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Showing papers in "American Journal of Psychiatry in 1996"


Journal ArticleDOI
TL;DR: Verbal memory and vigilance appear to be necessary for adequate functional outcome in schizophrenic patients and may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors."
Abstract: Objective : It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world. Method : The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of the neurocognitive correlates and predictors of psychosocial skill acquisition (six studies). Results : Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed. Conclusions : Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as neurocognitive rate-limiting factors. On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.

3,446 citations


Journal ArticleDOI
TL;DR: This study investigated the relationships between exposure to extreme stress, the emergence of PTSD, and symptoms traditionally associated with "hysteria," which can be understood as problems with stimulus discrimination, self-regulation, and cognitive integration of experience.
Abstract: ObjectiveA century of clinical research has noted a range of trauma-related psychological problems that are not captured in the DSM-IV framework of posttraumatic stress disorder (PTSD). This study investigated the relationships between exposure to extreme stress, the emergence of PTSD, and symptoms

888 citations


Journal ArticleDOI
TL;DR: Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear.
Abstract: Obiective : The therapeutic success of clozapine and risperidone has focused attention on the interaction between the serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance. Method : The authors synthesized information from more than 100 published articles obtained through electronic and bibliography-directed searches. Findings : The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symptoms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with doses that produce suprathreshold dopaminergic blockade. Conclusions : Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.

817 citations


Journal ArticleDOI
TL;DR: It is suggested that risk for suicide increases with age in individuals with major affective illness, and depressed elderly men are particular targets for suicide prevention strategies.
Abstract: OBJECTIVE: Psychiatric illness is a potent risk factor for suicide, rates of which differ markedly with age. The purpose of this study was to examine whether the psychiatric diagnoses of suicide victims vary predictably with age. METHOD: DSM-III-R axis I diagnoses of 141 persons aged 21 to 92 years who had completed suicide were established by the psychological autopsy method. Multiple logistic regression analyses were used to determine whether age, gender, or their interaction predicted the presence of specific disorders. RESULTS: One or more axis I conditions were diagnosable in 90.1% of the suicide victims. Substance use disorders were most frequent, followed by mood disorders and primary psychotic illness. Younger age at death was a significant predictor of substance abuse or dependence and primary psychoses, while older age predicted major mood disorders. Comorbidity of substance use and mood disorders was common. Among victims with substance abuse or dependence, older age at death predicted major depression; among victims with mood disorders, younger age at death predicted comorbid substance abuse or dependence. CONCLUSIONS: The distribution of psychiatric illnesses in suicide victims differs across the life course. Age-related patterns of addictive and psychotic disorders echo their prevalence in the general population. In contrast, the relationship between age and mood disorders among suicide victims is distinctly different from that of the general population. These findings suggest that risk for suicide increases with age in individuals with major affective illness. Depressed elderly men are particular targets for suicide prevention strategies. Language: en

713 citations


Journal ArticleDOI
TL;DR: Individuals who made serious suicide attempts had high rates of mental disorders and of comorbid disorders, and subjects with high levels of psychiatric comorbridity had markedly high risks of serious suicide attempt.
Abstract: Objective: The aim of this study was to compare the prevalence and comorbidity patterns ofpsychiatric disorders in subjects making medically serious suicide attempts and in corn panson subjects. Method: The association between mental disorders and the risk of a suicide attempt was examined in 302 consecutive individuals who made serious suicide attempts and 1,028 randomly selected comparison subjects. Each subject completed a semistructured interview, and a significant other underwent a parallel interview; best-estimate DSM-III-R diagnoses were then generated. Results: Of those who made serious suicide attempts, 90. 1 % had a mental disorder at the time of the attempt. Multiple logistic regression showed that those who made suicide attempts had high rates of mood disorders (odds ratio=33.4, 95% confidence interval=2 1. 9-51 .2); substance use disorders (odds ratio=2.6, 95% confidence interval=1.6-4.3); conduct disorder or antisocial personality disorder (odds ratio-_3.7, 95% confidence interval=2. 1-6.5); and nonaffective psychosis (odds ratio=1 6.8, 95% confidence interval=2.7-1 05.8). The relationship between psychiatric morbidity and suicide risk varied with age andgender. The incidence ofcomorbidity was high: 56.6% ofthose who made serious suicide attempts had two or more disorders. The risk of a suicide attempt increased with increasing psychiatric morbidity: subjects with two or more disorders had odds of serious suicide attempts that were 89. 7 times the odds of those with no psychiatric disorder. Conclusions: Individuals who made serious suicide attempts had high rates of mental disorders and ofcomorbid disorders. Subjects with high levels ofpsychiatnic comorbidity had markedly high risks of serious suicide attempts. (Am J Psychiatry 1996; 153:1009-1014)

