Prolactin, subjective well-being and sexual dysfunction: an open label observational study comparing quetiapine with risperidone.

INTRODUCTION: Sexual dysfunction is a frequent side effect of antipsychotic treatment. Increased prolactin levels are believed to be responsible for this sexual impairment despite contradictory results. AIM: The primary objective of the present study was to examine the relationship between sexual dysfunction, subjective well-being and prolactin levels in patients with schizophrenia treated either with risperidone or quetiapine. The secondary objective was to explore the relationship between testosterone and the severity of positive and negative symptoms of schizophrenia in male patients. METHODS: In a 4-week nonrandomized open label observational study, 102 inpatients with schizophrenia were recruited. Sexual functioning, subjective well-being and endocrinological parameters were assessed as well as psychopathological characteristics. MAIN OUTCOME MEASURES: Two self-rating questionnaires concerned with sexual functioning ("Essener Fragebogen zur Sexualität") and Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) were completed by the patients. Plasma levels of prolactin in male and female patients were measured. Furthermore, in male patients testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined. Positive and Negative Symptom Scale (PANSS) was applied. RESULTS: After 4 weeks, patients treated with quetiapine reported less severe sexual impairment, as well as lower PANSS negative and general score compared with patients treated with risperidone. Additionally, emotional regulation as measured with the SWN was higher in patients treated with quetiapine. Risperidone was significantly associated with elevated prolactin levels. Prolactin levels were not correlated either with sexual dysfunction or PANSS. However, in the group of patients treated risperidone, sexual impairment was significantly associated with the SWN subscale emotional regulation. CONCLUSIONS: Increased prolactin levels do not seem to be decisive for antipsychotic induced sexual dysfunction. Improvement of severity of illness and regaining the ability to regulate one's own emotion have positive influence on sexual functioning.

Executive performance of depressed suicide attempters: the role of suicidal ideation.

OBJECTIVE: Suicidal ideation has been related to cognitive rigidity whereas suicidal behaviour itself was associated with specific executive deficits. Yet it remains unclear if a distinct cognitive suicidal phenotype does exist. The aim of the present study was to further investigate the role of suicidal thinking for the neuropsychological performance in depressive suicide attempters. METHOD: Depressive inpatients after a recent suicide attempt, who either had present suicidal ideation (n=14) or not (n=15) and healthy controls (n=29) were recruited. The groups were assessed by means of executive tasks designed to capture impulsive decision-making, and with verbal memory and attention tests. Self-rating measures of impulsivity and aggression were further applied. RESULTS: Only patients with current suicidal ideation showed executive dysfunctions with impaired decision-making being the most salient. Verbal memory and attention were reasonably intact in all patients. All patients reported increased aggression. CONCLUSION: Suicidal ideation is clearly associated with impaired cognitive performance. Our results suggest that executive deficits seen in depressive suicide attempters have a state-dependent component.

Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA ("Ecstasy").

RATIONALE: In animal studies, the common club drug 3,4-methylendioxymethamphetamine (MDMA, "Ecstasy") consistently caused a prolonged loss of presynaptic serotonergic neurons, and evidence suggests that MDMA consumption may also affect the human serotonergic system. Serotonin (5-HT) has been implicated in the regulation of impulsivity and such executive functions as decision-making cognition. In fact, MDMA users have shown elevated impulsivity in two studies, but little is known about decision making in drug-free MDMA consumers. OBJECTIVE: The aim of this study was to examine the cognitive neurotoxicity of MDMA with regard to behavioral impulsivity and decision-making cognition. METHODS: Nineteen male, abstinent, heavy MDMA users; 19 male, abstinent cannabis users; and 19 male, drug-naïve controls were examined with the Matching Familiar Figures Test (MFFT) as well as with a Go/No-Go Task (GNG) for impulsivity and with a Gambling Task (GT) for executive functioning. RESULTS: MDMA users showed significantly elevated impulsivity in the MFFT Impulsivity score (I-score), but not in commission errors of the GNG, compared with controls. Cannabis users did not yield altered impulsivity compared with controls. In the GT, MDMA users performed significantly worse than cannabis consumers and controls, whereas cannabis users exhibited the same decision-making capacity as controls. In addition, the I-score as well as the decision-making performance was correlated with measures of MDMA intake. The I-score and the decision-making performance were also correlated. CONCLUSION: These results suggest that heavy use of MDMA may elevate behavioral impulsivity and impair decision-making cognition possibly mediated by a selective impairment of the 5-HT system.

Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine.

