Showing papers in "American Journal of Psychiatry in 2004"
TL;DR: Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder.
Abstract: Objective: Several studies have found reduced hippocampal volume in patients with unipolar depression, but discrepancies exist. The authors performed a systematic review and meta-analysis of volumetric studies of the hippocampus in patients with mood disorders. Method: Studies of hippocampal volume in unipolar and bipolar patients were identified. A meta-analysis of the 12 studies of unipolar depression fulfilling specific criteria was performed. The sample comprised 351 patients and 279 healthy subjects. Results: The studies were highly heterogeneous regarding age and gender distribution, age at onset of the disorder, average number of episodes, and responsiveness to treatment, but the pooled effect size of depression was significant in both hemispheres for the unipolar patients. The weighted average showed a reduction of hippocampal volume of 8% on the left side and 10% on the right side. The causes of the heterogeneity were analyzed, and a meta-regression showed that the total number of depressive episodes was significantly correlated to right but not left hippocampal volume reduction. Conclusions: Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder. Bipolar patients did not seem to show a reduction in hippocampal volume, but this has been much less investigated.
1,470 citations
TL;DR: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed.
Abstract: Objective: Most research on the effects of severe psychological stress has focused on stress-related psychopathology. Here, the author develops psychobiological models of resilience to extreme stress. Method: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed. Results: Eleven possible neurochemical, neuropeptide, and hormonal mediators of the psychobiological response to extreme stress were identified and related to resilience or vulnerability. The neural mechanisms of reward and motivation (hedonia, optimism, and learned helpfulness), fear responsiveness (effective behaviors despite fear), and adaptive social behavior (altruism, bonding, and teamwork) were found to be relevant to the character traits associated with resilience. Conclusions: The opportunity now exists to bring to bear the full power of advances in our understanding of the neurobiological basis of behavior to facilitate the discoveries needed to predict, prevent, and treat stress-related psychopathology.
1,442 citations
1,293 citations
TL;DR: A meta-analysis of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder found inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure.
Abstract: OBJECTIVE: A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. METHOD: A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. RESULTS: Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. CONCLUSIONS: Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclu...
1,059 citations
TL;DR: The prevalence of anxiety disorders in general and OCD in particular was much higher in people with anorexia nervosa and bulimia nervosa than in a nonclinical group of women in the community.
Abstract: OBJECTIVE: A large and well-characterized sample of individuals with anorexia nervosa and bulimia nervosa from the Price Foundation collaborative genetics study was used to determine the frequency of anxiety disorders and to understand how anxiety disorders are related to state of eating disorder illness and age at onset. METHOD: Ninety-seven individuals with anorexia nervosa, 282 with bulimia nervosa, and 293 with anorexia nervosa and bulimia were given the Structured Clinical Interview for DSM-IV Axis I Disorders and standardized measures of anxiety, perfectionism, and obsessionality. Their ratings on these measures were compared with those of a nonclinical group of women in the community. RESULTS: The rates of most anxiety disorders were similar in all three subtypes of eating disorders. About two-thirds of the individuals with eating disorders had one or more lifetime anxiety disorder; the most common were obsessive-compulsive disorder (OCD) (N=277 [41%]) and social phobia (N=134 [20%]). A majority of...
1,057 citations
TL;DR: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects, and cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission.
Abstract: Objective: The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning. Method: Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score ≥17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score ≥12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score ≤8, and Young Mania Rating Scale score ≤6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory. Results: The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts. Conclusions: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.
1,040 citations
TL;DR: Evidence suggests that the Hamilton depression scale is psychometrically and conceptually flawed, and the breadth and severity of the problems militate against efforts to revise the current instrument.
Abstract: OBJECTIVE: The Hamilton Depression Rating Scale has been the gold standard for the assessment of depression for more than 40 years. Criticism of the instrument has been increasing. The authors review studies published since the last major review of this instrument in 1979 that explicitly examine the psychometric properties of the Hamilton depression scale. The authors’ goal is to determine whether continued use of the Hamilton depression scale as a measure of treatment outcome is justified. METHOD: MEDLINE was searched for studies published since 1979 that examine psychometric properties of the Hamilton depression scale. Seventy studies were identified and selected, and then grouped into three categories on the basis of the major psychometric properties examined—reliability, item-response characteristics, and validity. RESULTS: The Hamilton depression scale’s internal reliability is adequate, but many scale items are poor contributors to the measurement of depression severity; others have poor interrater ...
