Jonathan Rabinowitz

The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis

The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for measuring severe psychopathology in adult patients with schizophrenia. Data, primarily on chronic patients, have been used to define factors for the PANSS. The present study examines the PANSS factor structure in a large sample of subjects with recent-onset schizophrenia, schizophreniform disorder and schizoaffective disorder who had been exposed to very limited antipsychotic medication. Equamax factor analysis was conducted on PANSS baseline assessments from a multicenter, 11 country drug trial that enrolled 535 patients. The forced five-factor solution essentially corresponds to the factors most frequently described previously, namely negative, positive, disorganized (or cognitive), excited and anxiety/depression. In the exploratory analysis, a seven-factor solution was obtained, with depression and anxiety symptoms separating and a motor component emerging. The results of this study partially support the use of a five-factor model for the PANSS, but suggest that scales for catatonia, depressive and anxiety syndromes should be included in future studies.

Correlates of cognitive deficits in first episode schizophrenia.

OBJECTIVE The presence of cognitive dysfunction in schizophrenia has been well documented, but questions remain about whether there are relationships between this dysfunction and clinical symptomatology. If present, such relationships should be most clearly observable in patients with first episode schizophrenia; that is, before the effects of chronic illness, institutionalization, or treatment might confound them. METHOD 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone. The psychopathology, cognitive functioning, early treatment history, and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized, double-blind treatment. Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment; however, the duration of treatment was limited to 12 weeks or less. RESULTS The severity of negative symptoms at the time of assessment was associated with deficits in memory, verbal fluency, psychomotor speed and executive function. Positive symptoms were not associated with cognitive deficits. Also, the duration of untreated illness (DUI) prior to assessment was not significantly associated with cognitive impairment. CONCLUSIONS The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction. However, that relationship accounts for only a minor portion of the variance (i.e., 10-15%) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors. This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping.

Cognitive performance in schizophrenia patients assessed before and following the first psychotic episode

BACKGROUND The purpose of this historical prospective study was to follow the cognitive impairment in schizophrenia from the premorbid period until shortly after the onset of the first psychotic episode within the same subjects. METHODS Forty-four first episode schizophrenia patients were enrolled in the study. Their cognitive performance was assessed as part of the Israeli Draft Board aptitude assessments at ages 16-17, when all were found to be in good mental health (first assessment) and again, following the manifestation of the first psychotic episode (second assessment). Forty-four healthy comparisons were also enrolled and tested twice, at the same ages as the patients. Both times, the assessments included four subtests assessing abstract reasoning (Raven Progressive Matrices-R), mental speed and concentration (Otis-R), verbal reasoning (Similarities-R), and mathematical abilities (Arithmetic-R). RESULTS A within group analysis did not reveal statistically significant changes between the first and the second assessment among the schizophrenia patients on any measure. However, a between group comparison of changes showed that relative to the healthy comparisons, schizophrenia patients deteriorated on the RPM-R (p=0.021) and Otis-R (p<0.001), but not on the Similarities-R and Arithmetic-R. Schizophrenia patients performed worse than comparisons in all four subtests on the first and second assessments (all p<0.01). CONCLUSIONS The results indicate that most of the cognitive impairment exhibited by first-episode schizophrenia patients precedes the first psychotic episode. A decline between ages 16 and 17 and the onset of psychosis is evident in some but not all cognitive functions.

Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data.

Increased attention has been given to treatment of negative symptoms and its potential impact on functional outcomes, however previous inferences have been confounded by the fact that measures of functional outcomes often use items similar to those of negative symptoms. We attempted to discern the relative effects of negative symptoms on functioning, as compared to other symptoms, using data from the National Institute of Mental Health CATIE trial of chronic schizophrenia (n=1447) by examining correlations of Positive and Negative Syndrome Scale factors, Calgary Depression Rating Scale and select items from Heinrichs and Lehmans Quality of Life Scales measuring aspects of functioning that did not overlap with negative symptoms. Baseline functioning and change in functioning were more strongly related to PANSS negative factor than any of the other symptoms - though the amount of variance explained by symptom changes in general was small. The data suggests that improvement in negative symptoms may have a distinctive and independent effect on functional outcome relative to other symptoms. This should be further tested in studies where negative symptoms improve without concomitant improvement of other symptoms.

