There are many new findings in the area of comorbid insomnia. Almost 50% of all cases of chronic insomnia are due to a mental disorder, with depressive illness explaining the majority of cases related to mental disorder (Slide 1). Other common causes of comorbid, or secondary, insomnia include chronic respiratory disease such as asthma and chronic obstructive pulmonary disease, chronic pain, degenerative neurological disease, and some medications such as glucocorticoids and serotonin reuptake inhibitors. A general principle of management of insomnia related to mental or medical disorders is that the principal disorder must be fully treated as part of the insomnia treatment plan. If there is an offending medication, it must be discontinued if possible.

Irritable bowel syndrome (IBS) is one of over 20 functional gastrointestinal disorders. There is considerable overlap of IBS with panic disorder as well as other anxiety disorders and depression. It has been proposed that the high prevalence of psychiatric disorders in clinical samples of IBS patients is a result of self-selection of individuals with anxiety and depression, which drives treatment-seeking behavior. Over the past several years, data from some community studies have shown that there is a high prevalence of psychiatric disorders in individuals with IBS who never sought treatment. This suggests that there may be a more fundamental linnk between IBS, anxiety and mood disorders, such as shared pathophysiology.

This month's issue of CNS Spectrums brings together reviews on the brain-gut axis, each of which provides a unique perspective, which is complementary to the other reviews.

Kirsten Tillisch, MD, and Emeran A. Mayer, MD, review the neurobiology of visceral sensation, focusing on visceral hyperalgesia in IBS. In their paper, the importance of expectancy, comorbidity, gender, and other issues on pain perception is discussed. One of the most fascinating points the authors make is that extra-intestinal functional disorders, such as fibromyalgia, which often coexists with IBS, may affect somatic perception and pain thresholds. The observation that these disorders not only co-exist, but can affect each other raises an important and often overlooked issue for researchers. Comorbid disorders should be assessed and taken into account when conducting studies in patients with IBS. The authors highlight advances in methodology and new conceptual frameworks for understanding the functional gastrointestinal disorders (FGIDs) as well as remaining gaps in our knowledge about visceral hyperalgesia.

The 12-month and lifetime prevalences of bipolar I and II disorder in the United States are 2.0% and 3.3%, respectively. Similar to schizophrenia, bipolar disorder is also associated with premature and excess mortality, with an estimated loss of ∼15 years of life expectancy. Most of the excess mortality in individuals with mood disorders results from natural causes, not suicide. Again, similar to schizophrenia, the most common cause of death in patients with bipolar disorder is cardiovascular disease (CVD), which occurs approximately twice as often in this group as in the general population. Although the data are more limited than in schizophrenia, people with bipolar disorder are differentially affected by medical comorbidity. Bipolar disorder is associated with elevated risk of a wide variety of comorbid medical illnesses, including migraine, asthma, chronic bronchitis, hypertension, and gastric ulcer, which compound disability and increase the burden of the disease.

Pharmacoepidemiology, the study of the effects of drugs in large numbers of people, is a relatively new discipline that applies the methods of epidemiology to clinical pharmacology. Premarketing clinical trials remain the only way to scientifically determine whether a drug is causally effective, yet these trials do not provide information that allows for estimates about rare, late, or off-label toxicities associated with the drug in question. Increasing concern about common and debilitating adverse effects of medications has highlighted the need for enhanced postmarketing surveillance to follow up on clinical trials. There is a further concern regarding the broader issue of the risk-benefit ratio of certain medications. Computerized databases are a good source of information on which to lay the foundations of postmarketing research. A system of cross-linked computerized medical records may better enable researchers and physicians to realistically monitor postmarketing safety and incorporate monitoring benefits. The same research could also elucidate the net public health effect of regulatory decisions. The Veterans Affairs database in the United States and PHARMO in the Netherlands may represent good models on which to base future postmarketing surveillance studies.

In this expert roundtable supplement, Brian L. Strom, MD, provides an overview of the appropriate use of large computer databases in pharmacoepidemiology studies. Philip Wang, MD, DrPH, discusses the advantages of pharmacoepidemiologic studies over clinical trials in correctly detecting drug safety issues. Francesca Cunningham, PharmD, reviews a large computer database that is currently in use within the VA healthcare system, and Ron M.C. Herings, PharmD, PhD, discusses the development of the PHARMO system in the Netherlands.

Are reproductive life events in women associated with an increased risk of sexual dysfunction? Female sexual dysfunction effects up to 40% of women in the United States between 18 and 59 years of age. Sexual dysfunction may be accompanied by fluctuations in gonadal hormone secretion, making women more vulnerable to sexual symptoms, especially during times of reproductive life events. Reproductive life events, such as the use of birth control pills, various phases of the menstrual cycles, postpartum and lactation states, and perimenopause, are highly correlated with changes in sex steroids. As an understanding of the role of sex steroids on sexual functioning is elucidated, clinicians will be able to offer more specific and effective treatment options for women during various phases of reproductive life. Several case studies are presented to illustrate the unique clinical considerations that a clinician must consider when treating the biologic component of female sexual dysfunction.

Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia.

In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

The lumping together of the seven deadly sins—pride, covetousness, jealousy, sloth, lust, gluttony, and anger—is, of course, a theological categorization rather than a medical nosology. Nevertheless, these seven sins are oddly reminiscent of various symptoms of a common medical disorder—one that has received increasing neuroscientific investigation in recent years—obsessive-compulsive disorder (OCD). Is such a parallel between sin and symptom purely coincidental, or is modern neurobiology able to provide a more coherent explanation?

Interestingly, the term “obsession” derives from the Roman Catholic concept of obsession—a state of being possessed by the devil. Indeed, obsessions—defined as recurrent intrusive and senseless thoughts and images—are some of the most overwhelming and distressing of psychiatric symptoms. While it is true that hallucinations and delusions lead to a loss of contact with reality, people with obsessions suffer from the very fact that they cannot resist ideas that they know full well to be irrational. Thus, OCD sufferers find themselves having to perform compulsions—recurrent rituals that relieve anxiety—but which are not realistically connected to the preceding obsessions or are clearly excessive.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The last 5 years have been marked by rapid developments in understanding the pathophysiology of PD as well as by the introduction of a number of new drugs for symptomatic treatment of the disease. On the other hand, the diagnosis of PD is still made purely on clinical grounds. Due to continuing advances in therapy, it is increasingly important to recognize PD in its earliest stages and to distinguish it from other causes of parkinsonism, for which prognosis and response to treatment differ. This article reviews the epidemiology of PD and then elaborates on the diagnosis and differential diagnosis.

While the public health perspective prioritizes large populations of affected individuals, our job as clinicians is to help one patient at a time. Over the last 10–20 years, there has been marked improvement in pharmacologic and psychosocial interventions available for patients with anxiety disorders (Slide 8).

The use of antidepressants, particularly the serotonergic and serotonergic noradrenergic agents, have received increased attention as first-line treatment for most of the anxiety disorders, including panic disorder, social phobia, posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Antidepressants are often used as first-line therapy for anxiety disorders because of their broad spectrum of efficacy against common comorbidities, especially depression, and because of concern about benzodiazepine-associated dependence, abuse liability, and lack of efficacy for depression and other comorbidities (Slide 9).

These newer antidepressants have advantages over the older antidepressants, particularly the tricyclics and the monoamine oxidase inhibitors, in that they are generally better tolerated and more appropriate for use in potentially suicidal patients because they are less lethal in overdose. However, there are some side effects that may limit their use in some patients. In the case of the serotonergic antidepressants, many patients are hesitant to initiate or maintain treatment due to concerns about sexual dysfunction.