Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome.

OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome. METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response. RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment. CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning.

Noradrenergic dysfunction and antidepressant treatment response.

The purpose of this study was to investigate differences in outcome following treatment with two different antidepressants in depressed patients according to their pretreatment hormonal response to clonidine. In all, 62 drug-free DSM-IV recurrent major depressed patients and 20 normal controls were studied. Patients were subsequently treated for 4 weeks with fluoxetine (n=28), or amitriptyline (n=34), and were then classified as responders or nonresponders according to their final Hamilton depression scale score. Compared to controls, depressed patients showed lower GH response to CLO (DeltaGH) (P<0.0002). One control (5%) and 35 depressed patients (56%) had blunted DeltaGH values. The efficacy of the two antidepressants was not significantly different: 15 patients responded to AMI (44%), seven patients responded to FLUOX (25%) (P>0.15). However, in the subgroup of patients with blunted DeltaGH levels, the rate of responders was higher for AMI (11/21) compared to FLUOX (1/14) treated patients (P<0.01). These results suggest that in depressed patients a blunted GH response to CLO could predict antidepressant response.

Spiking fevers with clozapine treatment.

Clozapine often causes low-grade fever and less frequently spiking fever. We describe three cases of spiking fever that occurred in the first 3 weeks of clozapine therapy. A new set of side effects of clozapine is identified, which includes spiking fever, respiratory and gastrointestinal symptoms, and neutrophilia. Possible mechanisms are discussed.

Prolactin response to D-fenfluramine and suicidal behavior in depressed patients.

Previous studies of the prolactin response to D-fenfluramine in depressed patients have yielded inconsistent results. This may be because they did not address the question of suicidality. We carried out this study to test the hypothesis that lower prolactin response to D-fenfluramine is more closely associated with suicidal behavior than with depression itself. A D-fenfluramine test was performed in a sample of 18 healthy control subjects and in 85 drug-free inpatients with a DSM-III-R diagnosis of major depressive episode (49 with a history of suicide attempt, 36 without). Depressed inpatients with a history of suicide attempt showed a significantly lower prolactin response to D-fenfluramine compared to depressed inpatients without such a history and compared to control subjects. Healthy control subjects and depressed inpatients without a history of suicide attempt showed comparable levels of prolactin after D-fenfluramine. Time elapsed since suicide attempt did not influence prolactin level (baseline or post-stimulation). Results show that in our depressed drug-free inpatient sample, prolactin response to D-fenfluramine seems to be a marker of suicidality, but not of depression itself. We suggest that it is a trait marker of suicidality.

[Personality changes in opioid-dependent subjects in a methadone maintenance treatment program]. / Changements psychologiques au cours d'un traitement de substitution de méthadone, mesurés par l'Inventaire de Personnalité d'Eysenck.

Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups.

[The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests]. / Impact d'un traitement de substitution par méthadone sur des sujets dépendants aux opiacés évalué par l'Addiction Severity Index et des contrôles urinaires.

Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. MMT has been developed in France since 1995, and over 5 000 patients receive this treatment. However no French study has yet been published on the efficacy of MMT as assessed by a validated scale. Retention in treatment for one year has been considered as a threshold to define maintenance of treatment benefits after discharge from a methadone program; determination of retention predictors is important. Over a three year period, we evaluated patients at admission and during treatment using the Addiction Severity Index (ASI), and urine drug screening was performed weekly; 95 patients (66 males and 29 females) were evaluated at intake. Their mean age was 30.2 5.5, and they had used opioids for a mean of 10.6 5.7 years. Their ASI severity scores for drugs were over 5, showing a clear need for treatment. Female patients differed from males only in the employment-finances ASI score; 43 patients completed at least one year of treatment, after which their drug and legal composite scores significantly improved. No significant changes in their consumption of cocaine, alcohol, benzodiazepines or cannabis were found, but they smoked fewer cigarettes at 12 months. Demographics, ASI severity scores, and history of suicide attempts did not differentiate one-year completers from dropouts (n=16). However, dropouts had used more buprenorphine and less methadone in the 30 days preceding their admission, and they received a lower dose of methadone during treatment. Our population is comparable to other French MMT populations; they enter treatment after a long history of opioid dependence. The improvement found on the ASI composite scores is also similar to the improvement described in other international studies. Dropouts in our study seem to be more treatment-resistant patients, in the sense that they had used more buprenorphine before intake and were not stabilized with it; and they may have had a more negative attitude towards methadone.

Forming first impressions of others in schizophrenia: impairments in fast processing and in use of spatial frequency information.

Individuals form first impressions of others all the time, which affects their social functioning. Typical adults form threat impressions in faces with neutral expressions quickly, requiring less than 40 ms. These impressions appear to be mediated by low spatial frequency (LSF) content in the images. Little is known, however, about mechanisms of first impression formation in schizophrenia. The current study investigated how quickly individuals with schizophrenia can form consistent impressions of threat compared with controls and explored the mechanisms involved. Patients and controls were presented intact, LSF- or high spatial frequency (HSF)-filtered faces with durations that varied from 39 to 1703 ms and were asked to rate how threatening each face was on a scale from 1 to 5. In order to assess the speed of impression formation for intact faces, correlations were calculated for ratings made at each duration compared to a reference duration of 1703 ms for each group. Controls demonstrated a significant relation for intact faces presented for 39 ms, whereas patients required 390 ms to demonstrate a significant relation with the reference duration. For controls, LSFs primarily contributed to the formation of consistent threat impressions at 39 ms, whereas patients showed a trend for utilizing both LSF and HSF information to form consistent threat impressions at 390 ms. Results indicate that individuals with schizophrenia require a greater integration time to form a stable "first impression" of threat, which may be related to the need to utilize compensatory mechanisms such as HSF, as well as LSF, information.

Enantioselective analysis of methadone in sweat as monitored by liquid chromatography/ion spray-mass spectrometry.

In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples, such as sweat. In a study conducted during a methadone maintenance program, PharmChek sweat patches were applied to 20 subjects. The subjects were orally administered methadone in 1 dosage/day, and doses ranged from 80 to 100 mg. The sweat patch was applied 10 minutes before administration and removed 72 hours later just before a new administration of methadone. The absorbent pad was stored at -20 degrees C until analysis in plastic tubes. Methadone was extracted in 5 ml methanol in presence of 200 ng of racemic methadone-d3, used as internal standard. After a 30-minute agitation, the methanol solution was evaporated to dryness. Enantioselective separation of methadone was obtained using an alpha-1-acid glycoprotein column (100 x 4 mm ID) and liquid chromatography/ion spray-mass spectrometry. In all 20 specimens obtained from subjects under racemic methadone treatment, R- (the active form) and S-enantiomers of methadone were identified with the following concentrations: 26 to 1118 ng/patch for R-methadone and 28 to 1114 ng/patch for S-methadone. The ratio between R- and S-methadone was in the range of 0.72 to 2.66 and was higher than 1.00 in 15 samples. No correlation between the doses of methadone administered and the concentrations of methadone in sweat was observed.