Acute catatonia in an adolescent or young adult can present complex clinical challenges. Prominent issues include those involving diagnosis, timely and effective treatment, and diminished capacity to provide consent. The authors describe a 19-year-old woman presenting initially with manic excitement followed by a lengthy period of mutism, immobility, and food and fluid refusal. Elevated temperature, an elevated creatine phosphokinase level, and autonomic dysfunction led to consideration of a malignant catatonic syndrome. The patient manifested rigidity accompanied by posturing and waxy flexibility. Neurologic, medical, and laboratory evaluations failed to identify an organic cause for the likely catatonia. Treatment with amantadine, bromocriptine, and lorazepam was unsuccessful. ECT was deemed appropriate but required emergency guardianship because of the patient's inability to provide consent. At the initial ECT session, the elicited seizure was followed by an episode of torsade de pointes requiring immediate cardioversion. In reviewing the ECT complication, it appeared that muscle damage due to catatonic immobility led to acute hyperkalemia with the administration of succinylcholine. Discussions were held with the patient's guardian outlining the clinical issues and the risks of additional ECT. The patient responded to eight subsequent ECT sessions administered with rocuronium, a nondepolarizing muscle relaxant. The authors provide a brief review of the diagnosis and treatment of catatonia and address issues surrounding ECT, cardiac effects, use of muscle relaxants, and the consent process.
]]>This essay outlines the historical context in which the Feighner criteria emerged; reconstructs, as far as possible, the process by which the criteria were developed; and traces the influence the criteria had on subsequent developments in American psychiatry. In the 1950s, when American psychiatry under psychoanalytic dominance had little interest in psychiatric diagnosis, Edwin Gildea recruited to the Department of Psychiatry at Washington University faculty who advocated a medical model for psychiatry in which diagnosis had a central role. In 1967, at the urging of the then-resident John Feighner, a discussion group led by Eli Robins and including Sam Guze, George Winokur, Robert Woodruff, and Rod Muñoz began meeting with the initial goal of writing a review of prior key contributions to psychiatric diagnosis. In their meetings over the next year, the task soon shifted to the development of a set of new diagnostic criteria. For three diagnoses, major depression, antisocial personality disorder, and alcoholism, the authors could identify the original criteria from which this group worked and the rationale for many of the changes they introduced. Published in 1972, the Feighner criteria were soon widely cited and used in research, and they formed the basis for the development of the Research Diagnostic Criteria, which in turn were central to the development of DSM-III. The team that developed the Feighner criteria made three key contributions to psychiatry: the systematic use of operationalized diagnostic criteria; the reintroduction of an emphasis on illness course and outcome; and an emphasis on the need, whenever possible, to base diagnostic criteria on empirical evidence.
]]>High rates of suicide have been described in HIV-infected patients, but it is unclear to what extent the introduction of highly active antiretroviral therapy (HAART) has affected suicide rates. The authors examined time trends and predictors of suicide in the pre-HAART (1988–1995) and HAART (1996–2008) eras in HIV-infected patients and the general population in Switzerland.
The authors analyzed data from the Swiss HIV Cohort Study and the Swiss National Cohort, a longitudinal study of mortality in the Swiss general population. The authors calculated standardized mortality ratios comparing HIV-infected patients with the general population and used Poisson regression to identify risk factors for suicide.
From 1988 to 2008, 15,275 patients were followed in the Swiss HIV Cohort Study for a median duration of 4.7 years. Of these, 150 died by suicide (rate 158.4 per 100,000 person-years). In men, standardized mortality ratios declined from 13.7 (95% CI=11.0–17.0) in the pre-HAART era to 3.5 (95% CI=2.5–4.8) in the late HAART era. In women, ratios declined from 11.6 (95% CI=6.4–20.9) to 5.7 (95% CI=3.2–10.3). In both periods, suicide rates tended to be higher in older patients, in men, in injection drug users, and in patients with advanced clinical stage of HIV illness. An increase in CD4 cell counts was associated with a reduced risk of suicide.
Suicide rates decreased significantly with the introduction of HAART, but they remain above the rate observed in the general population, and risk factors for suicide remain similar. HIV-infected patients remain an important target group for suicide prevention.
Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings.
A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care.
At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF-36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%).
Medical care management was associated with significant improvements in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings.
Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders?
Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects.
Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression.
These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7–13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older.
There is considerable interest in cognitive remediation for schizophrenia, but its essential components are still unclear. The goal of the current study was to develop a broadly targeted computer-assisted cognitive remediation program and conduct a rigorous clinical trial in a large group of schizophrenia patients.
Sixty-nine people with schizophrenia or schizoaffective disorder were randomly assigned to 36 sessions of computer-assisted cognitive remediation or an active control condition. Remediation broadly targeted cognitive and everyday performance by providing supportive, graduated training and practice in selecting, executing, and monitoring cognitive operations. It used engaging computer-based cognitive exercises and one-on-one training. A total of 61 individuals (34 in remediation group, 27 in control group) engaged in treatment, completed posttreatment assessments, and were included in intent-to-treat analyses. Primary outcomes were remediation exercise metrics, neuropsychological composites (episodic memory, working memory, attention, executive functioning, and processing speed), and proxy measures of community functioning.