642 citations


Journal ArticleDOI
TL;DR: Peritraumatic dissociation is strongly associated with the later development of PTSD and early dissociation and PTSD symptoms can help the clinician identify subjects at higher risk for developing PTSD.
Abstract: OBJECTIVE: The aim of this study was to prospectively examine the relationship between immediate and short-term responses to a trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: All patients consecutively admitted to a general hospital were screened for the presence of physical injury due to a traumatic event. Fifty-one eligible subjects were assessed 1 week and 6 months after the trauma. The initial assessment included measures of event severity, peritraumatic dissociation, and symptoms of intrusion, avoidance, depression, and anxiety. The follow-up assessments added the PTSD module of the Structured Clinical Interview for DSM-III-R--Non-Patient Version and the civilian trauma version of the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder. RESULTS: Thirteen subjects (25.5%) met PTSD diagnostic criteria at follow-up. Subjects who developed PTSD had higher levels of peritraumatic dissociation and more severe depression, anxiety, and intrusive symptoms at the 1-week assessment. Peritraumatic dissociation predicted a diagnosis of PTSD after 6 months over and above the contribution of other variables and explained 29.4% of the variance of PTSD symptom intensity. Initial scores on the Impact of Event Scale predicted PTSD status with 92.3% sensitivity and 34.2% specificity. Symptoms of avoidance that were initially very mild intensified in the subjects who developed PTSD. CONCLUSIONS: Peritraumatic dissociation is strongly associated with the later development of PTSD. Early dissociation and PTSD symptoms can help the clinician identify subjects at higher risk for developing PTSD. Language: en

612 citations


Journal ArticleDOI
TL;DR: The literature from the fields of geography, psychology, anthropology, and psychiatry was reviewed to develop a "psychology of place" and to determine the manner in which place-related psychological processes are affected by upheaval in the environment.
Abstract: Objective : The purpose of this article is to describe the psychological processes that are affected by geographic displacement. Method : The literature from the fields of geography, psychology, anthropology, and psychiatry was reviewed to develop a psychology of place and to determine the manner in which place-related psychological processes are affected by upheaval in the environment. Results : The psychology of place is an emerging area of research that explores the connection between individuals and their intimate environments. The psychology of place posits that individuals require a good enough environment in which to live. They are linked to that environment through three key psychological processes : attachment, familiarity, and identity. Place attachment, which parallels, but is distinct from, attachment to person, is a mutual caretaking bond between a person and a beloved place. Familiarity refers to the processes by which people develop detailed cognitive knowledge of their environs. Place identity is concerned with the extraction of a sense of self based on the places in which one passes one's life. Each of these psychological processes-attachment, familiarity, and place identity-is threatened by displacement, and the problems of nostalgia, disorientation, and alienation may ensue. Conclusions : As a result of war, decolonization, epidemics, natural disasters, and other disruptive events, millions of people are currently displaced from their homes. Protecting and restoring their mental health pose urgent problems for the mental health community.

572 citations


Journal ArticleDOI
TL;DR: Depressed patients exhibit enhanced baseline platelet activation and responsiveness in comparison with normal subjects, which may be a mechanism by which depression is a significant risk factor for ischemic heart and cerebrovascular disease and/or mortality after myocardial infarction.
Abstract: Objective: This study iizvestigated whether depressed patients exhibit exaggerated platelet reactivity. Method: In vivo platelet activatioiz, secretioz, and dose-response aggregation were measured in 12 depressed patients and eight normal comparison subjects after overizight bed rest aizd following orthostatic challenge. Results: The depressed patients exhibited increased platelet activation at baseli,ze, demonstrated by increased binding of monoclonal antibody (moAb) annexin V protein reacting with prothrombinase complex binding sites. Followizg orthostatic challeizge, the depressed patients exhibited increases in binding of moAbs PACI a,zd anti-LIBS1 agaiizst actii'atedglycoprotein Jib/lila and GEI2 against P-selecti,z expressed 111)01? secretion. The normal comparison subjects exhibited increases in platelet activatioz only with GE I 2. Conclusions: Depressed patients exhibit enhazced baseline platelet activation and respozsiveness in comparisoz with normal subjects. Heightened susceptibility to platelet acti- vation flltlV he a mechanism b�' which depression is a significant risk factor for ischemic heart azd cerebrovascular disease and/or mortality after myocardial infarction. (AmJ Psychiatry 1996; 153:1313-1317)

