Fluoxetine treatment of prepubescent rats produces a selective functional reduction in the 5-HT2A receptor-mediated stimulation of oxytocin

Various childhood mood disorders are being treated with serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine (Prozac(R)), yet limited data are available on their effects on serotonergic systems prior to maturation. This study investigated the effects of chronic fluoxetine treatment on 5-HT2A serotonin receptor-mediated neuroendocrine responses in young male rats. Prepubescent male rats were treated with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days, a treatment regimen producing maximal changes in postsynaptic 5-HT2A function in adults. Eighteen hours post-treatment, the rats received saline or increasing doses (0.5, 2.0, or 5.0 mg/kg, i.p.) of the 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl ((+/-)-DOI). Trunk blood was obtained to determine changes in oxytocin, ACTH, corticosterone, and renin responses. Fluoxetine produced a small ( approximately 6%) but significant reduction in body weight gain, but no changes were observed in basal hormone levels. In both saline- and fluoxetine-treated rats, (+/-)-DOI increased plasma oxytocin levels in a dose-dependent manner. However, the magnitude of the oxytocin responses to all doses of (+/-)-DOI were markedly attenuated ( approximately 50%) in the fluoxetine-treated rats, indicating a functional reduction in the E(max) of 5-HT(2A) receptor-mediated oxytocin responses. In contrast, fluoxetine did not alter the (+/-)-DOI-induced increases in plasma ACTH, corticosterone, or renin. These data provide the first demonstration of selective neuroadaptive responses in 55-HT2A serotonin receptor function due to prepubescent treatment with fluoxetine. These data may be clinically relevant with respect to the use of selective serotonin reuptake inhibitors in children and adolescents.     

Suicide after deliberate self-harm: a 4-year cohort study

OBJECTIVE: The purposes of this study were to estimate suicide rates up to 4 years after a deliberate self-harm episode, to investigate time-period effects on the suicide rate over the follow-up period, and to examine potential sociodemographic and clinical predictors of suicide within this cohort. METHOD: This prospective cohort study included 7,968 deliberate self-harm attendees at the emergency departments of four hospital trusts in the neighboring cities of Manchester and Salford, in northwest England, between September 1, 1997, and August 31, 2001. Suicide rates and standardized mortality ratios (SMRs) for the cohort were calculated. Potential risk factors were investigated by using Cox's proportional hazards models. RESULTS: Sixty suicides occurred in the cohort during the follow-up period. An approximately 30-fold increase in risk of suicide, compared with the general population, was observed for the whole cohort. The SMR was substantially higher for female patients than for male patients. Suicide rates were highest within the first 6 months after the index self-harm episode. The independent predictors of subsequent suicide were avoiding discovery at the time of self-harm, not living with a close relative, previous psychiatric treatment, self-mutilation, alcohol misuse, and physical health problems. CONCLUSIONS: The results highlight the importance in a suicide prevention strategy of early intervention after an episode of self-harm. Treatment should include attention to physical illness, alcohol problems, and living circumstances. Self-harm appears to confer a particularly high risk of suicide in female patients.     

Management of acute cerebellar stroke

Acute cerebellar infarction or hemorrhage may initially manifest in a clinically indolent manner only to later deteriorate into a life-threatening neurologic catastrophe. At the other end of the spectrum, some patients with cerebellar stroke may present in a moribund comatose state. In both patient groups, it is often unclear at what point surgical intervention should be considered either to prevent further neurologic deterioration or to try to salvage a meaningful neurologic recovery. In this review, we present clinical cases that illustrate decision points in the management of patients with acute cerebellar stroke, with emphasis on clinical and imaging characteristics. We conclude with an analysis of clinical decision making in the management of patients with space-occupying cerebellar stroke. The management of acute cerebellar infarction or hemorrhage often requires difficult and prompt decisions by treating neurologists, and certain easily identifiable clinical and imaging findings may assist in appropriate patient triage and timely neurosurgical intervention.     

A single-blind, open-label trial of sodium oxybate for myoclonus and essential tremor

The authors performed an open-label, rater-blinded, add-on study of sodium oxybate in 20 patients with ethanol-responsive myoclonus or essential tremor. Blinded ratings of videotaped examinations showed improvements in myoclonus at rest, stimulus-sensitive myoclonus, action myoclonus, functional performance, and postural and kinetic tremor. Tolerability was acceptable, and more than half of the patients chose to continue treatment after the trial. Double-blind placebo-controlled studies in these disorders are warranted.     

A visual aid for computer-based analysis of sleep-wake state in rats

Computer-based sleep scoring systems are often calibrated by reference to a conventional visual analysis of electroencephalographic (EEG) and electromyographic (EMG) traces. However, these types of data place high demands on digital storage capacity which may limit the duration or feasibility of some studies. The present paper describes an approach to visual analysis that involves reconstruction of a waveform (termed a "pseudopolygram" (PPG)) from conditioned data derived from the EEG and EMG. The PPG is the sum of three sine waves, each of which has a distinct frequency (non-REM sleep (NREM), 3 Hz; rapid eye movement sleep (REM), 7 Hz and wakefulness (WAKE), 60 Hz) and amplitude proportional to the value of a state-specific scoring variable. Thus, in NREM sleep the wave depicting the NREM quantifier has high amplitude and produces a PPG with dominant 3 Hz frequency. In REM sleep, the wave depicting the REM quantifier has high amplitude and produces a PPG with a dominant 7 Hz frequency, and in WAKE the PPG is dominated by 60 Hz. Thus, the PPG provides a means for visual discrimination of the three behavioural states. Validation studies found an overall reliability of 94% compared with conventional visual analysis of EEG and EMG. The PPG was also found to remain accurate in rats after 24 h of sleep deprivation.     

The Webcam system: a simple, automated, computer-based video system for quantitative measurement of movement in nonhuman primates

Investigations using models of neurologic disease frequently involve quantifying animal motor activity. We developed a simple method for measuring motor activity using a computer-based video system (the Webcam system) consisting of an inexpensive video camera connected to a personal computer running customized software. Images of the animals are captured at half-second intervals and movement is quantified as the number of pixel changes between consecutive images. The Webcam system allows measurement of motor activity of the animals in their home cages, without devices affixed to their bodies. Webcam quantification of movement was validated by correlation with measures simultaneously obtained by two other methods: measurement of locomotion by interruption of infrared beams; and measurement of general motor activity using portable accelerometers. In untreated squirrel monkeys, correlations of Webcam and locomotor activity exceeded 0.79, and correlations with general activity counts exceeded 0.65. Webcam activity decreased after the monkeys were rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the correlations with the other measures of motor activity were maintained. Webcam activity also correlated with clinical ratings of parkinsonism. These results indicate that the Webcam system is reliable under both untreated and experimental conditions and is an excellent method for quantifying motor activity in animals.