The catatonic dilemma expanded

Catatonia is a common syndrome that was first described in the literature by Karl Kahlbaum in 1874. The literature is still developing and remains unclear on many issues, especially classification, diagnosis, and pathophysiology. Clinicians caring for psychiatric patients with catatonic syndromes continue to face many dilemmas in diagnosis and treatment. We discuss many of the common problems encountered in the care of a catatonic patient, and discuss each problem with a review of the literature. Focus is on practical aspects of classification, epidemiology, differential diagnosis, treatment, medical comorbidity, cognition, emotion, prognosis, and areas for future research in catatonic syndromes

Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease

The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium 10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithiumchronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).FCT -Fundação para a Ciência e a Tecnologia(SFRH/BD/51059/2010

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies

The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia

A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects