What makes a drug a primary mood stabilizer?

The term 'mood stabilizer' has been applied to a number of medications for the treatment of patients with bipolar disorder. The operational definition of the properties of a mood-stabilizing medication has varied according to the properties of specific medications and the clinical characteristics of the illness. Randomized controlled trials of agents accepted or proposed as mood stabilizers are reviewed to marshall the available evidence in support of this claim. In addition, potential pharmacological mechanisms underlying mood-stabilizing effects of established compounds are reviewed.     

Is brain estradiol a hormone or a neurotransmitter?

Mounting evidence indicates that, besides their well-known hormonal mode of action at the genetic level, estrogens such as 17beta-estradiol also influence brain function by direct effects on neuronal membranes. Experimentally induced rapid changes in estradiol bioavailability in the brain have been shown to alter the expression of male sexual behavior significantly within minutes--probably too quickly to be accounted for by conventional genetic mechanisms. In parallel, recent studies indicate that aromatase, the enzyme that converts testosterone to estradiol in the brain, is expressed in presynaptic terminals and modulated within minutes by Ca(2+)-dependent phosphorylation. In this article, we develop the hypothesis that brain estrogens display many, if not all, functional characteristics of neuromodulators or even neurotransmitters.     

Is health care a right or a commodity? Implementing mental health reform in a recession

The Patient Protection and Affordable Care Act, signed into law by President Obama in March 2010, contains elements of two seemingly contradictory positions: health care as a commodity and as a right. The commodity argument posits that the marketplace should govern demand, supply, and costs of care. The law's establishment of state insurance exchanges reflects this position. The argument that health care is a right posits that it is a need, not a choice, and that government should regulate care standards that may be compromised as insurers attempt to minimize costs. The law's requirement for coverage of mental and substance use disorders reflects this position. This Open Forum examines these arguments in light of current state fiscal crises and impending reforms. Despite the federal government's interest in expanding prevention and treatment of mental illness, states may demonstrate varying levels of commitment, based in part on their perception of health care as a right or a commodity. The federal government should outline clear performance standards, with minimum services specified to maximize state commitments to services.     

CGRP en migraña: de la fisiopatología a la terapéutica

IntroductionIt has been observed in recent years that levels of such molecules as calcitonin gene–related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase–activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients’ migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity.DevelopmentThe Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics.ConclusionsThe clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.     

Can a generalized kindling seizure induce a reward state?

The postictal behavioral depression (PBD), characterized by behavioral immobility and unresponsiveness to environmental stimuli, observed after a stage 5 kindling seizure is opioid dependent. Morphine injection prolongs while naloxone and naltrexone (opioid antagonists) reduce or eliminate PBD. Opioids have clear rewarding actions that can be easily detected by place preference conditioning (PPC). In the present study, we evaluated if the opioid release after a stage 5 kindling seizure that produces PBD could induce PPC. Male rats were kindled in the medial preoptic area (MPOA), the amygdala (AMG) or insular cortex (IC). After kindling was established their initial preference in a three-compartment chamber was determined. During conditioning, subjects received a standard kindling stimuli that evoked a stage 5 seizure. At the end of the after discharge and during the PBD the animals were placed in the non-preferred chamber for 30 min. On alternate days they were placed without stimulation in the preferred chamber. At the end of conditioning the kindled groups showed a clear change of preference. This change of preference was completely blocked by injection of naloxone. These results suggest that opioid release after a stage 5 kindling seizure can induce a positive affect of sufficient intensity and duration to induce conditioning.     

L-tryptophan: a rational anti-depressant and a natural hypnotic?

L-tryptophan is an essential amino acid which is the metabolic precursor of serotonin. Because of the evidence that serotonin deficiency may be an aetiological factor in some sorts of affective disorder and that serotonin is important in the biochemistry of sleep, L-tryptophan has been suggested as a "rational" anti-depressant and as a "natural" hypnotic. This paper reviews the biochemistry and pharmacology of L-tryptophan as well as the literature of the clinical trials that have been conducted with it and suggests that, by itself, L-tryptophan may be useful in mild cases of depression accompanied by endogenous features and cases of bipolar disorder resistant to standard treatments. It also potentiates the monoamine oxidase inhibitors and possibly the serotonergic tricyclic drugs. L-tryptophan may improve the depressed mood of Parkinsonian patients and has a clinically useful hypnotic action. There is evidence it may be useful in organic mental disorders induced by levodopa. Dosage schedules, contraindications and complications are discussed.     

When is a sex difference not a sex difference?

Brain sexual differentiation in mammals requires activity of gonadal hormones; organizational effects of these steroids on brain development occur early in life while activational ones in adulthood ensure appropriate and timely sex-specific behaviors. This traditional view has long served as a reliable model for sexual differentiation of reproductively relevant brain structures. Here, we take a fresh look at this model but refocused in the context of sexual differentiation of non-reproductive parameters and with an emphasis on the hippocampus, a telencephalic brain structure predominantly involved in cognition and stress regulation. We explore sex differences in morphology, neurochemistry, and hippocampal-dependent behaviors to propose a new prototype that can be used to explain and further investigate the effects of steroid hormones, those synthesized gonadally or intracerebrally, on hippocampal development and function. We also propose that a new vernacular be employed, one that distinguishes hormonally modulated responses from sex differences, and argue these are mechanistically and functionally distinct. Understanding when and how the sexes are different is as important as understanding when and how they are the same, at the biological, social, and cultural level.     

Is a "vanishing tumor" always a lymphoma?

The authors report clinical and radiologic characteristics and ultimate diagnosis in 12 patients with a regressing cerebral mass lesion. Primary CNS lymphoma (PCNL) was found in only half of the patients with such a lesion. In patients showing a complete resolution of the enhancing lesion the probability of finding a PCNL is smaller and survival is longer.