Depersonalization disorder (DPD) is characterized by a subjective sense of detachment from one's own being and a sense of unreality. An examination of the psychobiology of depersonalization symptoms may be useful in understanding the cognitive-affective neuroscience of embodiment. DPD may be mediated by neurocircuitry and neurotransmitters involved in the integration of sensory processing and of the body schema, and in the mediation of emotional experience and the identification of feelings. For example, DPD has been found to involve autonomic blunting, deactivation of sub-cortical structures, and disturbances in molecular systems in such circuitry. An evolutionary perspective suggests that attenuation of emotional responses, mediated by deactivation of limbic structures, may sometimes be advantageous in response to inescapable stress.

Background: Lifetime prevalence rates of cognitive dysfunction and depression in multiple sclerosis (MS) have typically been reported to be ∼50%. However, an inconsistent relationship between these two common features of MS has been reported in the literature. Because neurovegetative depression symptoms overlap with MS symptoms, it may be that literature inconsistencies can partly be explained by the fact that only those depression symptom clusters unambiguously reflective of depression are associated with cognitive dysfunction.

Objective: To explore the relationship between different depression symptom clusters and a battery of tests measuring cognitive domains commonly impaired in MS and was examined at two time points 3 years apart.

Methods: The Chicago Multiscale Depression Inventory was employed to measure mood, negative evaluative, and neurovegetative symptom clusters in 53 MS patients who were also administered a battery of neuropsychological tests.

Results: At time point 1, Mood and Evaluative Chicago Multiscale Depression Inventory scales were significantly associated with tasks of complex speeded attention, planning, and working memory. At time point 2, the Evaluative scale was still significantly associated with these domains, in addition to spatial memory; however, all of the significant correlations with the Mood scale dropped out.

Conclusion: These results show that negative evaluative depression symptoms are most consistently predictive of cognitive dysfunction in MS. It may be that negative evaluative depression symptoms use up available cognitive capacity, thus compromising performance on cognitive capacity demanding tasks in MS patients.

The Diagnostic and Statistical of Mental Disorders, Fifth Edition (DSM-5) somatic symptom and related disorders chapter has a limited clinical utility. In addition to the problems that the single diagnostic rubrics and the deletion of the diagnosis of hypochondriasis entail, there are 2 major ambiguities: (1) the use of the term “somatic symptoms” reflects an ill-defined concept of somatization and (2) abnormal illness behavior is included in all diagnostic rubrics, but it is never conceptually defined. In the present review of the literature, we will attempt to approach the clinical issue from a different angle, by introducing the trans-diagnostic viewpoint of illness behavior and propose an alternative clinimetric classification system, based on the Diagnostic Criteria for Psychosomatic Research.

Introduction: Evidence from phenomenological, family, genetic, and treatment studies from Western centers have suggested that tic-related obsessive-compulsive disorder (OCD) could be different from non-tic-related OCD. This study from India investigated the differences in OCD with and without tics, with respect to sociode-mographics, symptom profile, and comorbidity, including obsessive-compulsive spectrum disorders, to examine whether the clinical profile of tic-related OCD is similar to that reported previously.

Methods: Fifty subjects with OCD and tics (chronic motor tics and Tourette syndrome) were compared with 141 OCD subjects without tics.

Results: Subjects having OCD with tics tended to be males, and had an earlier onset of illness. They had more of symmetry/aggressive and religious obsessions, and cleaning, ordering/arranging, hoarding, and repeating compulsions and were associated with trichotillomania and hypochondraisis. Stepwise backward (Wald) regression analysis showed that an early age of onset, male gender, aggressive obsessions, cleaning compulsions, and trichotillomania were significantly associated with tic-related OCD.

Conclusion: The findings of this study from India are broadly similar to those reported previously from the West indicating the universality of differences in tic- and non-tic-related OCD. Our findings also support the existing evidence that tics contribute to the heterogeneity of OCD.