991 citations
TL;DR: A consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings, including regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction are discussed.
Abstract: OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel’s recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17–18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardiv...
813 citations
TL;DR: The evidence supported a role for lithium as first-line agent for treatment of bipolar disorder when all four treatment roles are considered and highlights unmet needs and promising agents and provides a yardstick for evaluating new treatment strategies.
Abstract: OBJECTIVE: The term “mood stabilizer” is widely used in the context of treating bipolar disorder, but the U.S. Food and Drug Administration (FDA) does not officially recognize the term, and no consensus definition is accepted among investigators. The authors propose a “two-by-two” definition by which an agent is considered a mood stabilizer if it has efficacy in treating acute manic and depressive symptoms and in prophylaxis of manic and depressive symptoms in bipolar disorder. They review the literature on the efficacy of agents in any of these four roles to determine which if any agents meet this definition of mood stabilizer. METHOD: The authors conducted a comprehensive review of English-language literature describing peer-reviewed, U.S. Agency for Healthcare Research and Quality class A controlled trials in order to identify agents with efficacy in any of the four roles included in their definition of a mood stabilizer. The trials were classified as positive or negative on the basis of primary outcom...
755 citations
TL;DR: Psychosocial adversity interacts both with neuroticism and with sex in the etiology of major depression as the impact of neuroticism on illness risk is greater at high than at low levels of adversity, while the effect of sex on probability of onset is the opposite--greater at low than at high levels of stress.
Abstract: OBJECTIVE: Three potent risk factors for major depression are female sex, the personality trait of neuroticism, and adversity resulting from exposure to stressful life events. Little is known about how they interrelate in the etiology of depressive illness. METHOD: In over 7,500 individual twins from a population-based sample, the authors used a Cox proportional hazard model to predict onsets of episodes of DSM-III-R major depression in the year before the latest interviews on the basis of previously assessed neuroticism, sex, and adversity during the past year; adversity was operationalized as the long-term contextual threat scored from 15 life event categories. RESULTS: In the best-fit Cox model for prediction of depressive onsets, neuroticism, female sex, and greater adversity all strongly increased risk for major depression. An interaction was seen between neuroticism and adversity such that individuals with high neuroticism were at greater overall risk for major depression and were more sensitive to ...
754 citations
TL;DR: Studies on physicians' suicide collectively show modestly (men) to highly (women) elevated suicide rate ratios, and larger studies should help clarify whether female Physicians' suicide rate is truly elevated or can be explained by publication bias.
Abstract: OBJECTIVE: Physicians’ suicide rates have repeatedly been reported to be higher than those of the general population or other academics, but uncertainty remains. In this study, physicians’ suicide rate ratios were estimated with a meta-analysis and systematic quality assessment of recent studies. METHOD: Studies of physicians’ suicide rates were located in MEDLINE, PsycINFO, AARP Ageline, and the EBM Reviews: Cochrane Database of Systematic Reviews with the terms “physicians,” “doctors,” “suicide,” and “mortality.” Studies were included if they were published in or after 1960 and gave estimates of age-standardized suicide rates of physicians and their reference population or reported extractable data on physicians’ suicide; 25 studies met the criteria. Reviewers extracted data and scored each study for quality. The studies were tested for heterogeneity and publication bias and were stratified by publication year, follow-up, and study quality. Effect sizes were pooled by using fixed-effects (women) and ran...
TL;DR: While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.
