Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender.

BACKGROUND: The aim of the study was to examine extrastriatal dopamine D(2/3) receptor binding and psychopathology in schizophrenic patients, and to relate binding potential (BP) values to psychopathology. METHODS: Twenty-five drug-naive schizophrenic patients and 20 healthy controls were examined with single-photon emission computerized tomography (SPECT) using the D(2/3)-receptor ligand [123I]epidepride. RESULTS: In the hitherto largest study on extrastriatal D(2/3) receptors we detected a significant correlation between frontal D(2/3) BP values and positive schizophrenic symptoms in the larger group of male schizophrenic patients, higher frontal BP values in male (n = 17) compared to female (n = 8) patients, and - in accordance with this - significantly fewer positive schizophrenic symptoms in the female patients. No significant differences in BP values were observed between patients and controls; the patients, however, had significantly higher BP in the right compared to the left thalamus, whereas no significant hemispheric imbalances were observed in the healthy subjects. CONCLUSIONS: The present data are the first to confirm a significant correlation between frontal D(2/3) receptor BP values and positive symptoms in male schizophrenic patients. They are in agreement with the hypothesis that frontal D(2/3) receptor activity is significant for positive psychotic symptoms. Additionally, the data support a thalamic hemispheric imbalance in schizophrenia.

Integrated treatment of first-episode psychosis: effect of treatment on family burden: OPUS trial.

BACKGROUND: The families of patients with first-episode psychosis often play a major role in care and often experience lack of support. AIMS: To determine the effect of integrated treatment v. standard treatment on subjective burden of illness, expressed emotion (EE), knowledge of illness and satisfaction with treatment in key relatives of patients with a first episode of schizophrenia-spectrum disorder. METHOD: Patients with ICD-10 schizophrenia-spectrum disorders (first episode) were randomly assigned to integrated treatment or to standard treatment. Integrated treatment consisted of assertive community treatment, psychoeducational multi-family groups and social skills training. Key relatives were assessed with the Social Behaviour Assessment Schedule (SBAS, burden of illness), the 5-min speech sample (EE), and a multiple choice questionnaire at entry and after 1 year. RESULTS: Relatives in integrated treatment felt less burdened and were significantly more satisfied with treatment than relatives in standard treatment. There were no significant effects of intervention groups on knowledge of illness and EE. CONCLUSIONS: The integrated treatment reduced family burden of illness and improved satisfaction with treatment.

Validation of a digital video tracking system for recording pig locomotor behaviour.

We are introducing a system for automatically tracking pig locomotor behaviour. Transposing methods for the video-based tracking of rodent behaviour engenders several problems. We have therefore improved existing methods, based on image-subtraction, to offer increased flexibility and accuracy in tracking large-sized animals in situations with a constantly changing background. The improved tracking algorithms introduce a reference frame, which does not include the animal and is automatically updated, and implementation of an automatic threshold detection algorithm. This makes the system more robust to the tracking environment, which could even be of the same colour as the animal, and allows the tracking environment to change during recording. We validated the system by estimating the repeatability, accuracy, and basic noise level, and tested the system in different levels of animal activity evoked by administration of apomorphine (APO) to minipigs in an open field test. Seven pigs each received the vehicle and three doses of APO (0.05, 0.1, and 0.3 mg/kg i.m.), and the locomotor behaviour of each session was recorded for 60-min. The calculated coefficient of repeatability was 0.6%, indicating high repeatability and the basic noise level of the tracking system was estimated to be 2%. Administration of the two lowest doses of APO was accompanied by increased locomotor activity of the pigs. Thus, this digital video-based tracking system for automatically tracking the spontaneous locomotor behaviour of pigs is highly reliable and accurate, and was able to detect well-known effects of APO in pig locomotor activity.

Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine.

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg/kg with a paradigm including two levels of prepulses (82 and 88dB) and a prepulse (PP) interval of 60 and 120ms. We found an average PPI of the startle reflex of 25.6% and both of the investigated PP intensities and PP intervals were equally effective in this PP-inhibitive paradigm. AMPH significantly disrupted PPI and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable additional tool in assessing pig models of neuropsychiatric disorders.

Prepulse inhibition in patients with Alzheimer's disease.

Prepulse inhibition (PPI) is used as a measure for sensorimotor gating. Studies in animals have indicated that hippocampus and entorhinal cortex, structures which are affected in mild Alzheimer's disease (AD), are involved in the regulation of PPI. The objectives of this study were to determine if patients with very mild AD had altered PPI, and to study possible correlations between PPI and cognitive performance or neuropsychiatric symptoms. A passive acoustic PPI paradigm was applied in 48 patients with either mild AD or Mild Cognitive Impairment (MCI) and in 49 healthy controls. No differences were found between patients and healthy controls regarding PPI. Further, PPI was not found to correlate with cognitive performance or neuropsychiatric symptoms. PPI is significantly altered in patients with neuropsychiatric disorders associated with dopaminergic, glutamatergic and/or serotonergic dysfunctions, such as schizophrenia. Since mild AD is primarily associated with loss of cholinergic markers in the limbic regions this study suggests that acetylcholine only plays a minor role in the regulation of PPI.

Pre-pulse inhibition of the acoustic startle eye-blink in the Göttingen minipig.

Pre-pulse inhibition (PPI) of the startle response is a measure of sensorimotor gating which has been frequently shown to be deficient in schizophrenic patients. In humans it is typically measured as the attenuation of the startle eye-blink reflex EMG when a startle eliciting noise is preceded by a weak white noise pre-pulse (PP), the interval between the PP and the startle noise stimulus (SNS) determining the degree of inhibition. Aiming at developing a new animal model of schizophrenia, we have investigated the acoustic startle eye-blink and PPI in 10 Göttingen minipigs. The stimuli and the block design of the stimulation were similar to paradigms used in human research. Initially the startle habituation across trials and blocks, secondarily the PPI at PP to SNS intervals of 30, 60, 120, 220, 520, 1020 and 2020 ms was investigated. One pig out of ten did not have a startle response, and three other pigs did not have a startle response of a sufficient magnitude to demonstrate the PPI seen in the other six pigs at the expected PP intervals of 60, 120, and 220 ms. Maximal inhibition was seen at the 220 ms interval (mean PPI 58.6%, range -18.4 to 94.6%, N = 9). Most of the results in the pigs are in accordance with findings in studies of the human startle eye-blink EMG and this initial study promotes further studies and the use of the PPI measure in the validation of minipig models of psychiatric disorders.

Normal p50 gating in unmedicated schizophrenia outpatients.

OBJECTIVE: The hypothesis of a sensory gating defect in schizophrenia has been supported by studies demonstrating deficient auditory P50 gating in patients. P50 gating is the relative attenuation of P50 amplitude in the auditory evoked potential following the second auditory stimulus of a stimulus pair. METHOD: Auditory evoked potentials of 12 unmedicated male patients with schizophrenia and 24 healthy men were recorded during three runs of 40 click pairs. Three alternative waveform-processing strategies were used to analyze the data. RESULTS: Regardless of strategy used, the differences between subject groups regarding P50 amplitude and gating were nonsignificant. CONCLUSIONS: The P50 gating in the patient group was normal. The results do not support the concept of the P50 gating defect as a general trait marker of schizophrenia.