Showing papers in "Cns Spectrums in 2015"

The neurobiology of aggression and violence.

Abstract: Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.

The role of reproductive hormones in postpartum depression.

Abstract: Despite decades of research aimed at identifying the causes of postpartum depression (PPD), PPD remains common, and the causes are poorly understood. Many have attributed the onset of PPD to the rapid perinatal change in reproductive hormones. Although a number of human and nonhuman animal studies support the role of reproductive hormones in PPD, several studies have failed to detect an association between hormone concentrations and PPD. The purpose of this review is to examine the hypothesis that fluctuations in reproductive hormone levels during pregnancy and the postpartum period trigger PPD in susceptible women. We discuss and integrate the literature on animal models of PPD and human studies of reproductive hormones and PPD. We also discuss alternative biological models of PPD to demonstrate the potential for multiple PPD phenotypes and to describe the complex interplay of changing reproductive hormones and alterations in thyroid function, immune function, hypothalamic-pituitary-adrenal (HPA) axis function, lactogenic hormones, and genetic expression that may contribute to affective dysfunction. There are 3 primary lines of inquiry that have addressed the role of reproductive hormones in PPD: nonhuman animal studies, correlational studies of postpartum hormone levels and mood symptoms, and hormone manipulation studies. Reproductive hormones influence virtually every biological system implicated in PPD, and a subgroup of women seem to be particularly sensitive to the effects of perinatal changes in hormone levels. We propose that these women constitute a "hormone-sensitive" PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets.

Serotonin and impulsive aggression.

Abstract: Aggression is a behavior with evolutionary origins, but is often both destructive and maladaptive in today's society. Research over the past several decades has confirmed the involvement of neurotransmitter function in aggressive behavior. This research has centered around the "serotonin hypothesis." As this literature continues to grow, guided by pre-clinical research and aided by the application of increasingly sophisticated neuroimaging methodology, a more complex picture has emerged. As current pharmacological and therapeutic interventions are effective but imperfect, it is hoped that new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behavior.

Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder

Abstract: Flibanserin is a novel multifunctional serotonin agonist and antagonist (MSAA) that improves sexual functioning in premenopausal women who suffer from reduced sexual interest and desire.

Advances from neuroimaging studies in eating disorders.

Abstract: Over the past decade, brain imaging has helped to better define eating disorder–related brain circuitry. Brain research on gray matter (GM) and white matter (WM) volumes had been inconsistent, possibly due to the effects of acute starvation, exercise, medication, and comorbidity, but newer studies have controlled for such effects. Those studies suggest larger left medial orbitofrontal gyrus rectus volume in ill adult and adolescent anorexia nervosa after recovery from anorexia nervosa, and in adult bulimia nervosa. The orbitofrontal cortex is important in terminating food intake, and altered function could contribute to self-starvation. The right insula, which processes taste but also interoception, was enlarged in ill adult and adolescent anorexia nervosa, as well as adults recovered from the illness. The fixed perception of being fat in anorexia nervosa could be related to altered insula function. A few studies investigated WM integrity, with the most consistent finding of reduced fornix integrity in anorexia and bulimia nervosa—a limbic pathway that is important in emotion but also food intake regulation. Functional brain imaging using basic sweet taste stimuli in eating disorders during the ill state or after recovery implicated repeatedly reward pathways, including insula and striatum. Brain imaging that targeted dopamine-related brain activity using taste-reward conditioning tasks suggested that this circuitry is hypersensitive in anorexia nervosa, but hyporesponsive in bulimia nervosa and obesity. Those results are in line with basic research and suggest adaptive reward system changes in the human brain in response to extremes of food intake—changes that could interfere with normalization of eating behavior.

Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment

Abstract: Elevations of impulsive behavior have been observed in a number of serious mental illnesses. These phenomena can lead to harmful behaviors, including violence, and thus represent a serious public health concern. Such violence is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Despite the attention paid to violence, little is understood about its neural basis in schizophrenia. On a psychological level, aggression in schizophrenia has been primarily attributed to psychotic symptoms, desires for instrumental gain, or impulsive responses to perceived personal slights. Often, multiple attributions can coexist during a single aggressive incident. In this review, I discuss the neural circuitry associated with impulsivity and aggression in schizophrenia, with an emphasis on implications for treatment. Impulsivity appears to account for a great deal of aggression in schizophrenia, especially in inpatient settings. Urgency, defined as impulsivity in the context of strong emotion, is the primary focus of this article. It is elevated in several psychiatric disorders, and in schizophrenia, it has been related to aggression. Many studies have implicated dysfunctional frontotemporal circuitry in impulsivity and aggression in schizophrenia, and pharmacological treatments may act via that circuitry to reduce urgency and aggressive behaviors; however, more mechanistic studies are critically needed. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. It is hoped that these approaches will improve treatment efficacy.