Abstract: Objective: Posttraumatic stress disorder (PTSD) and major depression occur frequently following traumatic exposure, both as separate disorders and concurrently. This raises the question of whether PTSD and depression are separate disorders in the aftermath of trauma or part of a single general traumatic stress construct. This study aimed to explore the relationships among PTSD, depression, and comorbid PTSD/depression following traumatic injury. Method: A group of 363 injury survivors was assessed just prior to discharge from hospital and 3 and 12 months postinjury. Canonical correlations were used to examine the relationship between PTSD and depression symptom severity and a set of predictor variables. Multinomial logistic regression was used to identify whether the diagnostic categories of PTSD, depression, and comorbid PTSD/depression were associated with different groups of predictors. Results: The majority of psychopathology in the aftermath of trauma was best conceptualized as a general traumatic stress factor, suggesting that when PTSD and depression occur together, they reflect a shared vulnerability with similar predictive variables. However, there was also evidence that in a minority of cases at 3 months, depression occurs independently from PTSD and was predicted by a different combination of variables. Conclusions: While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.
TL;DR: Subjectively disturbed sleep in patients with insomnia is associated with greater brain metabolism, and daytime fatigue may reflect decreased activity in the prefrontal cortex resulting from inefficient sleep.
Abstract: OBJECTIVE: The authors investigated the neurobiological basis of poor sleep and daytime fatigue in insomnia. METHOD: [18F]Fluorodeoxyglucose positron emission tomography was used to assess regional cerebral glucose metabolism of seven patients with insomnia and 20 healthy subjects. RESULTS: Compared with healthy subjects, patients with insomnia showed greater global cerebral glucose metabolism during sleep and while awake, a smaller decline in relative metabolism from waking to sleep states in wake-promoting regions, and reduced relative metabolism in the prefrontal cortex while awake. CONCLUSIONS: Subjectively disturbed sleep in patients with insomnia is associated with greater brain metabolism. The inability to fall asleep may be related to a failure of arousal mechanisms to decline in activity from waking to sleep states. Further, daytime fatigue may reflect decreased activity in the prefrontal cortex resulting from inefficient sleep.
TL;DR: Results from 11 long-term studies support the idea that second- generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotic, although the doses of haloperidol used in the comparator studies were relatively high.
Abstract: OBJECTIVE: Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic. METHOD: Studies of treatment with second-generation antipsychotics lasting ≥1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed. RESULTS: In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of do...
TL;DR: Alarming high rates of both underuse and excessive filling of antipsychotic prescriptions were found in Medicaid beneficiaries with schizophrenia, and interventions on multiple levels are suggested.
Abstract: OBJECTIVE: The authors’ goal was to evaluate the relationship between adherence to treatment with antipsychotic medication and health expenditures. A secondary objective was to identify risk factors predictive of nonadherence. METHOD: Data included Medicaid eligibility and claims data from 1998 to 2000 for San Diego County, Calif. Pharmacy records were used to assess adherence to treatment with antipsychotic medication according to the cumulative possession ratio (the number of days medications were available for consumption divided by the number of days subjects were eligible for Medi-Cal). Regression models were used to examine risk factors, hospitalizations, and costs associated with nonadherence, partial adherence, adherence, and excess fills of antipsychotic medication. RESULTS: Forty-one percent of Medicaid beneficiaries with schizophrenia were found to be adherent to treatment with their antipsychotic medications: 24% were nonadherent, 16% were partially adherent, and 19% were excess fillers. Rates...
TL;DR: Lithium treatment reduces the risk of relapse in bipolar disorder and the preventive effect is clear for manic episodes, although it is equivocal for depressive episodes.
Abstract: OBJECTIVE: The authors sought to determine the efficacy and acceptability of lithium for relapse prevention in bipolar disorder. METHOD: A systematic review and meta-analysis of randomized controlled trials comparing lithium with placebo in the long-term treatment of bipolar disorders was conducted. Data were obtained from searching the registers of the Cochrane Collaboration; reviewing reference lists, journals, and conference abstracts; and contacting authors, experts, and pharmaceutical companies. Outcomes investigated included risk of relapse (manic, depressive, and total) as well as risk of specific adverse effects and total withdrawal rates. RESULTS: Five randomized controlled trials (770 participants) were included. Lithium was more effective than placebo in preventing all relapses (random effects relative risk=0.65, 95% CI=0.50 to 0.84) and manic relapses (relative risk=0.62, 95% CI=0.40 to 0.95). The protective effect of lithium on depressive relapses was smaller and was less robust (relative ris...
