Georg Kemmler

Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease☆

Alzheimers disease (AD) is a progressive neurodegenerative disorder with characteristic neuropathological changes of the brain. Great efforts have been undertaken to determine the progression of the disease and to monitor therapeutic interventions. Especially, the analysis of blood plasma had yielded incongruent results. Recently, Ray et al. (Nat. Med. 13, 2007, 1359f) identified changes of 18 signaling proteins leading to an accuracy of 90% in the diagnosis of AD. The aim of the present study was to examine 16 of these signaling proteins by quantitative Searchlight multiplex ELISA in order to determine their sensitivity and specificity in our plasma samples from AD, mild cognitive impairment (MCI), depression with and without cognitive impairment and healthy subjects. Quantitative analysis revealed an increased concentration in Biocoll isolated plasma of 5 out of these 16 proteins in MCI and AD patients compared to healthy subjects: EGF, GDNF and MIP1δ (in AD), MIP4 (in MCI) and RANTES (in MCI and AD). ROC analysis predicted a sensitivity of 65-75% and a specificity of 52-63% when comparing healthy controls versus MCI or AD. Depression without any significant cognitive deficits did not cause any significant changes. Depressed patients with significant cognitive impairment were not different from MCI patients. In conclusion, we detected a number of altered proteins that may be related to a disease specific pathophysiology. However, the overall expression pattern of plasma proteins could not be established as a biomarker to differentiate MCI from AD or from depression.

Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial.

Sexual dysfunctions (SDs) occur frequently in schizophrenia patients and have a huge impact on quality of life and compliance. They are often associated with antipsychotic medication. Nicotine consumption, negative or depressive symptoms, and physical illness are also discussed as contributing factors. Data on SD in first-episode schizophrenia patients are scarce. As part of the European First Episode Schizophrenia Trial, first-episode schizophrenia patients were randomly assigned to 5 medication groups. We assessed SD by analyzing selected items from the Udvalg for Kliniske Undersugelser at baseline and at 5 following visits. Differences between antipsychotics were small for all SDs, and fairly little change in the prevalence of SDs was seen over the course of the study. A significantly larger increase of amenorrhea and galactorrhea was seen with amisulpride than with the other medications. In men, higher age, more pronounced Positive and Negative Syndrome Scale general psychopathology symptoms, and higher plasma prolactin levels predicted higher rates of erectile and ejaculatory dysfunctions. Positive and Negative Syndrome Scale negative symptoms and higher age were predictors for decreased libido. In women, higher prolactin plasma levels were identified as a predictor of amenorrhea. Positive and Negative Syndrome Scale negative symptoms predicted decreased libido. All evidence taken together underscores the influence of the disease schizophrenia itself on sexual functioning. In addition, there is a strong correlation between the prolactin-increasing properties of amisulpride and menstrual irregularities.

Reversal of cocaine-conditioned place preference and mesocorticolimbic Zif268 expression by social interaction in rats

Little is known how social interaction, if offered as an alternative to drug consumption, affects neural circuits involved in drug reinforcement and substance dependence. Conditioned place preference (CPP) for cocaine (15u2003mg/kg i.p.) or social interaction (15 minutes) as an alternative stimulus was investigated in male Sprague‐Dawley rats. Four social interaction episodes with a male adult conspecific completely reversed cocaine CPP and were even able to prevent reacquisition of cocaine CPP. Social interaction also reversed cocaine CPP‐induced expression of the immediate‐early gene zif268 in the nucleus accumbens shell, the central and basolateral amygdala and the ventral tegmental area. These findings suggest that social interaction, if offered in a context that is clearly distinct from the previously drug‐associated ones, may profoundly decrease the incentive salience of drug‐associated contextual stimuli. The novel experimental design facilitates the neurobiological investigation of this phenomenon which may be beneficial for human drug users in treatment.

Facial emotion recognition and its relationship to subjective and functional outcomes in remitted patients with bipolar I disorder

Hoertnagl CM, Muehlbacher M, Biedermann F, Yalcin N, Baumgartner S, Schwitzer G, Deisenhammer EA, Hausmann A, Kemmler G, Benecke C, Hofer A. Facial emotion recognition and its relationship to subjective and functional outcomes in remitted patients with bipolar I disorder. Bipolar Disord 2011: 13: 537–544.

Quality of life trajectory in patients with advanced cancer during the last year of life.

INTRODUCTIONnDue to the high mortality of cancer a large number of patients pass a preterminal phase of their illness. Within this phase medical care aims at maintaining patients quality of life (QOL) and reducing symptom burden. Our study investigated the patient-reported severity of QOL impairments during the last year of life, with a special focus on their course at the end of life.nnnMETHODSnAll patients with cancer receiving palliative care at Natters State Hospital (Austria) were considered as eligible for the study. QOL data were collected with the EORTC QLQ-C30 questionnaire as part of computerized patient-reported outcome monitoring (ePROM) within clinical routine. QOL was investigated longitudinally in regard to its course toward death as well as to changes in determinants of global QOL.nnnRESULTSnEighty-five patients participated in the ePROM (255 assessments in total). Regarding trajectories, physical, role and cognitive functioning, fatigue and global QOL worsened sharply during the last 3 months of life. A steady decline was found for emotional functioning, pain, appetite loss and taste alterations. The impact of role functioning, sleep disturbances, and taste alterations on global QOL increased within the last 3 months of life.nnnCONCLUSIONnOur results indicate that most aspects of QOL are considerably impaired in patients with advanced cancer. Furthermore, they highlight the importance of assessing QOL in general and taste alterations in particular within palliative care.