The neuropsychology of obsessive-compulsive personality disorder : a new analysis

Abstract: BackgroundObsessive compulsive personality disorder (OCPD) is characterized by perfectionism, need for control, and cognitive rigidity. Currently, little neuropsychological data exist on this condition, though emerging evidence does suggest that disorders marked by compulsivity, including obsessive-compulsive disorder (OCD), are associated with impairment in cognitive flexibility and executive planning on neurocognitive tasks.AimThe current study investigated the neurocognitive profile in a nonclinical community-based sample of people fulfilling diagnostic criteria for OCPD in the absence of major psychiatric comorbidity.MethodTwenty-one nonclinical subjects who fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for OCPD were compared with 15 healthy controls on selected clinical and neurocognitive tasks. OCPD was measured using the Compulsive Personality Assessment Scale (CPAS). Participants completed tests from the Cambridge Automated Neuropsychological Test Battery including tests of set shifting (Intra-Extra Dimensional [IED] Set Shifting) executive planning (Stockings of Cambridge [SOC]), and decision making (Cambridge Gamble Task [CGT]).ResultsThe OCPD group made significantly more IED-ED shift errors and total shift errors, and also showed longer mean initial thinking time on the SOC at moderate levels of difficulty. No differences emerged on the CGT.ConclusionsNonclinical cases of OCPD showed significant cognitive inflexibility coupled with executive planning deficits, whereas decision-making remained intact. This profile of impairment overlaps with that of OCD and implies that common neuropsychological changes affect individuals with these disorders.

The clinical challenges of akathisia.

Abstract: Akathisia is one of the most vexing problems in neuropsychiatry. Although it is one of the most common side effects of antipsychotic medications, it is often difficult to describe by patients, and is difficult to diagnose and treat by practitioners. Akathisia is usually grouped with extrapyramidal movement disorders (ie, movement disorders that originate outside the pyramidal or corticospinal tracts and generally involve the basal ganglia). Yet, it can present as a purely subjective clinical complaint, without overt movement abnormalities. It has been subtyped into acute, subacute, chronic, tardive, withdrawal-related, and "pseudo" forms, although the distinction between many of these is unclear. It is therefore not surprising that akathisia is generally either underdiagnosed or misdiagnosed, which is a serious problem because it can lead to such adverse outcomes as poor adherence to medications, exacerbation of psychiatric symptoms, and, in some cases, aggression, violence, and suicide. In this article, we will attempt to address some of the confusion surrounding the condition, its relationship to other disorders, and differential diagnosis, as well as treatment alternatives.

The epidemiology and genetics of binge eating disorder (BED).

Abstract: This narrative review provides an overview of the epidemiology of binge eating disorder (BED), highlighting the medical history of this disorder and its entry as an independent condition in the Feeding and Eating Disorders section of the recently published Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Estimates of prevalence are provided, as well as recognition that the female to male ratio is lower in BED than in other eating disorders. Evidence is also provided of the most common comorbidities of BED, including mood and anxiety disorders and a range of addiction disorders. In addition, discussion of the viewpoint that BED itself may be an addiction - at least in severe cases - is presented. Although the genetic study of BED is still in its infancy, current research is reviewed with a focus on certain neurotransmitter genes that regulate brain reward mechanisms. To date, a focal point of this research has been on the dopamine and the μ-opioid receptor genes. Preliminary evidence suggests that a predisposing risk factor for BED may be a heightened sensitivity to reward, which could manifest as a strong dopamine signal in the brain's striatal region. Caution is encouraged, however, in the interpretation of current findings, since samples are relatively small in much of the research. To date, no genome-wide association studies have focused exclusively on BED.

