Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical recommendations.

With the widespread use of atypical or second-generation antipsychotics, switching treatment has become current practice and more complicated, as the pharmacological profiles of these agents differ substantially despite their similarity in being 'atypical'. All share the ability to block dopamine D₂ receptors, and most of them also block serotonin 5-HT2A receptors. Apart from these common features, some atypical antipsychotics are also able to block or stimulate other dopamine or serotonin receptors, as well as histaminergic, muscarinergic or adrenergic receptors.

Verbal memory deficits are correlated with prefrontal hypometabolism in (18)FDG PET of recreational MDMA users.

Introduction: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users.

N-acetylaspartylglutamate (NAAG) and N-acetylaspartate (NAA) in patients with schizophrenia.

Unlabelled: BACKGROUND : Imbalance of glutamatergic neurotransmission has been proposed as a key mechanism underlying symptoms of schizophrenia. The neuropetide N-acetylaspartylglutamate (NAAG) modulates glutamate release. NAAG provides a component of the proton magnetic resonance spectrum (1H-MRS) in humans.

The schizophrenia risk allele C of the TCF4 rs9960767 polymorphism disrupts sensorimotor gating in schizophrenia spectrum and healthy volunteers.

In a large-scale meta-analysis, it has been recently shown that the transcription factor 4 (TCF4) gene is among the most prominent susceptibility genes for schizophrenia. Moreover, transgenic mice overexpressing TCF4 in the brain display a reduction of sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is heritable and has been established as an important translational endophenotype of schizophrenia.

Predictors of response and remission in the acute treatment of first-episode schizophrenia patients--is it all about early response?

Background: To evaluate the predictive validity of early response compared to other well-known predictor variables in acutely ill first-episode patients.

Methods: 112 patients were treated with a mean dosage of 4.14 mg (±1.

Resting-state perfusion in nonmedicated schizophrenic patients: a continuous arterial spin-labeling 3.0-T MR study.

Purpose: To determine whether well-described patterns of altered perfusion in schizophrenia can be identified by using continuous arterial spin labeling (CASL) with a whole-brain imaging sequence.

Materials And Methods: This study was approved by the ethics committee of the local institutional review board, and written informed consent was obtained from all subjects. CASL was used to compare cerebral perfusion between 11 nonmedicated patients with schizophrenia and 25 healthy control subjects.

Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.

Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits.

Quality of life and subjective well-being in schizophrenia and schizophrenia spectrum disorders: valid predictors of symptomatic response and remission?

Objectives: To examine quality of life and subjective well-being as predictors of symptomatic treatment outcome.

Methods: Biweekly PANSS ratings were performed in 285 inpatients with schizophrenia spectrum disorders within a multicenter trial by the German Research Network on Schizophrenia. Quality of life and subjective well-being were assessed using the Medical Outcomes Study-Short Form 36-Item Health Survey (SF-36), the Subjective Well-being Under Neuroleptic Treatment Scale (SWN-K) and the Adjective Mood Scale (AMS).

A coding variant of the novel serotonin receptor subunit 5-HT3E influences sustained attention in schizophrenia patients.

Sustained attention as measured by the Continuous Performance Test (CPT) has proved a valuable endophenotype for schizophrenia. Recently pharmacological studies suggested a role of the serotonin (5-HT) 3 receptor in schizophrenia. The 5-HT3 receptors are the only ligand-gated ion channels within the 5-HT receptor family.

Influence of 5-HT3 receptor subunit genes HTR3A, HTR3B, HTR3C, HTR3D and HTR3E on treatment response to antipsychotics in schizophrenia.

Objectives: Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion channel. 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients. Moreover, many antipsychotic drugs are antagonists at 5-HT3 receptors.

DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis.

The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the D-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis.

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.

Functional serotonin 1A receptor variant influences treatment response to atypical antipsychotics in schizophrenia.

The serotonin (5-HT) 1A receptor has been found to be dysregulated in prefrontal cortex and other brain regions in schizophrenia, and 5-HT1A receptor levels in the amygdala have been related to negative schizophrenia symptoms. We have assessed the impact of the functional C-1019G variant of the 5-HT1A receptor on the response to risperidone or haloperidol in a prospective, randomized, double-blind study. Patients were treated for 4 weeks and negative symptoms assessed weekly.

Sensorimotor gating of schizophrenia patients depends on Catechol O-methyltransferase Val158Met polymorphism.

It has been recently shown that Catechol O-methyltransferase (COMT) Val(158)Met polymorphism strongly influences prepulse inhibition (PPI) of the acoustic startle response (ASR) in healthy human volunteers. Given that schizophrenia patients exhibit impairment in PPI and that COMT is a putative susceptibility gene for schizophrenia, we investigated the impact of the COMT Val(158)Met polymorphisms on PPI in schizophrenic inpatients. We analyzed COMT Val(158)Met polymorphisms and assessed startle reactivity, habituation, and PPI of ASR in 68 Caucasian schizophrenia inpatients.

Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia.

In recent years, evidence has been accumulating indicating a major role of glutamate in the pathogenesis and pathophysiology of schizophrenia. Of particular importance in this regard are the metabotropic glutamate receptors (GRM). Thus, a recently published trial of the amino acid analogue LY2140023, which exerts its effects through the activation of the glutamate receptors GRM3/GRM2, showed an improvement of positive and negative symptoms comparable to treatment with olanzapine.

Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia.

Background: Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), which is commonly interpreted as a sensorimotor gating deficit. To date, it is unclear when these gating deficits arise. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that gating deficits could be present before the onset of a full-blown psychosis.

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia.

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms.

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.

Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms.

Background: Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), suggesting a sensorimotor gating deficit. The serotonin-2A receptor (5-HT(2A)R) has been implicated in both the pathogenesis of schizophrenia and the PPI deficits of schizophrenia patients. Moreover, both schizophrenia and PPI are thought to be inheritable.

Depression during an acute episode of schizophrenia or schizophreniform disorder and its impact on treatment response.

The aim of the present study was to examine the relevance of depressive symptoms during an acute schizophrenic episode for the prediction of treatment response. Two hundred inpatients who fulfilled DSM-IV criteria for schizophrenia or schizophreniform disorders were assessed at hospital admission and after 6 weeks of inpatient treatment using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale for Depression (HAM-D). Depressive symptoms showed positive correlations with both positive and negative symptoms at admission and after 6 weeks, and decreased during 6 weeks of treatment.

Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia.

Objective: Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested.

5-HT2A receptor density is decreased in the at-risk mental state.

Rationale: Current perspectives on the pathophysiology of schizophrenia direct attention to serotonergic (serotonin, 5-HT) dysregulation in the prodrome or at-risk mental state (ARMS).

Objective: To study the cerebral 5-HT(2A) receptor (5-HT(2A)R) in the ARMS with [(18)F]altanserin positron emission tomography (PET) and a bolus-infusion paradigm.

Materials And Methods: We quantified the spatial distribution of 5-HT(2A)R binding potential (BP(1)') in never-medicated subjects assigned to early (n = 6) and late (n = 8) prodromal states of schizophrenia relative to healthy controls (n = 21).

Prediction of symptom remission in schizophrenia during inpatient treatment.

Objective: Standardized consensus criteria for remission in schizophrenia were recently proposed. The present study applied the symptom-severity component of these criteria to a sample of inpatients in order to determine the rates of remission during inpatient treatment and to explore predictors of remission.

Method: A total of 288 inpatients from a multi-centre follow-up programme who fulfilled ICD-10 criteria for schizophrenia were included in the present analyses.