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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.
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PMID:Functional neurosurgery for movement disorders: a historical perspective. 1966 Jun 68

Fentanyl is a potent Schedule II narcotic analgesic recommended for use in the management of unremitting pain not controlled by morphine or other opiate/opioid drugs. The danger inherent to fentanyl is its potency (greater than 50-100 times that of morphine) and rapidity of action, causing respiratory depression within minutes of administration. Advisories have been issued on a state and national level to health care providers and through manufacturers' package inserts for patients. Still, as will be demonstrated in this case review, the use of only a single transdermal patch taken as prescribed for the first time can prove fatal. A drug that requires such extensive warnings-that if unheeded lead to death because of its narrow therapeutic/toxic window, should have strict criteria and limited outpatient use. Initial medical observation and documentation for determining tolerance might be required before issuing a prescription. There has been a rise in the popularity of this drug evidenced by increased deaths among drug abusers and more prescriptions written. In the year 2006, the Center for Forensic Sciences in Onondaga County had 8 cases where fentanyl was considered the cause of death, often with other drugs detected in therapeutic concentrations. This number was a marked increase from the 1 to 2 cases occurring annually from 2002 to 2005. All of these 2006 overdoses because of fentanyl involved the transdermal formulation. The investigative data, blood and liver fentanyl levels, and autopsy findings will be presented.
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PMID:Deaths with transdermal fentanyl patches. 1991 62

A review of the literature suggests mixed findings on the effects of prenatal antidepressants. Although the critical question is the relative effects of depression versus antidepressants during pregnancy, randomized control studies do not exist for this comparison. Instead, nondepressed, nontreated control groups have been used for comparisons. Separate studies suggest that both untreated depression and exposure to antidepressants have been associated in some cases with unfavorable outcomes. Studies on long-term neurodevelopmental outcomes for children have also been inconclusive. Another problem for the mother and fetus is the discontinuation of antidepressants. Research on the selective serotonin reuptake inhibitors (SSRIs) suggests that late pregnancy exposure may have worse effects than first and second trimester exposure, leading to the neonatal abstinence syndrome. Still other data suggest a dual syndrome of abstinence/withdrawal and of serotonergic overstimulation, with symptoms of the two syndromes being very similar. Several confounding factors have contributed to this mixed literature including the already mentioned lack of a depressed, nonantidepressant control group as well as group variability on the types of SSRIs taken and severity of their effects, and limited longitudinal follow-up data. Future research would not only need to correct these problems but also further explore the different trimester effects and the withdrawal versus serotonin activity effects on the infant. In addition, alternative therapies need to be explored for their potential antidepression effects on the pregnant woman, the fetus, and the neonate.
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PMID:Prenatal depression and selective serotonin reuptake inhibitors. 2037 82

Use of the anti-acne drug, Accutane (ACC) (isotretinoin, 13-cis-retinoic acid), has been associated with neuropsychiatric events ranging from depression in animal models to depression and suicide ideation in humans. Our studies, however, have consistently indicated few effects on measures of depression in male and female rats. Still, the comorbidity of depression and anxiety suggests that anxiety assessments in ACC-treated rats could be informative. Such assessments must be balanced with measures of activity since drug-induced activity alterations may impact the expression of anxiety-like behaviors. Here, Sprague-Dawley rats (n=15/sex/dose) were gavaged daily with 0 (soy oil), 7.5, or 30 mg/kg/day ACC beginning on postnatal day (PND) 59. Blood ACC levels similar to humans taking recommended ACC doses are produced by 7.5mg/kg/day. Short-term activity was assessed in open fields prior to ACC treatment (PND 51) and again at PNDs 129 and 164 and in a complex environment at PNDs 66 and PND 184. Long-term residential activity was measured in running wheels (PNDs 85-92) and figure 8 mazes (PNDs 99-106). Anxiety-like behavior was assessed via elevated plus maze (EPM) activity on PND 98 and in a black/white apparatus on PND 125. The typical sex differences in most behaviors were exhibited (i.e., increased EPM open arm entries and overall activity in most measures in females); however, there were no significant effects of ACC treatment on open field activity, complex environment activity, residential running wheel activity, or EPM activity. Residential figure 8 maze activity indicated that male and female rats treated with 30 mg/kg/day were less active on all nights (p<0.05) and females treated with 7.5 or 30 mg/kg/day were less active than same-sex controls on most days (p<0.05). Similarly, rats of both sexes treated with 30 mg/kg/day were significantly less active in the black/white apparatus (p<0.05), entering the darkened area less frequently (p<0.05), although duration in the darkened area did not differ. These data indicate that at blood levels typically achieved by humans (i.e., the 7.5 mg/kg group), there are no significant anxiogenic effects associated with ACC treatment. At higher ACC levels, there are mild effects on activity but these appear to be apparatus- and/or age-specific.
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PMID:Chronic oral treatment with isotretinoin alters measures of activity but not anxiety in male and female rats. 2038 7