TL;DR: Although some patients with first-episode schizophrenia can achieve sustained symptomatic and functional recovery, the overall rate of recovery during the early years of the illness is low.
Abstract: OBJECTIVE: Follow-up studies have found that a substantial number of patients with schizophrenia achieve full recovery (i.e., sustained improvement in both symptoms and social/vocational functioning) when examined decades after an index admission. This study addressed recovery during the crucial early course of the illness. METHOD: Subjects in their first episode of schizophrenia or schizoaffective disorder (N=118) were assessed at baseline and then treated according to a medication algorithm. Full recovery required concurrent remission of positive and negative symptoms and adequate social/vocational functioning (fulfillment of age-appropriate role expectations, performance of daily living tasks without supervision, and engagement in social interactions). RESULTS: After 5 years, 47.2% (95% CI=36.0%–58.4%) of the subjects achieved symptom remission, and 25.5% (95% CI=16.1%–34.7%) had adequate social functioning for 2 years or more. Only 13.7% (95% CI=6.4%–20.9%) of subjects met full recovery criteria for 2...
TL;DR: Clinicians may find it useful to assess patients' current level of pessimism, aggressive/impulsive traits, and comorbidity with substance use disorders, including nicotine-related disorders, to help identify patients at risk for suicidal behavior after major depression.
Abstract: OBJECTIVE: The authors investigated the predictive potential of a stress-diathesis model for suicidal behavior based on correlates of past suicidal acts. In this model, suicidal acts are precipitated by stressors such as life events or a major depressive episode in the setting of a propensity for acting on suicidal urges. This diathesis is expressed as the tendency to develop more pessimism in response to a stressor and/or the presence of aggressive/impulsive traits. The predictive potential of the diathesis was tested by determining whether clinical correlates of past suicidal behavior predict suicidal acts during a 2-year follow-up of patients with a major depressive episode. METHOD: Patients with DSM-III-R major depressive disorder or bipolar disorder (N=308) were assessed at presentation for treatment of a major depressive episode. Potential predictors of suicidal acts in the 2 years after study enrollment were identified on the basis of an association with previous suicidal behavior and were tested b...
TL;DR: In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.
Abstract: OBJECTIVE: Alcohol and other drugs of abuse stimulate dopamine release in the ventral striatum, which includes the nucleus accumbens, a core region of the brain reward system, and reinforce substance intake. Chronic alcohol intake is associated with down-regulation of central dopamine D2 receptors, and delayed recovery of D2 receptor sensitivity after detoxification is positively correlated with high risk for relapse. Prolonged D2 receptor dysfunction in the ventral striatum may interfere with a dopamine-dependent error detection signal and bias the brain reward system toward excessive attribution of incentive salience to alcohol-associated stimuli. METHOD: Multimodal imaging, with the radioligand [18F]desmethoxyfallypride and positron emission tomography as well as functional magnetic resonance imaging (fMRI), was used to compare 11 detoxified male alcoholics with 13 healthy men. The authors measured the association of D2-like dopamine receptors in the ventral striatum with alcohol craving and central pr...
TL;DR: An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated, highlighting the need for greater clinical attention to anxiety in this population, particularly for enhanced clinical monitoring of suicidality.
Abstract: OBJECTIVE: The authors provide a detailed perspective on the correlates of comorbid anxiety in a large, well-characterized sample of bipolar disorder patients. METHOD: Anxiety and its correlates were examined in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS: Lifetime comorbid anxiety disorders were common, occurring in over one-half of the sample, and were associated with younger age at onset, decreased likelihood of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Although substance abuse disorders were particularly prevalent among patients with anxiety disorders, comorbid anxiety appeared to exert an independent, deleterious effect on functioning, includi...
TL;DR: A history of a suicide attempt by self-poisoning indicates suicide risk over the entire adult lifetime, and suicides continued to accumulate almost four decades after the index suicide attempt.
