Excellent treatment for Alzheimer's disease remains an unmet medical need. Although current therapies improve patients' abilities compared to placebo and temporarily maintain performance above baseline on a number of outcome measures, additional therapies are needed to augment the benefits over baseline and to prolong these improvements.

Depersonalization disorder (DPD) is characterized by a subjective sense of detachment from one's own being and a sense of unreality. An examination of the psychobiology of depersonalization symptoms may be useful in understanding the cognitive-affective neuroscience of embodiment. DPD may be mediated by neurocircuitry and neurotransmitters involved in the integration of sensory processing and of the body schema, and in the mediation of emotional experience and the identification of feelings. For example, DPD has been found to involve autonomic blunting, deactivation of sub-cortical structures, and disturbances in molecular systems in such circuitry. An evolutionary perspective suggests that attenuation of emotional responses, mediated by deactivation of limbic structures, may sometimes be advantageous in response to inescapable stress.

This discussion will focus on medical comorbidity and recovery in individuals with bipolar disorder. The complexity of care will be discussed in the context of a case study, with particular focus on the medical burden of mania, aging and bipolar disorder, and treatment approaches that promote functional recovery.

Jerome M. Siegel, PhD, is professor of psychiatry at the University of California, Los Angeles, former president of the Sleep Research Society, and the recipient of Merit and Javits awards from the National Institutes of Health and the Distinguished Scientist award from the Sleep Research Society. His laboratory has made discoveries concerning the role of hypocretin in human narcolepsy and Parkinson's disease. He has studied the phylogeny of sleep as a clue to sleep function, discovering that the primitive mammal platypus has rapid eye movement sleep and that marine mammals can go without extended periods of sleep for long periods without ill effects.

As a competitive adenosine antagonist, caffeine affects dopamine transmission and has been reported to worsen psychosis in people with schizophrenia and to cause psychosis in otherwise healthy people. We report of case of apparent chronic caffeine-induced psychosis characterized by delusions and paranoia in a 47-year-old man with high caffeine intake. The psychosis resolved within 7 weeks after lowering caffeine intake without use of antipsychotic medication. Clinicians might consider the possibility of caffeinism when evaluating chronic psychosis.

Review of extant biological data would suggest that major depressive disorder (MDD) is a term used to subsume a syndrome that may involve a variety of different pathophysiological processes. Current research has implicated a myriad of different factors in the pathogenesis of depressive disorders including: genetic predisposition, “hormonal” abnormalities, disturbances in neurostransmitters, disturbances in neurocircuitry, and immune dysfunction. Our most recent consensus suggests that the depressive disorders reflect the interplay between these biological systems and psychosocial experiences, such as early-life trauma and current life stressors. Thus, MDD truly represents a complex heterogeneous syndrome. This conceptualization suggests that a variety of different types of treatment approaches will be necessary to adequately ameliorate the symptoms of patients suffering from this syndrome. Although this is a daunting task, we are beginning to develop approaches that will enable us to add to our armamentation of biological treatments.

Introduction: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.

Methods: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.

Results: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.1%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).

Conclusion: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.

Medical presentations can be enhanced by systematically collecting audience feedback. This is readily accomplished with polling systems, called audience response systems. Several systems are now available that are small, inexpensive, and can be readily integrated into standard powerpoint presentations without the need for a technician. Use of audience response systems has several advantages. These include improving attentiveness, increasing learning, polling anonymously, tracking individual and group responses, gauging audience understanding, adding interactivity and fun, and evaluating both participant learning and instructor teaching. Tips for how to write questions for audience response systems are also included.

Background: Inadequate response to antidepressant monotherapy in women with major depressive disorder is common. Testosterone administration has been shown to be an effective augmentation therapy in depressed hypogonadal men with selective serotonin reuptake inhibitor-resistant depression. However, the effects of low-dose testosterone as augmentation therapy in women with treatment-resistant depression have not been studied.

Methods: Low-dose transdermal testosterone (300 mcg/day, Intrinsa, Procter and Gamble Pharmaceuticals) was administered to nine women with treatment-resistant depression in an 8 week open-label pilot protocol.

Results: There was a statistically significant improvement in mean Montgomery-Asberg Depression Rating Scale (MADRS) scores at 2 weeks, sustained through the 8 week period. Two-thirds of subjects achieved a response to the treatment (decrease in MADRS score of ≥50%) and 33% achieved remission (final MADRS score <10) after 8 weeks of therapy. Mean levels of fatigue, as measured by the MADRS lassitude item, significantly decreased at all time points with a mean 38% decrease from baseline to 8 weeks.

Conclusion: These preliminary pilot data suggest that low-dose transdermal testosterone may be an effective augmentation therapy in women with treatment-resistant depression. Further studies are warranted.

Introduction: We studied the relationship between obsessive-compulsive disorder (OCD) and lifetime history of any traumatic events among methadone maintenance treatment (MMT) patients.

Methods: In a cross-sectional sample of 167 patients, we clinically assessed for OCD using the Yale-Brown Obsessive Compulsive Scale and interviewed for their lifetime history of traumas.

Results: OCD was defined among 40.1% patients. Sixteen percent of patients reported having been victims of sexual abuse or rape, 21.6% had self-inflicted physical injuries, 34.1% attempted suicide, 44.9% sustained other physical violence or abuse, 28.7% were involved in a car accident as drivers and 6% as passengers, and 16.8% had significant falls. Patients with OCD compared with patients without OCD included more rape victims (28.4% vs. 9%), had more self-inflicted physical injuries (31.3% vs. 15%), and had more suicide attempts (46.3% vs. 26%), with no differences in other traumatic events exposure. The OCD group was characterized as being female (OR=4.0 [95% CI 1.7-9.3]), having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision Axis I psychiatric disorder (OR=2.6 [95% CI 1.2-5.5]), being Israeli born (OR=2.9 [95% CI 1.2-6.9]), abusing benzodiazepines (OR=2.2 [95% CI 1.02-4.6]), having attempted suicide (OR=2.5 [95% CI 1.1-5.4]), and having longer duration of opiate abuse before admission to MMT (OR=1.06 [95% CI 1.01-1.1]).