Treating to target in major depressive disorder: response to remission to functional recovery

Abstract: Treating to target in chronic diseases [eg Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health Several atypical antipsychotic agents (ie brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery Measurement-based care, health information technology/systems, and integrated care models (eg medical homes) provide requisite tools and health environments for optimal health outcomes in MDD Achieving remission in MDD does not equate to health Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (ie optimization of human capital) As in other chronic diseases, treating to target (eg cognitive function) further increases the probability of achieving optimal health outcomes

Overview of the treatment of binge eating disorder

Abstract: We performed a qualitative review of treatment studies of binge eating disorder (BED), focusing on randomized clinical trials (RCTs). Limited effectiveness has been demonstrated for self-help strategies, and substantial effectiveness has been shown for cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT and IPT may each be more effective than behavior weight loss therapy (BWLT) for reducing binge eating over the long term. The stimulant pro-drug lisdexamfetamine dimesylate (LDX) is the only drug approved by the FDA for the treatment of BED in adults based on 2 pivotal RCTs. Topiramate also decreases binge eating behavior, but its use is limited by its adverse event profile. Antidepressants may be modestly effective over the short term for reducing binge eating behavior and comorbid depressive symptoms, but are not associated with clinically significant weight loss. A RCT presented in abstract form suggests that intranasal naloxone may decrease time spent binge eating. There is no RCT of obesity surgery in BED, but many patients with BED seek and receive such surgery. While some studies suggest patients with BED and obesity do just as well as patients with obesity alone, other studies suggest that patients with BED have more post-operative complications, less weight loss, and more weight regain. This evidence suggests that patients with BED would benefit from receiving highly individualized treatment.

Cognitive biases in binge eating disorder: the hijacking of decision making.

Abstract: Binge eating disorder (BED) is the most common of eating disorders and is characterized by excessive, out-of-control, rapid food intake. This review focuses on cognitive impairments in BED, which represent an endophenotype that mediates brain function and behavior. Here we focus on reviewing impulsivity, compulsivity, attentional biases to food cues, and executive function. Behavioral regulation in BED appears to be influenced by the context of motivationally salient food cues and the degree of obesity. Deficits in delay discounting and risk taking under ambiguity are impaired in obesity irrespective of BED status. However, in BED subjects with milder obesity, greater risk seeking under explicit probabilistic risk is observed to monetary rewards, whereas this shifts to risk aversion and enhanced delay discounting in more severe obesity. Relative to non-BED obese subjects, BED is characterized by enhanced behavioral inflexibility or compulsivity across multiple domains, with subjects selecting the same choices despite change in relevance (set shifting), being no longer rewarding (habit formation), or irrespective of outcome (perseveration). The context of food cues was associated with multiple attentional and early and late inhibitory impairments and enhanced memory bias, although BED patients also have generalized cognitive interference in working memory. These findings may help explain the phenotype of binge eating. Motivationally salient food cues provoke attentional and memory biases along with impairing response inhibitory processes. Those with BED are also more susceptible to cognitive interference and have impaired decisional impulsivity, with the tendency to inflexibly stick with the same choices irrespective of changes in context. These findings suggest critical cognitive domains that may guide therapeutic interventions.

Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: evidence from neuroimaging research.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (eg, obesity, binge/loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, eg, functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing (i) reward processing, (ii) response inhibition, and (iii) emotional processing and regulation, and we outline 3 specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research.

Neurobiological features of binge eating disorder.

Abstract: Biobehavioral features associated with binge-eating disorder (BED) have been investigated; however, few systematic reviews to date have described neuroimaging findings from studies of BED. Emerging functional and structural studies support BED as having unique and overlapping neural features as compared with other disorders. Neuroimaging studies provide evidence linking heightened responses to palatable food cues with prefrontal areas, particularly the orbitofrontal cortex (OFC), with specific relationships to hunger and reward-sensitivity measures. While few studies to date have investigated non-food-cue responses; these suggest a generalized hypofunctioning in frontostriatal areas during reward and inhibitory control processes. Early studies applying neuroimaging to treatment efforts suggest that targeting neural function underlying motivational processes may prove important in the treatment of BED.

Mesolimbic dopamine and its neuromodulators in obesity and binge eating.