540 citations


Journal ArticleDOI
TL;DR: The high 1-year prevalence of subsyndromal depressive symptoms, combined with the associated functional impairment, emphasizes the clinical and public health importance and need for additional investigations into these symptoms.
Abstract: Objective: The authors’ goal was to evaluate the association between impairment in daily f unction and subsyndromal depressive symptoms as well as major depression to determine the economic and societal significance of these conditions. Method: Using 12-month prevalence data gathered by the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (ECA), based on responses to the NIMH Diagnostic Interview Schedule, the authors divided the 2,393 subjects from the Los Angeles ECA site into three groups: subjects with subsyndromal depressive symptoms (N=2 70), major depression (N= I 02), and no depressive disorder or symptoms (N=2,02 1). The groups were compared on I 0 domains of functional outcome and well-being. Results: Significantly more subjects with depressive symptoms than subjects who had no disorder reported high levels ofhousehold strain, social irritability, and f inancial strain as well as limitations in physical or job functioning, restricted activity days, bed days, and poor health status. Significantly more subjects with major depression than subjects with no disorder reported major financial losses, bed days, high levels of financial strain, limitations in physical or job functioning, and poor health status. Except for lower self-ratings of health status, no significant differences were found between subjects with subsyndromal symptoms and those with major depression. Conclusions: Significantly more people with subsyndromal depressive symptoms or major depression reported impairment in eight of I 0 functional domains than did subjects with no disorder. The high 1-year prevalence of subsyndromal depressive symptoms, combined with the associated functional impairment, emphasizes the clinical and public health importance and need for additional investigations iiito these symptoms. (AmJ Psychiatry 1996; 153:1411-1417)

532 citations


Journal ArticleDOI
TL;DR: Findings suggest that symptoms of PTSD begin soon after exposure to trauma, that hyperarousal symptoms are the first symptoms to occur, that the natural course of alcohol and substance abuse parallels that of PTSD, and that specific substances have specific effects on PTSD symptoms.
Abstract: Objective : The purpose of this study was to measure the longitudinal course of specific symptoms of posttraumatic stress disorder (PTSD) and related symptoms of alcohol and substance abuse and the effects of alcohol and substances on the symptoms of PTSD. Method : A structured interview for the assessment of PTSD and alcohol and substance abuse, as well as other factors such as life stressors and treatment, was administered to 61 Vietnam combat veterans with PTSD. Results : Onset of symptoms typically occurred at the time of exposure to combat trauma in Vietnam and increased rapidly during the first few years after the war. Symptoms plateaued within a few years after the war, following which the disorder became chronic and unremitting. Hyperarousal symptoms such as feeling on guard and feeling easily startled developed first, followed by avoidant symptoms and finally by symptoms from the intrusive cluster. The onset of alcohol and substance abuse typically was associated with the onset of symptoms of PTSD, and the increase in use paralleled the increase of symptoms. Patients reported a tendency for alcohol, marijuana, heroin, and benzodiazepines to make PTSD symptoms better, while cocaine made symptoms in the hyperarousal category worse. There was no relationship between treatment interventions and the natural course of PTSD. Conclusions : These findings suggest that symptoms of PTSD begin soon after exposure to trauma, that hyperarousal symptoms are the first symptoms to occur, that the natural course of alcohol and substance abuse parallels that of PTSD, and that specific substances have specific effects on PTSD symptoms.

527 citations


Journal ArticleDOI
TL;DR: Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics (haloperidol or chlorpromazine).
Abstract: Objective The purpose of this study was to examine the efficacy and side effects of haloperidol, chlorpromazine, and lorazepam for the treatment of the symptoms of delirium in adult AIDS patients in a randomized, double-blind, comparison trial. Method Nondelirious, medically hospitalized AIDS patients (N = 244) consented to participate in the study and were monitored prospectively for the development of delirium. Patients entered the treatment phase of the study if they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium Rating Scale. Thirty patients were randomly assigned to treatment with haloperidol (N = 11), chlorpromazine (N = 13), or lorazepam (N = 6). Efficacy and side effects associated with the treatment were measured with repeated assessments using the Delirium Rating Scale, the Mini-Mental State, and the Extrapyramidal Symptom Rating Scale. Results Treatment with either haloperidol or chlorpromazine in relatively low doses resulted in significant improvement in the symptoms of delirium as measured by the Delirium Rating Scale. No improvement in the symptoms of delirium was found in the lorazepam group. Cognitive function, as measured by the Mini-Mental State, improved significantly from baseline to day 2 for patients receiving chlorpromazine. Treatment with haloperidol or chlorpromazine was associated with an extremely low prevalence of extrapyramidal side effects. All patients receiving lorazepam, however, developed treatment-limiting adverse effects. Although only a small number of patients had been treated with lorazepam, the authors became sufficiently concerned with the adverse effects to terminate that arm of the protocol early. Conclusions Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics (haloperidol or chlorpromazine). Lorazepam alone appears to be ineffective and associated with treatment-limiting adverse effects.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated the impact of financial incentives on disability, symptoms, and objective findings after closed-head injury and found that the effect was particularly strong for mild head trauma.
Abstract: Objective : The authors evaluated the impact of financial incentives on disability, symptoms, and objective findings after closed-head injury. Method : Meta-analysis was used to review the literature. Seventeen reports, covering 18 study groups and a total of 2,353 subjects, contained data from which effect sizes could be calculated. Effect sizes were aggregated after weighting for group size. After discussion, there was 100% agreement between the authors on all calculations. Results : A moderate overall effect size, 0.47, was found. The effect was particularly strong for mild head trauma. The data showed more abnormality and disability in patients with financial incentives despite less severe injuries. Conclusions : Clinical evaluation of patients after closed-head injury, particularly mild head trauma, must include consideration of the effect of financial incentives on symptoms and disability.

