Showing papers in "Archives of General Psychiatry in 1999"
TL;DR: In this paper, a group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers).
Abstract: BACKGROUND
Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination.
METHODS
A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures.
RESULTS
All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period.
CONCLUSIONS
For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes.
3,048 citations
TL;DR: All significant risk factors were more strongly related to ideation than to progression from ideation to a plan or an attempt, and prevention efforts should focus on planned attempts because of the rapid onset and unpredictability of unplanned attempts.
Abstract: Background General population survey data are presented on the lifetime prevalence of suicide attempts as well as transition probabilities to onset of ideation, plans among ideators, and attempts among ideators either with or without a plan. Risk factors for these transitions are also studied. Methods Data are from part II of the National Comorbidity Survey, a nationally representative survey carried out from 1990 to 1992 in a sample of 5877 respondents aged 15 to 54 years to study prevalences and correlates of DSM-III-R disorders. Transitions are estimated using life-table analysis. Risk factors are examined using survival analysis. Results Of the respondents, 13.5% reported lifetime ideation, 3.9% a plan, and 4.6% an attempt. Cumulative probabilities were 34% for the transition from ideation to a plan, 72% from a plan to an attempt, and 26% from ideation to an unplanned attempt. About 90% of unplanned and 60% of planned first attempts occurred within 1 year of the onset of ideation. All significant risk factors (female, previously married, age less than 25 years, in a recent cohort, poorly educated, and having 1 or more of the DSM-III-R disorders assessed in the survey) were more strongly related to ideation than to progression from ideation to a plan or an attempt. Conclusions Prevention efforts should focus on planned attempts because of the rapid onset and unpredictability of unplanned attempts. More research is needed on the determinants of unplanned attempts.
2,402 citations
TL;DR: The results suggest that comorbidity results from common, underlying core psychopathological processes, and argue for focusing research on these core processes themselves, rather than on their varied manifestations as separate disorders.
Abstract: Background This report presents the results of confirmatory factor analyses of patterns of comorbidity among 10 common mental disorders in the National Comorbidity Survey, a national probability sample of US civilians who completed structured diagnostic interviews. Methods Patterns of comorbidity among DSM-III-R mental disorders were analyzed via confirmatory factor analyses for the entire National Comorbidity Survey sample (N=8098; age range, 15-54 years), for random halves of the sample, for men and women separately, and for a subsample of participants who were seeing a professional about their mental health problems. Four models were compared: a 1-factor model, a 2-factor model in which some disorders represented internalizing problems and others represented externalizing problems, a 3-factor variant of the 2-factor model in which internalizing was modeled as having 2 subfactors (anxious-misery and fear), and a 4-factor model in which the disorders represented separate affective, anxiety, substance dependence, and antisocial factors. Results The 3-factor model provided the best fit in the entire sample. This result was replicated across random halves of the sample as well as across women and men. The substantial empirical intercorrelation between anxious-misery and fear (0.73) suggested that these factors were most appropriately conceived as subfactors of a higher-order internalizing factor. In the treatment sample, the 2-factor model fit best. Conclusions The results offer a novel perspective on comorbidity, suggesting that comorbidity results from common, underlying core psychopathological processes. The results thereby argue for focusing research on these core processes themselves, rather than on their varied manifestations as separate disorders.
1,698 citations
TL;DR: There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder, and this risk is diminished by maintenance antipsychotic drug treatment.
Abstract: Background We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder. Methods Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse. Results Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse. Conclusions There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.
1,189 citations
TL;DR: The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbor a gene or genes relevant to the etiology of schizophrenic disease in the wider population.
