M.Z. received scientific grants from the German Research Foundation and Servier. Speaker and travel grants were provided from Otsuka, Servier, Lundbeck, Roche, Ferrer and Trommsdorff.

The rate of bleeding complications following arterial switch operation is too low to independently justify a prospective randomised study for benefit from recombinant factor VIIa. We aimed to evaluate factor VIIa in a pilot study.

We performed a retrospective cohort study of patients undergoing arterial switch operation from 2012 to 2017. Nearest-neighbour propensity score matching on age, gender, weight, and associated cardiac defects was used to match 27 controls not receiving recombinant factor VIIa to 30 patients receiving recombinant factor VIIa. Fisher’s exact test was performed to compare categorical variables. Wilcoxon’s rank-sum test was used to compare continuous variables between cohorts.

Post-operative thrombotic complications were not associated with factor VIIa administration (Odds Ratio (OR) 0.28, 95% CI 0.005–3.77, p = 0.336), nor was factor VIIa administration associated with any re-explorations for bleeding. No intraoperative transfusion volumes were different between the recombinant factor VIIa cohort and controls. Post-operative prothrombin time (10.8 [10.3–12.3] versus 15.9 [15.1–17.2], p < 0.001) and international normalised ratio (0.8 [0.73–0.90] versus 1.3 [1.2–1.4], p < 0.001]) were lower in recombinant factor VIIa cohort relative to controls.

In spite of a higher post-bypass packed red blood cell transfusion requirement, patients receiving recombinant factor VIIa had a similar incidence of bleeding post-operatively. With no difference in thrombotic complications, and with improved post-operative laboratory haemostasis, a prospective randomised study is warranted to evaluate recombinant factor VIIa.

Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances in association with disturbed synaptic plasticity and functions of the amino acid neurotransmitter glutamate.

We were interested in effects of ethanol during the terminal neurodevelopmental differentiation on glutamatergic neurotransmission.

To establish an animal model based on vapor chamber exposure and to assess the expression of vGluT1, EAAT1 to 4, NMDA receptor (NR) subunits 1, 2A to D and NR binding with 3H-labeled MK 801.

After delivery, female Wistar Han outbred rats (N = 4) and their pups were exposed until postnatal day 8 (P8). At the age of 5 months, the animals were behaviorally characterized. Both, at P8 and after the testing we performed in situ-hybridizations receptor binding assays.

PEA-pubs showed a pronounced and highly significant retardation of body weight and length. Behavioral testing revealed no differences in locomotion and anxiety (open field and elevated plus maze) as well as T-maze-learning, but significantly impaired hippocampus-dependent spatial learning (MWM). We observed significant inductions of vGluT1, EAAT1, EAAT3, NR2A, 2B, 2C and 2D, as well as trends of increased NR1 mRNA. NR binding was found increased in hippocampus (P8) and parietal cortex (P8 and 5M).

The observed inductions of glial glutamate transporters validate previous in vitro data. Altered glutamatergic neurotransmission in general might be considered a molecular correlate of the learning deficit in our PEA model. This further supports the glutamatergic theory of PEA and suggests new targets for therapeutic interventions.

Anxiety is a core symptom of schizophrenia which elicits significant subjective burden of disease and contributes to treatment resistance in schizophrenia. Anxious syndromes might be attributed to incompletely remitted delusions, the negative syndrome, depressive episodes, panic attacks, social phobia, avoidance after hospitalization and down-tapering of benzodiazepine medication. Previous treatment attempts involved several strategies of combination and augmentation.

Pregabalin, an antagonist at the α2δ-subunit of voltage-gated Ca2+-channels, modulates several neurotransmitter systems and was found able to alleviate anxiety in depression and other mental disorders.

In schizophrenia, this treatment option has not been evaluated before.

Here, we report a case series of 11 schizophrenic patients who suffered from treatment-resistant anxiety and received augmentation with pregabalin.

This observational investigation reveals that augmentation with pregabalin was able to significantly reduce scores on the Hamilton anxiety scale; furthermore, we observed improvements of psychotic positive and negative symptoms and mood as assessed by PANSS, SANS and CDSS. After augmentation, both a complete discontinuation of concomitant benzodiazepine (BZD) treatment as well as a dose reduction of antipsychotics could be achieved. We did not observe pharmacokinetic interactions or adverse events.

These observations suggest that treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable. Further investigations should differentiate schizophrenic sub-syndromes of anxiety and evaluate benefits and risks of pregabalin in comparison to placebo and active competitors.