Regression modeling indicated that performance on eight of 10 exercise metrics improved significantly more in the remediation condition than in the control condition. The mean effect size, favoring the remediation condition, was 0.53 across all 10 metrics. However, there were no significant benefits of cognitive remediation on any neuropsychological or functional outcome measure, either immediately after treatment or at the 3-month follow-up.
Cognitive remediation for people with schizophrenia was effective in improving performance on computer exercises, but the benefits of training did not generalize to broader neuropsychological or functional outcome measures. The evidence for this treatment approach remains mixed.
The purpose of the present study was to evaluate the efficacy and tolerability of olanzapine long-acting injection for maintenance treatment of schizophrenia.
Outpatients with schizophrenia who had maintained stability on an oral regimen of olanzapine (10, 15, or 20 mg/day) for 4 to 8 weeks were randomly assigned to 24 weeks of double-blind treatment with "low" (150 mg every 2 weeks; N=140), "medium" (405 mg every 4 weeks; N=318), or "high" (300 mg every 2 weeks; N=141) doses of olanzapine long-acting injection; a very low reference dose of olanzapine long-acting injection (45 mg every 4 weeks; N=144); or their stabilized dose of oral olanzapine (N=322). Rates of and time to psychotic exacerbation were estimated using Kaplan-Meier methodology.
At 24 weeks, the majority of oral olanzapine-treated patients (93%), as well as most olanzapine long-acting injection-treated patients receiving high (95%), medium (90%), low (84%), and very low doses (69%), remained exacerbation free, with the therapeutic 4-week regimen (medium dose) and pooled 2-week regimen (low and high doses) demonstrating efficacy similar to that of oral olanzapine as well as to each other. The three standard long-acting doses were superior to the very low reference dose based on time to exacerbation. Incidence of weight gain ≥7% of baseline was 21% for oral olanzapine compared with 21%, 15%, 16%, and 8% for the high, medium, low, and very low olanzapine long-acting treatment groups, respectively. No clinically significant differences were observed between the long-acting injection and oral olanzapine groups in general safety parameters. Few injection-site reactions occurred (3%). Two patients experienced sedation and delirium consistent with olanzapine overdose following possible accidental intravascular injection.
Olanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks, with a safety profile similar to oral olanzapine except for injection-related adverse events.
The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents.
A subsample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures.
No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91).
The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment.
Limited evidence reveals an elevated mortality risk in offspring of psychiatric patients after infancy. This nationwide population-based study in Taiwan aimed to investigate mortality risk in preschool children up to age 5 whose parents have severe mental illness.
Three nationwide population-based data sets were linked. A total of 3,166 children with one or both parents having schizophrenia or an affective disorder were identified, together with a comparison cohort of 25,328 children matched with the study group in terms of maternal age and year of delivery. Cox proportional hazard regressions were performed to compute hazard ratios, with adjustment for sociodemographic characteristics and maternal medical comorbidities.
During the preschool years, 54 (1.7%) deaths were documented among offspring of parents with severe mental illness and 155 (0.6%) in the comparison cohort. Parental mental illness was independently associated with a risk of death nearly 2.4 times higher (95% CI=1.72–3.28) than in the comparison cohort. The association was even more marked for unnatural causes of death, in which the mortality risk was 8.35 times greater (95% CI=4.04–17.24) in children of affected parents than in the comparison cohort. The proportional mortality rates were as high as 20.4% and 11.1% for accident and homicide, respectively, among offspring exposed to parental mental illness.
An elevated mortality risk, especially from unnatural causes of death, was identified for offspring of parents with severe mental illness during the preschool years in an Asian society. There is an urgent need for multidisciplinary team approaches and risk management strategies to support psychiatric patients who are having difficulty with the transition to parenthood.
Animal studies assessing mechanisms of self-starvation under conditions of stress and diet suggest a pivotal role for the mesolimbic reward system in the maintenance of core symptoms in anorexia nervosa, which is corroborated by initial empirical evidence in human studies. The authors examined activity in the ventral striatal system in response to disease-specific stimuli in women with acute anorexia nervosa.
Participants were 14 women with acute anorexia nervosa and 14 matched healthy comparison women who underwent functional magnetic resonance imaging (fMRI) during evaluation of visual stimuli depicting a female body with underweight, normal weight, and overweight canonical whole-body features according to standardized body mass indices. Participants were required to process each stimulus in a self-referring way. Ratings for each weight category were used as the control task.
Behaviorally, women with anorexia nervosa provided significantly higher positive ratings in response to underweight stimuli than in response to normal-weight stimuli, while healthy comparison women showed greater preference for normal-weight stimuli relative to underweight stimuli. Functionally, ventral striatal activity demonstrated a highly significant group-by-stimulus interaction for underweight and normal-weight stimuli. In women with anorexia nervosa, activation was higher during processing of underweight stimuli compared with normal-weight stimuli. The reverse pattern was observed in healthy comparison women.
These findings are consistent with predictions in animal studies of the pivotal role of the human reward system in anorexia nervosa and thus support theories of starvation dependence in maintenance of the disorder.