BACKGROUND: Schizophrenic patients exhibit impairments in prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR). Recent studies suggested that PPI deficits and habituation deficits are normalized after antipsychotic treatment. Despite clear evidence of gating and habituation mechanisms in animal models, it is still unknown which neurotransmitter systems are involved in schizophrenic patients. Thus, we compared the effects of a combined 5-HT2A/D2 and a pure D2/D3 antagonist on PPI and habituation of ASR in patients with schizophrenia. METHODS: The ASR was measured in 37 acute schizophrenic patients who were randomized and double-blinded as to treatment with amisulpride or olanzapine. Patients were assessed during the first week and after four and eight weeks of treatment. Twenty healthy matched control subjects were examined likewise. RESULTS: Schizophrenic patients showed a significant PPI deficit and significantly decreased startle amplitude at baseline. The gating deficit disappeared after antipsychotic treatment in both treatment groups. Amisulpride sensitized the startle amplitude, whereas startle amplitude was not changed by olanzapine. After correcting for startle amplitude, patients did not show a habituation deficit; however, amisulpride accelerated habituation, whereas olanzapine had no effect. CONCLUSIONS: Our findings suggest that the PPI-restoring effect of antipsychotics is probably attributed to a dopamine D2 receptor blockade.

Normal prepulse inhibition and habituation of acoustic startle response in suicidal depressive patients without psychotic symptoms.

BACKGROUND: Until now, there is a lack of useful biological markers to predict suicidal behavior in depressive patients. However, it is consistently found that suicidality is associated with a central serotonin deficit. Animal data suggest that prepulse inhibition (PPI) as well as habituation of the acoustic startle response (ASR), which are established as operational measures for sensorimotor gating, decreases after serotonin depletion. Thus, we investigated PPI and habituation of ASR in suicidal patients with depressive disorders as potential biological markers for suicidal behavior. METHODS: PPI and habituation of ASR was measured in 20 depressive patients who had at least one suicide attempt within the last three month. Eighteen healthy matched controls were examined likewise. RESULTS: Suicidal depressive patients did not differ from healthy controls in PPI, startle reactivity and habituation of ASR. Subgroup analyses showed that factors such as severity of depression, impulsiveness, gender, smoking, lethality of the last suicide attempt, number of suicide attempts, and medication had no influence on the results. CONCLUSIONS: These results suggest that neither PPI nor habituation of ASR could serve as useful markers for suicidality.

Attenuation of the prepulse inhibition of the acoustic startle response within and between sessions.

Prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR) are widely used biological markers in the study of psychiatric disorders and have been shown to be homologous across species. Previous studies in humans suggested that PPI is a stable and reliable measure between test sessions, but that PPI decreases within sessions. The purpose of this study was to explore the short- and long-term decrease in PPI as a potential confound in the measurement and interpretation of PPI. We investigated the progression of PPI and habituation of ASR in three test sessions spaced 4 weeks apart in a group of 20 healthy participants. Analysis revealed a significant decrease in the percent PPI within and between the test sessions. Nevertheless, PPI was reliable across three test sessions, indicating that the significant attenuation of PPI over time was a consistent phenomenon. These results suggest that PPI exhibits short- and long-term attenuation.

Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.

Combined serotonin-2A (5-HT(2A)) and dopamine-2 (D2) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D2/D3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT(2A)/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs.

Clozapine: acquittal of the usual suspect.

This report concerns the case of a 29-year-old male patient suffering from severe psychotic illness who had been satisfactorily treated with clozapine for 4 months. Clozapine had also been successfully administered during a psychotic episode 5 years previously. Though symptoms of psychosis were successfully controlled following the most recent psychotic episode, a medical consultation assessed that exacerbation of pancreatitis warranted discontinuation of the current antipsychotic treatment regime. Following a series of unsuccessful courses of neuroleptic medication, a magnetic resonance cholangiopancreaticography (MRCP) revealed marked cholecystolithiasis suggesting a biliary pancreatitis. Clozapine treatment was readministered following cholecystectomy. After 4 weeks of antipsychotic treatment the patient was discharged from hospital on clozapine monotherapy.

Neuropsychological performance in partly remitted unipolar depressive patients: focus on executive functioning.

BACKGROUND: Only few studies have investigated executive impairment in the euthymic phase of unipolar affective disorders, yielding diverging results. The role of impulsivity/orbitofrontal associated executive functioning in remitted depression has not yet been examined. METHODS: Partly remitted male out-patients (n = 15) with non-psychotic major depression (MDD) were compared with healthy males (n = 15) on several neuropsychological tests. Executive tasks focussed on orbitofrontal function (Go/No-Go, Iowa Gambling Task (IGT), delayed alternation task). Furthermore, the Barratt Impulsiveness Scale (BIS-11) was administered to all subjects. RESULTS: Executive skills of the patients were largely unimpaired. Patients exhibited significant deficits on measures of verbal memory only. Residual depressive symptoms in patients were correlated with diminished response inhibition. BIS-11 scores were not elevated in the patients. CONCLUSIONS: Both executive impairment related to orbitofrontal function and self-reported impulsive behaviour in major depression seem to be state-dependent. In accordance with other studies, patients with remitted unipolar depression showed a persistent verbal memory loss.