Abstract: OBJECTIVE: Attempted suicide is the strongest known predictor of completed suicide. However, suicide risk declines over time after an attempt, and it is unclear how long the risk persists. Risk estimates are almost exclusively based on studies of less than 10 years of follow-up. METHOD: The authors followed a cohort of 100 consecutive self-poisoned patients in Helsinki in 1963, for whom forensically classified causes of death during the following 37 years were investigated. RESULTS: They found that suicides continued to accumulate almost four decades after the index suicide attempt. CONCLUSIONS: A history of a suicide attempt by self-poisoning indicates suicide risk over the entire adult lifetime.
TL;DR: The results do not support theories that attempt to explain the mediation of offending behaviors in schizophrenia by single factors, such as substance abuse, active symptoms, or characteristics of systems of care, but suggest that offending reflects a range of factors that are operative before, during, and after periods of active illness.
Abstract: OBJECTIVE: This study examined the pattern of criminal convictions in persons with schizophrenia over a 25-year period marked by both radical deinstitutionalization and increasing rates of substance abuse problems among persons with schizophrenia in the community. METHOD: The criminal records of 2,861 patients (1,689 of whom were male) who had a first admission for schizophrenia in the Australian state of Victoria in 1975, 1980, 1985, 1990, and 1995 were compared for the period from 1975 to 2000 with those of an equal number of community comparison subjects matched for age, gender, and neighborhood of residence. RESULTS: Relative to the comparison subjects, the patients with schizophrenia accumulated a greater total number of criminal convictions (8,791 versus 1,119) and were significantly more likely to have been convicted of a criminal offense (21.6% versus 7.8%) and of an offense involving violence (8.2% versus 1.8%). The proportion of patients who had a conviction increased from 14.8% of the 1975 coho...
TL;DR: Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material and suggesting a mechanism of action potentially compatible with cognitive theories of anxiety and depression.
Abstract: OBJECTIVE: Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. METHOD: Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, ...
TL;DR: The trial data do not suggest that switching is a common early complication of treatment with antidepressants, and it may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment.
Abstract: OBJECTIVE: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. METHOD: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. RESULTS: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for...
TL;DR: Genetic or environmental factors that promote greater frontal capacity and reduced striatal dopaminergic reactivity might contribute to sparing people with schizotypal personality disorder from the psychosis and severe social and cognitive deterioration of chronic schizophrenia.
Abstract: Objective: This overview focuses on neurobiological abnormalities found in subjects with schizotypal personality disorder, the prototype of the schizophrenia spectrum disorders, and chronic schizophrenia in the context of common vulnerabilities shared by schizotypal personality disorder and schizophrenia, as well as the factors that protect against the severe cognitive/social deficits and frank psychosis of chronic schizophrenia. A pathophysiological model of the relationship between schizotypal personality disorder and schizophrenia was developed based on this data. Method: The authors provide a selective review of major findings regarding the pathophysiology of schizotypal personality disorder and integrate these results in conjunction with preclinical studies into a model of the pathophysiology of the spectrum. Results: People with schizotypal personality disorder share phenomenological, genetic, and cognitive abnormalities with people with chronic schizophrenia. While temporal volume reductions appear to be common to both groups, there may be preservation of frontal lobe volume in schizotypal personality disorder compared to schizophrenia. Findings to date regarding striatal volume, metabolic rate, and dopamine release in subjects with schizotypal personality disorder compared to subjects with chronic schizophrenia are consistent with hypotheses of reduced striatal dopaminergic activity in schizotypal personality disorder compared to schizophrenia. Conclusions: Genetic or environmental factors that promote greater frontal capacity and reduced striatal dopaminergic reactivity might contribute to sparing people with schizotypal personality disorder from the psychosis and severe social and cognitive deterioration of chronic schizophrenia. Further research is required to test these hypotheses more definitively.
TL;DR: Converging evidence from basic laboratory and clinical studies indicates that a withdrawal syndrome reliably follows discontinuation of chronic heavy use of cannabis or tetrahydrocannabinol, and findings suggest that the syndrome has clinical importance.
