Clinical Schizophrenia and Related Psychoses最新文献

Objective: Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity.

Methods: Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, χ ² tests, Student's t-tests, and 2×2 factorial analyses of variance.

Results: Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity.

Conclusions: The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset.

The diagnoses of serious psychiatric illnesses, such as schizophrenia, schizoaffective disorder, and bipolar disorder, rely on the subjective recall and interpretation of often overlapping symptoms, and are not based on the objective pathophysiology of the illnesses. The subjectivity of symptom reporting and interpretation contributes to the delay of accurate diagnoses and limits effective treatment of these illnesses. Proteomics, the study of the types and quantities of proteins an organism produces, may offer an objective biological approach to psychiatric diagnosis. For this pilot study, we used the Myriad RBM Discovery Map 250+ platform to quantify 205 serum proteins in subjects with schizophrenia (n=26), schizoaffective disorder (n=20), bipolar disorder (n=16), and healthy controls with no psychiatric illness (n=23). Fifty-seven analytes that differed significantly between groups were used for multivariate modeling with linear discriminant analysis (LDA). Diagnoses generated from these models were compared to SCID-generated clinical diagnoses to determine whether the proteomic markers: 1) distinguished the three disorders from controls, and 2) distinguished between the three disorders. We found that a series of binary classification models including 8-12 analytes produced separation between all subjects and controls, and between each diagnostic group and controls. There was a high degree of accuracy in the separations, with training areas-under-the-curve (AUC) of 0.94-1.0, and cross-validation AUC of 0.94-0.95. Models with 7-14 analytes produced separation between the diagnostic groups, though less robustly, with training AUC of 0.72-1.0 and validation AUC of 0.69-0.89. While based on a small sample size, not adjusted for medication state, these preliminary results support the potential of proteomics as a diagnostic aid in psychiatry. The separation of schizophrenia, schizoaffective disorder, and bipolar disorder suggests that further work in this area is warranted.

Objective: Long-acting injectable (LAI) antipsychotics improve treatment outcomes in patients with schizophrenia but are often reserved for only the most severely affected or nonadherent. Studies show cultural/racial differences in prescribing. This pilot study examined prescriber-patient interactions and cultural/racial differences in perceptions of LAIs among patients.

Methods: A linguist analyzed 120 prescriber-patient conversations representing selected patient cultural/racial subgroups (European American, African American, Latino American; n=40 each) to identify similarities and differences in conceptualization and attitudes toward LAIs.

Results: Of 35 LAI-naive patients offered LAIs, 9% (3/35) responded favorably, 46% (16/35) were neutral/passive, and 46% (16/35) had concerns or viewed LAIs as unfavorable. Among LAI-naive patients, favorable or neutral/passive responses were reported for 50% (7/14) of European Americans, 63% (10/16) of African Americans, and 40% (2/5) of Latino Americans. The majority of LAI-naive patients (57% [20/35]) accepted LAI prescriptions, including 53% (17/32) of those who initially were neutral/passive or refused treatment (European American, 42% [5/12]; African American, 53% [8/15]; Latino American, 80% [4/5]). Fifty-seven percent (68/120) of patients expressed treatment goals. Goals of positive/negative symptom control were associated with positive attitudes toward LAIs while patients with goals focused on control of anxiety and insomnia tended to have negative attitudes toward LAIs. Latino-American patients who expressed treatment goals seemed more focused on discomfort control (67% [12/18]); goals of European Americans and African Americans were more equally distributed.

Conclusions: Equal numbers of LAI-naive patients had unfavorable/concerned or neutral/passive attitudes toward treatment; relatively few patients responded favorably. The limited sample size precludes cultural/racial-specific conclusions.

Cognitive impairment is nearly ubiquitous in schizophrenia. First-degree relatives of persons with schizophrenia often show similar but milder deficits. Current methods for the treatment of schizophrenia are often ineffective in cognitive remediation. Since transcranial direct current stimulation (tDCS) can enhance cognitive functioning in healthy adults, it might provide a viable option to enhance cognition in schizophrenia. We sought to explore whether tDCS can be tolerated by persons with schizophrenia and potentially improve their cognitive functioning. We examined the effects of anodal versus cathodal tDCS on working memory and other cognitive tasks in five outpatients with schizophrenia and six first-degree relatives of persons with schizophrenia. Each participant completed tasks thought to be mediated by the prefrontal cortex during two 30-minute sessions of tDCS to the left and right dorsolateral prefrontal cortex (DLPFC). Anodal stimulation over the left DLPFC improved performance relative to cathodal stimulation on measures of working memory and aspects of verbal fluency relevant to word retrieval. The patient group showed differential changes in novel design production without alteration of overall productivity, suggesting that tDCS might be capable of altering self-monitoring and executive control. All participants tolerated tDCS well. None withdrew from the study or experienced any adverse reaction. We conclude that adults with schizophrenia can tolerate tDCS while engaging in cognitive tasks and that tDCS can alter their performance.

Aim: Early engagement in care is thought to reduce disabling social losses related to the duration of untreated psychosis (DUP), such as school dropout, homelessness, and incarceration, which contribute to chronic disability. Early-intervention services that promote recovery will not be effective if eligible persons drop out of treatment after an initial hospitalization for a psychotic disorder. We had the unique opportunity to examine the treatment disengagement rate of patients with early psychosis after an initial hospitalization.