Symptomatic remission and neurocognitive functioning in patients with schizophrenia.

BACKGROUNDnA cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome.nnnMETHODnPsychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis.nnnRESULTSnOut of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients employment status.nnnCONCLUSIONSnIn the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.

Slowing of high-speed memory scanning in Parkinson's disease is related to the severity of parkinsonian motor symptoms

SummaryHigh-speed memory scanning (Sternberg paradigm) was tested in a collective of 20 parkinsonian patients (10 newly diagnosed, untreated patients, duration of the disease 0.5–3.8, mean 1.5 years; 10 levodopa-treated patients, duration of the disease 4.2 to 11, mean 7.6 years). The levodopa-treated patients stopped taking levodopa before the test. There was a tendency towards retarded memory scanning in the patients collective compared with 20 healthy controls with similar ages and verbal IQs (p=0.076, Mann-Whitney U test). The mental slowing correlated significantly with bradykinesia and the sum-score of the Columbia University Parkinson Rating Scale (p=0.021 and 0.019; Spearman rank correlation). Kruskal-Wallis ANOVA revealed a significant mental slowing in the subgroup of patients with Parkinsons disease for >4 years compared with the newly diagnosed patients and the controls (H=8.54; p=0.019 and 0.006, Mann-Whitney U test). The findings suggest a mental slowing in Parkinsons disease, which is associated with the progression of parkinsonian motor symptoms and not with depression.

New risk factors for donor site seroma formation after latissimus dorsi flap breast reconstruction: 10-year period outcome analysis ☆

INTRODUCTIONnLatissimus dorsi flap breast reconstruction is associated with a high incidence of donor site seromas. After using several preventive operative techniques, we were able to reduce postoperative complications in a standard operation procedure. The aim of this study was to evaluate the effect of various risk factors related to incidence, volume and frequency of seroma aspiration.nnnMETHODSnA retrospective review of 87 latissimus dorsi breast reconstructions over a 10-year period was carried out. Associations between potential risk factors and outcome (total drainage volume, number of aspirations and total seroma volume) were investigated on a descriptive level by means of correlation analysis and on an analytical level by multiple linear regression analysis.nnnRESULTSnCorrelation analysis showed that co-morbidity and higher body mass index (BMI, in kilograms per square metre) were associated with larger seroma volumes. BMI remained a significant risk factor also after adjustment for other co-variates (p<0.001, linear regression). Moreover, patients receiving selective serotonin reuptake inhibitors (SSRIs) presented significantly higher seroma volumes (p=0.047, linear regression). At a trend level (p<0.1), post-operative hypertension, lower Ca ± - levels and a reduction in haemoglobin levels (before vs. after operation) were also associated with larger seroma volumes.nnnDISCUSSIONnThis study, besides observing the effects of well-established risk factors such as age, BMI and surgical operation techniques, identified new risk factors, in particular the perioperative use of SSRIs and the calcium balance, which should be considered in patients in pre- and postoperative care.

Influence of Serotonin Transporter Genotype and Catechol-O-Methyltransferase Val158Met Polymorphism on Recognition of Emotional Faces

Monoamines, such as serotonin, dopamine, and norepinephrine, play a crucial role in the regulation of emotion processing and mood. In this study, we investigated how polymorphisms of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) influence emotion recognition abilities. We recruited 88 female undergraduate students and assessed 5-HTT genotype and the COMT Val158Met polymorphism. The subjects completed two computerized tasks: The Penn Emotion Recognition Test (ER40) and the Penn Emotion Acuity Test (PEAT). For the ER40, we found that s-allele carriers performed significantly worse in the recognition of happy faces, but did better in the recognition of fearful faces, compared with homozygous l-carriers of the 5-HTT gene. Neither 5-HTT nor COMT genotypes influenced the ability to discriminate between different intensities of sadness or happiness on the PEAT. Moreover, there was no significant interaction between the two polymorphisms in their effect on performance on the ER40 or the PEAT.

Combined clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia: clinical and cognitive outcomes.

Abstract For treatment-refractory schizophrenia, electroconvulsive therapy (ECT) remains controversial because of its cognitive adverse effects. We report here on clinical and cognitive outcomes of a treatment-resistant schizophrenia patient treated with clozapine and right unilateral ECT. The patient was administered 300 mg of clozapine and 12 right unilateral ECT sessions. Psychopathology was rated by means of the Positive and Negative Syndrome Scale. The neurocognitive test battery included the Wisconsin Card Sorting Test, the Münchner Gedächtnis Test, an attentional performance test, the Trail Making Test, and the Hamburger-Wechsler Intelligence Test. The Positive and Negative Syndrome Scale total score decreased, and all cognitive measures improved. Electroconvulsive therapy would seem to be a safe treatment option for treatment-refractory schizophrenia patients.