As gambling becomes available to more and more individuals in this country, the problem of compulsive or pathological gambling (PG) will also increase. As with other forms of addiction, both environmental and genetic factors are involved in PG. Identification of the genes that play a role in increasing a person's risk for PG will lead to a better understanding of the disorder and to more rational and effective treatment. Although studies of the molecular genetics of PG are just beginning, a number of interesting observations have been made and are reviewed in this article. As with other addictive behaviors, abnormalities in dopaminergic reward pathways a likely to be involved. Consistent with this, we have observed a significant association between PG and the D1, D2, D3, and D4 dopamine receptor genes. The fact that each these genes has an effect is consistent with a polygenic inheritance of a susceptibility to PG The involvement of multiple dopamine genes consistent with the “reward deficiency syndrome,” which suggests that addictive impulsive disorders are due, at least in part, to genetic abnormalities of the dopamine reward pathways. On the basis of this hypothesis, we describe other genes also likely to play a role in a person's susceptibility to PG.

Compulsive hoarding is a common and often disabling neuropsychiatric disorder. This article reviews the phenomenology, etiology, neurobiology, and treatment of compulsive hoarding. Compulsive hoarding is part of a discrete clinical syndrome that includes difficulty discarding, urges to save, clutter, excessive acquisition, indecisiveness, perfectionism, procrastination, disorganization, and avoidance. Epidemiological and taxometric studies indicate that compulsive hoarding is a separate but related obsessive-compulsive spectrum disorder that is frequently comorbid with obsessive-compulsive disorder (OCD). Compulsive hoarding is a genetically discrete, strongly heritable phenotype. Neuroimaging and neuropsychological studies indicate that compulsive hoarding is neurobiologically distinct from OCD and implicate dysfunction of the anterior cingulate cortex and other ventral and medial prefrontal cortical areas that mediate decision-making, attention, and emotional regulation. Effective treatments for compulsive hoarding include pharmacotherapy and cognitive-behavioral therapy. More research will be required to determine the etiology and pathophysiology of compulsive hoarding, and to develop better treatments for this disorder.

Neuropsychiatric illnesses including mood disorders are accompanied by cognitive impairment, which impairs work capacity and quality of life. However, there is a lack of treatment options that would lead to solid and lasting improvement of cognition. This is partially due to the absence of valid and reliable neurocircuitry-based biomarkers for pro-cognitive effects. This systematic review therefore examined the most consistent neural underpinnings of cognitive impairment and cognitive improvement in unipolar and bipolar disorders. We identified 100 studies of the neuronal underpinnings of working memory and executive skills, learning and memory, attention, and implicit learning and 9 studies of the neuronal basis for cognitive improvements. Impairments across several cognitive domains were consistently accompanied by abnormal activity in dorsal prefrontal (PFC) cognitive control regions—with the direction of this activity depending on patients’ performance levels—and failure to suppress default mode network (DMN) activity. Candidate cognition treatments seemed to enhance task-related dorsal PFC and temporo-parietal activity when performance increases were observed, and to reduce their activity when performance levels were unchanged. These treatments also attenuated DMN hyper-activity. In contrast, nonspecific cognitive improvement following symptom reduction was typically accompanied by decreased limbic reactivity and reversal of pre-treatment fronto-parietal hyper-activity. Together, the findings highlight some common neural correlates of cognitive impairments and cognitive improvements. Based on this evidence, studies are warranted to examine the reliability and predictive validity of target engagement in the identified neurocircuitries as a biomarker model of pro-cognitive effects.

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.

Introduction: The objective of the study was to examine gender differences in the relationship between weight group (under-weight to severely obese), and Axis I and Axis II psychopathology.

Methods: Data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) were analyzed. Logistic regression models examined the past-year likelihood for meeting diagnostic criteria for psychiatric disorders. Interactions between weight group and gender were utilized to determine whether associations were significantly different in men and women after adjusting for demographic characteristics.

Results: First, consistent with previous NESARC analyses, the prevalence estimates of psychiatric disorders were higher among people of higher body mass index groups, regardless of gender. However, these patterns differed across genders. Both severely obese women and men, in comparison to normal weight respondents, were much more likely to meet criteria for affective and anxiety disorders, but these associations were significantly (1.5–2 times) stronger among women. For Axis II disorders, while there were very few associations between personality disorders and weight in men, among women increases in weight group were associated with increases in the likelihood of meeting criteria for a personality disorder.

Conclusion: Weight and psychopathology appear more strongly associated in women than in men. While these data do not allow for identification of underlying mechanisms, they highlight the importance of assessing for psychopathology in overweight and obese patients, and suggest that weight management may be an important consideration in the treatment of psychiatric disorders.

