Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention

Selective serotonin reuptake inhibitors (SSRIs) are frequently combined to the antipsychotic medication of schizophrenia patients, to treat their depressed, cognitive or negative symptoms. No convincing neurochemical theory exists for this combination. The role of serotonin in those psychophysiological parameters of attention that are already found to be disturbed in schizophrenia, e.g. processing negativity (PN), mismatch negativity (MMN) and P300 amplitude, is poorly understood. In the present study the effects of increased serotonergic activity on these psychophysiological parameters is investigated. In a balanced, double-blind, placebo-controlled, cross-over experiment 18 healthy male volunteers received an oral dose of either placebo or of 10 mg escitalopram (a highly specific SSRI) on two separate test days, after which they were tested in an auditory selective attention paradigm and a MMN paradigm. Escitalopram significantly increased PN and MMN compared to placebo, without affecting the P300 amplitude. Furthermore, administration of escitalopram resulted in a small, yet significant, reduction of task performance in the selective attention paradigm compared to placebo, while it did not affect reaction time. Contrary to what was expected, escitalopram enhanced PN and MMN, without affecting the P300 amplitude. The results are discussed in the light of dosage issues and subtypes of serotonergic receptors.     

LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high-density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis-free survival in node-negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress-induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.     

Blinding is compromised for transcranial direct current stimulation at 1 mA for 20 min in young healthy adults

Transcranial direct current stimulation (tDCS) is a non‐invasive brain stimulation method that is frequently used to study cortical excitability changes and their impact on cognitive functions in humans. While most stimulators are capable of operating in double‐blind mode, the amount of discomfort experienced during tDCS may break blinding. Therefore, specifically designed sham stimulation protocols are being used. The “fade‐in, short‐stimulation, fade‐out” (FSF) protocol has been used in hundreds of studies and is commonly believed to be indistinguishable from real stimulation applied at 1 mA for 20 min. We analysed subjective reports of 192 volunteers, who either received real tDCS (n = 96) or FSF tDCS (n = 96). Participants reported more discomfort for real tDCS and correctly guessed the condition above chance‐level. These findings indicate that FSF does not ensure complete blinding and that better active sham protocols are needed.     

Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra‐high risk for psychosis

In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra‐high risk for psychosis. One hundred and sixteen individuals at ultra‐high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion‐weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract‐based spatial statistics. Group differences in cognitive functions, voxel‐wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra‐high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra‐high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra‐high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction‐effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.     

Neurocognitive performance,subjective well-being,and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo

European Archives of Psychiatry and Clinical Neuroscience - Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether...     

Characterization of infecting strains and superantigen-neutralizing antibodies in Staphylococcus aureus bacteremia

Staphylococcus aureus superantigens (SAgs) are highly potent T cell mitogens. Antibodies against non-enterotoxin gene cluster (non-egc) SAgs are common in healthy adults, whereas neutralizing antibodies against egc SAgs are rare. We investigated the infecting S. aureus strains and the anti-SAg antibody response during S. aureus bacteremia (SAB). This prospective clinical study (www.clinicaltrials.gov, NCT00548002) included 43 injection drug users (IDUs) and 44 group-matched nonaddicts with SAB. spa genotypes and SAg gene patterns (multiplex PCR) of the S. aureus isolates were determined. The neutralizing capacities of sera obtained at the acute phase and the convalescent phase of SAB were tested against the SAg cocktail of the respective infecting strain and a panel of recombinant SAgs. The lineages CC59 and CC30 were more prevalent among bacteremia strains from IDUs than among strains from nonaddicts. SAg gene patterns in isolates from IDUs and nonaddicts were similar. At the acute phase of bacteremia, IDUs had more neutralizing antibodies against non-egc SAgs than did nonaddicts. Antibody titers frequently increased during infection. In contrast, there were no neutralizing antibodies against egc SAgs at disease onset and such antibodies were not induced by SAB. SAB triggers an antibody response only against non-egc SAgs. Preimmunization in IDU patients is probably due to previous exposure to the infecting strain.