Methadone maintenance treatment and survival of schizophrenic patients with a lifetime comorbid substance use disorders: a long-term follow-up study.

Background Methadone maintenance treatment (MMT) remains the most widely used effective therapeutic approach for opioid use disorders. However, there is paucity of empirical data regarding the relationship between the MMT and survival of subjects with schizophrenia. Aim The aim of this study was to examine the effect of MMT on the long-term survival of subjects with schizophrenia and a lifetime comorbid substance use disorders. Methods The charts of 277 consecutive subjects admitted in our center during a period from January 1, 2002 to February 1, 2007 were assessed. Psychiatric diagnoses have been established according to international classification of diseases and health related problems-10th edition (ICD-10). The risk of all-cause mortality was assessed by Cox proportional-hazards regression models, including time-dependent covariates. Results Out of MMT subjects, 31 (11.2%) had mental and behavioral disorders due to multiple psychoactive substance use, 5 (1.8%) had mental and behavioral disorders due to use of opioids. All of 13 (4.7%) subjects with opioid use disorders were treated. MMT has been found to be predictive of lower long-term survival, in time-independent (hazard ration [HR] = 1.88; 95%CI: 1.06-3.37; p<.05) and in time-dependent adjusted models (HR = 2.01; 95%CI: 1.21-3.60; p<.05). MMT daily dose of <120 mg (adjusted HR = 1.83; 95%CI: .95-3.54) and MMT daily dose of ≥120 mg (adjusted HR = 2.70; 95%CI: .97-7.54) were associated with less long-term survival, all compared with no lifetime MMT (p<.046). Conclusions Among subjects with schizophrenia and a lifetime comorbid substance use disorders, overall mortality was higher in those who received lifetime MMT, then in patients without MMT.

Association between golli-MBP and schizophrenia in the Jewish Ashkenazi population: are regulatory regions involved?

Multiple studies have reported oligodendrocyte and myelin abnormalities, as well as dysregulation of their related genes, in brains of schizophrenia patients. One of these genes is the myelin-basic-protein (MBP) gene, which encodes two families of proteins: classic-MBPs and golli-MBPs. While the classic-MBPs are predominantly located in the myelin sheaths of the nervous system, the golli proteins are more widely expressed and are found in both the immune and the nervous systems. In the present study we performed a case-control association analysis of golli-MBP in two separate Jewish Ashkenazi cohorts (cohort I: 120 patients, 236 controls; cohort II: 379 patients, 380 controls). In addition we performed an expression analysis of golli-MBP mRNA in post-mortem dorsolateral prefrontal cortex samples of schizophrenia patients, and matched controls. In the first cohort we observed association between six (out of 26 genotyped) single nucleotide polymorphisms (SNPs) and the disease (p<0.05). Of these, three are from one linkage disequilibrium (LD) block which contains a CTCF binding region. Haplotype analysis revealed significant 'risk'/'protective' haplotypes (strongest p=0.005, each) for schizophrenia. The three SNPs (rs12458282, rs2008323, rs721286) were then genotyped in the second cohort. The combined results showed strong effects, both in the single marker and in haplotype analyses (strongest OR 1.77, p=0.0005; OR 1.61, p=0.00001, respectively). Sequencing the CTCF binding region revealed three SNPs in complete LD with the associated haplotypes, located in close proximity to the CTCF binding site. Expression analysis found no significant differences in golli-MBP mRNA levels. These findings suggest that golli-MBP is a possible susceptibility gene for schizophrenia.

Clinical utility of biomarkers of the hand in the diagnosis of schizophrenia.