Adolescence is characterized by heightened risk-taking, including substance misuse. These behavioral patterns are influenced by ontogenic changes in neurotransmitter systems, particularly the dopamine system, which is fundamentally involved in the neural coding of reward and motivated approach behavior. During adolescence, this system evidences a peak in activity. At the same time, the dopamine (DA) system is neuroplastically altered by substance abuse, impacting subsequent function. Here, we describe properties of the dopamine system that change with typical adolescent development and that are altered with substance abuse. Much of this work has been gleaned from animal models due to limitations in measuring dopamine in pediatric samples. Structural and functional neuroimaging techniques have been used to examine structures that are heavily DA-innervated; they measure morphological and functional changes with age and with drug exposure. Presenting marijuana abuse as an exemplar, we consider recent findings that support an adolescent peak in DA-driven reward-seeking behavior and related deviations in motivational systems that are associated with marijuana abuse/dependence. Clinicians are advised that (1) chronic adolescent marijuana use may lead to deficiencies in incentive motivation, (2) that this state is due to marijuana’s interactions with the developing DA system, and (3) that treatment strategies should be directed to remediating resultant deficiencies in goal-directed activity.

Attention-deficit/hyperactivity disorder (ADHD) is an impairing but usually treatable condition. Popular culture propagates the myth that ADHD recedes with age; this is not the case. Although it is common, <20% of adults with ADHD are diagnosed or treated. Adults with ADHD show significant comorbidities with depressive disorders, anxiety disorders, substance use, oppositional defiant disorder, personality disorders, sleep problems, and learning disabilities. However, symptoms that result from ADHD, such as mood symptoms or lability, are often mistaken for comorbid disorders. Comorbidity with ADHD impacts treatment compliance, treatment response, and patient insight. Insufficient data on the interaction between ADHD and comorbidities impedes proper diagnosis and treatment. Better clinical tools for assessing these conditions are needed. Food and Drug Administration-approved pharmacologic treatments for adult ADHD include stimulants, dexmethylphenidate, and the nonstimulant atomoxetine. Effect sizes of approved medicines at approved doses are half those seen in children. Adults may also need longer duration of medication effects than children. Short-acting stimulants are likely to result in poorer adherence and have a higher risk for diversion or abuse. Risk of abuse is a major concern; stimulant treatments are controlled substances, and children with ADHD show increased risk of substance abuse. Psychosocial interventions may be beneficial in treating both ADHD and comorbidities.

In this expert roundtable supplement, Margaret Weiss, MD, PhD, presents a comprehensive overview of complications surrounding differential diagnosis in adults with ADHD. Next, Mark A. Stein, PhD, reviews evaluation, comorbidity, and development of a treatment plan in this population. Finally, Jeffrey H. Newcorn, MD, provides a discussion on the pharmacologic options available for adults with ADHD, considering dosages specific to adults and common comorbidities.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented, followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content and incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.

Neuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

Parkinson’s disease psychosis (PDP) is theoretically a serotonin-dopamine imbalance syndrome due to disruption of the normal balance between the serotonergic and dopaminergic neurotransmitter systems in key brain circuits.

Introduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations.

Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated.

Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the “early onset” group (EOG): before 11 years of age, 75 patients had

Results: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the “aggression/violence” and “miscellaneous” dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the “contamination/cleaning” dimension.

Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

Women with epilepsy are at risk for reproductive health dysfunction. Sex-steroid hormone abnormalities have been reported in women with epilepsy, but it has been difficult to determine whether these abnormalities are due to epilepsy-related hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84 reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20 nonepileptic controls. Estrone, free testosterone, and androstenedione were significantly lower in subjects receiving enzyme-inducing AEDs than in nonepileptic controls. Free testosterone was significantly elevated in subjects receiving valproate compared to nonepileptic controls. Subjects with epilepsy receiving gabapentin or lamotrigine were no different from the nonepileptic controls in any of the endocrine variables. Subjects with epilepsy who are receiving AEDs that alter cytochrome P450 enzymes are at risk for significant abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones compared with nonepileptic controls. With new AEDs available that do not alter cytochrome P450 enzymes, physician selection of therapy should consider not only seizure control, but also potential effects on reproductive physiology.

The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.