Little is known about the prevalence, typology, and natural course of non—drug-induced sexual dysfunction in patients with depression. Loss of libido has been reported in various studies to affect from 25% to 75% of patients with unipolar depression, and its prevalence appears to be correlated with the severity of depression. Disorders of arousal also appear to be relatively common in both men and women with major depression, of whom ~25% may experience problems with erection or lubrication. The scant available data regarding orgasmic difficulties in patients with depression who have not yet taken antidepressant medication suggest that they are more common than in the general population. The potential causes of sexual dysfunction in patients with depression are complex and little investigated, and future research must distinguish and explore the various biological, psychological, and psychosocial factors that are likely to be involved.

The understanding of the eating disorders (EDs) anorexia (AN) and bulimia nervosa (BN) has undergone remarkable advancements in the past decade. Most studies that have been done in AN show brain gray and white matter volume loss during the ill state that, at least in part, remit with recovery. Similar patterns occur for brain phopsholipids assessed using magnet resonance spectroscopy (MRS). Imaging studies have been used to provide functional information regarding serotonin neuroreceptor dynamics, regional cerebral blood flow, or cerebral glucose metabolism. Such studies have implicated cingulate, frontal, temporal, and parietal regions in AN. Investigators have found that challenges such as food and body image distortions may activate some of these regions, raising the possibility that such studies may shed light on puzzling AN symptoms, such as body image distortions or extremes of appetitive behaviors. Emerging data suggest these disturbances persist after recovery from AN, suggesting the possibility that these are traits that may create a vulnerability to develop an ED. While fewer studies have been done in BN or binge eating disorder, there may be disturbances of serotonin metabolism in similar brain regions. Taken together, these findings give promise for future investigations with the hope of delineating brain pathways that contribute to the etiology of EDs.

Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, γ-aminobutyric acid, μ-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.

Introduction: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.

Methods: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.

Results: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.1%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).

Conclusion: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.

Dyskinesia is an extrapyramidal movement disorder characterized by involuntary, repetitive, irregular motions that affect the mouth and face and/or the limbs and trunk. Tardive dyskinesia (TD) is a well-known complication of long-term treatment with antipsychotic drugs. Dyskinesia is also induced with levodopa, a treatment for Parkinson's disease, and it occurs spontaneously as a symptom of Huntington's disease. Research on the pathogenesis of TD has focused on a dysfunction of either the dopaminergic or serotonergic system. However, recent evidence has suggested that we should focus on the possible damage of GABAergic medium spiny neurons (MSNs). MSNs are the first station in the cortico-striato-thalamo-cortical circuit that regulates the amplitude and velocity of movements. Two pathways can be distinguished in this circuit: a direct pathway, which increases movements (hyperkinesia), and an indirect pathway, which decreases movements (hypokinesia). Both pathways are activated by glutamatergic corticostriatal neurons. Here, we discuss some evidence that supports the hypothesis that indirect pathway MSNs are damaged in dyskinesia.

Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300–2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.

The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and to light since its first conceptualization. Aspects of SAD that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid response to a nonpharmacologic treatment, the specific neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing on circadian rhythms, neurotransmitters, and molecular genetics. Integrative issues and future directions for the study of SAD, including the heuristic value of a dualvulnerability hypothesis that conceptualizes seasonality as a dimensional construct and the importance of studying endophenotypes, will be discussed.

Pollutant agents are exponentially increasing in modern society since industrialization processes and technology are being developed worldwide. Impact of pollution on public health is well known but little has been described on the association between environmental pollutants and mental health. A literature search on PubMed and EMBASE has been conducted and 134 articles published on the issue of pollution and mental health have been included, cited, reviewed, and summarized. Emerging evidences have been collected on association between major environmental pollutants (air pollutants, heavy metals, ionizing radiation [IR], organophosphate pesticides, light pollution, noise pollution, environmental catastrophes) and various mental health disorders including anxiety, mood, and psychotic syndromes. Underlying pathogenesis includes direct and indirect effects of these agents on brain, respectively, due to their biological effect on human Central Nervous System or related to some levels of stress generated by the exposure to the pollutant agents over the time. Most of emerging evidences are still nonconclusive. Further studies should clarify how industrial production, the exploitation of certain resources, the proximity to waste and energy residues, noise, and the change in lifestyles are connected with psychological distress and mental health problems for the affected populations.

Although obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the DSM-IV, recent considerations for a reclassification into an obsessive-compulsive spectrum disorders (OCSDs) cluster are gaining prominence. Similarities in symptomatology, course of illness, patient population, and neurocircuitry of OCD and OCSD are supported by comorbidity, family, and neurological studies, which also offer a critical re-evaluation of the relationship between OCD and anxiety disorders. This review examines potential classifications of OCD among the wider spectrum of affective disorders and at the interface between affective disorders and addiction. In addition, it has been suggested that the categorical diagnostic approach would be enhanced by an additional dimensional approach, including parameters such as stability of mood and ability to sustain attention. With further studies, it is ultimately the goal to define OCD and related disorders based on endophenotypes.