A number of biomarkers were assessed in photos and prints of the hands of 95 patients with a variety of mental disorders to determine whether patients with schizophrenia could be distinguished from the others. Patients were recruited as consecutive admissions from an outpatient psychiatric day hospital population. Fourteen patients were diagnosed with schizophrenia/schizoaffective disorder and 81 were diagnosed with other mental disorders. A discriminant analysis yielded an overall 80% correct classification, with a sensitivity (schizophrenia patients identified correctly) of 78.6% and a specificity (non-schizophrenia patients identified correctly) of 80.2%. Significant differences were noted in the proximal interphalangeal joint, eponychium of the middle digit and fingernails. To determine biomarker frequency distribution patients with bipolar disorder were then compared to those with schizophrenia/schizoaffective disorder and then to patients with PTSD. The former yielded an overall 78.6% correct classification, with a sensitivity of 71.4% and a specificity of 85.7% and with similar biomarker frequency distribution for bipolar disorder as for the entire non schizophrenia group. The latter comparison yielded an overall 58.6% correct classification, with no significant differences between the features. The application of these biomarkers in clinical practice could constitute an additional tool for the psychiatrist in cases lacking diagnostic clarity.

Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia.

Schizophrenia patients have well-established deficits in facial emotion perception, which contribute to their poor social functioning. A number of studies have related these deficits to a differential dysfunction in the magnocellular (M) versus parvocellular (P) visual pathway. We assessed 35 schizophrenia patients and 35 healthy individuals on an emotion identification task, in which facial stimuli were either unaltered (broad spatial frequency, BSF) or manipulated to contain only high (HSF) or low (LSF) spatial frequencies, thereby respectively biasing the visual system toward the P- or M- pathways. As expected, patients were less accurate and slower in recognizing emotions across all conditions, relative to controls. Performance was best in the BSF condition followed by the HSF and finally the LSF condition, in both groups. A significant group by spatial frequency interaction reflected a smaller magnitude of impairment in the HSF condition, compared to the other two conditions that preferentially engage the M-system. These findings are consistent with studies showing a differential M-pathway abnormality in schizophrenia with a less pronounced impairment in P-function. The current study suggests that patients have less difficulty extracting emotional content from faces when LSFs are attenuated and supports the need to remediate basic visual processing deficits in schizophrenia.

Do biometric parameters of the hand differentiate schizophrenia from other psychiatric disorders? A comparative evaluation using three mental health modules.

The link between schizophrenia and anomalies in the distal upper limb is well documented. Preliminary studies have identified a number of biometric parameters of the hand by which schizophrenics can be distinguished from matched controls. The current study seeks to determine whether patients with schizophrenia can be singled out from a disparate group of other mental disorders by using the same parameters. We studied three groups, totaling 134 men: 51 diagnosed with schizophrenia, 29 with anxiety and mood disorders, and 54 comprising a control group. Seven parameters were studied: the proximal interphalangeal joint, the eponychia of the middle and ring digits, two dermatoglyphic features, and two constitutional factors. Examiners evaluated the parameters based on photographs and prints. An initial Mann Whitney comparison showed no significant difference between the control group and those identified with anxiety and mood disorders. We therefore accounted for them as a single group. In a discriminant analysis, an overall accuracy of 78.4% was established with a sensitivity of 80.4% (schizophrenics identified correctly) and a specificity of 77.1% (controls identified correctly). These results suggest that the biometric parameters employed may be useful in identifying patients with schizophrenia from a disparate group of other mental disorders.

Olanzapine vs. haloperidol in the treatment of elderly chronic schizophrenia patients.

OBJECTIVE: Most of the data supporting the use of atypical antipsychotics (AA) is based on studies in young adult patients. The present study is an open-label naturalistic follow-up study of olanzapine treatment vs. haloperidol for elderly chronic schizophrenia patients. MEHTOD: 20 patients (mean age 72.7+/-5.9 years, mean disease duration 33.1+/-12.0 years) who met the DSM-IV criteria for schizophrenia were randomly assigned to olanzapine (n=10) or haloperidol (n=10) treatment during acute exacerbation. Primary outcome measure was rating on the Clinical Global Impression (CGI) scale and the Positive and Negative Symptom Scale (PANSS). RESULTS: Between-group differences were computed using analysis of covariance. PANSS Total score decreased from 84 at baseline to 65 after treatment with olanzapine while decreased only from 79 to 74 with haloperidol treatment (F= 6.66, P=.02). PANSS Negative subscale decreased from 19 at baseline to 15 with olanzapine treatment while increased (deteriorated) from 18 to 20 with haloperidol treatment (F=23.37, P=.0003). CGI decreased from baseline with both olanzapine and haloperidol treatments (1.1 vs. 0.4) but the decrease in the olanzapine group was significantly greater (F=4.63, P=.05). Mean weight increased in both groups but without statistical difference between groups. CONCLUSIONS: In elderly chronic schizophrenia patients, olanzapine treatment is superior to haloperidol in reducing negative symptoms as well as less induction of extrapyramidal symptoms (EPS).