Journal ArticleDOI
TL;DR: A paradigm is presented to help understand the long-term effects of psychotropic drugs, including the latency in onset of their therapeutic actions, as well as to a better understanding of the architecture and function of neural systems.
Abstract: Objective: This article describes a paradigm-initiation and adaptation-within which to conceptualize the drug-induced neural plasticity that underlies the long-term actions of psychotropic drugs in the brain. Method: Recent advances in neurobiology are reviewed. j� .sjjj�.j Recent developments in cellular and molecular neurobiology provide new conceptual and experimental tools for understanding the mechanisms by which psychotropic drugs pro- duce long-lived alterations in brain function. Because ofthe availability ofmore robust animal models, the mechanisms by which drugs ofabuse produce dependence are better understood than the mechanisms by which antidepressants, antipsychotics, and lithium produce their therapeutic effects. Nonetheless, the fundamental types of mechanisms appear to be similar: chronic drug administration drives the production of adaptations in postreceptor signaling pathways, including regulation of neural gene expression. Whether the results are deleterious or therapeutic depends on the precise neural systems targeted by a particular drug. Conclu- sions: Biological investigation in psychiatry has often focused too narrowly on synaptic phar- macology, especially on neurotransmitter turnover and neurotransmitter receptors. This re- view focuses on molecular and cellular changes in neural function that are produced as adaptations to chronic administration ofaddictive drugs such as psychostimulants and thera- peutic drugs such as antidepressants. To understand normal brain function, psychopathology, and the actions of psychiatric treatments, and to exploit the eventual findings of psychiatric genetics, psychiatric research must now extend its efforts beyond the synapse, to an under- standing of cellular and molecular neurobiology (in particular, postreceptor signal transduc- tion) as well as to a better understanding of the architecture and function of neural systems. A paradigm is presented to help understand the long-term effects of psychotropic drugs, in- cluding the latency in onset of their therapeutic actions. (AmJ Psychiatry 1996; 153:151-162)

Journal ArticleDOI
TL;DR: Findings underscore the need for definitive in vivo interaction studies of plasma from phenotyped patients treated with clinically effective antidepressant doses of medication, for direct comparative clinical studies, and for studies assessing the utility of phenotyping in clinical practice.
Abstract: Objective This review evaluates the in vitro and in vivo evidence for inhibition of cytochrome P450 enzymes by the newer antidepressants and provides clinical recommendations for avoiding and managing drug interactions. Method The international literature on the cytochrome P450 system and related drug interactions from 1966 to 1995 was reviewed. In vitro studies, pharmacokinetic trials in human subjects, and case reports were assessed. Results The newer antidepressants each inhibit a different cluster of cytochrome P450 enzymes, which are of relevance to the potential for drug interactions. Cytochrome P450 1A2 is inhibited by fluvoxamine and is implicated in drug interactions with theophylline, clozapine, and others. Fluoxetine, norfluoxetine, sertraline, and paroxetine are potent in vitro inhibitors of cytochrome P450 2D6 and are capable of causing marked elevations in plasma desipramine and nortriptyline concentrations. Fluoxetine, sertraline, and fluvoxamine are believed to inhibit cytochrome P450 2C because of observed interactions with phenytoin, diazepam, and other drugs metabolized by these enzymes. Cytochrome P450 3A4 metabolizes terfenadine, astemizole, carbamazepine, alprazolam, triazolam, and other benzodiazepines. Plasma concentrations of these drugs have increased when they are administered with fluvoxamine, nefazodone, fluoxetine, and sertraline. Conclusions The majority of the newer antidepressants are associated with a risk for clinically significant drug interactions. A rapidly growing body of literature provides evidence for a distinct profile of cytochrome P450 inhibition and drug interaction risks by individual antidepressants. These findings underscore the need for definitive in vivo interaction studies of plasma from phenotyped patients treated with clinically effective antidepressant doses of medication, for direct comparative clinical studies, and for studies assessing the utility of phenotyping in clinical practice.

