Dieter Naber

The impact of substance use disorders on clinical outcome in 643 patients with first-episode psychosis.

Objective:  Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross‐sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms.

Current Issues in Schizophrenia: Overview of Patient Acceptability, Functioning Capacity and Quality of Life

The increasing interest in the subjective wellbeing and quality of life (QoL) of patients with schizophrenia represents a conceptual extension of therapeutic outcome criteria. For a long time, the reduction of positive symptoms alone was the most important outcome parameter, but the development of atypical antipsychotic drugs in the early 1990s resulted in the adoption of more wide-reaching measures of therapeutic outcome. Patient satisfaction appears to be strongly related to their willingness to be or stay engaged in psychosocial and pharmacological treatment, and therefore to the symptomatic and functional outcome. Existing studies that deal with QoL and subjective wellbeing differ in their methodology and are difficult to compare because of varying underlying concepts of QoL or subjective wellbeing, different assessment scales or small sample sizes. Although QoL is a heterogeneous concept, it is clearly correlated with a number of factors, including illness, medication and stress process-related variables. Various protective factors have been identified; among these are personality traits, the degree of social support and treatment interventions. In clinical studies, atypical antipsychotic agents are associated with greater improvements in QoL and subjective wellbeing than are conventional agents. The reason for this is probably the ability of atypical agents to have a positive impact on factors most associated with QoL, such as negative and affective symptoms and drug tolerability. The most appropriate clinical approach to maximize QoL and subjective wellbeing for patients with schizophrenia is to use atypical antipsychotic drugs as a first-line treatment approach. Ideally, an atypical drug which is known not to have a negative effect on attention, affect or motivation should be chosen.

Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment. A prospective study

Corticosteroids often induce a variety of psychiatric symptoms, such as alterations of mood, neuropsychological deficits and even psychotic states. To date, only a few studies have specifically addressed behaviour as well as cognitive functioning in patients under steroid treatment. Fifty ophthalmologic patients participated in this prospective study. They received methylprednisolone or fluocortolone at doses of 119 +/- 41 mg/day in the beginning and 75 +/- 22 mg after 8 days of treatment. Psychopathology and neuropsychological functioning were examined before and after steroid therapy, mood was self-rated on days 0, 3, 5 and 8. No marked psychopathological abnormalities such as psychosis, dementia or delirious states were observed. However, a significant proportion of patients suffered from an organic mood disorder, 26-34% experienced a hypomanic syndrome, 10-12% a depressive syndrome. Most neuropsychological tests did not reveal significant effects of steroid treatment. Performance of Word Fluency and Trail Making A improved, while the Auditory-Verbal-Learning and the Digit-Symbol showed a worsening. Psychopathological and neuropsychological effects were not significantly correlated.

Memory and attention performance in psychiatric patients: Lack of correspondence between clinician-rated and patient-rated functioning with neuropsychological test results

In the present study, the correspondence between clinician-assessed and self-reported neurocognitive performance was contrasted with scores obtained from psychometric neuropsychological tests in 148 psychiatric in-patients. Results revealed that self-reported cognitive functioning was strongly associated with depressive symptomatology but was only poorly related to psychometric neurocognitive performance, particularly in schizophrenia. After illness denial was controlled for, the overall association between subjective and objective test performance was slightly increased but still failed to reach significance in six out of eight analyses. In approximately 20% to 40% of all cases, clinicians judged memory performance to be normal despite substantial impairment revealed by neuropsychological test results (attention parameters: 7-51%). Since (ecological) validity and reliability have been demonstrated for many neurocognitive paradigms, the present results question the validity of non-psychometric neurocognitive assessment and call for a complementation of clinical judgment with neurocognitive assessment. Reasons for decreased sensitivity of self-reported and clinician-assessed neurocognitive functioning are discussed.

Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor.

IN the present study we tested the hypothesis that individual response to clozapine treatment and/or the occurrence of side-effects may be influenced by genetic variation in the serotonin 5-HT2C receptor. We investigated the frequency of a common Cys23Ser substitution, which is known to alter the pharmacological properties of the protein, in 152 patients treated with clozapine. Presence of the Ser23 variant was previously reported to predict a good response to clozapine. However, our results did not support an association between genetic variation of the 5-HT2C receptor and response to clozapine. This held true whether the patients were subgrouped for sex and length of treatment. Moreover, we found no consistent association with any of the observed side-effects.

Rates and predictors of remission and recovery during 3 years in 392 never-treated patients with schizophrenia

Objective:  Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia.

Circadian and seasonal rhythms in α- and β-adrenergic receptors in the rat brain

Summary Circadian rhythms in the numbers of α- and β-adrenergic receptors exist in the rat forebrain and hypothalamus. These rhythms are endogenous as they persist in the absence of time cues. The α- and β-receptor rhythms differ both in their shapes (wave form) and in the timing (phase) of the peak numbers. In the course of the year, there are shifts in the timing of both α- and β-receptor peaks. Circadian rhythms in α- and β-adrenergic receptors may modulate synaptic events in brain transmission, synchronizing both the synaptic events and the behaviors related to them to the photoperiod of the natural environment.

Circadian rhythm in rat brain opiate receptor.

To investigate diurnal variations in opiate receptor binding, the amount of specifically bound [3H]naloxone was measured at 4-h intervals across a 24-h period in the forebrains of rats that had been housed under a controlled light--dark cycle (lights on from 07.00 to 19.00 h) for 3 weeks. A significant rhythm with a peak at 22.00 h was found, the amplitude was 46--78%. In the absence of time cues, this circadian rhythm persisted with a peak at 02.00--06.00 h and an amplitude of 88%. Scatchard analysis indicated that the differences in binding throughout the day were due not to changes in affinity, but to changes in the number of binding sites.

Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results.

Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia. We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year prospective, observational study in outpatients with schizophrenia in 10 European countries. Patients (n=7728) who started antipsychotic monotherapy were analyzed. Medication discontinuation for any cause ranged from 34% and 36% for clozapine and olanzapine, respectively, to 66% for quetiapine. Compared to olanzapine, the risk of treatment discontinuation before 36 months was significantly higher for quetiapine, risperidone, amisulpride, and typical antipsychotics (oral and depot), but similar for clozapine. Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia, whereas higher symptom severity, treatment with mood stabilizers, substance abuse, having hostile behaviour were associated with lower medication maintenance. Antipsychotic maintenance in SOHO was higher than the results of previous randomized studies.

Dopamine receptor binding in rat striatum: ultradian rhythm and its modification by chronic imipramine.

To investigate diurnal variations in dopamine receptor binding, the amount of specifically bound 3H-spiroperidol was measured at 4-h intervals over a 24-h period in the striatum of rats which had been housed under a controlled 12-h light-dark cycle (lights on 7 a.m.). A highly significant ultradian rhythm with peaks at 2 a.m. and 2 p.m. was found with an amplitude of about 75%. Chronic imipramine modified the rhythm such that the two peaks occurred 4 h later and amplitude as well as 24-h mean of binding decreased. Scatchard analysis at times of least and greatest binding indicated that the differences in binding were due not to changes in the affinity, but in the number of binding sites. These results are interpreted with regard to the mode of action of psychoactive drugs and to postulated changes of receptor sensitivity in neurological and psychiatric disorders.