follow-up. The predictive relationships observed were independent of patient medication compliance, treatment regimen, baseline symptoms, demographics, and illness history. Results suggest that the emotional atmosphere of the family during the postdischarge period may be an important predictor of the clinical course of bipolar disorder.
TL;DR: There was a marked (23%) reduction in the number of CRF binding sites in the frontal cortex of the suicide victims compared with the controls, which is consistent with the hypothesis that CRF is hypersecreted in depression.
Abstract: \s=b\Previous studies have provided evidence that corticotropin releasing factor (CRF) is hypersecreted in patients with major depression. This CRF hypersecretion is believed to contribute at least in part to hyperactivity of the hypothalamicpituitary-adrenal axis in depressed patients. If CRF is chronically hypersecreted in depressed patients, then, due to downregulation, a reduced number of CRF receptor binding sites should be present in patients with profound depressive disorder. To test this hypothesis, we measured the number and affinity of CRF binding sites in the frontal cortex of 26 suicide victims and 29 controls who died of a variety of causes. There was a marked (23%) reduction in the number of CRF binding sites in the frontal cortex of the suicide victims compared with the controls. These data are consistent with the hypothesis that CRF is hypersecreted in depression. (Aren Gen Psychiatry 1988;45:577-579)
TL;DR: Using a two-stage case identification process, patients from a rural primary care practice were assessed for psychiatric disorders over a 15-month period, finding that suggests restricted usefulness of specialty-based categories for the range of clinical presentations in primary care.
Abstract: • Using a two-stage case identification process, patients from a rural primary care practice were assessed for psychiatric disorders (Research Diagnostic Criteria [RDC] categories) over a 15-month period. The prevalence of all psychiatric disorders was 26.5%; 10.0% were specific RDC depressive disorders, and 5.3% were disorders without depression, usually anxiety related. Another 11.2% of patients were thought to have a disorder with significant depressive symptomatology that could not be classified into a specific depressive disorder category, a finding that suggests restricted usefulness of specialty-based categories for the range of clinical presentations in primary care. The relationship of demographic variables to specific disorders was examined; there were age, sex, and marital status differences in the rates for certain disorders, although these findings need replication using large patient samples. The prevalence findings emphasize the need for research on outcome and treatment response for depression presentations in primary care.
TL;DR: Assessment of immediate and later follow-up treatment of psychotic patients indicates that moderate doses are adequate for most patients, and moderate doses of neuroleptics appear, on average, to be about as effective as, and probably safer than, the larger doses that have been popular in the United States in recent years.
Abstract: The clinical use of antipsychotic agents may be enhanced by considering their dose-effect characteristics. In particular, assessment of immediate and later follow-up treatment of psychotic patients (1) indicates that moderate doses are adequate for most patients, (2) fails to support the utility of unusually high doses, and (3) even suggests the existence of a biphasic relationship of antipsychotic efficacy to dose of neuroleptics and possibly to plasma concentrations of the drugs as well. Trends toward lesser overall clinical benefits of high doses may reflect untoward extrapyramidal or other central nervous system effects leading to behavioral and cognitive symptoms. Thus, moderate doses of neuroleptics appear, on average, to be about as effective as, and probably safer than, the larger doses that have been popular in the United States in recent years.
TL;DR: Alprazolam was found to be effective and well tolerated in patients with agoraphobia with panic attacks and panic disorder and significantly more placebo recipients subsequently dropped out of the trial, primarily citing ineffectiveness of placebo as the reason.
Abstract: • Following promising preliminary evidence, the benzodiazepine-derivative alprazolam was studied in a large, placebocontrolled, eight-week, flexible-dose trial in patients with agoraphobia with panic attacks and panic disorder. Of 526 patients, 481 completed three weeks of treatment; however, significantly more placebo (102/234) than alprazolam (21/247) recipients subsequently dropped out of the trial, primarily citing ineffectiveness (of placebo) as the reason. Alprazolam was found to be effective and well tolerated. There were significant alprazolam-placebo differences in improvement for (1) spontaneous and situational panic attacks, (2) phobic fears, (3) avoidance behavior, (4) anxiety, and (5) secondary disability, all significant by the end of week 1. At the primary comparison point (week 4), 82% of the patients receiving alprazolam were rated moderately improved or better vs 43% of the placebo group. At that point, 50% of the alprazolam recipients vs 28% of placebo recipients were free of panic attacks.
TL;DR: Children aged 7 to 11 years visiting their primary care pediatrician for a wide range of reasons were studied to determine the one-year prevalence of DSM-III disorders and the risk factors associated with them.
