This review begins with a description of some problems that recently have beset an influential circuit model of fear conditioning and goes on to look at neuroanatomy that may subserve conditioning viewed in a broader perspective, including not only fear but also appetitive conditioning. The column will then focus on basal forebrain functional-anatomical systems, or macrosystems, as they have come to be called. Yet, more specific attention is then given to the relationships of the dorsal and ventral striatopallidal systems and extended amygdala with the dopaminergic mesotelencephalic projection systems, culminating with the hypothesis that all macrosystems contribute to behavioral conditioning.

Introduction: Pathological love (PL)–behavior characterized by providing repetitive and uncontrolled care and attention to the partner in a romantic relationship–is a rarely studied condition, despite not being rare and causing suffering. This study aims at investigating impulsivity, personality, and characteristics related to the romantic relationship in this population.

Methods: Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder) were compared regarding impulsivity, personality, type of attachment, satisfaction with romantic relationship, and love style.

Results: Individuals with PL have higher levels of impulsivity (P<.001; Barratt Impulsiveness Scale), higher self-transcendence, that is, are more unconventional and hold sense of communion with a wider reality (P<.001; Temperament and Character Inventory) and keep dissatisfactory romantic relationships (P<.001; Adapted Relationship Assessment Scale).

Conclusion: Individuals with PL present personality traits and relationship aspects that must be taken into account in devising assessment and therapeutic strategies for this population.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Unravelling the mystery of dopamine neurotransmission, especially at its 3 most clinically relevant receptors, D3, D2, and D1, helps explain the pathophysiology of numerous psychiatric and neurologic symptoms in various CNS disorders that are theoretically caused by dysregulation of this neurotransmitter.

Attention-deficit/hyperactivity disorder is a prevalent and disabling disorder that is characterized by inattention and/or hyperactivity-impulsivity, impairment in executive functions, structural and functional abnormalities in frontal-striatal circuitry, associations with particular catecholamine gene variants, and responsiveness to dopaminergic and noradrenergic agents. There is a growing integration of findings from basic and clinical studies, of data from different methods (eg, genetics and imaging), and of empirical data with hypotheses drawn from evolutionary thinking. Here we briefly summarize work on the cognitive-affective neuroscience of attention-deficit/hyperactivity disorder.

There is a complex overlap between major depressive disorder (MDD) and attention-deficit/hyperactivity disorder (ADHD). The different therapeutic options for adult ADHD mirror those used for children with ADHD. Both stimulant and nonstimulant medications are used to treat the disorder.

Epilepsy is a significant health problem. Ten percent of people living a normal lifespan will experience at least one epileptic seizure and one third will develop a chronic epileptic condition. At any given time, 0.5% to 1% of the world's population has active epilepsy, amounting to over 40 million people. A World Health Organization-sponsored study determined that epilepsy accounts for 1% of the global burden of disease, measured as disability-adjusted life years equivalent to the global burden of lung cancer in men and to breast cancer in women. Disability-adjusted life years measure years of productivity lost as a result of disability or death, which is relatively high for epilepsy because this condition often begins in childhood. The cost of epilepsy in the United States has been estimated at $12.5 billion/year, and 80% of this cost is borne by the 30% of patients whose seizures are not controlled.

The cost of uncontrolled epileptic seizures to society, and to individuals with epilepsy and their families, is measured not only in economic terms, but also in terms of human suffering. In this month's first article, Michael R. Sperling, MD, who has authored seminal papers on consequences of epilepsy, provides evidence that epilepsy is not a benign disorder; that early control of epileptic seizures is important to avoid irreversible disability due to the development of psychological and social disturbances and progressive cerebral dysfunction, as well as epilepsy-related death. The burden imposed on society and on individuals by uncontrolled epileptic seizures is all the more tragic because many suffer needlessly. For a significant number of adults who have had recurrent seizures since infancy, childhood, or adolescence, more aggressive early intervention might have rescued them from a lifetime of disability. Consequently, the goal of therapy today should be no seizures and no side effects, as soon as possible.

Obsessive-compulsive disorder (OCD) has been recognized as mainly characterized by compulsivity rather than anxiety and, therefore, was removed from the anxiety disorders chapter and given its own in both the American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Beta Draft Version of the 11th revision of the World Health Organization (WHO) International Classification of Diseases (ICD-11). This revised clustering is based on increasing evidence of common affected neurocircuits between disorders, differently from previous classification systems based on interrater agreement. In this article, we focus on the classification of obsessive-compulsive and related disorders (OCRDs), examining the differences in approach adopted by these 2 nosological systems, with particular attention to the proposed changes in the forthcoming ICD-11. At this stage, notable differences in the ICD classification are emerging from the previous revision, apparently converging toward a reformulation of OCRDs that is closer to the DSM-5.

