Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.

Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.

Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.

Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.

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.

Implicit memories like consumption habits and conditioned reactions to drug-related stimuli are operational in addiction and relapse. The affective startle paradigm is an attractive tool for the measurement of the incentive salience of drug-related cues. We tested whether the stronger appetitive valence of drug cues, shown in two recent startle studies in smokers, does persist after prolonged abstinence, and may thus contribute to relapse.

We examined the auditory startle reflex magnitude of mildly deprived (4-6 hours) heavy smokers (n = 24), former smokers (n = 16, mean abstinence interval 18 months), and non-smokers (n = 24) while they viewed smoking-related scenes or standardized unpleasant, neutral and pleasant control scenes from the International Affective Picture System.

As expected, non-smokers showed no appetitive reactions toward smoking-cues. In smokers, smoking-cues had both appetitive implicit (startle suppression) and explicit (ratings for valence and craving) motivational effects, resembling those of pleasant scenes and differing from neutral and unpleasant scenes. This effect was more pronounced in smokers who later relapsed after a smoking cessation program, and in smokers consuming less than 20 cigarettes per day. Former smokers, despite reporting no craving and negative reactions to smoking cues, still showed evidence of implicit appetitive valence of these cues.

Nicotine addiction results in automatic appetitive reactions to drug-cues, which does not vanish after prolonged abstinence and which may thus contribute to relapses. Heavy smoking may result in a progressive internalization of smoking habits and a decline in reactivity towards external smoking-associated cues.

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).

Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms.

Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient’s symptoms.

The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of > 6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors.

The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms.

Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.