Abstract: Background Velo-cardio-facial syndrome (VCFS), a syndrome characterized by an increased frequency of schizophrenia and bipolar disorder, is associated with small interstitial deletions of chromosome 22q11. Methods We evaluated 50 adults with VCFS using a structured clinical interview (Schedules for Clinical Assessment in Neuropsychiatry or Psychiatric Assessment Schedule for Adults With Developmental Disability if IQ DSM-IV diagnosis. The schizophrenia phenotype in individuals with VCFS and schizophrenia was compared with a matched series of individuals with schizophrenia and without VCFS (n=12). The King's Schizotypy Questionnaire was administered to individuals with VCFS (n=41), their first-degree relatives (n=68), and a series of unrelated normal controls (n=316). All individuals with VCFS deleted for the N25 probe (n=48) were genotyped for a genetic polymorphism in the COMT gene that results in variations in enzymatic activity. Results Fifteen individuals with VCFS (30%) had a psychotic disorder, with 24% (n=12) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia and without VCFS. We found no evidence that possession of the low-activity COMT allele was associated with schizophrenia in our sample of individuals with VCFS. Conclusions The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbor a gene or genes relevant to the etiology of schizophrenia in the wider population.
936 citations
TL;DR: In this article, the authors used data from a community-based longitudinal study to investigate whether childhood abuse and neglect increases risk for personality disorders (PDs) during early adulthood and found that persons with documented childhood abuse or neglect were more than 4 times as likely as those who were not abused or neglected to be diagnosed with PDs during early maturity after age, parental education, and parental psychiatric disorders were controlled statistically.
Abstract: Background: Data from a community-based longitudinal study were used to investigate whether childhood abuse and neglect increases risk for personality disorders (PDs) during early adulthood. Methods: Psychosocial and psychiatric interviews were administered to a representative community sample of 639 youths and their mothers from 2 counties in the state of New York in 1975, 1983, 1985 to 1986, and 1991 to 1993. Evidence of childhood physical abuse, sexual abuse, and neglect was obtained from New York State records and from offspring self-reports in 1991 to 1993 when they were young adults. Offspring PDs were assessed in 1991 to 1993. Results: Persons with documented childhood abuse or neglect were more than 4 times as likely as those who were not abused or neglected to be diagnosed with PDs during early adulthood after age, parental education, and parental psychiatric disorders were controlled statistically. Childhood physical abuse, sexual abuse, and neglect were each associated with elevated PD symptom levels during early adulthood after other types of childhood maltreatment were controlled statistically. Of the 12 categories of DSM-IV PD symptoms, 10 were associated with childhood abuse or neglect. Different types of childhood maltreatment were associated with symptoms of specific PDs during early adulthood. Conclusions: Persons in the community who have experienced childhood abuse or neglect are considerably more likely than those who were not abused or neglected to have PDs and elevated PD symptom levels during early adulthood. Childhood abuse and neglect may contribute to the onset of some PDs. Arch Gen Psychiatry. 1999;56:600-606
806 citations
TL;DR: Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
Abstract: Background ω3 Fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether ω3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. Methods A 4-month, double-blind, placebo-controlled study, comparing ω3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. Results A Kaplan-Meier survival analysis of the cohort found that the ω3 fatty acid patient group had a significantly longer period of remission than the placebo group ( P =.002; Mantel-Cox). In addition, for nearly every other outcome measure, the ω3 fatty acid group performed better than the placebo group. Conclusion ω3 Fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
787 citations
TL;DR: A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear.
Abstract: Background Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders. Methods A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied. Results A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other. Conclusions Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.
777 citations
TL;DR: A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants, satisfaction with care, and depressive outcomes compared with usual care.
Abstract: Background Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects, many patients treated with antidepressant medications by primary care physicians have persistent symptoms. Methods A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were randomized to a collaborative care intervention (n = 114) or usual care (n = 114) by the primary care physician. Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment. Follow-up assessments were completed at 1, 3, and 6 months by a telephone survey team blinded to randomization status. Results Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls. Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months. Conclusions A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants, satisfaction with care, and depressive outcomes compared with usual care.
685 citations
TL;DR: Findings support recent evidence suggesting that gay, lesbian, and bisexual young people are at increased risk of mental health problems, with these associations being particularly evident for measures of suicidal behavior and multiple disorder.