The magnocellular visual pathway and facial emotion misattribution errors in schizophrenia.

Many individuals with schizophrenia show impairment in labeling the emotion depicted by faces, and tend to ascribe anger or fear to neutral expressions. Preliminary research has linked some of these difficulties to dysfunction in the magnocellular (M) visual pathway, which has direct projections to subcortical emotion processing regions. The current study attempted to clarify these relationships using a novel paradigm that included a red background. Diffuse red light is known to suppress the M-pathway in nonpsychiatric adults, and there is preliminary evidence that it may have the opposite (stimulating) effect in schizophrenia-spectrum disorders (SSDs). Twenty-five individuals with SSDs were compared with 31 nonpsychiatric controls using a facial emotion identification task depicting happy, angry, fearful, and sad emotions on red, green, and gray backgrounds. There was a robust interaction of group by change in errors to the red (vs. green) background for misattributing fear expressions as depicting anger (p=.001, ή(2)=.18). Specifically, controls showed a significant decrease in this type of error with the red background (p=.003, d=0.77), while the SSD group tended to increase this type of error (p=.07, d=0.54). These findings suggest that the well-established M-pathway abnormalities in SSDs may contribute to the heightened misperception of other emotions such as anger, which in turn may cause social misperceptions in the environment and elicit symptoms such as paranoia and social withdrawal. As the ventral striatum plays a primary role in identifying anger and receives efferent input from the M-pathway, it may serve as the neuroanatomical substrate in the perception of anger.

Biometric parameters of the hand as an index of schizophrenia--a preliminary study.

Since abnormalities in distal upper limb development are among the minor physical anomalies associated with schizophrenia we attempted to determine whether patients with schizophrenia can be identified on the basis of specific morphologic and dermatoglyphic features of the hand. Photographs and prints of the hands of 38 patients with schizophrenia and those of 42 control subjects were evaluated and graded on 13 biometric parameters. Results were statistically evaluated. A combination of three of the parameters was found to have good predicting abilities to distinguish between schizophrenics and controls. Subjects having high values in these three parameters were found to have a higher propensity to be defined as schizophrenics. In order to define a simple rule for classifying subjects we chose a criterion of having a value of 3 (in a scale from 1 to 3) in at least one of these three discriminating variables. This rule yielded an overall accuracy of 81.2%. Among controls, 85.7% of subjects did not fulfill such criteria, while 14.3% were defined as false positives. Among schizophrenics 76.3% achieved this condition while 23.7% were false negatives. The technique's objectivity and ease of application could facilitate the diagnosis of this disease.

The Positive and Negative Symptoms Questionnaire: a self-report scale in schizophrenia.