Journal ArticleDOI
TL;DR: Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low.
Abstract: Objective : Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. Method : A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. Results : Three primary effects are associated with medication use during pregnancy : 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. Conclusions : Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.

Journal ArticleDOI
TL;DR: Pseudoseizure subjects have high rates of the psychiatric disorders found in traumatized groups; they closely resemble patients with dissociative disorders.
Abstract: Objective The goal of this study was to determine current and lifetime rates of DSM-III-R disorders in patients with pseudoseizures and to ascertain whether trauma is associated with the occurrence of pseudoseizures. Methods Adult pseudoseizure patients (N = 45) were interviewed regarding seizure course and life events, and they were given the Structured Clinical Interview for DSM-III-R--Patient Version, the Structured Clinical Interview for DSM-III-R Dissociative Disorders, the Dissociative Experiences Scale, and the Personality Diagnostic Questionnaire--Revised. The pseudoseizures were diagnosed in a tertiary-care video-EEG facility. Most of the subjects (78%) were female, and the mean age of the overall patient group was 37.5 years (SD = 9.7). Results The mean duration of the subjects' seizure history was 8.3 years (SD = 8.0). Common current psychiatric diagnoses included somatoform disorders (89%), dissociative disorders (91%), affective disorders (64%), personality disorders (62%), posttraumatic stress disorder (PTSD) (49%), and other anxiety disorders (47%). The lifetime occurrence of nonseizure conversion disorders was 82%. The mean Dissociative Experiences Scale score was 20.2 (SD = 18.2). Trauma was reported by 84% of the subjects: sexual abuse by 67%, physical abuse by 67%, and other traumas by 73%. Conclusions Pseudoseizure subjects have high rates of the psychiatric disorders found in traumatized groups; they closely resemble patients with dissociative disorders. Reclassification of conversion seizures with the dissociative disorders should be considered. Pseudoseizures often appear to express distress related to abuse reports. Clinicians should screen pseudoseizure patients for adult and childhood trauma, dissociative disorders, depression, and PTSD.

Journal ArticleDOI
TL;DR: The predictive power of medication resistance is generalizable across diverse clinical settings, particularly for heterocyclic antidepressants, which perhaps suggests an overlap in the mechanisms of actions of ECT and this medication class.
Abstract: Objective: Traditionally, it has been widely assumed that the likelihood of response to ECT is independent ofthe adequacy ofprevious treatment with antidepressant medications. However, recent research has raised the possibility that medication-resistant patients with depression have a poorer clinical ECT outcome than patients who have not failed previous adequate medication trials. Method: Medication resistance of 100 patients with primary, unipolar, nonpsychotic major depression was evaluated during the index episode with the Antidepressant Treatment History Form. Patients were recruited and treated with ECT at three sites; standardized ECT and clinical assessment procedures were used. Clinical outcome was assessed immediately and 1 week after completion of the ECT course. Results: Patients who previously had failed one or more adequate antidepressant medication trials were less likely to respond to subsequent ECT than patients not known to be medication resistant. This finding held within each study site, whether clinical response was assessed categorically or in terms of the magnitude of symptomatic improvement and after the authors accounted for other potential predictors of clinical outcome. Resistance to heterocyclic antidepressants predicted poorer outcome after ECT, while resistance to selective serotonin reuptake inhibitors and monoamine oxidase inhibitors did not show significant predictive relations. Conclusions: While a substantial percentage of medication-resistant patients respond to ECT, clinical outcome in this group is inferior to that of patients without established medication resistance. The predictive power ofmedication resistance is generalizable across diverse clinical settings, particularly for heterocyclic antidepressants, which perhaps suggests an overlap in the mechanisms ofactions of ECT and this medication class. (AmJ Psychiatry 1996; 153:985-992)

Journal ArticleDOI
TL;DR: The efficacy of a variety of different family intervention models, as well as social skills training, is supported by a large body of research.
Abstract: Objective This review is an update on the research evidence supporting psychosocial treatment for schizophrenia. It extends previous review articles by summarizing the literature on social skills training, family interventions, cognitive rehabilitation, and coping with residual positive symptoms. Me

Journal ArticleDOI
TL;DR: Data from both animals and humans suggest that the biological and behavioral responses to androgens are context-dependent, which is further suggested by gender-related differences in pharmacokinetics/pharmacodynamics.
Abstract: Objective: This article defines androgens (and anabolic steroids), describes their mechanisms of action, and summarizes their behavioral effects and relevance in animals and humans. Method: A MEDLINE-derived review of the literature on androgens and behavior was perIormed; pivotal earlier publications were also obtained and included in the review. Results: In animals, the effects of androgens on brain structure and function are well-established and profound, with behavioral implications extending far beyond reproduction. Androgens play a prominent role in the organization or programming ofbrain circuits, which are subsequently activated by gonadal steroids. In humans, roles for androgens have been described, albeit inconsistently, in the regulation ofsexuality, aggression, cognition, emotion, and personality. The relevance of androgens for psychiatry is further suggested by gender-related differences in pharmacokinetics/pharmacodynamics and in the prevalence, course, and treatment response characteristics ofseveral psychiatric disorders. Direct psychoactive effects ofexogenously administered androgens have been described for many years, most recently in reports of the psychotoxic effects of anabolic steroids. Conclusions: Data from both animals and humans suggest that the biological and behavioral responses to androgens are context-dependent. (Am J Psychiatry 1996; 153:974-984)