Abstract: The authors review the literature examining the validity and significance of cannabis withdrawal syndrome. Findings from animal laboratory research are briefly reviewed, and human laboratory and clinical studies are surveyed in more detail. Converging evidence from basic laboratory and clinical studies indicates that a withdrawal syndrome reliably follows discontinuation of chronic heavy use of cannabis or tetrahydrocannabinol. Common symptoms are primarily emotional and behavioral, although appetite change, weight loss, and physical discomfort are also frequently reported. The onset and time course of these symptoms appear similar to those of other substance withdrawal syndromes. The magnitude and severity of these symptoms appear substantial, and these findings suggest that the syndrome has clinical importance. Diagnostic criteria for cannabis withdrawal syndrome are proposed.
TL;DR: Occupancy of 80% across five SSRIs occurs at minimum therapeutic doses, which suggests that 80% 5-HTT blockade is important for therapeutic effect.
Abstract: OBJECTIVE: Minimum therapeutic doses of paroxetine and citalopram produce 80% occupancy for the serotonin (5-HT) transporter (5-HTT). The authors used [11C]DASB positron emission tomography to measure occupancies of three other selective serotonin reuptake inhibitors (SSRIs) at minimum therapeutic doses. The relationship between dose and occupancy was also investigated. METHOD: Striatal 5-HTT binding potential was measured in 77 subjects before and after 4 weeks of medication administration. Binding potential is proportional to the density of receptors not blocked by medication. Subjects received citalopram, fluoxetine, sertraline, paroxetine, or extended-release venlafaxine. Healthy subjects received subtherapeutic doses; subjects with mood and anxiety disorders received therapeutic doses. Percent reduction in 5-HTT binding potential for each medication and dose was calculated. To obtain test-retest data, binding potential was measured before and after 4 weeks in six additional healthy subjects. RESULTS:...
TL;DR: Whether second-trimester levels of four cytokines, a family of soluble polypeptides, are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects is investigated.
Abstract: OBJECTIVE: Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines—interleukin-8 (IL-8), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)—are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects. METHOD: The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959–1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective...
TL;DR: A medial prefrontal response to symptom-provoking stimuli was identified as a common feature of anorexia and bulimia nervosa and supports a conceptualization of eating disorders as being transdiagnostic at the neural level.
Abstract: OBJECTIVE: The authors sought to identify neural correlates of eating disorders in order to contribute to the debate on the genesis and classification of eating disorders and provide endophenotypes for genetic research. METHOD: Twenty-six female patients with eating disorders (10 with bulimia nervosa, 16 with anorexia nervosa) and 19 healthy female comparison subjects matched for age and education were presented with food and aversive emotional images while brain activity was recorded with functional magnetic resonance imaging. RESULTS: Women with eating disorders identified the food stimuli as threatening and disgusting. In response to these stimuli, the women with eating disorders had greater activation in the left medial orbitofrontal and anterior cingulate cortices and less activation in the lateral prefrontal cortex, inferior parietal lobule, and cerebellum, relative to the comparison group. In addition, women with bulimia nervosa had less activation in the lateral and apical prefrontal cortex, relat...
TL;DR: Exposed disaster workers are at increased risk of acute stress disorder, depression, or PTSD and seek care for emotional problems at an increased rate and are more likely to develop PTSD.
Abstract: OBJECTIVE: The events of Sept. 11, 2001, highlighted the importance of understanding the effects of trauma on disaster workers. To better plan for the health care of disaster workers, this study examined acute stress disorder, posttraumatic stress disorder (PTSD), early dissociative symptoms, depression, and health care utilization in disaster workers. METHOD: Exposed disaster workers (N=207) and unexposed comparison subjects (N=421) were examined at 2, 7, and 13 months after an airplane crash. RESULTS: Exposed disaster workers had significantly higher rates of acute stress disorder, PTSD at 13 months, depression at 7 months, and depression at 13 months than comparison subjects. Those who were younger and single were more likely to develop acute stress disorder. Exposed disaster workers with acute stress disorder were 3.93 times more likely to be depressed at 7 months. Those with high exposure and previous disaster experience or who had acute stress disorder were more likely to develop PTSD. Similarly, th...