Abstract: Background This study examines the extent to which gay, lesbian, and bisexual young people are at increased risk of psychiatric disorder and suicidal behaviors using data gathered on a New Zealand birth cohort studied to age 21 years. Methods Data were gathered during the course of the Christchurch Health and Development Study, a 21-year longitudinal study of a birth cohort of 1265 children born in Christchurch, New Zealand. At 21 years of age, 1007 sample members were questioned about their sexual orientation and relationships with same-sex partners since the age of 16 years. Twenty-eight subjects (2.8%) were classified as being of gay, lesbian, or bisexual sexual orientation. Over the period from age 14 to 21 years, data were gathered on a range of psychiatric disorders that included major depression, generalized anxiety disorder, conduct disorder, and substance use disorders. Data were also gathered on suicidal ideation and suicide attempts. Results Gay, lesbian, and bisexual young people were at increased risks of major depression (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.8-9.3), generalized anxiety disorder (OR, 2.8; 95% CI, 1.2-6.5), conduct disorder (OR, 3.8; 95% CI, 1.7-8.7), nicotine dependence (OR, 5.0; 95% CI, 2.3-10.9), other substance abuse and/or dependence (OR, 1.9; 95% CI, 0.9-4.2), multiple disorders (OR, 5.9; 95% CI, 2.4-14.8), suicidal ideation (OR, 5.4; 95% CI, 2.4-12.2), and suicide attempts (OR, 6.2; 95% CI, 2.7-14.3). Conclusions Findings support recent evidence suggesting that gay, lesbian, and bisexual young people are at increased risk of mental health problems, with these associations being particularly evident for measures of suicidal behavior and multiple disorder.
636 citations
TL;DR: There appears to be a broad range of risk factors for anorexia nervosa and bulimia nervosa, some of which are shared with other psychiatric disorders.
Abstract: Background Many risk factors have been implicated in the development of anorexia nervosa. Little is known about their relative contributions, nor in most cases is it clear whether they are specific to anorexia nervosa or risk factors for all eating disorders or for psychiatric disorder in general. Methods We used a case-control design involving the comparison of 67 female subjects with a history of anorexia nervosa with 204 healthy control subjects, 102 subjects with other psychiatric disorders, and 102 subjects with bulimia nervosa. A broad range of risk factors was assessed by interview. Results The subjects with anorexia nervosa and the healthy controls differed in their exposure to most of the putative risk factors. There was no greater exposure to factors that increased the likelihood of dieting, once the influence of other classes of risk factors had been taken into account. Premorbid perfectionism and negative self-evaluation were especially common and more so than among the general psychiatric controls. Parental obesity and an early menarche, together with parental psychiatric disorder, distinguished those with bulimia nervosa from those with anorexia nervosa. Conclusions There appears to be a broad range of risk factors for anorexia nervosa and bulimia nervosa, some of which are shared with other psychiatric disorders. Factors that increase the likelihood of dieting seem to have more important influence as risk factors for bulimia nervosa than anorexia nervosa. Perfectionism and negative self-evaluation appear to be particularly common and characteristic antecedents of both eating disorders.
TL;DR: A neo-Bleulerian unitary model is described, which defines the illness as a neurodevelopmentally derived "misconnection syndrome," involving connections between cortical regions and the cerebellum mediated through the thalamus.
Abstract: Finding a unifying concept behind the diversity of signs and symptoms in schizophrenia is a central challenge to contemporary research A neo-Bleulerian unitary model is described, which defines the illness as a neurodevelopmentally derived "misconnection syndrome," involving connections between cortical regions and the cerebellum mediated through the thalamus (the cortico-cerebellar-thalamic-cortical circuit [CCTCC]) An abnormality in this circuitry, normally used to coordinate both motor and mental activity, leads to misconnections in many aspects of mental activity, or "cognitive dysmetria" As Bleuler originally proposed, "thought disorder" is the primary defining feature of schizophrenia, rather than the more obvious signs and symptoms such as delusions and hallucinations Cognitive dysmetria, or a disorder in the CCTCC, may provide a heuristic theoretical framework for strategies to explore etiology, pathophysiology, intervention, or prevention
TL;DR: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators.