Journal ArticleDOI
TL;DR: Findings suggest that maternal smoking during pregnancy is a risk factor for ADHD, and will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age.
Abstract: OBJECTIVE This study investigated the role of maternal smoking during pregnancy in the etiology of attention deficit hyperactivity disorder (ADHD). METHOD Subjects were 6-17-year-old boys with DSM-III-R ADHD (N = 140) and normal comparison subjects (N = 120) and their first-degree biological relatives. Information on maternal smoking was obtained from mothers in a standardized manner by raters who were blind to the proband's clinical status. RESULTS Twenty-two percent of the ADHD children had a maternal history of smoking during pregnancy, compared with 8% of the normal subjects. This positive association remained significant after adjustment for socioeconomic status, parental IQ, and parental ADHD status. Significant differences in IQ were found between those children whose mothers smoked during pregnancy and those whose mothers did not smoke (mean IQ = 104.9, SD = 12.3, and mean = 115.4, SD = 12.2, respectively). CONCLUSIONS These findings suggest that maternal smoking during pregnancy is a risk factor for ADHD. If confirmed, these findings will stress the importance of programs aimed at smoking prevention in nonsmoking women and smoking cessation in smoking women of childbearing age.

Journal ArticleDOI
TL;DR: These findings support an unusually strong association between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q11 chromosomal locus may be involved in its pathogenesis.
Abstract: Objective The purpose of this study was to conduct a systematic assessment of psychiatric illness in patients diagnosed with velo-cardio-facial syndrome, a genetic syndrome that involves over 40 somatic anomalies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q11. Method Subjects were referred for psychiatric diagnostic evaluation without regard to age or previous psychiatric history. In order to establish DSM-III-R consensus clinical diagnoses for patients who ranged in age from 5 to 34 years, the Diagnostic Interview for Children and Adolescents--Revised or the Structured Clinical Interview for DSM-III-R (SCID) was used. A review of available medical and psychiatric records and a clinical interview performed by two research psychiatrists to validate specific symptoms and syndromes reported in the Diagnostic Interview for Children and Adolescents--Revised and the SCID were used to elucidate the chronological appearance and duration of symptoms. Results Sixty-four percent (N = 16 of 25) of this unselected series of patients with velo-cardio-facial syndrome met DSM-III-R criteria for a spectrum of bipolar disorders with full syndromal onset in late childhood or early adolescence (mean age at onset = 12 years, SD = 3). In addition, 20% (N = 5) met DSM-III-R criteria for attention deficit hyperactivity disorder (ADHD), while 16% (N = 4) met criteria for attention deficit disorder without hyperactivity. In contrast to previous reports of a high prevalence of schizophrenia, none of the patients was diagnosed with schizophrenia, and only four had psychotic symptoms during a phase of their illness, all in their 20s or 30s. Conclusions Given that the prevalence of bipolar disorder in the general population is estimated to be 1.5% and that the average age at onset is 24, these findings support an unusually strong association between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q11 chromosomal locus may be involved in its pathogenesis. If confirmed, these findings may provide a new and fruitful line of investigation into the molecular basis of bipolar spectrum disorders.


Journal ArticleDOI
TL;DR: The more severe the obsessive-compulsive disorder, the lower were the patients' social functioning scores, even after depression ratings were controlled for; scores on instrumental role performance did not correlate with severity of obsessive- compulsive disorder.
Abstract: Objective: The health-related quality of life ofpatients with obsessive-compulsive disorder was comnpared to published norms for the general U.S. population and for patients with either depressive disorders or diabetes. Method: Sixty medication-free outpatients with moderate to severe obsessive-compulsive disorder were evaluated by using the Structured Clinical Interview for DSM-III-R and the Yale-Brown Obsessive Compulsive Scale. Health-related quality of life was measured with the self-rated Medical Outcomes Study 36-Item Short-Form Health Survey. Results: The instrumental role performance and social functioning of the patients with obsessive-compulsive disorder were worse than those of the general population and of diabetes patiemits. The more severe the obsessive-compulsive disorder, the lower were the patients ‘ social f unctioning scores, even after depression ratings were controlled for; scores on instrumental role performnance did miot correlate with severity ofobsessive-compulsive disorder. The ratings of the obsessive-compulsive disorder patients on physical health domains resembled those of the general population and exceeded those of the diabetes patients. The general health and physical health ratings of the obsessive-comnpulsive disorder patients exceeded those of the depressed patients. in mental health domains, after adjustment for differences in gender distribution, quality of life ratings were similar for the patients with obsessive-compulsive disorder amid those with depressive disorders. Conclusions: Moderate to severe obsessive-compulsive disorder is associated with impaired social functioning and impaired instrumental role performance, but only impairment in social functioning is linearly related to severity of obsessii’e-compulsive disorder. (Am J Psychiatry 1996; 153:783-788)

