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High cortisol levels are found in severe mood disorders, particularly bipolar disorder. Hypercortisolaemia may cause or exacerbate both neurocognitive impairment and depressive symptoms. We hypothesized that antiglucocorticoid treatments, particularly corticosteroid receptor antagonists, would improve neurocognitive functioning and attenuate depressive symptoms in this disorder. To test this hypothesis, 20 bipolar patients were treated with 600 mg/day of the corticosteroid receptor antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind crossover design. Over the total 6 weeks of the study, neurocognitive and neuroendocrine function were evaluated at baseline, days 21 and 42. Mood symptoms were evaluated weekly. Nineteen subjects completed the protocol; there were no drop-outs due to adverse events. Following treatment with mifepristone, selective improvement in neurocognitive functioning was observed. Spatial working memory performance was significantly improved compared to placebo (19.8% improvement over placebo). Measures of verbal fluency and spatial recognition memory were also improved after mifepristone. Beneficial effects on mood were found; Hamilton Depression Rating Scale scores were significantly reduced compared to baseline (mean reduction of 5.1 points) as were Montgomery-Asberg Depression Rating Scale scores (mean reduction of 6.05 points). No significant change occurred after placebo. These data require replication but provide preliminary evidence that glucocorticoid receptor antagonists may have useful cognitive-enhancing and possibly antidepressant properties in bipolar disorder.

Systemic (but lawful) political corruption reduces well-being and equity in America. The original form of Madisonian democracy is no longer capable of containing such corruption. Proposals currently on the table to stem corruption are unlikely to be effective and tend to undermine basic rights. This Essay describes a new, but still Madisonian, approach—regulating the output of corrupted legislative and administrative processes, rather than the inputs. Providing for substantive ex post review of direct and delegated legislation would be far more protective of the “general welfare” of the People than other reforms, while no more or less difficult to implement. Supporting an “umpire” branch may be a dominant strategy for elites themselves.

Whether the firms that supply Internet hardware and software should face restrictions on the use of their property is an important and controversial policy issue. Advocates of \"net neutrality\"—including President Obama and the current FCC majority—believe that owners of broadband distribution systems (hardware used to distribute Internet and video services) and producers of certain \"must-have\" video content should be subject to prophylactic regulation that transcends present-day antitrust law enforcement. In the economic terms that are used in debates on competition policy, the concern is with vertical integration that may give firms both the opportunity (through denial of access or price discrimination) and incentive (increased profit) to restrict competition. This paper's central point is that virtually every production process in the economy is vertically integrated, and economics predicts changes in the extent of vertical integration—that is, changes in the boundaries of the firm—in response to changes in relative prices, technology, or institutions. Both vertical integration and changes in the extent of vertical integration are benign characteristics of efficient, dynamic, competitive markets. While there is no shortage of theoretical models in which vertical integration may be harmful, most such models have restrictive assumptions and ambiguous welfare predictions—even when market power is assumed to be present. Empirical evidence that vertical integration or vertical restraints are harmful is weak, compared to evidence that vertical integration is beneficial—again, even in cases where market power appears to be present. Thus, it is reasonable to conclude that prophylactic regulation is not necessary, and may well reduce welfare. Sound policy is to wait for ex post evidence of harm to justify interventions in specific cases. Net neutrality, recently enacted by the FCC but subject to judicial review, is an unfortunate idea.

On Aug 30, 2007, China's National People's Congress finally adopted the Anti-Monopoly Law (AML). The AML has provisions found in most other countries' antitrust laws, such as the prohibition of horizontal agreements and abuse of market power, and requirements for pre-merger notifications and reviews. The AML also contains many provisions not typical of antitrust laws, such as provisions regarding State-Owned Enterprises (SOEs) in important economic sectors, trade associations, and monopolies created by government agencies. The AML was being drafted -- and will be enforced -- against the backdrop of China's historic transformation from a centrally planned economy to a market economy. While the AML specifically prohibits enterprises in strategic sectors -- all of which are SOEs currently -- from hurting consumer interests by virtue of their dominant status, it is not clear whether such prohibitions will be vigorously enforced. In enforcing the AML, China needs to actively pursue these broader competition policy reforms.

The effect of early-life vulnerability factors on the subsequent pathophysiology of severe mood disorders has yet to be fully elucidated. This study examines the relationship between early adverse life experience, family history and hypothalamic-pituitary-adrenal (HPA) axis function. Childhood trauma questionnaire (CTQ) scores, family history data and the cortisol response to the dexamethasone/corticotrophin releasing hormone (dex/CRH) test were examined in 40 patients with severe mood disorder. Normative data for the CTQ was also obtained. The study demonstrated that mood disorder patients reporting high levels of childhood emotional neglect (n = 26) had an HPA axis response which did not differ from controls, whereas patients reporting low levels (n = 19) had an enhanced response (p = 0.011). A positive family history of mood disorder further enhanced this response. These data suggest that early adverse life events and genetic susceptibility have dissociable effects on glucocorticoid receptor-mediated negative feedback of the HPA axis in adult patients with severe mood disorders.

Enhancement of dopamine (DA) release by corticosteroids may be of aetiological importance in substance misuse. To examine the effect of sub-chronic administration of hydrocortisone on the response to amphetamine in healthy male volunteers. Following baseline assessment, 20 volunteers were pretreated for 7 days with 20 mg of hydrocortisone or placebo at 0800 hours and 2000 hours in a double-blind, random order, cross-over design prior to receiving 0.15 mg/kg metamphetamine intravenously. Blood samples for cortisol and prolactin were taken every 15 min. Subjects also underwent tests of neuropsychological function including sustained attention using the rapid visual information processing test (RVIP), which has been shown to be sensitive to changes in DA function. Metamphetamine produced a substantial reduction in prolactin levels, and increased subjective mood ratings of \"mind-race\" and \"buzz\". Sub-chronic hydrocortisone administration had no effect on these neuroendocrine responses, subjective mood changes or neurocognitive performance on a task of sustained attention (RVIP). Despite measurable changes in neuroendocrine and affective functioning in response to metamphetamine, pretreatment with hydrocortisone did not significantly affect any of the variables measured. This suggests that this model of DA function is not affected by this regimen of corticosteroid administration.

This concise and practical handbook covers the breadth of psychiatric conditions with which sportspeople may present.