Abstract: Background Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing γ-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. Methods Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. Results Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. Conclusions These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.
TL;DR: This study provides the first evidence of abnormally low cortical GABA concentrations in the brains of depressed patients through in vivo proton magnetic resonance spectroscopy.
Abstract: Background: Several lines of emerging evidence suggest that dysfunction of g-aminobutyric acid (GABA) systems is associated with major depression. However, investigation of this hypothesis is limited by difficulty obtaining noninvasive in vivo measures of brain GABA levels. In this study we used in vivo proton magnetic resonance spectroscopy to investigate the hypothesis that abnormalities in the GABA neurotransmitter system are associated with the neurobiologic processes of depression. Methods: The GABA levels were measured in the occipital cortex of medication-free depressed patients meeting DSM-IV criteria (n = 14) and healthy control subjects with no history of mental illness (n = 18) using a localized difference editing proton magnetic resonance spectroscopy protocol. An analysis of covariance was employed to examine the effects of depression, sex, and age. Results: The depressed patients demonstrated a highly significant (52%) reduction in occipital cortex GABA levels compared with the group of healthy subjects. While there were significant age and sex effects, there was no interaction of diagnosis with either age or sex. Conclusion: This study provides the first evidence of abnormally low cortical GABA concentrations in the brains of depressed patients.
TL;DR: Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can-similar to pharmacological GC treatment-reversibly decrease specific elements of memory performance in otherwise healthy individuals.
Abstract: Background Glucocorticoids (GCs) can regulate hippocampal metabolism, physiologic functions, and memory. Despite evidence of memory decreases during pharmacological GC treatment, and correlations between memory and cortisol levels in certain disease conditions, it remains unclear whether exposure to the endogenous GC cortisol at levels seen during physical and psychological stress in humans can inhibit memory performance in otherwise healthy individuals. Methods Randomized, double-blind, placebo-controlled comparison of 2 fixed oral doses of cortisol (40 mg/d and 160 mg/d using split doses to approximate circadian rhythm) given for 4 days to matched groups of healthy subjects (n=51). Lower-dose treatment approximated cortisol exposure during mild stress, whereas the higher dose approximated cortisol exposure during major stress. Cognitive testing and plasma sampling were done at baseline, after 1 and 4 days of treatment, and after a 6-day washout period, hypothesizing dose-dependent decreases in verbal declarative memory. Results Cortisol treatment at the higher dose produced reversible decreases in verbal declarative memory without effects on nonverbal memory, sustained or selective attention, or executive function. A significant interaction between time and treatment condition for paragraph recall was explained by treatment-induced differences in performance after 4 treatment days, with lower immediate and delayed recall performance during higher-dose cortisol treatment compared with lower-dose treatment and placebo. Conclusions Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can—similar to pharmacological GC treatment—reversibly decrease specific elements of memory performance in otherwise healthy individuals.
TL;DR: Brain structural volumes were not significantly associated with duration of illness, prior medication exposure, number of previous hospital admissions, or duration of substance abuse, while the amygdala was enlarged in the patients.