Journal ArticleDOI
TL;DR: The results confirmed the authors' previous findings demonstrating the distinction between symptoms of complicated grief and symptoms of bereavement-related depression and anxiety.
Abstract: Obiective : This study sought to confirm in an independent, nonclinical study group previous work which demonstrated that the symptoms of complicated grief were distinct from the symptoms of bereavement-related depression and anxiety. Method : Data used in the analyses were derived from a group of 150 widowed individuals who were interviewed 6 months after their deceased spouses' hospital admission (study entry). Complicated grief was measured with a modified version of the Grief Measurement Scale. Principal axis factoring was used to determine the distinctiveness of complicated grief, depression, and anxiety. Results : The principal axis factoring showed that the symptoms of complicated grief loaded quite highly on the first (complicated grief) factor and loaded very poorly on the anxiety and depression factors. Conclusions: The results confirmed the authors' previous findings demonstrating the distinction between symptoms of complicated grief and symptoms of bereavement-related depression and anxiety.

Journal ArticleDOI
TL;DR: The Psychiatric Research Interview for Substance and Mental Disorders (PRISM) as discussed by the authors was designed to improve the reliability for substance-abusing patients by using a semistructured diagnostic interview.
Abstract: Objective : The purpose of this study was to investigate the reliability of a new semistructured diagnostic interview, the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), for substance-abusing patients. The reliability of psychiatric diagnoses for individuals who drink heavily or use drugs has been shown to be problematic. The PRISM was designed to improve the reliability for such individuals. Method : A test-retest reliability study of the PRISM was conducted with 172 patients being treated in dual-diagnosis or substance abuse settings. Results : Good to excellent reliability was shown for many diagnoses, including affective disorders, substance use disorders, eating disorders, some anxiety disorders, and psychotic symptoms. The interview has recently been updated for DSM-IV diagnoses. Conclusions: The PRISM offers a method of producing psychiatric diagnoses with improved reliability for patients and other research subjects who have problems with alcohol or drugs.

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TL;DR: Standardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder, however, the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients.
Abstract: Objective : Major depression occurs with generalized anxiety disorder and panic disorder in up to 60% of psychiatric and primary care patients. This comorbidity has been associated with greater severity of depression, poorer psychosocial functioning, and poorer treatment outcomes in psychiatric samples. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder. Method : A total of 157 primary care patients who met criteria for major depression were randomly assigned to standardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression, psychosocial functioning, and health-related functioning. Results : Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone. Both standardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder, although time to recovery was longer for the former. Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy. Conclusions : Standardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder. However, the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention.

Journal ArticleDOI
TL;DR: The provision of parenting is influenced by attitudes derived from the parent's family of origin as well as by genetically influenced parental temperamental characteristics, which are influenced by temperamental traits of the offspring that are under partial genetic control.
Abstract: Objective : To understand the relation between parenting and later psychopathology, it is important to clarify the role of genetic and environmental factors in both the elicitation and the provision of parenting behavior. Method : A 16-item version of the Parental Bonding Instrument was administered to 1) 606 fathers and 848 mothers of an epidemiologic sample of adult female-female twin pairs, who reported on their parenting of their twins ; 2) the twins (both members of 546 monozygotic and 390 dizygotic pairs), who reported on the parenting they had received from their father and mother ; 3) co-twins from these pairs, who reported on the parenting provided by their father and mother to their twin sister ; and 4) members of the adult twin pairs (145 monozygotic and 117 dizygotic) who both had children, who reported on the parenting they provided to their offspring. The data were subjected to model fitting decomposing three sources of variance : additive genetic factors ; family, or common, environment ; and an individual's unique environment. Results : Responses to the Parental Bonding Instrument produced three factors : parental warmth, protectiveness, and authoritarianism. According to parents, these factors were largely a common environmental experience for their children. Responses from twins, however, indicated that genetic factors played a substantial role in the elicitation of warmth from parents and a more modest role in influencing parental protectiveness and authoritarianism. While reports of twins and co-twins on protectiveness and authoritarianism yielded similar results, analysis of responses from co-twins indicated a degree of importance of genetic factors in eliciting parental warmth which was midway between that from parents' reports and twins' reports. Answers from twins as parents indicated that provision of warmth was substantially heritable, while resemblance between twins in providing protectiveness and authoritarianism was due to family environment. Conclusions: The provision of parenting is influenced by attitudes derived from the parent's family of origin as well as by genetically influenced parental temperamental characteristics. The elicitation of parenting is influenced by temperamental traits of the offspring that are, in turn, under partial genetic control. Genetic factors in both parent and child are more important for warmth than for protectiveness or authoritarianism.