Methods: In a predominantly male, African-American, and socioeconomically disadvantaged group of 33 participants with first-episode psychosis assessed at initial hospitalization and six months after discharge, we compared clinical characteristics (medication adherence attitudes and behaviors, knowledge about schizophrenia, insight, symptom severity, and persistence of alcohol and drug use) among those who disengaged and people who engaged in care.

Results: More than half (18, 54.5%) attended <3 outpatient appointments in the six months after hospital discharge and, of those, nearly all (15, 83.3%) attended no outpatient appointments. Disengaged people were much less adherent to medications in the past month and six months, and scored lower on medication adherence attitudes, knowledge about psychosis, and insight. They had greater positive symptom severity and a higher likelihood of continuing drug use. Clinical Relevancy: Initial treatment disengagement is very common among young people with first-episode psychosis and is associated with poorer clinical status. More research is needed on the causes of disengagement during this critical period and ways to improve initial treatment engagement among people with first-episode psychosis.

Purpose: This study aimed to examine the effect of add-on treatment with the neurosteroid pregnenolone (PREG) on neurocognitive dysfunctions of patients with recent-onset schizophrenia (SZ) and schizoaffective disorder (SA).

Method: Sixty out- and inpatients that met DSM-IV criteria for SZ/SA were randomized to an 8-week, double-blind, randomized, placebo-controlled, 2-center trial. Participants received either pregnenolone (50 mg/d) or placebo added on to antipsychotic medications. Computerized Cambridge Automated Neuropsychological Test Battery measures were administered at baseline and after 4 and 8 weeks of treatment. ANOVA and paired t- or z-tests were applied to examine between- and within-group differences over time.

Results: Compared to placebo, adjunctive PREG significantly reduced the deficits in visual attention measured with the Matching to Sample Visual Search task (p=0.002), with moderate effect sizes (d=0.42). In addition, a significant improvement was observed from baseline to end-of-study with respect to the visual (p=0.008) and sustained attention (Rapid Visual Information Processing, p=0.038) deficits, and executive functions (Stockings of Cambridge, p=0.049; Spatial Working Memory, p<0.001) among patients receiving PREG but not among those receiving placebo (all p's>0.05). This beneficial effect of PREG was independent of the type of antipsychotic agents, gender, age, education, and illness duration.

Conclusions: Pregnenolone augmentation demonstrated significant amelioration of the visual attention deficit in recent-onset SZ/SA. Long-term, large-scale studies are required to obtain greater statistical significance and more confident clinical generalization.

Treatment research studies employ criteria that determine which patients are eligible to participate and which are not. When such exclusion criteria produce a treatment research sample that is a small and unrepresentative subset of all patients with a particular disease, clinicians may be hesitant to apply the research results in front-line clinical practice. Accordingly, the present paper reviews the English-language literature on exclusion criteria in schizophrenia treatment research and draws initial conclusions about their impact. Empirically derived estimates of the rate of exclusion vary widely (31.0-98.2%), but the best available evidence suggests that about 4 in 5 patients with schizophrenia would be ineligible to enroll in a typical treatment research study. Women are particularly likely to be excluded from schizophrenia treatment research, which is problematic from both a clinical and social justice viewpoint. Excluded patients also tend to be older than eligible patients, and, though it has been examined in only a few studies, they also tend to have more severe problems at baseline and different outcomes over time than patients who are allowed to participate in research. More limited use of exclusion criteria in schizophrenia treatment research would be beneficial in terms of increasing generalizability, but would also potentially involve costs, particularly a need for larger samples. More modest steps that would improve treatment outcome research reports include requiring a full description of the rationale for, and nature of, any exclusion criteria, and, having a designated place in the discussion section which draws attention to the proper scope of generalization.

It is not known why mentally ill persons smoke excessively. Inasmuch as endogenous opioid and dopaminergic systems are involved in smoking reinforcement, it is important to study mu opioid receptor (OPRM1) A118G (rs1799971), dopamine D2 receptor (DRD2) Taq1A (rs1800497) genotypes, and sex differences among patients with schizophrenia or bipolar disorder. Smokers and nonsmokers with schizophrenia (n=177) and bipolar disorder (n=113) were recruited and genotyped. They were classified into three groups: current smoker, former smoker, and never smoker by tobacco smoking status self-report. The number of cigarettes smoked per day was used as the major tobacco smoking parameter. In patients with schizophrenia, tobacco smoking prevalence was greater in males than in females as expected, but women had greater daily cigarette consumption (p<0.01). Subjects with schizophrenia who had the OPRM1 *G genotype smoked more cigarettes per day than the AA allele carriers with schizophrenia (p<0.05). DRD2 Taq1A genotype differences had no effect on the number of cigarettes smoked per day. However, female smokers with schizophrenia who were GG homozygous of the DRD2 receptor smoked more than the *A male smokers with schizophrenia (p<0.05). In bipolar patients, there were no OPRM1 and DRD2 Taq1A genotype differences in smoking status. There also were no sex differences for smoking behavior among the bipolar patients. The results of this study indicate that single nucleotide polymorphism (SNP) of the less functional mu opioid receptor increases tobacco smoking in patients with schizophrenia. Alteration of DRD2 receptor function also increased smoking behavior in females with schizophrenia.