Abstract: Background: The neuropathogenesis of bipolar disorder remains poorly described. Previous work suggests that patients with bipolar disorder may have abnormalities in neural pathways that are hypothesized to modulate human mood states. We examined differences in brain structural volumes associated with these pathways between patients with bipolar disorder hospitalized with mania and healthy community volunteers. Methods: Twenty-four patients with bipolar disorder and mania were recruited from hospital admission records. Twenty-two healthy volunteers were recruited from the community who were similar to the patients in age, sex, race, height, handedness, and education. All subjects were scanned using a 3-dimensional radiofrequency‐spoiled Fourier acquired steady state acquisition sequence on a 1.5-T magnetic resonance imaging scanner. Scans were analyzed using commercial software. Prefrontal, thalamic, hippocampal, amygdala, pallidal, and striatal volumetric measurements were compared between the 2 groups. Results: Patients with bipolar disorder demonstrated a significant (L = 0.64; F6,37= 3.4; P = .009) overall difference in structural volumes in these regions compared with controls. In particular, the amygdala was enlarged in the patients. Brain structural volumes were not significantly associated with duration of illness, prior medication exposure, number of previous hospital admissions, or duration of substance abuse. Separating patients into first-episode (n = 12) and multiple-episode (n = 12) subgroups revealed no significant differences in any structure (P..10). Conclusion: Patients with bipolar disorder exhibit structural abnormalities in neural pathways thought to modulate human mood. Arch Gen Psychiatry. 1999;56:254-260
TL;DR: Evidence is provided for the short-term efficacy of slow repetitive TMS in patients with recurrent major depression as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.
Abstract: Background Transcranial magnetic stimulation (TMS), a noninvasive technique for stimulation of the brain, has recently been suggested to be effective for the treatment of major depression. We conducted a double-blind, placebo-controlled study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major depression. Methods Seventy patients with major depression (53 women, 17 men; mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions during a 2-week period. Severity of depression was blindly assessed before, during, and after completion of the treatment protocol. Results All patients completed the first week of treatment and 67 completed the entire protocol. Patients who received rTMS had a significantly greater improvement in depression scores compared with those who received sham treatment. At the end of 2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham-treated group, had an improvement of greater than 50% in their depression ratings. Conclusions This controlled study provides evidence for the short-term efficacy of slow rTMS in patients with recurrent major depression. Additional studies will be necessary to assess the efficacy of rTMS as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.
TL;DR: These preliminary findings support the feasibility, acceptability, and efficacy of 12 weeks of IPT-A in acutely depressed adolescents in reducing depressive symptoms and improving social functioning and interpersonal problem-solving skills.
Abstract: Background Psychotherapy is widely used for depressed adolescents, but evidence supporting its efficacy is sparse. Methods In a controlled, 12-week, clinical trial of Interpersonal Psychotherapy for Depressed Adolescents (IPT-A), 48 clinic-referred adolescents (aged 12-18 years) who met the criteria for DSM-III-R major depressive disorder were randomly assigned to either weekly IPT-A or clinical monitoring. Patients were seen biweekly by a "blind" independent evaluator to assess their symptoms, social functioning, and social problem-solving skills. Thirty-two of the 48 patients completed the protocol (21 IPT-A–assigned patients and 11 patients in the control group). Results Patients who received IPT-A reported a notably greater decrease in depressive symptoms and greater improvement in overall social functioning, functioning with friends, and specific problem-solving skills. In the intent-to-treat sample, 18 (75%) of 24 patients who received IPT-A compared with 11 patients (46%) in the control condition met recovery criterion (Hamilton Rating Scale for Depression score ≤6) at week 12. Conclusions These preliminary findings support the feasibility, acceptability, and efficacy of 12 weeks of IPT-A in acutely depressed adolescents in reducing depressive symptoms and improving social functioning and interpersonal problem-solving skills. Because it is a small sample consisting largely of Latino, low socioeconomic status adolescents, further studies must be conducted with other adolescent populations to confirm the generalizability of the findings.
TL;DR: Major depression is equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes, however, genes may exist that act differently on the risk for MD in men vs women.
