Wegener granulomatosis (WG) is an uncommon, idiopathic disorder that is characterized by granulomatous inflammation of the upper and lower respiratory tract, disseminated vasculitis involving small and medium-sized vessels, and focal segmental glomerulonephritis. Approximately 25% to 50% of patients have nervous system involvement. The brain is less frequently involved. We report a case of a 74 year-old previously well woman who presented with rapidly progressing WG that culminated in subarachnoid hemorrhage. Only six cases of subarachnoid hemorrhage in the setting of WG have previously been reported. We review the common presenting signs and symptoms, diagnosis, treatment, and complications of WG.

Objective: To assess the impact of childhood conduct disorder (CD) and intelligence quotient (IQ) on later substance use in adolescence.

Methods: Neuropsychological and structured diagnostic evaluations were initially administered to 32 children with disruptive behavior disorder when they were 7–11 years of age. They were then re-evaluated on average 6.7 years later using an array of interviews and rating scales with a focus on substance use.

Results: Early CD and IQ scores together accounted for a significant proportion of the variance in later substance use (R2=.248). In addition, there was a significant CD and Verbal IQ interaction (R2=.164) such that high Verbal IQ was linked to increased substance use in adolescents who had childhood CD.

Conclusion: These data indicate that the presence of conduct disorder may interact with high Verbal IQ during childhood in such a way as to predict later adolescent substance use in disruptive behavior disorder populations.

Genetic anticipation refers to an inheritance pattern within a pedigree showing a decrease in age of onset or an increase in disease severity or both in successive generations. This phenomenon has become the focus of important research in schizophrenia and bipolar mood disorder. The results to date have been controversial and far from conclusive. To attempt to resolve some of the earlier findings, we compared age at onset and disease severity between two generations in 24 Portuguese families ascertained for genetic linkage studies of bipolar mood disorder. There was a significant decrease in age of onset (P<. 00001) and increase in frequency of episodes (P<.0001)from the first to the second generation. This difference was significant under each of the four data-sampling schemes, one of which excluded probands. The second generation experienced onset 12.4 to 15.9 years earlier and illness 2.3 to 2.6 times more severe than did the first generation. We found no evidence for a specific effect in anticipation related to the transmitting parent's sex. Results of the present study, analyzed carefully for a variety of possible biases, suggest evidence for genetic anticipation in these Portuguese bipolar families.

Patients with involuntary emotional expression disorder (IEED) have impaired social and occupational functioning and there is currently no Food and Drug Administration-approved treatment. Treatment options include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), dopaminergic agents, and a combination of dextromethorphan and quinidine. Studies of monaminergic agents have typically been small and executed in single-center settings. Assessment measures generally show significant symptomatic improvements, including a reduction in the number of laughing or crying episodes and improvements in patients' clinical condition. The tolerability profiles of these agents are well defined, and include dizziness, tachycardia, and QTc prolongation (TCAs), and sleep and sexual disturbances (SSRIs). The combination of dextromethorphan and quinidine has also been assessed in two large multicenter studies in patients with amyotrophic lateral sclerosis and multiple sclerosis. Compared with placebo and either agent alone, there were significant improvements in symptoms, quality of life, and relationships. The most common side effects were dizziness and nausea, and potential drug interactions with quinidine should also be considered. Choice of treatment should be evidence-based, taking into account both efficacy and tolerability.

This case report describes a patient with reportedly new onset of tics, beginning at 21 years of age, in the context of posttraumatic stress disorder (PTSD) and comorbid alcohol abuse, with no known head injury. The setting is an American Society of Addiction Medicine intensive outpatient substance abuse rehabilitation program in an United States Army Medical Center. The patient is a 22-year-old male diagnosed with alcohol abuse and delayed PTSD who presented to the program's medical officer due to insomnia. We discovered he had a reportedly new ocular tic of ∼9 months duration, which he claimed developed at 21 years of age soon after returning from 1 year of combat duty. The patient was thoroughly evaluated, and we surmised the tic was a symptom of PTSD. After achieving full remission from alcohol, the tic persisted. However, as his PTSD symptoms remitted, so did his tic symptoms. At 6-month follow-up, the patient reported he was essentially free from PTSD symptoms, and his tic was significantly reduced.

Behavioral patterns of addiction include compulsive drug-seeking, persistent abuse of substances despite the often dire consequences on social functioning and physical health, and the high probability of relapse even after prolonged drug-free periods.The recent focus on the biological basis of addiction has provided evidence to support the hypothesis that behavioral manifestations for addiction are influenced by biological factors, and biological factors often produce behavioral changes that can further increase risk. The current understanding of the role of the dopaminergic, glutamatergic, γ-aminobutyric acidergic, and opioid receptor systems in the pathophysiology of addiction as well as the clinical implications of these systems for new and emerging treatments will be discussed. This article will also review the pharmacologic agents used in the treatment of substance abuse disorders and presents evidence-based data for their safety, efficacy, and feasibility of use in different patient populations.