The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

The two approved treatments for tardive dyskinesia both inhibit the vesicular monoamine transporter type 2 (VMAT2) yet have pharmacologic properties that distinguish one from the other. Knowing these differences may help optimize which treatment to select for individual patients.

Introduction: The characteristics of Asian American and white problem gamblers using a gambling helpline were examined to identify race-related differences.

Methods: Logistic regression analyses were conducted on data obtained from callers to a gambling helpline serving southern New England in 2000–2003, inclusive.

Results: Of the 144 phone calls used in the analyses, 72 were from Asian American callers and 72 were from white callers who were matched on gender, education, income, marital/cohabitation status, and age. Race-related differences were observed in forms of gambling problems, psychiatric problems secondary to gambling, substance use problems, and family history. Asian American gamblers were more likely to report suicide attempts related to gambling and problems with non-strategic gambling. White gamblers were more likely to report both casino and non-casino gambling problems and personal and familial alcohol use problems. High proportions of both groups reported problems with strategic gambling, gambling-related anxiety, family and financial problems secondary to gambling, financial debt, daily tobacco use, and a family history of problem gambling.

Conclusion: Race-related differences should be considered in optimizing prevention and treatment strategies related to problem gambling.

Ziprasidone is a second-generation antipsychotic that received Food and Drug Administration approval in February 2001. It has a unique receptor profile that includes high-affinity antagonist activity at dopamine D2 receptors, inverse agonist activity at serotonin (5-HT)2A receptors, agonist activity at 5-HT1A receptors, and a relatively high affinity for the serotonin and norepinephrine transporters. The 5-HT1A affinity, together with the inhibitory effect on monoamine reuptake, may underlie the hypothesized beneficial effects on comorbid affective and cognitive abnormalities in schizophrenia and schizoaffective disorder. The short-term efficacy of ziprasidone for core positive symptoms of schizophrenia appears to be comparable to other conventional and atypical antipsychotics. The short-term efficacy of ziprasidone in acute mania has been established based on two 3-week, double-blind, placebo-controlled trials. Open-label treatment for up to 52 weeks confirms the sustained efficacy and safety of ziprasidone in bipolar disorder. Maintenance studies in schizophrenia and schizoaffective disorder indicate that long-term ziprasidone therapy is effective in preventing relapse, while maintaining cognitive and psychosocial benefits. The safety database suggests that the overall cardiovascular and cerebrovascular risk associated with ziprasidone is lower than with other atypicals, with notably lower risk of drug-related increases in weight, glucose, or lipids. The data also suggest a modestly increased risk of QTc prolongation that is not dose related or linked to torsades de pointes. Switching to ziprasidone from other atypicals appears to improve both clinical symptoms and metabolic parameters, though more studies are needed to fully characterize these benefits. This monograph summarizes the efficacy, tolerability, and safety of oral ziprasidone in the treatment of schizophrenia, schizoaffective disorder, and bipolar mania.

Neuropathic pain and fibromyalgia are prevalent diseases which have major consequences on healthcare resources and the individual. From the clinical point of view neuropathic pains represent a heterogeneous group of aetiologically different diseases ranging from cancer to diabetes. Patients with fibromyalgia also display clinical features common in neuropathic pain suggesting that there might be some overlap. The mechanisms responsible for symptoms and signs in both diseases are still unknown. Recently, there have been numerous reports of various pharmacological treatments of neuropathic pain and fibromyalgia with often disappointing results. Most of the studies were of short duration, had high attrition rates, and displayed other methodological problems. Some compounds had high rates of adverse effects which makes it often difficult for the patients to tolerate the treatment, especially in the long-term. At present, the best options for medication treatment are tricyclic antidepressants in lower dosage than usual in psychiatric disorders and a wide range of anticonvulsants. Opioids are sometimes recommended but have been found to have minor efficacy. Recently, there have been more controlled trials, which are reported here if they had been published between 2002 and 2004. Various compounds have been tested in different studies. Treatment of fibromyalgia, which has many features in common with depressive symptoms, became the focus of interest. New promising studies with dual serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipram) and a newer antiepileptic drug (pregabalin) are in progress. Future research will have to apply new approaches (eg, using a mechanism based classification of neuropathic pain and carrying out studies in populations with the same symptom but not necessarily the same disease) in order to find effective treatments for these common and often debilitating diseases.

Basic animal studies and human imaging studies have contributed to our understanding of the psychobiology of love and attachment. There are overlaps and distinctions in the neuronal circuitry of maternal love, romantic love, and long-term attachment. In these circuits, important molecules, which have been demonstrated to play a role in the psychobiology of social bonding include dopamine, serotonin, opioids, oxytocin, and vasopressin. Particular genetic and environmental variations contribute to social-bonding phenotypes, consistent with an evolutionary perspective on the value of these behaviors. Advances in the psychobiology of social bonds have led to hypotheses about the pharmacotherapy of disorders of attachment.