Abstract: Background Women report higher rates of major depression (MD) than men. Although genetic factors play an important etiologic role in MD, we are uncertain whether genetic factors are of equal importance in men and women, and whether the same genetic factors predispose men and women to MD. Methods We obtained, by telephone interview, a lifetime history of MD, defined by the DSM-III-R , from 3790 complete male-male, female-female, and male-female twin pairs, identified through a population-based registry. Results were analyzed using probandwise concordance, odds ratios, and biometrical twin modeling. Results The odds ratios (plus tetrachoric correlations) for lifetime MD were as follows: (1) male-male monozygotic, 3.29 (+0.37); (2) male-male dizygotic, 1.86 (+0.20); (3) female-female monozygotic, 3.02 (+0.39); (4) female-female dizygotic, 1.59 (+0.18); and (5) male-female dizygotic, 1.39 (+0.11). In the best-fitting twin model, the heritability of liability to MD was the same in men and women and equal to 39%, while the remaining 61% of the variance in liability was due to individual-specific environment. We rejected, with only modest confidence, the hypothesis that the genetic risk factors for MD were the same in men and women. The best-fitting model estimated the genetic correlation in the liability to MD in the 2 sexes to be +0.57. While we found no evidence to suggest a violation of the equal environment assumption, MD was less common in women from opposite-sex vs same-sex twin pairs. Conclusions Major depression is equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes. However, genes may exist that act differently on the risk for MD in men vs women.
TL;DR: In this article, the authors studied the course of obsessive-compulsive disorder in patients who were followed up for 40 years and found that after several decades, most individuals with OCD improve, although most patients continue to have clinical or subclinical symptoms.
Abstract: Background The long-term course of obsessive-compulsive disorder is insufficiently known. We studied the course of this disorder in patients who were followed up for 40 years. Methods Patients admitted with a diagnosis of obsessive-compulsive disorder to the Department of Psychiatry, Sahlgrenska University Hospital, Goteborg, Sweden, between 1947 and 1953 were examined by an experienced psychiatrist using a semistructured interview between 1954 and 1956 (n=251). The diagnosis was made according to the criteria of Schneider. A reexamination was performed by the same psychiatrist between 1989 and 1993 (n=122). In another 22 patients, the necessary information was obtained from close informants and medical records. The response rate in surviving patients was 82%. The mean length of follow-up from onset was 47 years. Results Improvement was observed in 83%, including recovery in 48% (complete recovery, 20%; recovery with subclinical symptoms, 28%). Among those who recovered, 38% had done so already in the 1950s. Forty-eight percent had obsessive-compulsive disorder for more than 30 years. Early age of onset, having both obsessive and compulsive symptoms, low social functioning at baseline, and a chronic course at the examination between 1954 and 1956 were correlated with a worse outcome. Magical obsessions and compulsive rituals were correlated with a worse course. Qualitative symptom changes within the obsessive-compulsive disorder occurred in 58% of the patients. Conclusion After several decades, most individuals with obsessive-compulsive disorder improve, although most patients continue to have clinical or subclinical symptoms.
TL;DR: The formulation of a 15- to 25-year plan for research on mental disorders in elderly persons should include studies of prevention, translation of findings from bench to bedside, large-scale intervention trials with meaningful outcome measures, and health services research.
Abstract: It is anticipated that the number of people older than 65 years with psychiatric disorders in the United States will increase from about 4 million in 1970 to15 million in 2030. The current health care system serves mentally ill older adults poorly and is unprepared to meet the upcoming crisis in geriatric mental health. We recommend the formulation of a 15- to 25-year plan for research on mental disorders in elderly persons. It should include studies of prevention, translation of findings from bench to bedside, large-scale intervention trials with meaningful outcome measures, and health services research. Innovative strategies are needed to formulate new conceptualizations of psychiatric disorders, especially those given scant attention in the past. New methods of clinical and research training involving specialists, primary care clinicians, and the lay public are warranted.
TL;DR: In this difficult-to-treat group of patients with residual depression who showed only partial response despite antidepressant treatment, cognitive therapy produced worthwhile benefit.
