The diagnosis of radiologically isolated syndrome (RIS) is untenable in the modern era as new diagnostic criteria for multiple sclerosis (MS) continue to evolve. Even without optic nerve involvement, the shift in the diagnostic criteria for MS forces clinicians to make a diagnosis at the earliest possible time and appropriate treatment initiated. In this analysis, we revisit the original RIS criteria as published and conclude that RIS as a diagnostic entity is obsolete.

Congratulations to the scientific poster winners of the 2015 NEI Psychopharmacology Congress!

1stPLACE: Tardive Dyskinesia in the Era of Second Generation Antipsychotics: A Case Report and Literature Review (page 22)

2ndPLACE: Comparing Deep Brain Stimulation (DBS) and ECT for Treatment Resistant Depression in Elderly Population (page 37)

3rdPLACE: The Complex Multimodal Management of First-Psychotic Episode in Patients with Morphometric Alteration in Hippocampal Formation (page 30)

Psychiatry has a long tradition of believing that too much sex is a bad thing. The classical literature provides detailed accounts of men and women who demonstrated apparently pathological sexual appetites. Since Freud, psychoanalytic authors have held that masturbation is unhealthy, and psychodynamically oriented thinkers have written on Don Juanism and nymphomania.

Since the risk of antipsychotic-induced adverse events is often related to plasma drug concentrations, factors that influence the metabolic transformation of these agents can substantially influence this risk. The cytochrome P450 (CYP) enzyme system, particularly CYP2D6, is very important for the metabolism of many typical and atypical antipsychotic agents. However, there is substantial ethnic/racial pharmacogenetic variability in the phenotypic (ie, metabolic rate) or genotypic (ie, presence of functional or nonfunctional alleles) expression of these enzyme systems. Caucasians have a bimodal distribution of CYP2D6 enzyme activity, with individuals classified either as extensive or poor metabolizers. In contrast, while there are few poor metabolizers among people of Asian descent, a substantial proportion of this population exhibits an intermediate rate of metabolism. African American populations also have a substantial number of intermediate metabolizers, and about the same number of poor metabolizers as Caucasians. Mexican Americans may have a slightly higher metabolic rate than other ethnic groups. Numerous studies have demonstrated that CYP2D6 metabolic status influences the clearance of conventional and atypical antipsychotics. African Americans and Asians, with CYP2D6 phenotypes or genotypes indicative of poor metabolizers, frequently exhibit significantly higher plasma drug concentrations and longer half-lives compared to extensive metabolizers. Importantly, this increased drug exposure is associated with an increased risk of extrapyramidal symptoms. Data on metabolic polymorphism of antipsychotics are lacking among African Americans. There are also some data suggesting that genetic polymorphism can influence the risk of antipsychotic-induced weight gain. These findings highlight the need to consider race/ethnicity when prescribing, dosing, and monitoring antipsychotic agents.

Fibromyalgia syndrome (FMS) is a common, chronically painful condition that is still seeking a home among the clinical professions. It is characterized by moderately severe soft-tissue pain and allodynia, which suggests a role for one group of specialists, but its pathogenesis is in the nociceptive machinery of the central nervous system, which defines the territory of other specialties. Comorbidities such as insomnia, cognitive dysfunction, depression, anxiety, recurrent headaches, dizziness, fatigue, morning stiffness, dysesthesia, irritable bowel syndrome, and irritable urethra logically invoke input from practitioners from almost every field of medicine.

The precipitating causes of FMS may vary among individuals, but a mechanism underlying the painful symptoms involves central sensitization leading to an amplified perception of pain. As a result, this condition is recognized as the human model for chronic widespread allodynia. Biological abnormalities that are detected in most patients by objective methods include dysfunctional sleep (polysomnography), central sensitization (functional magnetic resonance imaging), temporal summation (windup, second pain), and facilitation of nociception (elevated spinal fluid levels of substance P, deficient biogenic amines that fail to maintain descending inhibition, and, in primary FMS, elevated spinal fluid levels of nerve growth factor).

Treatment of FMS is symptomatic and multimodal, including education, physical modalities, and medications that target central neural pathways. Rehabilitation goals include improved physical function, social adaptation, emotional balance, and a better quality of life. Several series of placebo-controlled clinical trials have made available new medications with unique therapeutic mechanisms. Thus, it can be predicted that the next 10 years will see validation of a clinical case definition, more interest in the underlying pathogenesis, a better understanding of how medical care should be adapted to subgroup variations, new medications with specific domain indications, mechanism-directed polypharmacy, characterization of the genetic predisposition, and more emphasis on preventable inciting events.

The cause of anorexia nervosa (AN) is unclear, but is likely multifactorial, including psychological, familial, environmental, societal, genetic, and other biological factors. This case report of identical 12-year-old female triplets simultaneously concordant for AN illustrates the importance of addressing all these components in evaluation and treatment, and the difficulty of determining the relative importance of each factor in the cause of an individual's eating disorder. An overly close relationship and competitiveness between the girls, treated at times as a triplet group rather than as individuals, as well as stressful family dynamics, were probably important antecedents to the girls' AN. The girls encouraged each other and competed to lose weight. Brief individual and family psychotherapy, parent counseling, nutritional counseling, and psychoeducation led to successful treatment. The triplets were encouraged in treatment to compete with and encourage each other to obtain treatment goals, including eating more healthily and achieving healthy weights. A literature review of AN twins studies is also presented, as these studies add to our understanding of the relative importance of shared genes and shared environment in the development of AN. These studies also add insight into treating individuals from families with multiple affected relatives.