Abstract: Obesity has reached epidemic prevalence, and much research has focused on homeostatic and nonhomeostatic mechanisms underlying overconsumption of food. Mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), is a key substrate for nonhomeostatic feeding. The goal of the present review is to compare changes in mesolimbic dopamine function in human obesity with diet-induced obesity in rodents. Additionally, we will review the literature to determine if dopamine signaling is altered with binge eating disorder in humans or binge eating modeled in rodents. Finally, we assess modulation of dopamine neurons by neuropeptides and peripheral peptidergic signals that occur with obesity or binge eating. We find that while decreased dopamine concentration is observed with obesity, there is inconsistency outside the human literature on the relationship between striatal D2 receptor expression and obesity. Finally, few studies have explored how orexigenic or anorexigenic peptides modulate dopamine neuronal activity or striatal dopamine in obese models. However, ghrelin modulation of dopamine neurons may be an important factor for driving binge feeding in rodents.

Prevalence of physical violence in a forensic psychiatric hospital system during 2011-2013: Patient assaults, staff assaults, and repeatedly violent patients.

Abstract: Introduction We examined physical violence in a large, multihospital state psychiatric system during 2011-2013, and associated demographic and clinical characteristics of violent patients to better understand issues of patient and staff safety. METHOD: Acts of physical violence committed by patients against other patients (n=10,958) or against staff (n=8429) during 2011-2013 were collected and analyzed for all hospitalized patients during the same time period to derive prevalence rates and associated odds ratios. RESULTS: Overall, 31.4% of patients committed at least 1 violent assault during their hospitalization. Differential risk factor patterns were noted across patient and staff assault. Younger age was associated with a higher prevalence of both patient and staff assault, as was nonforensic legal status. Females had a higher prevalence of staff assault than patient assault. Ethnic groups varied on rates of patient assault, but had no significant differences for staff assault. Schizoaffective disorder was associated with higher prevalence and odds of patient (OR 1.244, 95% CI 1.131 to 1.370) and staff (OR 1.346, 95% CI 1.202 to 1.507) assault when compared to patients diagnosed with schizophrenia. Most personality disorder diagnoses also had a higher prevalence and odds of physical violence. One percent of patients accounted for 28.7% of all assaults. Additionally, violent patients had a significantly longer length of hospitalization. DISCUSSION Implications of these findings to enhance patient safety and inform future violence reduction efforts, including the need for new treatments in conjunction with the use of violence risk assessments, are discussed. Language: en

Detection and treatment rates for perinatal depression in a state Medicaid population

Abstract: Background The purpose of this investigation was to assess detection and treatment rates for perinatal depression among women enrolled in the California State Medicaid (Medi-Cal) program in comparison to female beneficiaries of reproductive age who did not give birth during the same study period. Methods Investigators conducted a retrospective longitudinal cohort analysis of women between the ages of 18 and 39 years old who were continuously enrolled in the Medi-Cal fee-for-service program between January 2006 and December 2009. The perinatal cohort consisted of women with evidence of a live birth occurring between October 2007 and March 2009. The control cohort consisted of women in the same age group and health plan without evidence of pregnancy during this time frame. The primary outcome of this investigation was diagnosis of depression during 3 contiguous 9-month time frames: immediately prior to presumed conception, during pregnancy, and throughout the postpartum period. Secondary outcomes included within-group and cohort comparisons of treatment patterns (antidepressant or psychotherapy). A multivariable analysis of demographic factors predicting depression diagnosis or treatment was conducted as well. Results A total of 6030 women was identified in the perinatal cohort, and 56,709 women were included in the control group. The perinatal cohort was significantly less likely than nonpregnant controls to receive a diagnosis of depression both during pregnancy (prevalence=1.6% vs 3.5%; OR=0.45; 95% CI=0.35–0.55) and postpartum (2.2% vs 3.6%; OR=0.59; 95% CI=0.50–0.71). Similar differences were noted in antidepressant prescribing patterns apparent during these 2 time frames. A subgroup analysis of women who received a depression diagnosis revealed that only 48% of the perinatal cohort was provided any treatment during pregnancy (vs 72% of the control group; p<0.0001) or postpartum (57% vs 73%; p<0.0001). Specific demographic factors predicting a lower prevalence of depression detection or treatment included Hispanic descent, age <25 years, or primary residence in an rural setting. Conclusions Depression was often overlooked and undertreated among women who are pregnant or postpartum in comparison to services delivered to similar nonpregnant controls. Significant disparities in the healthcare received by certain subpopulations of perinatal women suggest that research into barriers to care and subsequent interventions are warranted.