Abstract: Background Previous studies indicate that depressed patients with partial remission and residual symptoms following antidepressant treatment are common and have high rates of relapse. There is evidence that cognitive therapy may reduce relapse rates in depression. Methods One hundred fifty-eight patients with recent major depression, partially remitted with antidepressant treatment (mean daily doses equivalent to 185 mg of amitriptyline or 33 mg of fluoxetine) but with residual symptoms of 2 to 18 months' duration, were included in a controlled trial. Subjects were randomized to receive clinical management alone or clinical management plus cognitive therapy for 16 sessions during 20 weeks, with 2 subsequent booster sessions. Subjects were assessed regularly throughout the 20 weeks' treatment and for a further year. They received continuation and maintenance antidepressants at the same dose throughout. Results Cognitive therapy reduced relapse rates for acute major depression and persistent severe residual symptoms, in both intention to treat and treated per protocol samples. The cumulative relapse rate at 68 weeks was reduced significantly, from 47% in the clinical management control group to 29% with cognitive therapy (hazard ratio 0.54; 95% confidence interval, 0.32-0.93; intention to treat analysis). Cognitive therapy also increased full remission rates at 20 weeks but did not significantly improve symptom ratings. Conclusion In this difficult-to-treat group of patients with residual depression who showed only partial response despite antidepressant treatment, cognitive therapy produced worthwhile benefit.
TL;DR: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.
Abstract: Background This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. Methods Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index–Drug Use Composite score and the number of days of cocaine use in the past month. Results Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index–Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. Conclusion Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.
TL;DR: Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia.
Abstract: Background Disturbances of N -methyl-D-aspartate (NMDA) receptor–mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia. Glycine, a small nonessential amino acid, functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex. Glycine-induced augmentation of NMDA receptor–mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia. Methods Twenty-two treatment-resistant schizophrenic patients participated in a double-blind, placebo-controlled, 6-week, crossover treatment trial with 0.8 g/kg per day of glycine added to their ongoing antipsychotic medication. Clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Simpson-Angus Scale for Extrapyramidal Symptoms, and the Abnormal Involuntary Movement Scale, were performed biweekly throughout the study. Clinical laboratory values and amino acid serum levels were monitored. Results Glycine treatment was well tolerated and induced increased glycine ( P =.001) and serine ( P =.001) serum levels. Glycine administration resulted in (l) a significant ( P P r =0.80) clinical response. Conclusion These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness.
TL;DR: In this paper, the effect of both minor and major depression on mortality was determined and the role of confounding and explanatory variables on this relationship was examined. But the association between depression and mortality in older community-dwelling populations is still unresolved.
Abstract: Background The association between depression and mortality in older community-dwelling populations is still unresolved. This study determined the effect of both minor and major depression on mortality and examined the role of confounding and explanatory variables on this relationship. Methods A cohort of 3056 men and women from the Netherlands aged 55 to 85 years were followed up for 4 years. Major depression was defined according to DSM-III criteria by means of the Diagnostic Interview Schedule. Minor depression was defined as clinically relevant depression (defined by a Center for Epidemiologic Studies Depression score ≥16) not fulfilling diagnostic criteria for major depression. Results After adjustment for confounding variables (sociodemographics, health status), men with minor depression had a 1.80-fold higher risk of death (95% confidence interval, 1.35-2.39) during follow-up than nondepressed men. In women, minor depression did not significantly increase the mortality risk. Irrespective of sex, major depression was associated with a 1.83-fold higher mortality risk (95% confidence interval, 1.09-3.10) after adjustment for sociodemographics and health status. Health behaviors such as smoking and physical inactivity explained only a small part of the excess mortality risk associated with depression. Conclusion Even after adjustment for sociodemographics, health status, and health behaviors, minor depression in older men and major depression in both older men and women increase the risk of dying.
TL;DR: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.
Abstract: Background Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. Methods Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. Results Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. Conclusions Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.
TL;DR: Transcranial magnetic stimulation is a promising new research and therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium.
