Psychoneuroendocrinology (PNE) has been a method used in the past to investigate brain biochemical functions in normal and pathological mentation. These studies have subsequently uncovered variations in normal biochemical functioning. It is still being debated, however, how these variations correlate with well-defined psychopathologies.

Future studies in PNE shows promise in many areas of contemporary neurospychiatry. For example, research focusing on variations in neurotransmitter, neuropeptide, and neurohormone secretory tonus might enhance our understanding of specific personality characteristics and behavior. PNE may also be essential in investigating the correlation between hormonal variations and symptoms observed across various psychiatric disorders. PNE might likewise be important for new therapeutic approaches. Finally, PNE can be used to investigate psychoneuroimmunoendocrine relationships.

New PNE methodologies must be developed to make this branch of neuroscience more appropriate for the study of localized brain functions.

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.

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.

In this monograph, David A. Mrazek, MD, provides an overview of the context of genetic testing in clinical psychiatric practice. Next, Jordan W. Smoller, MD, ScD, discusses some of the practical issues related to medication selection. Finally, Jose de Leon, MD, presents a comprehensive review of antidepressant and antipsychotic treatment based on drug metabolism, and reviews the available testing methods for CYP 2D6 and 2C19 genotypes.

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.

Epilepsy is common, but conditions that imitate epilepsy are even more common. In order to make a correct diagnosis of epilepsy, the clinician must carefully elicit a detailed history of the seizure episode. Realizing the overlap that exists between seizures that define epilepsy and those of other psychiatric conditions can also help in differentiating between epilepsy and an imitator of epilepsy. Deciphering the features of a seizure episode is also key to correct diagnosis.

In this article, the physiological and psychological imitators of epilepsy are described, as well as the features of a seizure episode that should be considered in making a diagnosis. Seizure presentations are also explained followed by a description of common diagnostic pitfalls to avoid.

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.

There is mounting evidence to suggest that the efficacy of all available antidepressants when used as monotherapy to treat major depressive disorder (MDD) is, at best, modest. For example, a meta-analysis of all double-blind placebo-controlled studies of antidepressants published since 1980 revealed response rates of 53% for antidepressants versus 36% for placebo (difference in response rate of 16.8%) (Slide 1). To make matters worse, if one is to assume that “negative trials” (ie, trials which do not demonstrate the superiority of a drug over placebo) are less likely to be published than “positive trials” (trials which demonstrate the superiority of a drug versus placebo), it is quite possible that the margin of efficacy of antidepressants when compared to placebo is ≤16.8%. Thus, if one were to include all unpublished along with published double-blind, placebo-controlled trials of antidepressants for MDD, this efficacy margin could be ≤10%.

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.

Which mood stabilizers are the most effective in reducing suicide rates in patients with bipolar disorder? This paper reviews the literature and compares the data on two types of mood-stabilizing agents, lithium and anticonvulsants. Compared with the large amount of data on lithium, there is surprising little information available on the effects of anticonvulsants on mortality in manic-depressive illness. Each was also assessed in terms of suicide risk factors such as depression and mixed episodes, rapid cycling, substance abuse, anxiety and panic, and central serotonergic function. Only two studies that provide data demonstrating anticonvulsant efficacy in preventing suicide in bipolar disorder are available, and the data are incomplete at best. Further research in this area should include an emphasis on the outcome of mortality in patients treated with any of the anticonvulsants or with lithium-anticonvulsant combinations.

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.