Lou Ann McAdams

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out‐patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out‐patients meeting DSM‐III‐R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi‐automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/ cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Functioning and Well-Being of Middle-Aged and Older Patients with Schizophrenia: Measurement with the 36-Item Short-Form (SF-36) Health Survey

OBJECTIVE The authors compared the subjective functioning of 137 middle-aged and elderly outpatients with schizophrenia or schizoaffective disorder with that of 77 normal subjects, using the Medical Outcomes Study (MOS) 36-Item Short Form (SF-36) Health Survey. The SF-36 is a generic outcome measure that provides a profile of functioning in several different domains. METHODS Measures included the MOS-SF-36, along with standardized instruments for assessing psychopathology, cognition, dyskinesia, quality of well-being, and everyday functioning. RESULTS Schizophrenia patients reported greater disability than normal subjects in all areas (mental and physical) assessed by the SF-36 except for bodily pain. Logistic-regression analysis suggested that the best predictors for being in the schizophrenia group were 1) physical and emotional functioning and 2) pain. Among patients, age at onset of illness, depressive symptoms, and cognitive functioning predicted 39% of the variance in the SF-36 Mental Health Composite score. CONCLUSIONS Subjective functioning of older people with schizophrenia is affected by perceived physical health, depressive symptoms, and cognitive impairment.

Minor Physical Anomalies in Older Patients With Late-Onset Schizophrenia, Early-Onset Schizophrenia, Depression, and Alzheimer's Disease

The authors assessed five groups of older subjects (age > 45) for evidence of minor physical anomalies. The groups were patients with early-onset schizophrenia (onset at age < 45; n = 15), late-onset schizophrenia (onset at age > 45; n = 8), Alzheimers disease (AD; n = 11), and unipolar depression (n = 11), and normal comparison (NC) subjects (n = 15). Patients with late- and early-onset schizophrenia, and unipolar depression were found to have significantly more anomalies than NC subjects. Patients with AD did not have significantly more anomalies than NC subjects, although the patients with AD were significantly older than the NC subjects. The authors discuss implications of these findings on the pathophysiology of schizophrenia.

Neuroleptic treatment of HIV-associated psychosis

The aim of this rater-blinded randomized study was to evaluate the efficacy and side effects of haloperidol and thioridazine in the treatment of new-onset psychosis in HIV-positive individuals. Participants were 13 men who had no history of psychosis prior to infection with HIV, and whose psychosis was not attributable to delirium or to non-HIV-related organic factors. Participants were evaluated at baseline after at least one month without neuroleptic treatment and then weekly for six weeks of the experimental treatment using several rating scales. The mean daily dose in chlorpromazine equivalents was 124 mg. Both neuroleptics produced modest but significant reduction in overall level of psychosis and in positive symptoms, but not in negative symptoms. All the haloperidol-treated patients developed extrapyramidal side effects and required treatment with anticholinergic medication, whereas three of the five thioridazine-treated patients had noticeable side effects. We make recommendations for the treatment of HIV-associated psychosis with neuroleptics.

Risk factors for orofacial and limbtruncal tardive dyskinesia in older patients: a prospective longitudinal study

Although there is a consensus that orofacial and limbtruncal subtypes of tardive dyskinesia (TD) exist and may represent distinct pathophysiologic entities, few studies have examined the incidence of and risk factors associated with the development of these TD subtypes. Two hundred and sixty-six middle-aged and elderly outpatients with a median duration of 21 days of total lifetime neuroleptic exposure at study entry were evaluated at 1- to 3-month intervals. Using “mild” dyskinesia in any part of the body for diagnosis of TD, the cumulative incidence of orofacial TD was 38.5 and 65.7% after 1 and 2 years, respectively, whereas that of limbtruncal TD was 18.6 and 32.6% after 1 and 2 years. Preclinical dyskinesia was predictive of both orofacial and limbtruncal TD. History of alcohol abuse or dependence was a significant predictor of orofacial TD only whereas tremor was a significant predictor of limbtruncal TD only. Findings support suggestions that orofacial and limbtruncal TD may represent specific subsyndromes with different risk factors.

Validation of the Scale of Functioning in Older Outpatients With Schizophrenia

The authors investigated the reliability and validity of the Scale of Functioning (SOF), a 15-item scale, in 78 middle-aged and elderly outpatients with schizophrenia. The SOF score had both high internal consistency and high interrater reliability and significantly discriminated between these patients and 45 normal comparison subjects. SOF scores correlated significantly with scores on several psychopathology rating scales as well as a number of existing instruments assessing cognitive or functional ability. Principal-components analysis using different scales of functional ability, psychopathology, and global cognitive performance and treated by orthogonal rotation revealed two domains of functioning, one of which was defined by the SOF along with scales for activities of daily living, negative symptoms, and cognitive impairment. The other domain was defined by scales for quality of well-being, social adjustment, and positive and depressive symptoms. Results support the construct validity of the SOF in late-life schizophrenia.

