Vortioxetine is an antidepressant with multiple pharmacologic modes of action that enhance release of dopamine, norepinephrine, acetylcholine, and histamine.

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.

Vortioxetine is an antidepressant with multiple pharmacologic modes of action at targets where serotonin neurons connect with other neurons. 5HT3 receptor antagonism is one of these actions, and this leads to increased release of norepinephrine (NE), acetylcholine (ACh), and serotonin (5HT) within various brain circuits.

Research advances have led to three methods for selectively activating one half of the autonomic nervous system in humans.The first method is an ancient yogic technique called unilateral forced nostril breathing (UFNB) that employs forced breathing through only one nostril while closing off the other. The second method works by stimulation of an autonomic reflex point on the fifth intercostal space near the axilla. The most recent method employs unilateral vagus nerve stimulation (VNS) via the mid-inferior cervical branch and requires surgical implantation of a wire and pacemaker. UFNB is non-invasive and seems to selectively activate the ipsilateral branch of the sympathetic nervous system with a possible compensation effect leading to contralateral VNS. UFNB and VNS have been employed to treat psychiatric disorders. While UFNB has been studied for its potential effects on the endogenous ultradian rhythms of the autonomic and central nervous system, and their tightly coupled correlates, VNS has yet to be studied in this regard. This article reviews these three methods and discusses their similarities, putative mechanisms, their studied effects on the endogenous autonomic nervous system and central nervous system rhythms, and their implications for the treatment of psychiatric disorders.

A large proportion of the persons who join terrorist groups as well as lone-acting terrorists have a history of violent behavior or mental disorder that predated their becoming terrorists. This suggests that brain alterations found to occur in violent perpetrators may also be present in a significant percentage of terrorists. After a short delineation of phylogenetically old neuronal networks that are important for the generation of aggressive behavior in inconspicuous brains, this review summarizes structural and functional brain-imaging studies in violent offenders published over the last 10 years. Depending on the subtype of violence (impulsive or instrumental), deviations in structure or function were mainly found in the prefrontal, orbitofrontal, and insular cortex, as well as in temporolimbic structures (e.g., the amygdala, hippocampus, and parahippocampus). These brain areas are essentially responsible for the control of the archaic neuronal generators of aggression located in the hypothalamus and limbic system. This regional distribution of brain alterations also shows a remarkable overlap with those brain regions that are crucial for such prosocial traits as empathy and compassion. Feelings of superiority, dominance, and satisfaction gained by performing violent and terroristic attacks suggest that a hedonistic component via an activation of brain reward systems plays an additional role. In our current debate about the causes of terrorism, aspects of brain dysfunction should receive more attention.

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.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by deficits in social interactions and perseverative and stereotypical behavior. Growing evidence points toward a critical role for synaptic dysfunction in the onset of ASD, and synaptic function is influenced by glial cells. Considering the evidence that neuroinflammation in ASD is mediated by glial cells, one hypothesis is that reactive glial cells, under inflammatory conditions, contribute to the loss of synaptic functions and trigger ASD. Ongoing pharmacological treatments for ASD, including oxytocin, vitamin D, sulforaphane, and resveratrol, are promising and are shown to lead to improvements in behavioral performance in ASD. More importantly, their pharmacological mechanisms are closely related to anti-inflammation and synaptic protection. We focus this review on the hypothesis that synaptic dysfunction caused by reactive glial cells would lead to ASD, and discuss the potentials of antineuroinflammatory therapy for ASD.

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.

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.

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.

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.

Body dysmorphic disorder (BDD) has a significant impact on the patients’ quality of life (QOL). This is an initial literature review of QOL in patients with BDD, examining the extent of QOL impairments, the impact of psychiatric comorbidity on QOL, and the effect of treatment on QOL in BDD. Studies were identified through PubMed, MEDLINE, and PsycINFO searches from 1960–2011 using the keywords: “quality of life,” “body dysmorphic disorder,” “dysmorphophobia,” and “body image.” Studies included in this review were selected using specific criteria by two authors reaching consensus. Most BDD research studies have used symptom severity measures mainly to study BDD and its treatments. BBD with or without comorbidities is significantly associated with poor QOL and functioning. Studies show that treatment of BDD, either by psychopharmacological treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavior therapy, might have positive effects on QOL, although these results need to be replicated in larger studies. In conclusion, QOL could add significant value to the assessment of BDD if used as one of the primary measures in research and clinical work in BDD, by providing more information and clearer understanding on the impact of the illness on satisfaction with activities of daily life and overall sense of wellbeing before and after treatment.

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.

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.

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.

Introduction: Major depressive disorder (MDD) is thought to negatively impact cognitive function; however, the relationship has not been well explored.

Objective: This study examined the association between depression severity and global cognitive function and memory in subjects with severe, treatment-resistant MDD.

Methods: We enrolled 66 subjects with Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosed unipolar MDD in a multicenter trial to assess the efficacy and neurocognitive effects of electroconvulsive therapy (ECT). We measured depression severity with the 24 item Hamilton Rating Scale for Depression (HRSD24). Neuropsychologic measures included the Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and the Complex Figure Test (CFT). Correlational and regression analyses were conducted to explore associations between depression severity and cognitive function.

Results: The mean age of the subjects was 53.6 years (SD=15.8), 65% were female, and mean HRSD24 was 33.9 (SD=6.7). Mean demographic-corrected T-scores for each neurocognitive measure were in the average to borderline range, and HRSD24 values were unrelated to performance on the MMSE, RAVLT immediate and delayed recall, and CFT immediate and delayed recall.

Conclusion: In this sample of severely depressed subjects referred for ECT, depression severity was unrelated to global cognitive function or memory. Future research should examine the interactions between other depressive characteristics and neurocognitive function.

Medical students from New York City were integrally involved in the response by health professionals to aid the families of victims of the September 11, 2001, attacks on the World Trade Center. The present study was performed to investigate the emotional impact of this involvement on medical students from the Mount Sinai School of Medicine in New York City. One hundred fifty-seven students responded to a mail survey that explored their personal and professional involvement in the disaster as well as their psychiatric symptoms in the week after the event and at the time of the survey (3.5 months after the event). Findings suggested a differential emotional impact on female students and on students involved in less supervised and more emotionally intense activities. However, involvement in the relief effort, per se, did not contribute to psychiatric symptomatology. It may have been associated with enhanced professional self-esteem among the students. These findings have implications for future planning of psychiatric response to disasters.