According to the vulnerability-stress-coping (V-S-C-) model, the probability of occurrence of a schizophrenic episode depends on the degree of imbalance between vulnerability factors, stressors, and protectors. The present study aims at investigating the effects of psychotherapy and antipsychotic medication on the interaction of these factors and their contribution to course and outcome.

Within the German Research Network on Schizophrenia (Wölwer et al. 2003, Eur Arch Psychiatr Clin Neurosci 253: 321-329) a multi-center study on the optimization of long-term treatment in n=159 first-episode schizophrenia (ICD-10 F20) was recently finished (Gaebel et al. 2004, Eur Arch Psychiatr Clin Neurosci 254: 129-140). Risperidone and low-dose haloperidol were compared in a two-year randomized double-blind study within the framework of psychological interventions. In the second treatment year continued neuroleptic treatment was compared with stepwise drug withdrawal substituted by prodrome-based early intervention (intermittent treatment). Vulnerability indicators were cognitive and motor functioning (e.g. TMT-A/-B), neuromorphology (MRI) and -physiology (EEG). Stress was monitored by means of the occurrence of stressful life events, family atmosphere and catecholamine-levels in blood, coping competence was assessed with several questionnaires (e.g. SVF, FSKN).

Although no relapse (according to predefined criteria) occurred in the first treatment year under study treatment, direct treatment effects on vulnerability, on stress or on coping competence were rare if detectable at all.

Results will be discussed with respect to the validity of the contemporary V-S-C-Model as etiopathogenetic concept as well as with respect to consequences in regard to treatment and prevention.

Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. In two separate studies, we examined antisaccade task performance, a measure of inhibitory control, in first degree relatives of schizophrenic patients (genetic risk without manifest disorder) and in clinical high risk subjects with symptoms suggestive of a prodromal phase of schizophrenia.

In the first study, 41 parents of schizophrenia patients and 22 controls were tested with with a prosaccade task and an antisaccade task. Parents were grouped into more likely, less likely, and indeterminate risk carriers. The second study involved 160 subjects clinically at risk for schizophrenia, 32 first episode schizophrenic patients, and 76 healthy controls.

In study 1 we found an increase of antisaccade latencies and error rates in parents of schizophrenics which varied with inferred genetic load, more likely gene carriers performing worst. In study 2, antisaccade performance varied with symptom load: subjects at risk with basic symptoms only were unimpaired, while at-risk subjects who had experienced brief psychotic episodes (BLIPS) showed deficits similar to first episode patients.

Reduced inhibitory control of oculomotor performance is associated with genetic loading for schizophrenia, and also with symptoms placing subjects at imminent risk of psychosis.

Psychosis is preceded by cognitive and physiological alterations. This may be useful in the risk assessment in subjects with putatively prodromal symptoms, and could contribute to better understand the temporal unfolding of the disease.

The early recognition and intervention program of the German Research Network on schizophrenia defines early and late prodromal stages according to psychopathological criteria. For concurrent and prospective validation of these risk stages, subjects undergo neurocognitive, electrophysiological and oculomotor assessments of putative vulnerability markers. About 125 early prodromal subjects (defined by the presence of basic symptoms, Klosterkoetter et al. 2001), and 90 late prodromal subjects (defined by attenuated positive symptoms or by brief occurrences of psychotic symptoms) have been assessed at inclusion.

As compared to psychiatrically healthy matched controls, late prodromals have significantly inferior verbal memory, verbal fluency, visual motor skills, and working memory. Impairments are qualitatively similar, but less pronounced in subjects in an early prodromal stage, with deficits of immediate verbal memory, verbal fluency and visuomotor performance being significant. Both groups show reduced auditory startle prepulse inhibition. Impairments are not correlated with depression and general distress scores, and are also largely independent of prodromal and attenuated positive symptoms. In early prodromals, global cognitive performance is related to the occurrence of psychotic symptoms during follow-up. Auditory P 300 is reduced in both prodromal groups, and predicts transitions to psychosis.

Neurocognitive and neurophysiological assessments validate and improve psychopathological risk assessment, and allow to disentangle stable vulnerability markers from indicators of imminent risk.

Funded by the German Federal Ministry for Education and Research BMBF (grant 01 GI 9934).

Schizophrenia patients exhibit impairments in facial affect recognition associated with neurophysiological abnormalities. Using the Training of Affect Recognition (TAR) developed by our group behavioural performance in facial affect recognition improved significantly in schizophrenia patients [1]. Purpose of the presented work was to identify the underlying mechanisms and associated generators of neuroelectric activity.

In a randomized controlled (waiting group) design 19 schizophrenia patients received TAR. Concomitant to facial affect recognition performance, ERPs were recorded and analyzed with respect to underlying generators of cortical activity using low resolution brain electromagnetic tomography (LORETA) software.

Schizophrenia patients showed noticeable deviations in neuroelectric correlates of emotion recognition associated with poorer performance in the administered task. As a result of TAR treatment no significant changes in event related potentials were found. However, LORETA results showed a significant increase of activity within relevant brain areas, specific for the processing stages associated with facial emotion recognition (N170 and P240).

EEG findings of the present study indicate that neurophysiologic abnormalities corresponding with poorer performance in schizophrenia patients can be attenuated by training.

Impairments in facial emotion recognition have proven to be a trait-like characteristic in schizophrenia mostly unaffected by traditional treatment. This raised the question whether cognitive remediation strategies may be a treatment option for these impairments.

A special Training of Affect Recognition (TAR) was evaluated in three consecutive studies using pre-post-control group designs with either an active control treatment (studies 1 and 2), a „passivetreatment as usual group (study 1), or a waiting group (study 3). The active control treatment consisted of a Cognitive Remediation Training (CRT) aiming at improvement of basic neurocognitive functioning. Outcome measures comprised facial and prosodic affect recognition, basic cognitive functioning and social interaction.

Analyses revealed specific training effects in the form of a double dissociation both in studies 1 and 2: the TAR improved facial and prosodic affect recognition as well as understanding of social scenes, but had no effects on memory, attention and executive functioning. Patients under CRT and those without training did not show improvements in affect recognition, though patients under CRT improved in some memory functions. Positive effects of the TAR on facial affect recognition could also be replicated in forensic schizophrenia patients (study 3) and proved to be stable for at least 4–6 weeks after the end of training (studies 2, 3).

According to these results, improvements in disturbed facial affect recognition in schizophrenia patients are not obtainable with a traditional cognitive remediation program like CRT, but need a functional specific training like the newly developed TAR.