The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Sleep disturbances, including nightmares and insomnia, are prominent following trauma and with posttraumatic stress disorder (PTSD) and likely contribute to the pathogenesis of the disorder. Findings from laboratory studies of PTSD have been inconsistent in terms of documenting objective impaired sleep maintenance but have been somewhat more consistent in indicating alterations of rapid eye movement (REM) sleep. Studies of the early aftermath of trauma can reduce the complexity associated with chronicity and comorbidity, and may have implications for early diagnosis and prevention. Multiple studies indicate that dream content is affected by recent threatening experiences. The development of PTSD is associated with a more replicative type of nightmare content. Sleep is reported to be generally disrupted following trauma especially among those developing PTSD. The limited number of studies that provide objective recorded indices during the early aftermath of trauma also provide a mixed picture regarding overall sleep maintenance. Recent data suggest that a more specific disruption of REM sleep may be associated with the development of PTSD and that this disruption is associated with an increased signal of sympathetic nervous system activation during REM sleep. Disrupted REM sleep and increased sympathetic/noradrenergic activity may have implications for understanding recent promising interventions for PTSD sleep disturbance that can be applied to early intervention.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the limbs accompanied by uncomfortable sensations, leading to sleep disturbances. It is associated with psychiatric comorbidities and a decreased quality of life. RLS is common and most severe among females and the elderly. It may be primary or secondary to other conditions and may be familial. Linkage to several chromosomal loci have been demonstrated. The pathogenesis of RLS involves dopaminergic dysfunction, iron metabolism, and abnormalities in supraspinal inhibition. The mainstay of RLS therapy are dopamine agonists or levodopa.This article reviews the clinical characteristics, epidemiology, diagnosis, pathogenesis, and treatment of RLS.

The low prevalence of extrapyramidal symptoms associated with atypical antipsychotics has led to their widespread use during the past decade. Aripiprazole, the newest medication in this class, has been associated with extrapyramidal symptoms (eg, akathisia) and with improvement of tardive dyskinesia (TD), but to date it has not been associated with the development of TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for 18 months for refractory depression. Symptoms of TD resolved within several weeks of discontinuation of aripiprazole.

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.

Behavioral addictions are considered as the repetitive occurrence of impulsive behaviors without consideration of their potential negative consequences. These addictions represent an increasing cost to society and are an important new field of research in psychiatric genetics. There has been a growing body of evidence on the familial aggregation and genetic influences on the development of behavioral addictions and mainly on pathological gambling. The aim of this article is to critically review findings of family and molecular genetic studies on behavioral addictions, focusing on pathological gambling and commenting on other disorders where appropriate. This review provides a comprehensive approach to genetic studies on behavioral addiction and points out the necessity of expanding the genetic research in this field. Future directions for genetic studies in this field are also discussed.

Worldwide, patients with common mental disorders, such as depression and anxiety, have a tendency to present first to primary care exhibiting idiopathic physical symptoms. Typically, these symptoms consist of pain and other physical complaints that remain medically unexplained. While in the past, traditional psychopathology emphasized the relevance of somatic presentations for disorders, such as depression, in the last few decades, the “somatic component” has been neglected in the assessment and treatment of psychiatric patients. Medical specialties have come up with a variety of “fashionable” labels to characterize these patients and the new psychiatric nomenclatures, such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, attempt to classify these patients into a separate “somatoform disorders” category. These efforts fall short, and revisionists are asking altogether for the elimination of “somatoform disorders” from future nomenclatures.

This review emphasizes the importance of idiopathic physical symptoms to the clinical phenomenology of many psychiatric disorders, offers suggestions to the diagnostic conundrum, and provides some hints for the proper assessment and management of patients with these common syndromes.

Patients in psychiatric settings may present with medical conditions, such as brain tumors, which may or may not be associated with neurological symptoms. In some cases, patients may only have psychiatric symptoms, such as mood changes (depression or mania), psychotic symptoms, panic attacks, changes in personality, or memory difficulties. Brain tumors may be detected in patients at their first presentation to mental health services or sometimes in patients with well-established psychiatric diagnoses.This article presents the case of a 29-year-old woman who was treated for >4 years for posttraumatic stress disorder and borderline personality traits, who developed depressive symptoms and memory difficulties. However, she did not develop any major neurological signs or symptoms. Brain imaging showed the presence of a left thalamic tumor, later confirmed as glioblastoma multiforme. She underwent surgical treatment and radiation therapy. With this we show that in some cases, brain tumors can be neurologically silent and only present atypical psychiatric symptoms.

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.

The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions.To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the “cheese-reaction”). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.

Antiepileptic drugs (AEDs) have diverse psychotropic profiles. Some AEDs have proven to be efficacious in the treatment of mood disorders, especially bipolar disorder. Others are ineffective as primary treatments but may be useful adjuncts for mood disorders or comorbid conditions. Valproate (acute mania and mixed episodes), carbamazepine (acute mania and mixed episodes), and lamotrigine (maintenance to delay recurrence) have United States Food and Drug Administration indications for the treatment of bipolar disorder. This article provides an overview of data on the use of AEDs in bipolar disorder, including acute mania and depression, prophylaxis, and rapid cycling.

Posttraumatic stress disorder (PTSD) symptoms may develop as a result of an acute, life-threatening traumatic event. Such acute events are quite common in patients with cardiovascular illnesses (ie, a myocardial infarction, acute exacerbations of heart failure or edema). Indeed, PTSD symptoms have been described in a substantial minority of patients who had such events (10% to 25%), and have been shown to be associated with medical morbidity and with non-adherence to medications. This review summarizes available information about these symptoms in patients with cardiovascular illnesses. It also describes the importance of recognizing PTSD as a distinct psychiatric disorder (that can be addressed by specific treatments) and as an important compounding factor in studies of psychopathology in cardiovascular patients. In particular, an argument is made that the understanding of depressive disorders in patients with cardiovascular illnesses should incorporate conceptual and treatment information from the emotional trauma literature if indeed depressive and anxiety disorders are to be successfully treated in these patients. The authors conclude with a description of the challenges and promise of an effort to implement a clinical program to screen for PTSD symptoms in patients with cardiovascular illnesses, and with recommendations for future efforts.

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that “chronically” implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

A growing number of common traumatic events involve both physical and emotional injuries. In contrast to previously held beliefs, the rapidly growing body of literature shows quite convincingly that physical injury, over and above exposure to the traumatic event itself, increases rather than decreases the risk for posttraumatic stress disorder (PTSD). A pertinent question becomes how bodily injury contributes to the risk of developing PTSD. In this article, we review contemporary findings regarding the neurobiological and psychological mechanisms by which bodily injury may augment or independently contribute to chronic posttraumatic stress. In addition, we propose three theoretical pathways through which physical injury can increase the risk for PTSD. These pathways are: additive, unique, and recovery impeding. Finally, we highlight unresolved issues pertaining to each one of these pathways and propose directions for future research to address them.

The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.

Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.

Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.

Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as “much improved” on the Clinical Global Impression–Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction ≥35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.