Obesity and dissociable forms of impulsivity in young adults.

Abstract: This research was supported by a Center for Excellence in Gambling Research grant to Dr. Grant from the National Center for Responsible Gaming (USA) and by the Academy of Medical Sciences (UK; grant to Dr. Chamberlain).

Early-life adversity and adolescent depression: mechanisms involving the ventral striatum.

Abstract: Early-life adversity is a well-established risk factor for the development of depression later in life. Here we discuss the relationship between early-life adversity and depression, focusing specifically on effects of early-life caregiver deprivation on alterations in the neural and behavioral substrates of reward-processing. We also examine vulnerability to depression within the context of sensitive periods of neural development and the timing of adverse exposure. We further review the development of the ventral striatum, a limbic structure implicated in reward processing, and its role in depressive outcomes following early-life adversity. Finally, we suggest a potential neurobiological mechanism linking early-life adversity and altered ventral striatal development. Together these findings may help provide further insight into the role of reward circuitry dysfunction in psychopathological outcomes in both clinical and developmental populations.

Neuroimaging of the dopamine/reward system in adolescent drug use.

Abstract: 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.

Prevalence and correlates of anger in the community: results from a national survey.

Abstract: Introduction Little is known about the prevalence and correlates of anger in the community Methods We used data derived from a large national sample of the US population, which included more than 34,000 adults ages 18 years and older We defined inappropriate, intense, or poorly controlled anger by means of self-report of the following: (1) anger that was triggered by small things or that was difficult to control, (2) frequent temper outbursts or anger that lead to loss of control, or (3) hitting people or throwing objects in anger Results The overall prevalence of inappropriate, intense, or poorly controlled anger in the US population was 78% Anger was especially common among men and younger adults, and was associated with decreased psychosocial functioning Significant and positive associations were evident between anger and parental factors, childhood, and adulthood adverse events There were strong associations between anger and bipolar disorder, drug dependence, psychotic disorder, borderline, and schizotypal personality disorders There was a dose-response relationship between anger and a broad range of psychopathology Conclusions A rationale exists for developing screening tools and early intervention strategies, especially for young adults, to identify and help reduce anger

Neurobiological correlates of social anxiety disorder: an update.

Abstract: Social anxiety disorder (SAD) is a condition characterized by pervasiveness and impairment in social functioning, with a prevalence in the general population between 1.9% and 12.1%. The most consistent findings on its neurobiological underpinnings involve a wide range of neurotransmitters (serotonin, norepinephrine, glutamate, and GABA) and neuropeptides (oxytocin), but no comprehensive hypothesis is yet available. In particular, oxytocin is becoming increasingly established as a "prosocial neuropeptide" and, as such, is a major focus of current research, with a great range of therapeutic applications including SAD treatment. Specifically, the amygdala plays a pivotal role in conditioning and processing of fear, and exaggerated amygdala responses in SAD patients have been observed during various social-emotional stimuli. In addition to the amygdala, other brain areas of interest in SAD-related circuitry are represented by the medial prefrontal cortex, dorsal raphe, striatum, locus coeruleus, prefrontal cortex, insular cortex, and anterior cingulate cortex. The aim of this review is to provide an update on neurobiological correlates of SAD, with a special focus on neurotransmitters and brain areas possibly involved, and suggestions for future research that could lead to more specific therapeutic interventions.

Neuroimaging Endophenotypes in Autism Spectrum Disorder

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response, and lead to the development of new therapies.

Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors)

Abstract: Vortioxetine is an antidepressant that targets multiple pharmacologic modes of action at sites--or nodes--where serotonergic neurons connect to various brain circuits. These multimodal pharmacologic actions of vortioxetine lead to enhanced release of various neurotransmitters, including serotonin, at various nodes within neuronal networks.

Risk reduction treatment of psychopathy and applications to mentally disordered offenders

Abstract: Therapeutic nihilism on treating psychopathy is widespread and is largely based on many outdated and poorly designed studies. Important recent advances have been made in assessing psychopathy and recidivism risks, as well as in offender rehabilitation to reduce reoffending, all of which are now well supported by a considerable literature based on credible empirical research. A 2-component model to guide risk reduction treatment of psychopathy has been proposed based on the integration of key points from the 3 bodies of literature. Treatment programs in line with the model have been in operation, and the results of early outcome evaluations are encouraging. Important advances also have been made in understanding the possible etiology of mentally disordered offenders with schizophrenia and history of criminality and violence, some with significant features of psychopathy. This article presents a review of recent research on risk reduction treatment of psychopathy with the additional aim to extend the research to the treatment of mentally disordered offenders with schizophrenia, violence, and psychopathy.

