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OBJECTIVE: The complex composition-activity relationship of botanicals such as St John's Wort (SJW) presents a major challenge to product development, manufacture, and establishment of appropriate quality and performance standards for the formulated products. As part of a larger study aimed at addressing that challenge, the goals of the present study are to (1) determine and compare the phytochemical profiles of 3 commercial SJW extracts; (2) assess the possible impact of humidity, temperature, and light on their stability; and (3) evaluate several physical properties important to the development of solid dosage forms for these extracts. METHODS: An adapted analytical method was developed and validated to determine phytochemical profiles and assess their stability. The extract physical properties measured were particle size (Malvern Mastersizer), flow (Carr's compressibility index; minimum orifice diameter), hygroscopicity (method of Callahan et al), and low-pressure compression physics (method of Heda et al). RESULTS: The phytochemical properties differed greatly among the extracts and were extremely sensitive to changes in storage conditions, with marked instability under conditions of elevated humidity. All extracts exhibited moderate to free-flow properties and were very hygroscopic. Compression properties varied among the extracts and differed from a common use excipient, microcrystalline cellulose. CONCLUSIONS: Three commercial sources of SJW extracts exhibited different physical and chemical properties. Standardization to 1 or 2 marker compounds does not ensure chemical equivalence nor necessarily equivalent pharmacological activity. Flow and compression properties appear suitable for automatic capsule-filling machines, but hygroscopicity and the moisture sensitivity of the phytochemical profile are concerns.

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Research has not consistently indicated that negative symptoms in schizophrenia are temporally stable. One possible explanation for this is that stable negative symptoms are a characteristic of only some individuals with schizophrenia. The current study explored whether cognitive impairment and stimulant abuse history were associated with amount of change in negative symptom level over a 1-year period. Results indicated that among 72 subjects with schizophrenia, performance on the Wisconsin Card Sorting Test and history of stimulant abuse significantly accounted for 18% of the variance in symptom variability after age, intelligence quotient, and initial symptom severity were controlled. As hypothesized, poorer performance on the Wisconsin Carding Sorting Test was associated with less symptom variability, whereas a more extensive stimulant abuse history was associated with greater variability. A discriminant function analysis was able to correctly classify 96% of subjects as having stable symptoms but only 30% as having unstable symptoms indicating a sensitive, but not specific, classification. This finding suggests that cognitive deficits may be a necessary but insufficient condition for temporal stability of negative symptoms and that negative symptoms in schizophrenia are a complex phenomenon best understood in the context of other features of illness and psychosocial variables.

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While the impact of social learning programs upon social deficits in schizophrenia has been widely studied, less is understood about which patients have the poorest social skills, and among those which patients have deficits most refractory to rehabilitation. To explore these questions, this study compared the symptom levels and performance on neuropsychological testing of 91 subjects with impaired and unimpaired social skills enrolled in a vocational rehabilitation program. After 10 weeks of rehabilitation and a supportive group treatment, social skills among a subsample of 41 subjects with initially impaired social skills were reassessed. Results indicate that subjects with initially impaired social skills had significantly higher levels of negative symptoms. However, multiple regression analysis revealed that cognitive impairments at intake, rather than level of negative symptoms, predicted improvement among subjects with initially impoverished social skills (R2 = .35). Results suggest that level of cognitive impairment is associated with the persistence of social skills deficits in schizophrenia.

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Weekly assessments of depression, anxiety, and positive and negative symptoms were performed on 80 subjects with schizophrenia or schizoaffective disorder. Using procedures previously reported in another study, the frequency of significant correlations between the sum of anxiety and depression ratings and positive symptoms was compared with the frequency of significant correlations between the sum of anxiety and depression ratings and negative symptoms. Results confirm that dysphoria in schizophrenia tends to be more frequently associated with positive versus negative symptoms, regardless of diagnostic subtype or symptom type. This provides further evidence of the independence of negative symptoms from dysphoria and suggests that the level of positive symptoms and level of dysphoria may mutually influence one another.

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