M Das

Cognitive functioning in siblings discordant for schizophrenia

Objective:  The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings.

Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia

Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

Neural correlates of deficient response inhibition in mentally disordered violent individuals

In this study, response inhibition and associated neural activation during a motor inhibition paradigm were investigated in (i) men with antisocial personality disorder (APD) with a history of violence (n = 14), (ii) men with schizophrenia with a history of violence (n = 12), (iii) men with schizophrenia without a history of violence (n = 12), and (iv) healthy control subjects (n = 14) using functional magnetic resonance imaging (fMRI). At the behavioural level, individuals with schizophrenia showed impaired performance across all conditions, whereas an increased error rate was seen in the APD group only during the conditions requiring inhibition. At the neural level, both violent groups showed reduced thalamic activity, compared with controls, in association with modulation of inhibition by task demands. In addition, the violent schizophrenia group, compared with controls, showed reduced activity in the caudate nucleus during the condition requiring inhibition. It is concluded that violence may not be specifically associated with impaired voluntary inhibition in schizophrenia but this is likely in APD. Reduced thalamic function, perhaps due to its known association with sensorimotor disturbances, is implicated in violent behaviour across both disorders. In addition, caudate dysfunction may contribute, given its role in timing and temporal processing as well as suppression of motor actions, to deficient inhibition and violent behaviour in schizophrenia.

Effects of acute procyclidine administration on prepulse inhibition of the startle response in schizophrenia: a double-blind, placebo-controlled study.

Prepulse inhibition (PPI) of the startle response refers to a reduction in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Consistent with theories of deficiencies in early stages of information processing, PPI is found to be reduced in patients with schizophrenia. Atypical antipsychotics are found to be more effective than typical antipsychotics in improving PPI in this population. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication, especially by typical antipsychotics, in schizophrenic patients and are known to disrupt cognitive functions in both normal and schizophrenic populations. The effect of anticholinergics on PPI in schizophrenia has not yet been examined. This study determined the effects of procyclidine, an anticholinergic drug, on PPI in patients with schizophrenia given risperidone or quetiapine and not on any anticholinergic drugs, employing a placebo-controlled, cross-over design. Under double-blind conditions, subjects were administered oral 15 mg procyclidine and placebo on separate occasions, 2 weeks apart, and tested for acoustic PPI (prepulse 8 dB and 15 dB above the background and delivered with 30-ms, 60-ms and 120-ms prepulse-to-pulse intervals). Procyclidine significantly impaired PPI compared to placebo (assessed as percentage reduction) with 60-ms prepulse-to-pulse trials and increased the latencies to response peak across all trials. The use of anticholinergics needs to be carefully controlled/examined in investigations of information processing deficits using a PPI model and reduced to the minimum level in clinical care of schizophrenia.

P03-257 - Dysfunctional impulsivity in schizophrenia: a functional MRI investigation

Introduction Dysfunctional impulsivity reflects ‘recklessness without deliberation and evaluation of consequences’ and has negative consequences whereas functional impulsivity reflects ‘rapid responding to situational demands in order to maximise ones circumstances’ and often has positive consequences (1). Objective To examine the functional brain basis of dysfunctional impulsivity in healthy people and in people with schizophrenia. Methods Thirteen healthy controls and 21 schizophrenia patients (10/21 with serious repetitive violence) underwent fMRI during a Go/ NoGo task. Dysfunctional impulsivity was indexed using the Impulsiveness subscale and functional impulsivity using the Venturesomeness subscale of the Impulsiveness-Venturesomeness-Empathy questionnaire (2). Results Violent patients had elevated Impulsiveness scores relative to non-violent patients and controls. Impulsiveness did not correlate significantly with task performance in healthy controls or patients. Impulsiveness, but not Venturesomeness, scores correlated during the NoGO condition with lower activity in the anterior cingulate (AC) in controls, and lower inferior temporal and hippocampal activity in patients. Conclusions These findings accord with previously reported associations between reduced hippocampal volume and dysfunctional impulsivity in schizophrenia (3) and, combined with our earlier observations of reduced AC activation during a working memory task in violent antisocial individuals (4), suggest that the influence of dysfunctional impulsivity in antisocial and criminal behaviour is mediated via deficient (inhibitory) functions of the AC and hippocampus.