Abstract: Children aged 7 to 11 years visiting their primary care pediatrician for a wide range of reasons were studied to determine the one-year prevalence of DSM-III disorders and the risk factors associated with them. Parents completing the Child Behavior Checklist about their children identified problems that placed 24.7% of 789 children in the clinical range. Detailed psychiatric interviews with 300 parents and children, using the Diagnostic Interview Schedule for Children, yielded a one-year weighted prevalence of one or more DSM-III disorders of 22.0% +/- 3.4%, combining diagnoses based on either the child or the parent interview.
TL;DR: Rates of both substance abuse and schizophrenia were elevated among individuals who had been homeless many times or for long periods of time, and there is a need for simultaneous attention to the social welfare and mental health needs of homeless mentally ill individuals.
Abstract: • Lifetime and current prevalence of Diagnostic Interview Schedul/DSM-IIIdisorders were determined for a probability sample of homeless adults in the Skid Row area of Los Angeles. Compared with findings from a household sample, prevalence was substantially higher for every disorder assessed. Rates of major mental illnesses were the most disproportionately high. Substance abuse was more highly prevalent among older individuals and Native Americans, while schizophrenia was most highly prevalent among those subjects between 31 and 40 years of age. Rates of both substance abuse and schizophrenia were elevated among individuals who had been homeless many times or for long periods of time. it was estimated that 28% of subjects in this inner-city homeless sample were chronically mentally ill, a percentage that was consistent with results of well-designed studies employing nondiagnostic standardized measures of mental illness, but lower than results of studies relying on clinical judgment to assess the prevalence of specific disorders. There is a need for simultaneous attention to the social welfare and mental health needs of homeless mentally ill individuals.
TL;DR: The performance of schizophrenic patients was compared with nonschizophrenic control subjects in their ability to direct visual attention and the patients demonstrated deficits in attention similar to patients from previous studies who had unilateral lesions of the left hemisphere.
Abstract: • Investigators have long suggested that schizophrenia might be related to an impairment in the regulation of attention. In this report, the performance of schizophrenic patients was compared with nonschizophrenic control subjects in their ability to direct visual attention. In the first experiment, patients were distinguished from controls by a slower response to a target in the right visual field than to a target in the left visual field when attention was not first directed to the target location. In the second experiment, patients were distinguished from controls by a stronger bias in favor of symbolic information over language information about spatial direction. In both experiments, the patients demonstrated deficits in attention similar to patients from previous studies who had unilateral lesions of the left hemisphere. The identification of performance abnormalities using tasks that are simple, have dissectable cognitive components, have been related to discrete neural systems, and control for nonspecific variables provide the basis for constructing reasonable hypotheses about the cognitive psychology and functional neuroanatomy of schizophrenia.
TL;DR: Patterns of pharmacological response may provide clues to biological mechanisms underlying dysphoria and behavioral dyscontrol in patients with borderline personality disorder.
Abstract: • Sixteen female outpatients with borderline personality disorder and prominent behavioral dyscontrol, but without a current episode of major depression, were studied in a doubleblind, crossover trial of placebo and the following four active medications: alprazolam (average dose, 4.7 mg/d); carbamazepine (average dose, 820 mg/d); trifluoperazine hydrochloride (average dose, 7.8 mg/d); and tranylcypromine sulfate (average dose, 40 mg/d). Each trial was designed to last six weeks. Tranylcypromine and carbamazepine trials had the highest completion rates. Physicians rated patients as significantly improved relative to placebo while receiving tranylcypromine and carbamazepine. Patients rated themselves as significantly improved relative to placebo only while receiving tranylcypromine. Patients who tolerated a full trial of trifluoperazine showed improvement, those receiving carbamazepine demonstrated a marked decrease in the severity of behavioral dyscontrol, and those receiving alprazolam had an increase in the severity of the episodes of serious dyscontrol. As an adjunct to psychotherapy, pharmacotherapy can produce modest but clinically important improvement in the mood and behavior of patients with borderline personality disorder. As a research tool, patterns of pharmacological response may provide clues to biological mechanisms underlying dysphoria and behavioral dyscontrol.
TL;DR: Patients with affective disorders had patterned deficits characterized by bilateral impairments that disclosed a preponderance of deficits in spatial learning and memory; depressives demonstrated impairments in digit span.