Despite efforts in this field, there are several fundamental unresolved issues, including the question of which disorders should be grouped together in this category and which characteristics to include as their shared common features. A reclassification of OCD among the OCSDs would allow for better scrutiny of distinct obsessive-compulsive symptoms, as currently this disorder often goes undetected in patients who complain of a broad symptom of anxiety. Advantages and disadvantages of establishing OCSDs and its implications for diagnosis, treatment, and research are discussed.

Women's mental health during pregnancy has important implications not only for the well-being of the mother, but also for the development, health, and well-being of her unborn child. A growing body of empirical evidence from population-based studies suggests that two indicators of women's mental health during pregnancy—psychosocial stress and social support—may exert a significant influence on fetal development and infant birth outcomes, such as birth weight and length of gestation, even after controlling for the effects of established sociodemographic, obstetric, and behavioral risk factors. This paper describes the role of three major biological systems involved in the physiology of pregnancy and stress physiology: neuroendocrine, immune/inflammatory, and cardiovascular systems. These systems have been hypothesized to mediate the effects of maternal mental health on fetal developmental and health outcomes, and a central role has been proposed for placental corticotropin-releasing hormone in this process. However, not all women reporting high prenatal stress and/or low social support proceed to develop adverse birth outcomes, raising the question of the determinants of susceptibility/vulnerability in the context of high stress and/or low social support. In this context, the role of race/ethnicity and genetic predisposition are. discussed as two promising avenues of further investigation.

Depression is a widespread and serious disorder that afflicts an estimated 13.1 to 14.2 million adults in the United States each year. Even more compellingly, the lifetime prevalence rate of depression in the US has recently been estimated to include 16.2% of adults (21% women, 13% men), or >32.6 million people. There are multiple putative “causes” of depression, with approximately one-third of an individual's propensity for unipolar depression due to genetic vulnerability, while the remaining two-thirds is due to environmental factors. Although the selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to mainly act by selectively binding to the serotonin (5-HT) transporter to block reuptake of 5-HT from the synapse into the presynaptic nerve terminal, thereby increasing synaptic serotonin concentrations, some of the SSRIs also exhibit other neuropharmacologic effects. One such example is the high affinity for paroxetine in blocking norepinephrine reuptake. Another is the inhibition of dopamine reuptake by sertraline. In depression, hyperactivity of corticotropin-releasing factor (CRF)-producing neurons contribute to the well-characterized hypothalamic-pituitary-adrenal axis hyperactivity of depression. Increased activity of extrahypothalamic CRF circuits are believed to contribute to several depressive symptoms. Treatment and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use.

Introduction: An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder.

Methods: Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of −308 (G/A) tumor necrosis factor-α (TNF-α), +874 (T/A) interferon-γ (IFN-γ), -174 (G/C) interleukin (IL)-6, and −1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique.

Results: We observed different genotype and allele distributions of TNF-α, IFN-γ, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-α (P<.001) and a lower percentage of TT high producer genotype of IFN-γ (P <.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048).

Conclusion: These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.

What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healtcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been perform Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Although modern community-based studies have shown that a majority of people with newly diagnosed epilepsy will enter long-term remission, seizures remain refractory to treatment in a substantial proportion of this population—perhaps as much as 40%. A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of “rational polytherapy” for patients not responding to monotherapy, and to identify efficiently patients suitable for “curative” resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.

Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action.

We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale–Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up.

While the hypermetabolism theory for OCD involves the cortico–striato–thalamo–cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

The successful management of schizophrenia is an enormous public health issue. Although antipsychotic medications can be very helpful in reducing rates of relapse and rehospitalization, nonadherence to medication is a frequent cause of exacerbations in psychopathology, psychotic relapse, and rehospitalization. Relapses can have devastating consequences in a variety of clinical and functional domains. Nonadherence can result from a variety of factors that vary from patient to patient and vary over time in individual patients. A number of strategies have been developed to assess and facilitate adherence. The first critical step is clinician awareness of the scope of the problem and consideration of appropriate strategies to address it.

Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior.

When a person has a goal of drinking alcohol or using another addictive substance, the person appears to be automatically distracted by stimuli related to the goal. Because the attentional bias might propel the person to use the substance, an intervention might help modify it. In this article, we discuss techniques that have been developed to help people overcome their attentional bias for alcohol, smoking-related stimuli, drugs, or unhealthy food. We also discuss how these techniques are being adapted for use on mobile devices. The latter would allow people with an addictive behavior to use the attentional training in privacy and as frequently as needed. The attentional training techniques discussed here appear to have several advantages. They are inexpensive, can be fun to use, and have flexibility in when, where, and how often they are used. The evidence so far also suggests that they are effective.