The assessment of various symptoms in schizophrenia has received much interest, although few studies have compared evaluations by clinicians to those of their patients. Self-report tools may improve service delivery, data collection, and possibly also treatment adherence. We constructed the Positive and Negative Symptoms Questionnaire (PNS-Q), a self-report measure, after items from the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). The PNS-Q contained 68 items and was administered to 61 schizophrenic inpatients. We examined its psychometric properties and utility as a self-report tool in schizophrenia. The PNS-Q exhibited high internal consistency for both its positive and negative subscales. External validity with the SAPS and SANS was low. The positive symptoms subscale correlated significantly with the SAPS ( r = .341, P < .01), whereas the negative symptoms subscale did not correlate at all with the SANS ( r = -0.086, P > .1). The correlation between patients' insight and scores of the PNS-Q was mixed. A partial correlation analysis failed to confirm a relationship between the rating of the patients' level of insight (measured by the Amador Scale to Assess Unawareness of Mental Disorders [SUMD]) and the disparity between the PNS-Q and the SAPS and SANS. However, the PNS-Q correlated highly with McEvoy's Vignettes, a measure of self-perception of symptoms. The results of this study are discussed in light of current research and methodologic issues. The PNS-Q reflects schizophrenics' self-perception, an important, yet neglected, aspect of schizophrenia. Using this new measure, we believe that clinicians and researchers will be able to gain insight to the inner world of these patients and improve their condition, as well as enhance patients' involvement in treatment planning.

Would a switch from typical antipsychotics to risperidone be beneficial for elderly schizophrenic patients? A naturalistic, long-term, retrospective, comparative study.

Elderly chronic schizophrenia patients are particularly difficult to treat because of aging-related changes, cognitive impairment, and comorbid physical illness. This article describes a naturalistic, retrospective study of typical antipsychotic treatment versus risperidone for elderly psychotic inpatients. Fifty-one patients, mean age 72.7 + 5.9 years, mean disease duration 33.1 + 12.0 years, who met the DSM-IV criteria for schizophrenia or schizoaffective disorder were treated by risperidone (n = 26) or typical antipsychotic treatment (n = 25) during acute exacerbation and followed up for 18 months. Patients were rated using the clinical global impression (CGI) scale and positive and negative symptom scale (PANSS), and their body weight was recorded at baseline, 6 months, and 18 months. Both treatment groups improved on all rating scales at 18 months. Levels of decrease in PANSS positive and total scores were more prominent in patients treated with risperidone (p < 0.01 and p < 0.05, respectively). The change in CGI scores reached significance only after 18 months and was more pronounced in the risperidone group (p < 0.01). Anti-Parkinsonian medications were used more frequently in the typical antipsychotic group, whereas benzodiazepines were used more frequently in the risperidone group. Body mass index increased minimally after 18 months in the risperidone group (+ 0.3 kg/m2), whereas a larger (+ 1.1 kg/m2), albeit not statistically significant, increase was recorded in the typical antipsychotic group. Emergence of side effects was less frequent in patients treated with risperidone (4/26 vs. 16/25 patients, p < 0.01). The results of this study demonstrate that in elderly chronic schizophrenic patients, switching from typical antipsychotics to risperidone is effective and well tolerated.

Switching elderly chronic psychotic patients to olanzapine.

The purpose of this study was to examine whether elderly chronic schizophrenia or schizoaffective disorder patients would clinically improve if switched to olanzapine from previous neuroleptic treatment. Twenty-one hospitalized patients, aged 6088 yr, with a diagnosis of chronic schizophrenia or schizoaffective disorder who were being treated with typical neuroleptic medication were switched to olanzapine. The Positive and Negative Symptom Scale (PANSS), Geriatric Depression Scale (GDS) and Clinical Global Impression Severity (CGI-S) Scale were completed while patients were on their previous medication regimen and again 6 months after the last patient had been started on olanzapine. The mean duration of treatment was 289 d (S.D.=139). Three patients discontinued the medication. Mean end dose of olanzapine was 12.9 mg (S.D.=5.7). Paired sample t tests were used to test change on PANSS Positive, Negative and Total scales, CGI, GDS and body weight. PANSS (Positive, p=0.002; Negative, p=0.003; General, p=0.003; and Total, p=0.000) and CGI (p=0.000) but not the GDS (p=0.67) demonstrated statistically significant improvement. There was no significant change in body weight (p=0.61). Elderly patients with aggravation of chronic schizophrenia showed improvement after being switched to olanzapine with no weight gain. Clinically meaningful change was observed in positive and negative psychotic symptomatology but not in depressive symptoms.