The glutamatergic theory of schizophrenia proposes a dysfunction of ionotropic N-Methyl-D-aspartate (NMDA)-receptors (NR). Several therapeutic strategies address NR function and effects of antipsychotic agents on NR expression have been described.

The partial dopaminergic and serotonergic agonist aripiprazole (APZ) was able to counteract behavioural effects of NR antagonists, but effects of APZ on NR expression have not been investigated.

To evaluate effects of APZ on NR mRNA and protein expression

We treated Sprague-Dawley rats for 4 weeks or 4 months with APZ in daily oral doses of 10 and 40 mg per kg body weight. Expression of the NR subunits NR1, NR2A, NR2B, NR2C and NR2D was assessed by semiquantitative radioactive in situ-hybridization, and in parallel receptor binding using 3H-MK-801 receptor autoradiography.

Increased expression levels of NR1 (4 weeks), NR2A (4 weeks), NR2C (4 weeks and 4 months) and NR2D (4 months) were observed in several hippocampal and cortical brain regions. The parallel reduced expression of NR2B mRNAs (4 months) resulted in a relative increase of the NR2A/NR2B ratio. Marked differences between specific brain regions, the doses and time points of assessment became obvious. On the receptor level, increased MK-801-binding was found after 4 weeks in the 40 mg-group and after 4 months in the 10 mg-group.

The effects of APZ converge in enhanced NMDA-receptor expression and a shift of subunit-composition towards adult-type receptors. Our results confirm regulatory connections between dopaminergic, serotonergic and glutamatergic neurotransmission with relevance for cognitive and negative symptoms of schizophrenia.

Cognitive deficits impair social and vocational rehabilitation in schizophrenic patients but little is known to which extend these symptoms are perceived by psychiatrists and how they influence antipsychotic treatment. Therefore, an online survey was performed in four European countries (Germany, Greece, Italy and Spain).

The survey involving 744 psychiatrists and assessed demographic characteristics including vocational status, presenting symptomatology, cognitive dysfunction severity, and current antipsychotic treatement. Methodology is described in full detail by Gorwood (2010).

Out of 3,996 patients, 29% were clinically assessed as having mild, 54% moderate and 17% severe cognitive dysfunction. In the mild dysfunction group, mean time since diagnosis was 9.7 years, 12.0 years in the moderate dysfunction group, and 17.0 years in the severe dysfunction group, and majority were outpatients (74.7%, 57.9% and 56.7%, respectively). The respective mean number of previous episodes was 5.1, 6.2 and 7.2 (6.0 for the total sample). Full or part time employment was reported in 32,2%, 19.1% and 11.8% of the patients, respectively. Olanzapine was the most frequently used antipsychotic in the mild group (21.0%) and severe group (24.9%), and risperidone in the moderate group (23.0%). Ziprasidone was used in 10.2%, 0.8% and 7.1% of subjects.

Cognitive dysfunction is frequently perceived by psychiatrist in every day clinical practice and severely interferes with the vocational status. Major associations between specific antipsychotics and the levels of cognitive impairment were not observed. Irrespective of the level of cognitive dysfunction, > 50% of subjects were outpatients.

Patients with psychotic disorders often suffer from intercurrent major depressive episodes (MDEs). Case reports suggested successful antidepressive treatment with duloxetine, a selective dual reuptake inhibitor of serotonin and norepinephrine (SSNRI). We initiated this open prospective clinical trial in order to evaluate efficacy, safety and tolerability of this approach.

Patients with a psychotic lifetime diagnosis suffering from mildly severe MDEs were treated with duloxetine over a period of 6 weeks. We evaluated effects on mood, monitored the psychotic psychopathology and assessed side effects, basal clinical and pharmacological parameters.

Twenty patients were included and experienced a significant improvement of their MDE during the observation period (CDSS: Calgary Depression Scale for Schizophrenia, HAMD: Hamilton Depression scale). Psychotic positive symptoms remained stably absent while negative syndrome and global psychopathology considerably improved (PANSS: Positive and Negative Syndrome Scale). In general, the treatment was well tolerated, serum prolactin levels stayed unchanged, but pharmacokinetic interactions with a number of antipsychotic agents were observed.

This open prospective evaluation revealed antidepressive efficacy of duloxetine in patients with co-morbid psychotic disorders. With regard to the psychotic disorder, the treatment appears to be safe and well tolerable. Further investigations should involve a randomized control group.