Optimal management of depression remains a long-term challenge. Long-term maintenance treatment with antidepressants has been shown to be effective for preventing or delaying recurrence for many patients with a history of previous multiple episodes. However, aside from a history of multiple recurrences, it remains difficult to identify patients who are most likely to experience recurrence and when. Thus we do not really know who might particularly benefit from maintenance therapy and what type may be efficacious. In patients with depression, research has shown there are structural and functional alterations in the brain, particularly in patients with recurrent or chronic depression. These changes have been generally viewed to be consequences of the disease, which are seen to worsen with a longer duration of untreated illness and with a greater number of depressive episodes. However, these neurobiological characteristics may also represent risk factors or vulnerabilities that predispose some patients to chronic or recurrent depression. Additional research has demonstrated that antidepressant treatment may reduce or modulate these functional and structural changes, suggesting that long-term treatment may, in fact, benefit patients not only by controlling symptoms but also by managing these underlying vulnerabilities. A new treatment paradigm, which focuses on identifying patients with risk factors and managing the disease process rather than suppression of symptoms, is needed for recurrent depression.

Although psychotic symptoms are a recognized manifestation of epilepsy, these are more often associated with seizures of the temporal lobe type. While 10% of children with temporal lobe epilepsy develop a psychotic disorder by adulthood, the literature does not report any cases of psychotic disorders associated with frontal lobe seizures in children. This article presents a unique case of a girl whose frontal lobe seizures were associated with delusional psychotic symptoms. Once her seizure disorder was identified through electroencephalography (EEG) and appropriate anticonvulsant therapy was initiated, her associated psychotic symptoms resolved.

In this review, we describe proposed circuits mediating the mechanism of action of pherines, a new class of synthetic neuroactive steroids with demonstrated antianxiety and antidepressant properties, that engage nasal chemosensory receptors. We hypothesize that afferent signals triggered by activation of these peripheral receptors could reach subgroups of olfactory bulb neurons broadcasting information to gamma-aminobutyric acid (GABAergic) and corticotropin-releasing hormone (CRH) neurons in the limbic amygdala. We propose that chemosensory inputs triggered by pherines project to centrolateral (CeL) and centromedial (CeM) amygdala neurons, with downstream effects mediating behavioral actions. Anxiolytic pherines could activate the forward inhibitory GABAergic neurons that facilitate the release of neuropeptide S (NPS) in the locus coeruleus (LC) and GABA in the bed nucleus of the stria terminalis (BNST) and inhibit catecholamine release in the LC and ventral tegmental area (VTA) leading to rapid anxiolytic effect. Alternatively, antidepressant pherines could facilitate the CRH and GABAergic neurons that inhibit the release of NPS from the LC, increase glutamate release from the BNST, and increase norepinephrine (NE), dopamine (DA), and serotonin release from the LC, VTA, and raphe nucleus, respectively. Activation of these neural circuits leads to rapid antidepressant effect. The information provided is consistent with this model, but it should be noted that some steps on these pathways have not been demonstrated conclusively in the human brain.

Los Angeles County’s Office of Diversion and Reentry (ODR) has removed over 3800 people from the largest jail system in the country. Across various diversion programs, ODR’s fundamental goal is to provide permanent, lifetime care for each diverted person. This article describes ODR’s various diversion programs, and elucidates the types of elaborate clinical and court-related interventions that are necessary to remove persons with serious mental disorders from jail custody. As Los Angeles continues to build the necessary community-based continuum of mental health care, ODR’s model proves that thoughtfully removing persons with serious mental disorders from jail is possible and necessary for the health of both patients and community.

More than a decade of failure to find disease-modifying treatments for Alzheimer’s dementia has driven the field back to finding better symptomatic treatments for behavioral symptoms of dementia, especially psychosis and agitation.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions.

Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.

Dosing patterns with second-generation antipsychotic medications (SGAs) are dynamic, with some SGAs surpassing current recommendations while others are declining in dose since their initial regulatory guidelines. Pertinent recent studies and available pharmacoepidemiologic reports, information, and expert consenses are reviewed herein to illuminate current thinking on the topic of dosing with SGAs. There is a need for fixed-dose studies of each SGA. Additionally, dosing should be a primary consideration when designing and subsequently interpreting comparative studies between SGAs.

Many commonly prescribed drugs exist as a mixture of two distinct chiral isomer forms (enantiomers), each with its own unique chemistry, receptor affinity, and pharmacokinetic profile. Much is unknown concerning the clinical utility of these single enantiomers. This review of the stereoisomers of two commonly used drugs—albuterol for asthma and omeprazole for gastroesophageal reflux disease (GERD) and peptic ulcers—examines the improved efficacy, pharmacokinetics, decreased adverse effects, and fewer drug-drug interactions associated with single enantiomers.