Clinical categorization of childhood syncope.

Syncope is a self-limited loss of consciousness produced by cerebral hypoperfusion/hypoxia. The objective of this study was to categorize the etiology and determine the frequency of concurrent epilepsy and whether laboratory testing is diagnostically useful. This was an institutional review board-approved retrospective chart review. Data were analyzed using descriptive statistics. There were 141 subjects (90 girls [63.8%]; mean age, 12.01 years). Of the syncope referrals, 86 of 123 (69.9%) had simple syncope, 35 of 123 (28.4%) had syncopal convulsions, and 2 of 123 (1.6%) had epilepsy alone. An electroencephalogram was performed in 64.7% (91/141) of the subjects but was diagnostic in 1 of 91 (1.4%) for epilepsy. Magnetic resonance imaging and/or computed tomography scans, electrocardiograms/Holter monitoring/stress testing, and blood tests were primarily normal or nondiagnostic, with 6 of 238 (2.5%) total tests contributing to the diagnosis. Primary neurocardiogenic syncope was identified in 78% (111/141) of all subjects (82% boys, 75% girls). Thirty-eight percent had syncopal convulsions, and 2.8% (4/141) had concurrent epilepsy. A detailed medical history was the most useful diagnostic tool.

New therapeutic targets for mood disorders.

Existing pharmacological treatments for bipolar disorder (BPD) and major depressive disorder (MDD) are often insufficient for many patients. Here we describe a number of targets/compounds that clinical and preclinical studies suggest could result in putative novel treatments for mood disorders. These include: (1) glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC), (2) the purinergic system, (3) histone deacetylases (HDACs), (4) the melatonergic system, (5) the tachykinin neuropeptides system, (6) the glutamatergic system, and (7) oxidative stress and bioenergetics. The paper reviews data on new compounds that have shown antimanic or antidepressant effects in subjects with mood disorders, or similar effects in preclinical animal models. Overall, an improved understanding of the neurobiological underpinnings of mood disorders is critical in order to develop targeted treatments that are more effective, act more rapidly, and are better tolerated than currently available therapies.

The Timing of Antidepressant Effects: A Comparison of Diverse Pharmacological and Somatic Treatments.

Currently available antidepressants used to treat major depressive disorder (MDD) unfortunately often take weeks to months to achieve their full effects, commonly resulting in considerable morbidity and increased risk for suicidal behavior. Our lack of understanding of the precise cellular underpinnings of this illness and of the mechanism of action of existing effective pharmacological treatments is a large part of the reason that therapies with a more rapid onset of antidepressant action (ROAA) have not been developed. Other issues that need to be addressed include heterogeneous clinical concepts and statistical models to measure rapid antidepressant effects. This review describes the timing of onset of antidepressant effects for various therapies used to treat MDD. While several agents produce earlier improvement of depressive symptoms (defined as occurring within one week), the response rate associated with such agents can be quite variable. These agents include both currently available antidepressants as well as other pharmacological and non-pharmacological interventions. Considerably fewer treatments are associated with ROAA, defined as occurring within several hours or one day. Treatment strategies for MDD whose sustained antidepressant effects manifest within hours or even a few days would have an enormous impact on public health.