Antidepressant medication use, depression, and the risk of preeclampsia

Abstract: Objective To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. Methods We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. Results The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for selective serotonin reuptake inhibitor (SSRI) use, although a nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Conclusion Study findings suggest that antidepressant use during pregnancy may increase the risk of preeclampsia, especially use during the second trimester.

Relationship of prenatal depression and comorbidities to infant outcomes.

Abstract: Objective The purpose of this study was to provide information on the effect of prenatal depression and anxiety as assessed in the context of obstetrical care on key infant outcomes (gestational age at birth, birth weight, and APGAR scores), while simultaneously considering interactions with maternal medical conditions among primarily Medicaid enrollees. Methods Obstetrical medical records of 419 women presenting consecutively for prenatal care at a health system serving primarily Medicaid patients were examined. Information on maternal characteristics (age, race, education) and maternal medical health (BMI, high blood pressure, diabetes, and kidney problems), as well as mental health information, was extracted. Depression was assessed as part of routine care using the Patient Health Questionnaire-9 (PHQ-9), and any documentation of depression or anxiety by the obstetrics clinician was also used in the analyses. Results Approximately one-third of the sample showed some evidence of prenatal depression, either based on PHQ-9 score (≥10) or clinician documentation of depression, and close to 10% showed evidence of anxiety. Multivariate analyses showed significant interactions between depression and anxiety on gestational age and birth weight, between depression and high blood pressure on gestational age, and also between anxiety and kidney problems on gestational age. Conclusion Among this sample, the effect of maternal depression and anxiety on birth outcomes was more evident when considered along with maternal chronic medical conditions. This information may be used to assist prenatal care clinicians to develop risk assessment based on knowledge of multiple risk factors that may exert and additive influence on poor birth outcomes.

Neuroimaging findings in disruptive behavior disorders

Abstract: Decades of research have shown that youths with disruptive behavior disorders (DBD) are a heterogeneous population. Over the past 20 years, researchers have distinguished youths with DBD as those displaying high (DBD/HCU) versus low (DBD/LCU) callous-unemotional (CU) traits. These traits include flat affect and reduced empathy and remorse, and are associated with more severe, varied, and persistent patterns of antisocial behavior and aggression. Conduct problems in youths with HCU and LCU are thought to reflect distinct causal vulnerabilities, with antisocial behavior in youths with DBD/HCU reflecting a predominantly genetic etiology, while antisocial behavior in youths with DBD/LCU is associated primarily with environmental influences. Here we selectively review recent functional (fMRI) and structural (sMRI) magnetic resonance imaging research on DBD, focusing particularly on the role of CU traits. First, fMRI studies examining the neural correlates of affective stimuli, emotional face processing, empathy, theory of mind, morality, and decision-making in DBD are discussed. This is followed by a review of the studies investigating brain structure and structural connectivity in DBD. Next, we highlight the need to further investigate females and the role of sex differences in this population. We conclude the review by identifying potential clinical implications of this research.

The role of the opioid system in binge eating disorder.

Abstract: Binge eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. Excessive intake of palatable food is thought to be driven by hedonic, rather than energy homeostatic, mechanisms. However, reward processing does not only comprise consummatory actions; a key component is represented by the anticipatory phase directed at procuring the reward. This phase is highly influenced by environmental food-associated stimuli, which can robustly enhance the desire to eat even in the absence of physiological needs. The opioid system (endogenous peptides and their receptors) has been strongly linked to the rewarding aspects of palatable food intake, and perhaps represents the key system involved in hedonic overeating. Here we review evidence suggesting that the opioid system can also be regarded as one of the systems that regulates the anticipatory incentive processes preceding binge eating hedonic episodes.

Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies.

Abstract: Objective Depressive symptoms are common in schizophrenia and can worsen outcomes and increase suicide risk. Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia and for the treatment of major depressive episodes associated with bipolar I disorder. This post hoc analysis evaluated the effect of lurasidone on depressive symptoms in patients with schizophrenia.