Aim was to evaluate influencing factors of response and symptomatic remission in first-episode schizophrenia patients treated with risperidone or haloperidol.

229 first-episode schizophrenic patients were examined within a double blind controlled trial of the German Study Group on first-episode schizophrenia with biweekly PANSS ratings. Response was defined according to the definition by Lieberman et al. (2003) and symptomatic remission as the severity component of the consensus remission criteria by the Remission in Schizophrenia Working Group. Sociodemographic, psychopathological and functional variables as well as the treatment applied were evaluated regarding their potential predictive validity for treatment outcome. Univariate tests, logistic regression and CART-analyses were consulted as statistical methods.

126 patients (55%) achieved response and 118 patients (52%) symptomatic remission at discharge with no significant differences between the risperidone (51%) and haloperidol (49%) treated patients. Better baseline functioning, early treatment response, less depressive symptoms and a shorter duration of untreated psychosis were revealed significant predictors of response. Patients with symptomatic remission also had a significantly shorter duration of untreated psychosis and significantly less depressive symptoms at baseline. Logistic regression and CART-analyses revealed low general psychopathology, early treatment response and a high score in the Strauss-Carpenter-Prognostic-Scale at admission to be significantly positive predictive for symptomatic resolution.

Early treatment response, depressive symptoms and the level of psychosocial functioning were revealed to significantly predict outcome, with no significant differences between risperidone and haloperidol. The importance of an early adequate symptom control and the implementation of early intervention programs is highlighted.

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.

Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being.

The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome.

Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission.

Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

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).

To assess the dosing patterns for risperidone long-acting injectable (RLAI) in patients with schizophrenia, participating in the 6-month, open-label Switch to Risperidone Microspheres (StoRMi) trial.

Treatment was initiated at RLAI 25 mg intramuscularly every 2 weeks, although higher (starting) doses were permitted if clinically necessary. Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) and Global assessment of functioning (GAF). Treatment-emergent adverse events (AEs) were monitored.

A total of 1,849 patients were included. The mode dose was 25 mg for 52.9% of patients, the remainder evenly distributed among 37.5 and 50 mg doses. At baseline, patients treated with lower RLAI doses were more likely to be female, have shorter disease duration, milder symptoms, and be using less polypharmacy. The strongest predictors that a patient would remain on 25 mg RLAI were baseline PANSS hallucinatory behaviour item (OR = 0.78), baseline CGI (OR = 0.69), gender (OR = 1.56) and country (P< 0.001 for all). Efficacy measures improved for all dosage groups, with the greatest improvement in patients treated with lower doses. AEs were more frequent in patients treated with 50 mg RLAI (68% vs. 57% with lower doses, P<0.0001). Most AEs were mild to moderate in severity.

In this large, European sample, most patients were treated with 25 mg RLAI. Patients treated with lower doses tended to have milder baseline symptoms. Dosing patterns varied among different countries. RLAI was effective and well tolerated over the full range of allowed doses.

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.

Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.

Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.

Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.

The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.

Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).

For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.

Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.

AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.