Abstract: • Experimental neuropsychologic tests were administered to acute patients with schizophrenia and affective psychosis and to normal controls. Patients had remitting illnesses. Tests included memory for recurring digit and block spans (left and right temporohippocampal), digit and block spans (lateralized parietal/frontal), spatial and nonspatial conditional associate learning (frontohippocampal), and oral word fluency to letter-designated categories (frontal) and semantic-designated categories (left-sided). In 81% of schizophrenic patients patterned deficits incompatible with generalized losses of function were disclosed. Patterns were heterogeneous and characterized by (1) the frequency and severity of left temporohippocampal impairment; (2) asymmetric frontohippocampal function such that severity of bilateral impairment was associated with poorer nonspatial learning and superior performance with better nonspatial learning; (3) syndrome relationships predicted by the hemisphere imbalance syndrome model pertaining to positive and negative symptoms and the catatonic syndrome; (4) a generalized deficit independent of temporohippocampal functions; and (5) no relationship between performance and computed tomographic signs or medication. Patients with affective disorders had patterned deficits characterized by bilateral impairments that disclosed a preponderance of deficits in spatial learning and memory; depressives demonstrated impairments in digit span.
TL;DR: The data suggest that there may be a higher prevalence of anxiety disorder and major depressive illness in homosexual men when compared with sociodemographically matched heterosexual men and that the psychiatric morbidity may have preceded the onset of the AIDS epidemic.
Abstract: • We used structured diagnostic interviews and rating scales to assess lifetime prevalence of psychiatric disorders, by DSM-III criteria, among an unselected sample of 56 ambulatory homosexual men in four groups: men with acquired immunodeficiency syndrome (AIDS), men with AIDS-related complex (ARC), men asymptomatic or mildly symptomatic but seropositive for antibody to human immunodeficiency virus (HIV), and HIV-seronegative men. An age- and demographically matched comparison group of 22 healthy, heterosexual controls was also studied. The homosexual men had lifetime rates of alcohol or nonopiate drug abuse (22/56 [39.3%]), generalized anxiety disorder (22/56 [39.3%]), and major depression (17/56 [30.3%]) that often preceded diagnosed medical illness or knowledge of HIV status. The six-month point prevalence of these disorders in homosexual men was also high, especially alcohol abuse in patients with AIDS-related complex, and the occurrence of a DSM-III disorder within the previous six months significantly exceeded that in heterosexual controls. The data suggest that there may be a higher prevalence of anxiety disorder and major depressive illness in homosexual men when compared with sociodemographically matched heterosexual men and that the psychiatric morbidity may have preceded the onset of the AIDS epidemic. These findings indicate that awareness of psychiatric history is necessary to comprehensive medical care of men at high risk for AIDS, even among relatively healthy outpatients.
TL;DR: There was no tendency for schizoaffective diagnosis or acute psychoses to aggregate separately from schizophrenia, and there were not significant differences in the number of relatives with nonbipolar psychoses.
Abstract: • Two hundred thirty-seven relatives of 48 patients with chronic psychosis, diagnosed as either schizophrenia or schizoaffective disorder, along with 380 relatives of psychiatrically normal controls, were studied using systematic diagnostic interviews, information from relatives, and review of medical records where appropriate. A variety of nonbipolar psychotic disorders was found in the relatives of the patients. Comparing relatives of patients with schizophrenia with relatives of patients with schizoaffective disorder, there was no tendency for schizoaffective diagnosis or acute psychoses to aggregate separately from schizophrenia. Increased incidence of bipolar disorder was found in relatives of patients with schizoaffective disorder but not in relatives of patients with schizophrenia. Incidence of major affective disorder (bipolar and unipolar) was increased in relatives of probands with both types of psychoses. If we subdivide the ill probands according to whether or not they had a history of substance abuse, relatives of probands with substance abuse had greater frequency of affective disorder and substance abuse, but there were not significant differences in the number of relatives with nonbipolar psychoses.
TL;DR: Patients with panic disorder may have hypersensitive CO2 receptors that, when triggered, evoke a subjective panic associated with an exaggerated ventilatory response and consequent hypocapnic alkalosis.
Abstract: • Thirty-one patients withDSM-IIIpanic disorder or agoraphobia with panic attacks, 13 normal controls, and 12 patients with other anxiety disorders were studied during ventilatory challenge with room air hyperventilation and 5% carbon dioxide inhalation. Patients also underwent sodium lactate infusion. Among the patients with panic disorder, 58% panicked with sodium lactate, 39% with 5% CO2, and 23% with room air hyperventilation. Of the other patients, four panicked with sodium lactate, none with 5% CO2, and one with room air hyperventilation. One normal control panicked with both sodium lactate and 5% CO2. Panic with CO2was associated with an exaggerated ventilatory response and increases in plasma norepinephrine level and diastolic blood pressure. Patients with panic disorder may have hypersensitive CO2receptors that, when triggered, evoke a subjective panic associated with an exaggerated ventilatory response and consequent hypocapnic alkalosis.