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TL;DR: The reduced thalamic activity observed in this study lends further support to the concept of deficits in sensory filtering in schizophrenia.
Abstract: Objective; This study reports the first paired measurements ofglucose metabolism and size of thalamic regions in never-medicated schizophrenic patients using coregistered magnetic resonance imaging (MRI) templates. Method: Positron emission tomography with [‘8F]fluorodeoxyglucose and matching MRI scans were obtained in 20 never-medicated patients with schizophrenia and 15 normal volunteers. Methods for thalamic edge finding, statistical testing ofshape differences with chi-square maps, and MRI localization ofmajor thalamic subregions were developed. Results: Patients with schizophrenia showed a diminished metabolic rate in the right thalamus, with a loss ofthe normalpattern ofrightgreater than left asymmetry. Division into anterior/posterior segments revealed that the left anterior and right posterior showed the decrease. Differences were greater for metabolism in the weighted thalamic area (ratexarea) than for rate per unit area, a finding consistent with reported greater decreases in total neuron number than of neuron density in the thalami of schizophrenic patients. The area of the thalamus was smaller in the patients than in the volunteers, and this difference was greatest in the left anterior region. Conclusions: The reduced thalamic activity observed in this study lends further support to the concept of deficits in sensory filtering in schizophrenia. (Am J Psychiatry1996; 153:191-199)

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TL;DR: Whether the diagnosis of attention deficit hyperactivity disorder (ADHD) is retained from childhood into adulthood is assessed and the rate of ADHD in a given age group appears to decline by 50% approximately every 5 years.
Abstract: Objective : This study was undertaken to assess whether the diagnosis of attention deficit hyperactivity disorder (ADHD) is retained from childhood into adulthood. Method : A search of the literature yielded nine prospective studies in which cohorts of children with the disorder were formed and then reexamined 4-16 years later to determine the level of retained ADHD. The resulting data were subjected to nonlinear regression analysis to ascertain the relationship with chronological age. Results : The data followed an exponential decline over time to a high degree of accuracy. Conclusions : The rate of ADHD in a given age group appears to decline by 50% approximately every 5 years. If a prevalence of ADHD in childhood of 4% is assumed and the exponential decline extrapolated the estimated rate of adult ADHD ranges from about 0.8% at age 20 to 0.05% at age 40.

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TL;DR: The findings indicate that chronic posttraumatic stress reactions among adolescents exposed to catastrophic disaster are associated with hypothalamic-pituitary-adrenal (HPA) axis alterations and are congruent with those previously described in adults with chronic PTSD.
Abstract: Objective: This study evaluated basal salivary cortisol, 3-methoxy-4-hydroxyphenylglycol (MHPG), and cortisol suppression following dexamethasone administration in adolescents exposed to two levels of earthquake-related trauma. Method: Five years after the 1988 earthquake, saliva samples were obtained from 37 adolescents from two cities in Armenia at different distances from the epicenter. Baseline saliva samples were obtained at 8:00 a.m., 4:00 p.m., and 11:00 p.m., following which 0.5 mg of dexamethasone was administered. Nine and 17 hours later, saliva samples were again obtained. Subjects were evaluated for posttraumatic stress and depressive reactions through use of self-report instruments. Results: Significantly lower mean baseline 8:00 a.m. cortisol levels and greater day 2 4:00 p.m. cortisol suppression following dexamethasone were observed in the more symptomatic adolescents living in the city closer to the epicenter. Of the three symptom categories of posttraumatic stress disorder (PTSD), only intrusion (category B) symptoms were significantly correlated with basal morning cortisol levels and percent suppression hy dexamethasone. The more highly exposed adolescents also exhibited a more rapid decline in MHPG levels over the course of day 1. Conclusions : The findings indicate that chronic posttraumatic stress reactions among adolescents exposed to catastrophic disaster are associated with hypothalamic-pituitary-adrenal (HPA) axis alterations. The findings are congruent with those previously described in adults with chronic PTSD. Persistent intrusion (category B) symptoms may constitute continued episodes of distress and evoke repeated physiological stress responses, which, over time, alter HPA axis function. The MHPG findings suggest that there may be diurnal changes associated with severity of posttraumatic stress symptoms.