Personality profiles among normal aged individuals as measured by the NEO-PI-R

Abstract The revised Neuroticism (N), Extraversion (E), Openness (O) to experience Personality Inventory (NEO-PI-R) is a multidimensional measure of normal personality traits that is intended to assess five major personality dimensions or domains—N, E, O, Agreeableness (A), and Conscientiousness (C). Although several studies have been conducted examining N; E, and O factors in people 65 through to 85 years old, there has been little research examining all five-core domains of personality in individuals 85 and older. We compared the NEO-PI-R domains and facet traits in the middle-aged/young-old versus old-old normal subjects. Thirty-eight community-dwelling subjects (22 women, 16 men) free from major neuropsychiatric disorders were given the NEO-PI-R, a self-administered 240-item personality inventory, assessing 30 facet traits within the five domains. We compared the scores of 21 middle-aged and young-old (age 50–84) individuals, to those of 17 old-old (age 85–100) subjects. The personality profiles of the two groups were similar except that the old-old group had lower scores on Extraversion, and four of the 30 facet traits (warmth, positive emotions, impulsiveness, and order) compared to the middle-aged/young-old group. These results were limited by the cross- sectional design and small sample size. Nonetheless, the findings suggest that the middle-aged/young-old and the old-old normal subjects have fairly similar personality traits.

Cognitive performance and mood in patients with chronic insomnia during 14-day use of flurazepam and midazolam.

The 99 chronic insomniacs examined in the present multicenter study were given three cognitive tasks (reading comprehension, addition, and digit symbol substitution test [DSST]) as well as the Hopkins Symptom Checklist (HSCL) and the Profile of Mood States (POMS) in order to evaluate the effects of flurazepam (Dalmane) 15 and 30 mg, midazolam 15 mg, and placebo on cognitive performance and mood. Subjective evaluation of performance was also obtained. A significant person in the patients life was also asked to evaluate the patients mood before and during the 14-day treatment interval. After a 20-day washout, next-day performance and mood were evaluated after placebo nights -1 and 0 (baseline) and after treatment nights 1, 2 (early interval), 7 (middle interval), and 13 and 14 (late interval). Analysis of variance (ANOVA) on changes from baseline indicated no significant between-groups treatment effects for reading comprehension or any of the mood variables at any interval. Patients on flurazepam 30 mg performed less well compared with other groups even though, after completion of the tasks, this group believed that they performed as well as those on the other regimens. Performances by flurazepam 15 mg, midazolam, and placebo groups were similar. Significant others tended to rate high-dose flurazepam patients more negatively. High-dose flurazepam patients had a significant change on the DSST and addition tasks due to treatment after the first night, and change in performance remained significantly impaired for the DSST task relative to that of the other groups thereafter.

Validating specific psychopathology scales in older outpatients with schizophrenia.

To our knowledge, there have been no published studies validating commonly used psychopathology rating scales in older outpatients with schizophrenia. We studied specific psychopathology rating scales (three subscales of the Brief Psychiatric; Rating Scale: positive symptoms, negative symptoms, and depression subscales; the Scale for the Assessment of Positive Symptoms; the Scale for the Assessment of Negative Symptoms; and the Hamilton Depression Rating Scale) in 101 older (age > 45 years) DSM- III-R-diagnosed schizophrenia outpatients. We found high interrater reliability (intra-class correlation coefficient >.77) on these scales. Using principal components analysis, we demonstrated satisfactory construct validity, suggesting three factors—positive symptoms, negative symptoms, and depressive symptoms.

Validity of specific subscales of the positive and negative symptom scales in older schizophrenia outpatients

We investigated the construct validity of subscales of the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) along with other measures of psychopathology in 109 schizophrenia outpatients aged 45-84 years. Scores on subscales of the SAPS, SANS and Brief Psychiatric Rating Scale (BPRS) and on the Hamilton Depression Scale (HAM-D) were subjected to a principal components analysis and orthogonal rotation followed by an extension analysis. In both analyses, three of four SAPS subscales had their highest loading on the positive symptom factor and four of five SANS subscales had their highest factor loading on the negative symptom factor. The SAPS bizarre behavior subscale, however, had a much higher loading on the depressive symptom factor than on the positive symptom factor, and the SANS avolition-apathy subscale had moderate loadings on both the negative symptom factor and the depressive symptom factor. The use of SAPS and SANS subscales to represent two constructs was largely (but not entirely) validated among middle-aged and elderly schizophrenia outpatients. The SAPS bizarre behavior subscale and, to a lesser extent, the SANS avolition-apathy subscale appear to represent in this older population a separate construct which may be related to depressive symptoms.