TL;DR: Results of family studies support aPutative biochemical marker, low levels of plasma dopamine-beta-hydroxylase, and a putative cognitive marker, ie, normal visuospatial but low verbal functioning, in autism, which is offered as one explanation of the observed sex difference in the prevalence of autism.
Abstract: • The last ten years of research on the genetics of infantile autism were critically reviewed. Epidemiologic findings have shown that autism is a rare disorder with a prevalence of two to five per 10 000, a male-female ratio of 3:1, and an association with mental retardation (66% to 75% of autistic subjects have full-scale IQ scores [70). Autism is familial, as reflected in an empiric sibling recurrence risk of 3% and pooled monozygotic and dizygotic concordance rates of 64% and 9%, respectively, which are much greater than the population prevalence of 0.02% to 0.05%. Genetic heterogeneity is pronounced with potential genetic subgroups, including autosomal recessive inheritance, X-linked inheritance, and sporadic chromosomal anomalies. Studies of subclinical markers in autism have elucidated potential markers at various levels of phenotypic expression from the DNA to the behavioral level. Linkage and cytogenetic studies point to two chromosome regions as putative markers, 9q34 and Xq27. Results of family studies support a putative biochemical marker, low levels of plasma dopamine-β-hydroxylase, and a putative cognitive marker, ie, normal visuospatial but low verbal functioning, in autism. The frequency of minor physical anomalies and presence or absence of mental retardation are two dimensions of the physical and behavioral phenotype that may demark etiologically distinct subgroups. Genetic heterogeneity is offered as one explanation of the observed sex difference in the prevalence of autism. Directions for potentially fruitful research should be considered.
TL;DR: The concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported and the superiority of either phenelzine or imipramine to placebo is supported.
Abstract: • One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.
TL;DR: Findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment and suggest a similar alteration in the response to endogenous serotonin may mediate clomIPramine's antiobsessional effects.
Abstract: • Clomipramine is a potent serotonin reuptake blocker that decreases the symptoms of obsessive-compulsive disorder (OCD). To investigate whether clomipramine treatment in OCD affects brain serotonergic responsiveness, metachlorophenylpiperazine (mCPP), a selective serotonin agonist, and placebo were given under double-blind conditions to nine patients with OCD before and after treatment with clomipramine. Unlike our previous observations of a marked transient increase in obsessional symptoms and anxiety following 0.5 mg/kg of mCPP, readministration of mCPP after four months of treatment with clomipramine did not significantly increase obsessional symptoms and anxiety. Similarly, the hyperthermic effect of mCPP observed before treatment was eliminated after treatment with clomipramine. These findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment. A similar alteration in the response to endogenous serotonin may mediate clomipramine's antiobsessional effects.
TL;DR: In this article, the authors investigated the role of "behavioral inhibition to the unfamiliar" as an early temperamental characteristic of children at risk for adult panic disorder and agoraphobia (PDAG), and compared children of parents with PDAG with those from psychiatric comparison groups.
Abstract: • To investigate the role of "behavioral inhibition to the unfamiliar" as an early temperamental characteristic of children at risk for adult panic disorder and agoraphobia (PDAG), we compared children of parents with PDAG with those from psychiatric comparison groups. Fifty-six children aged 2 to 7 years, matched for age, socioeconomic status, ethnic background, and ordinal position, were blindly evaluated at the Harvard Infant Study laboratory, Cambridge, Mass. The rates of behavioral inhibition in children of probands with PDAG, with or without comorbid major depressive disorder (MDD), were significantly higher than for our comparison group without PDAG. Further, the data suggest a progression of increasing rates of inhibition from the comparison group without MDD (15.4%), to MDD (50.0%), and to comorbid PDAG and MDD (70%) and PDAG (84.6%). In contrast, the rate of behavioral inhibition in children of probands with MDD did not meaningfully differ from the comparison group without MDD. Behavioral inhibition to the unfamiliar, as defined and measured in the previous work of the Harvard Infant Study program, is highly prevalent in the offspring of adults in treatment for PDAG. These children appear to be at risk for distress and disability in childhood and also perhaps for development of psychiatric disorder in later childhood and adulthood.