Abstract: In the 1990s, it is difficult to open a newspaper or watch television and not find someone claiming that magnets promote healing. Rarely do these claims stem from double-blind, peer-reviewed studies, making it difficult to separate the wheat from the chaff. The current fads resemble those at the end of the last century, when many were falsely touting the benefits of direct electrical and weak magnetic stimulation. Yet in the midst of this popular interest in magnetic therapy, a new neuroscience field has developed that uses powerful magnetic fields to alter brain activity—transcranial magnetic stimulation. This review examines the basic principles underlying transcranial magnetic stimulation, and describes how it differs from electrical stimulation or other uses of magnets. Initial studies in this field are critically summarized, particularly as they pertain to the pathophysiology and treatment of neuropsychiatric disorders. Transcranial magnetic stimulation is a promising new research and, perhaps, therapeutic tool, but more work remains before it can be fully integrated in psychiatry's diagnostic and therapeutic armamentarium.
TL;DR: The findings are in concert with others demonstrating that significant cognitive impairment across multiple ability domains is a core characteristic of schizophrenia and is not caused by chronic illness, treatment, or institutionalization.
Abstract: Background Cognitive impairment is recognized as a core characteristic of schizophrenia. There has always been a debate about the nature, selectivity, and time of onset of these deficits in relationship to the onset of illness and treatment factors. To our knowledge, the present study represents the largest sample of mostly neuroleptic-naive patients with first-episode schizophrenia that has been reported to date. Methods A group of 94 patients experiencing their first episode of schizophrenic illness and 305 normal comparison subjects were administered a comprehensive clinical and neuropsychological evaluation. Seventy-three patients were neuroleptic naive, 14 had received treatment for less than 1 week, and the remaining 7 had been medicated for less than 2 weeks. Results Patients performed significantly worse than the comparison subjects on every neuropsychological variable except those assessing savings scores (ie, forgetting over time). Twenty-five of 30 tests had an effect size (ES) greater than 0.75 when the 2 groups were compared. An ES analysis within the schizophrenia group revealed that the greatest relative impairments were on the Wechsler Adult Intelligence Scale–Revised digit symbol (ES, −0.52) and comprehension (ES, −0.42) subscales. Conclusions Our findings are in concert with others demonstrating that significant cognitive impairment across multiple ability domains is a core characteristic of schizophrenia and is not caused by chronic illness, treatment, or institutionalization. The ES analysis emphasizes that patients with schizophrenia have a generalized deficit that is not easily explained by a single anatomical region or ability area.
TL;DR: A common genetic vulnerability to nicotine and alcohol dependence in men is suggested, which may partially explain the clinical and epidemiological observations that alcoholics are often dependent smokers.
Abstract: Results: The heritability of nicotine dependence was 60.3% (95% confidence interval [CI], 55.4%-65.2%); that of alcohol dependence, 55.1% (95% CI, 49.7%-60.5%). The best-fitting model for the co-occurrence of lifetime nicotine and alcohol dependence included a substantial genetic correlation between both disorders (r = 0.68; 95% CI, 0.61-0.74) and a modest unique environmental correlation (r = 0.23; 95% CI, 0.14-0.32). Conclusions: These data suggest a common genetic vulnerability to nicotine and alcohol dependence in men. This common genetic influence may partially explain the clinical and epidemiological observations that alcoholics are often dependent smokers.
TL;DR: Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.
Abstract: Background Early childhood maltreatment has been associated with adverse adult health outcomes, but little is known about the magnitude of adult health care use and costs that accompany maltreatment. We examined differences in annual health care use and costs in women with and without histories of childhood sexual, emotional, or physical abuse or neglect. Methods A random sample of 1225 women members of a health maintenance organization completed a 22-page questionnaire inquiring into childhood maltreatment experiences as measured by the Childhood Trauma Questionnaire. Health care costs and use data were obtained from the automated cost-accounting system of the health maintenance organization, including total costs, outpatient and primary care costs, and emergency department visits. Results Women who reported any abuse or neglect had median annual health care costs that were $97 (95% confidence interval, $0.47-$188.26) greater than women who did not report maltreatment. Women who reported sexual abuse had median annual health care costs that were $245 (95% confidence interval, $132.32-$381.93) greater than costs among women who did not report abuse. Women with sexual abuse histories had significantly higher primary care and outpatient costs and more frequent emergency department visits than women without these histories. Conclusion Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.