Somatization disorder, multiple chemical sensitivities, chronic fatigue syndrome, fibromyalgia, Gulf War syndrome, neurasthenia, irritable bowel syndrome, conversion disorder…idiopathies one and all. These syndromes and the many others like them have perhaps one overriding commonality: enormous unexplained heterogeneity. Patients and clinicians gaze into the suffering and impact of these symptoms and see as many potential causes as there are symptom combinations.

Whose explanation is best? When I am speaking with psychiatrists, the notion of somatoform symptoms goes largely unchallenged. When I am with rheumatologists, however, fibromyalgia is anything but a psychiatric problem and certainly not a somatoform disorder. Among my toxicologist colleagues, it is readily accepted that low-tevel toxic exposures could account for many idiopathic “sensitivities.”

But what of the high rate of depression and anxiety disorders we see in these patients?” I sometimes unwisely retort.

“Well, it could be a co-factor or an interaction,” is a common response.

Unshaken, I step further into the abyss: “How, then, do you explain the high rate of adverse childhood experiences among people with idiopathic symptom syndromes?”

The response is swift. “You cannot rule out biased recall. We cannot expect people to remember these things accurately in such a negative state of mind.”

And so it goes. After several of these kinds of conversations, I have finally concluded there is no point in arguing.The debate is largely irreconcilable, a debate that strikingly parallels the conflicts many primary care physicians experience with symptomatic patients. “How is your personal life?” the doctor may ask a symptomatic patient, suspecting a psychosocial explanation.

This article examines the issue of atypical antipsychotics, glucose/insulin, and other metabolic derangements (ie, metabolic syndrome), including a general introduction to the health, concerns of our patients, a review of the literature, possible mechanisms of antipsychotic induced glucose dysregulation, monitoring approaches, and management and prevention of metabolic syndrome. Literature review leads to mechanism hypotheses and risk estimations, leading to guidelines for monitoring and treatment. The patient population suffers from a higher degree of baseline metabolic dysregulation resulting in cardiovascular disease through components of the metabolic syndrome, and this risk increases with administration of atypical antipsychotic medication at different rates, depending on both drug and patient risk factors. The growing knowledge of mechanisms behind drug induced glucose/insulin and other metabolic dysregulation, as well as advances in pharmacogenomics, will help refine drug selection and monitoring for adverse, life-threatening metabolic effects.

Anxiety disorders are common in depressed patients. Several studies of the full range of Diagnostic and Statistical Manual of Mental

Disorders-defined anxiety disorders in depressed psychiatric outpatients each found that when diagnoses are based on semi-structured diagnostic interviews >40% of the patients had a comorbid anxiety disorder. The recognition of comorbidity is not simply of academic interest, but it has important clinical significance. Epidemiological studies, such as the National Comorbidity Study, have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from the depression. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients, primary care patients, and epidemiological samples. Recent research has suggested that clinicians underrecognize anxiety disorder comorbidity in depressed patients. The clinical significance of this underrecognition is highlighted by the finding that patients often want treatment to address their anxiety disorder comorbidity. When anxiety disorders are detected they often influence clinicians' selection of antidepressant medication, though some of clinicians' prescribing biases are not supported by empirical data.

In this monograph, Iwona Chelminski, PhD, reviews the significance of anxiety in patients with depression as well as diagnostic instruments for recognizing this comorbidity. Next, Mark Zimmerman, MD, addresses the factors that affect the clinician's choice of antidepressant, focusing on the influence of comorbid anxiety. Finally, Sidney Zisook, MD, discusses the differential efficacy of antidepressants as well as the role of psychotherapy in patients with comorbid anxiety and depression.

The familial nature of Tourette syndrome (TS) was first described by Georges Gilles de la Tourette in 1885. Formal investigations of TS since the 1970s have consistently demonstrated an increased risk for TS among relatives of patients with TS. Family studies, twin studies, and segregation analyses all indicate that TS has significant genetic determinants. The mode of transmission, while mildly controversial, is generally believed to be due to at least one major locus inherited either as an autosomal dominant trait with reduced penetrance, or as a trait with intermediate inheritance in which some heterozygotic persons manifest the disorder. There is evidence for a TS spectrum of symptoms that includes chronic tics and obsessive-compulsive disorder. Systematic genome linkage studies of TS are progressing. To date, however, no significant linkage findings exist, although the search has included many neurologically relevant candidate genes.

Sixty-three trichotillomania (TTM) patients treated in a specialty clinic were retrospectively studied for treatment referral patterns, comparison of treatment outcomes, and long-term follow-up. Patients subjectively rated their individual treatments based on success, logicality, confidence in recommending the treatment to others, outcome expectations, and compliance. Subjects referred for combined behavior therapy (BT) and medication treatment (MT) were more depressed, more anxious, and reported greater psychosocial impairment and impact secondary to hair pulling than individuals referred for either treatment alone. Neither the Massachusetts General Hospital Hair Pulling Severity Scale (HPS) nor the Rosenberg Self-Esteem Scale (SES) scores differed between those referred for combined treatment vs those receiving monotherapy. The combination therapy patients showed a greater reduction in HPS scores than those receiving single-modality treatment and no longer differed significantly from monotherapy patients following treatment in terms of Beck Depression Inventory (BDI), Beck Anxiety Index (BAI), and Sickness Impact Profile (SIP) scores. Patients treated with both BT and MT rated BT as more successful and had greater confidence in recommending the intervention. Conversely, compliance was significantly higher for MT than BT. Other treatments, especially support groups, were rated positively. Comparison of patients currently receiving treatment with those no longer in active treatment revealed no statistically significant differences. Ten of 19 patients who were out of treatment for over 1 year rated themselves as treatment responders. Significant improvements in HPS, BDI, BAI, and SES scores were reported in the few hair pullers out of treatment more than 1 year for whom objective rating scale scores were available.