M. van der Gaag

Duration of untreated psychosis and the long-term course of schizophrenia.

This study examines the relationship between duration of untreated psychosis (DUP) and long-term symptomatic and social outcome in 205 patients with schizophrenia, whose parents are member of a consumer organisation. We found only a tendency that longer DUP was related to negative symptoms, but no relation to other outcome domains. The results of this study do not support antipsychotic intervention at the earliest sign of psychosis in order to protect the brain.

Psycho-education on extra-ordinary experiences and risky thinking styles for people with an At Risk Mental State

Since the early days of schizophrenia research, hyper-responsivity within the dopamine system was believed to underlie the positive symptoms of this disorder; however, the source of this disruption has been unknown. However, recent studies from human schizophrenia patents suggest that hyperactivity within the hippocampal formation may drive this psychosis. In a rodent developmental disruption model of schizophrenia, we found that the ventral subiculum of the hippocampus is hyperactive secondary to a loss of GABAergic interneuron markers. Moreover, we found that activity within the ventral subiculum drives tonic dopamine neuron firing, thereby controlling the “gain” of the phasic dopamine response to stimuli. Inactivation of the ventral subiculum in the rodent model was found to reverse the dopamine system overdrive and the behavioral hyper-responsivity to amphetamine, providing an important link between the hippocampus and dopamine system regulation. The ventral subiculum is also recognized as a central mediator of the stress response, and receives potent drive from stress-related areas such as the noradrenergic system and the amygdala. Given the high sensitivity of hippocampal neurons to stress-induced damage, these data suggest that stress may be a precipitating factor in schizophrenia onset via disruption of hippocampal interneuron function. We propose that the resultant loss of interneuron gating within the hippocampus leads to a condition whereby there is an inappropriate assignment of context, leading the individual to interpret all stimuli as being highly salient. Moreover, the transition to schizophrenia may be circumvented by treating the maladaptive responses to stressors during the premorbid state that contribute to hippocampal dysfunction. Plenary Lecture I

Prodromal questionnaire in a help-seeking population as a self-report instrument preceding the CAARMS

The treatment of individuals during the early phase of a psychotic disorder is critically important. First, it might have a significant impact on subsequent course and outcome, and second, the initial treatment experience can have a powerful effect on patient (and family) attitudes towards the illness and subsequent engagement in appropriate treatment. Pharmacotherapy needs to be thoroughly integrated with psychosocial and psychoeducation intervention strategies as well. It is in this context that we should design and conduct psychopharmacology trails in early phase illness. In addition, these trials involve a number of important challenges that are unique to early phase illness. Given the incidence of psychotic illness, identifying subjects eligible to participate in clinical trials can be a challenge. Generally multicenter studies are required to recruit an adequate number of subjects. Individuals with early phase illness are often lacking in insight or have not fully accepted the need for treatment, making recruitment into trials particularly challenging. Developing appropriate control or comparison conditions can be a challenge from both an ethical and scientific perspective. If true prevention or impact of treatment on illness course is a focus of the investigation, a lengthy trial might be required. Even if an intervention is found to be effective in delaying the onset of a more full blown illness or altering the course of an existing illness, how can we determine if and when it is feasible to discontinue or step down treatment? These are some of the issues and challenges that need to be considered and will be reviewed in more detail.