Major depression (MD) has been projected to be the first leading cause of disability worldwide. Still, the pathophysiological processes and factors leading to depression remain largely unknown. The present study investigated the differential effects of selective medial prefrontal cortex (mPFC) and subthalamic nucleus (STN) lesions on depression-like and depression-associated behavior in rats, using the following behavioral paradigms: (i) learned helplessness model testing depressive behavior, (ii) elevated plus-maze testing anxious behavior, (iii) 8-arm radial maze testing cognitive performance and (iv) the open-field testing locomotion. Lesion of both, the mPFC or the STN selectively increased depression-like behavior in rats. These effects were not biased by any effects on depression-associated behavior, such as increased anxiety, cognitive impairment or deficits in locomotion. The behavioral data presented in this study support a specific involvement of the mPFC in the pathophysiology of MD and point towards a potent regulatory function of the STN in processing limbic information towards cortical and subcortical regions in the brain pathophysiologically relevant in the manifestation of MD.
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PMID:Lesion of the medial prefrontal cortex and the subthalamic nucleus selectively affect depression-like behavior in rats. 2043 89

Lithium occurs naturally in food and water. Low environmental concentrations in drinking water are associated with mental illnesses and behavioural offences, and at therapeutic dosages it is used to treat psychiatric (especially affective) disorders, partly by facilitating serotonergic (5-HT) neurotransmission. As little is known about the psychophysiological role of nutritional lithium in the general population, endogenous lithium concentrations were hypothesised to be associated with measurable effects on emotional liability and the loudness dependence (LD) that is proposed as one of the most valid indicators of 5-HT neurotransmission. Auditory evoked potentials of healthy volunteers [N=36] with high (>2.5 microg/l) or low (<1.5 microg/l) lithium serum concentrations were recorded. Emotional liability was assessed using the Brief Symptom Inventory (BSI). Low-lithium levels correlated with Somatisation while correlations between lithium and LD were not significant. Still, LD correlated positively with Paranoid Ideation, negatively with Anxiety and, in the high-lithium group, inversely with further aspects of emotional liability (Depression, Psychological Distress). In conclusion, the effects of low levels of endogenous lithium are associated with emotional liability, and high levels with some protective effects, although findings remain inconclusive regarding LD. Potential benefits of endogenous lithium on neurobehavioural functioning, especially in high-risk individuals, would have public health implications.
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PMID:Differential effects of endogenous lithium on neurobehavioural functioning: a study on auditory evoked potentials. 2045 41

Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.
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PMID:Suicide in schizophrenia. 2058 95

Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo.
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PMID:Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data. 2243 69

Recent developments in neuromorphic hardware engineering make mixed-signal VLSI neural network models promising candidates for neuroscientific research tools and massively parallel computing devices, especially for tasks which exhaust the computing power of software simulations. Still, like all analog hardware systems, neuromorphic models suffer from a constricted configurability and production-related fluctuations of device characteristics. Since also future systems, involving ever-smaller structures, will inevitably exhibit such inhomogeneities on the unit level, self-regulation properties become a crucial requirement for their successful operation. By applying a cortically inspired self-adjusting network architecture, we show that the activity of generic spiking neural networks emulated on a neuromorphic hardware system can be kept within a biologically realistic firing regime and gain a remarkable robustness against transistor-level variations. As a first approach of this kind in engineering practice, the short-term synaptic depression and facilitation mechanisms implemented within an analog VLSI model of I&F neurons are functionally utilized for the purpose of network level stabilization. We present experimental data acquired both from the hardware model and from comparative software simulations which prove the applicability of the employed paradigm to neuromorphic VLSI devices.
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PMID:Compensating Inhomogeneities of Neuromorphic VLSI Devices Via Short-Term Synaptic Plasticity. 2103 Oct 27

Expertise in medicating depression requires experience with all types of antidepressants, including several medications within each type. Likewise, electroconvulsive therapy (ECT) proficiency includes experience with each of the modern electrode placements, of which there are four. Besides traditional bilateral and right unilateral placements, ECT electrode placement includes bifrontal and left anterior right temporal (LART) placements. In comparing antidepressant drugs, clinical trials have proven few differences of statistical significance, and useful proven differences are still more unusual. Analogously, few differences have been proven between ECT electrode placements, and many reported differences can be accounted for by large differences in electrical stimulus dosage. Still, the absence of proven differences does not show that there are no useful variations. This paper reviews the meaningful differences that are generally appreciated from clinical experience and biomedical principles for ECT electrode placement as well as antidepressant drugs.
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PMID:Rational electroconvulsive therapy electrode placement. 2115 59


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