Correlates of insight in first episode psychosis

Impaired insight is common in schizophrenia and may be related to poor treatment adherence. Few studies have examined the clinical and neurocognitive correlates of insight in early schizophrenia. Early course schizophrenia, schizoaffective, and schizophreniform disorder patients (n=535) were studied. The Positive and Negative Symptom Scale (PANSS) was used to assess psychopathology, and a broad range of neuropsychological functions was assessed. Using hierarchical stepwise multiple regression analyses, we examined the association of clinical, neurocognitive, and premorbid measures with the level of insight. Impaired insight was associated with overall symptomatology, including positive, negative, and general psychopathology and with deficits in cognitive functioning. In descending order of robustness, the significant variables were PANSS general psychopathology (p<0.0001), Rey Auditory Verbal Learning Test (p<0.0004), Clinical Global Impression (p<0.005), PANSS positive (p<0.007), and premorbid adjustment-general subscale (p=0.02). Among the PANSS general psychopathology items, unusual thought content was most robustly associated with impaired insight (p<0.00000). Insight impairment is very common in early schizophrenia, and appears to be associated with a broad range of psychopathology and deficits in multiple cognitive domains. These observations suggest that deficits in insight may be related to a generalized dysfunction of neural networks involved in memory, learning, and executive functions.

Paternal age and intelligence: implications for age-related genomic changes in male germ cells.

Background A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. Objective An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. Method We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. Results A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parents age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for ∼2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. Conclusion We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

A population based elaboration of the role of age of onset on the course of schizophrenia

BACKGROUND Despite suggestions that an earlier age of onset and being male confer to a poorer course of schizophrenia, evidence regarding when these effects are most salient appears to be ambiguous. AIMS To examine the relationship of age of first hospitalization and sex with the course of hospitalization in a population based cohort. METHOD All first admissions for schizophrenia in a national population based cohort in Israel from 1978 to 1992 were followed through 1996 (n=12,071) using data from the National Psychiatric Hospitalization Case Registry of the State of Israel, a complete national registry of psychiatric admissions. Recursive partitioning was conducted to empirically determine cut-off points for age groups showing the greatest difference on the variables of interest. RESULTS A younger age of first hospital admission was associated with a greater likelihood of having more than one hospital admission, longer first admissions, more hospital admissions and more inpatient days per year. Of patients with age of first admission below 17, 82.5% had more than one admission which decreased for subsequent age groups to 73.54% (18-28), 69.36% (29-31), 62.88% (32-45), and 50.77% (over 45). Men had an earlier first admission than women, and had slightly more cut-off values. Irrespective of sex, the relationship between age at first admission and later hospitalization conformed to a linear trend. CONCLUSIONS An earlier onset corresponds linearly with the severity of the course of illness and appears to have prognostic value.

School-based obesity prevention programs: A meta-analysis of randomized controlled trials

Attempts have been made to reduce childhood obesity through school‐based programs. Systematic reviews of studies until 2006 reported a lack of consistency about effectiveness of such programs. Presented is an updated systematic review and meta‐analysis.

Hopelessness as a Predictor of Attempted Suicide among First Admission Patients with Psychosis: A 10-Year Cohort Study.

Little is known about the longitudinal relationship of hopelessness to attempted suicide in psychotic disorders. This study addresses this gap by assessing hopelessness and attempted suicide at multiple time-points over 10 years in a first-admission cohort with psychosis (n = 414). Approximately one in five participants attempted suicide during the 10-year follow-up, and those who attempted suicide scored significantly higher at baseline on the Beck Hopelessness Scale. In general, a given assessment of hopelessness (i.e., baseline, 6, 24, and 48 months) reliably predicted attempted suicide up to 4 to 6 years later, but not beyond. Structural equation modeling indicated that hopelessness prospectively predicted attempted suicide even when controlling for previous attempts. Notably, a cut-point of 3 or greater on the Beck Hopelessness Scale yielded sensitivity and specificity values similar to those found in nonpsychotic populations using a cut-point of 9. Results suggest that hopelessness in individuals with psychotic disorders confers information about suicide risk above and beyond history of attempted suicide. Moreover, in comparison with nonpsychotic populations, even relatively modest levels of hopelessness appear to confer risk for suicide in psychotic disorders.

Correlates of a perceived need for mental health assistance and differences between those who do and do not seek help

AbstractBackground: This study examined prevalence of perceived need for mental health assistance, characteristics of people with a perceived need, and how persons with a need who sought help were different from those who did not. Methods: A national random phone survey (n = 1,394) was conducted in Israel, which included questions about (1) perceived need for mental health assistance and (2) help seeking. Results: Prevalence of life-time and recent perceived need for males was 21% and 10.7%, and for females 31% and 15.1%. Of those with a perceived need, 31.4% of males and 41.6% of females had gone for help. Based on logistic regression models, the variables associated with need were being female, divorced, having a chronic physical disease, and low income (for males only), while predictors of help seeking were living in a big city and not being a recent immigrant. The major sources of help in descending order were: mental health professionals (46%), family physician (25%), family or friends (19%), and other (10%). Conclusions: A majority of people who feel that they need help for mental health problems do not get help.