Neurobiological Profiles Research Articles

O3.4. PSYCHOSIS PHENOTYPES FROM B-SNIP FOR CLINICAL ADVANCES: BIOTYPE CHARACTERISTICS AND TARGETS

BackgroundPsychiatry aspires to disease understanding and precision medicine. Biological research supporting such missions in psychosis may be compromised by continued reliance on clinical phenomenology in the search for pathophysiological mechanisms. A transdiagnostic deep phenotyping approach, such as that used by the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP), offers a promising strategy for discovery of biological mechanisms underlying psychosis syndromes. The B-SNIP consortium has identified biological subtypes of psychosis, Biotypes, which outperform conventional DSM diagnoses when accounting for variance of multiple external validating measures. While these biological distinctions are scientifically remarkable, their resulting clinical manifestations and potential utility in clinical practice is of paramount importance.MethodsApproximately 1500 psychosis cases and 450 healthy persons were administered the B-SNIP biomarker battery (including MRI, EEG, ocular motor, and cognition measures). Psychosis cases were also clinically characterized using multiple measures, including MADRS, PANSS, YMRS, and Birchwood. Numerical taxonomy approaches were used for identifying biologically homogenous psychosis subgroups (gap and TWO-STEP cluster identifications, k-means clustering, and canonical discriminant analysis). ANOVA models were used to analyze external validating measures. Multivariate discriminant models were used to identify clinical features differentiating conventional psychosis syndromes and psychosis Biotypes.ResultsThere was remarkable similarity between previously published biomarker profiles for DSM psychosis syndromes and a new sample of psychosis cases (average r=.92). Numerical taxonomy on biomarker data recovered three subgroups (replicating previous findings), and the biomarker profiles were highly similar to previous results (average r=.87). Schizoaffective cases were both the most diverse and the most clearly differentiated from schizophrenia and bipolar cases (on conative negative symptoms, depression, and mania) in clinical feature space. The only feature that uniquely distinguished schizophrenia was social-relational negative symptoms. Biotype-1 was characterized by accentuations on clinical features consistent with their biomarker deviations (relational negative symptoms, poor social functioning, and dysfunction of cognition). Alternatively, Biotype-2, also consistent with their biomarker deviations, had clinical features indicating neurophysiological dysregulation (most specifically physiological and behavioral dysregulation). Biotype-3 cases, the most normal across biomarkers, were noticeably absent of Biotype-1 clinical features and had more restricted clinical manifestations than any other Biotype or DSM subgroup. We illustrate three possible Biotype-specific treatment targets.DiscussionReplication of B-SNIP psychosis Biotypes indicates the possible utility and importance of neurobiological subtyping within psychosis that can yield specific treatment targets. In an analysis of clinical features, B-SNIP found that Biotypes have unique and defining clinical features that are consistent with their neurobiological profiles. Biotypes and DSM psychosis subgroups are neither neurobiologically nor clinically redundant. Specific treatment targets for psychosis Biotypes are not derivable from conventional clinical psychosis diagnoses. B-SNIP outcomes provide a background for future work that could establish psychiatry as a laboratory discipline, at least with regard to care of psychosis patients. This path is hypothetical at the moment but aspirational for the field.

General Overview of “Human Dementia Diseases”: Definitions, Classifications, Neurobiological Profiles and Clinical Treatments

This work focuses on the specific analysis of the general, neurobiological and clinical profiles of human dementias, starting from classifications and definitions, and then extending the field of study to clinical and psychological symptomatologic data, to conclude with treatments and better management of these patients.

Appetite Changes in Depression are Associated With Salience Neurocircuitry

Increasing evidence suggests that neurovegetative features of Major Depressive Disorder (MDD), specifically appetite changes, are associated with specific immunometabolic and neurobiological profiles. Although MDD in general has been associated with aberrant resting-state functional connectivity, it remains to be elucidated whether neurovegetative symptoms are associated with distinct neural connectivity patterns.

Identification of a Serotonin 2A Receptor Subtype of Schizophrenia Spectrum Disorders With Pimavanserin: The Sub-Sero Proof-of-Concept Trial Protocol.

BackgroundAll current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naïve patients will respond to serotonin 2A receptor (2AR) blockade.AimsThis investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin.Materials and EquipmentForty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses.Outcome MeasuresThe primary clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary clinical endpoints comprise multiple clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response.Anticipated ResultsClinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored.PerspectivesSub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a “serotonergic subtype” of schizophrenia spectrum patients, thereby promoting development of precision medicine in clinical psychiatry.Clinical Trial RegistrationClinicalTrials, identifier NCT03994965.

Comorbid Anxiety and Depression: Clinical and Conceptual Consideration and Transdiagnostic Treatment.

Although anxiety and depression have been considered as two distinct entities according to the diagnostic criteria, anxious depression (comorbid anxiety and depression) is relatively a common syndrome. According to the DSM-5 criteria, it uses "with anxious distress specifier" to define anxious depression in its MDD section. Anxious depression is known to have different neurobiological profiles compared to non-anxious depression. Several studies have revealed significant differences between anxious depression and non-anxious depression regarding the hypothalamic-pituitary-adrenal (HPA) axis function, structural and functional brain imaging findings, inflammation markers, etc. Patients with anxious depression were significantly more likely to be found in primary care setting and more likely to be associated with female gender, non-single, unemployed, less educated, and more severe depression. Previous reports also showed that patients with anxious depression had more frequent episodes of major depression and a higher risk of suicidal ideation and previous suicide attempts than those with non-anxious depression. Although anxious depression is known to be associated with poor treatment outcomes in several studies, recent researches have sought to find better treatment strategy to improve patients with anxious depression.

Examining the functional activity of different obsessive-compulsive symptom dimensions in Tourette syndrome.

Tourette syndrome (TS) is commonly comorbid with obsessive-compulsive disorder (OCD) and many phenomenological similarities exist between tics and obsessive-compulsive symptoms (OCS). Therefore, due to the clinical importance of comorbid OCD, the goal of this study was to investigate the neural substrates of OCS in TS using functional magnetic resonance imaging. Forty patients with TS and 20 healthy controls underwent functional magnetic resonance imaging while viewing blocks of OCS-provoking pictures relating to washing, checking and symmetry symptoms, as well as generally disgusting and neutral scenes. Statistical comparisons were made between patients with moderate/severe OCS, absent/mild OCS and healthy controls. As well, within the entire TS patient group, significant associations with clinical measures were assessed for each of the provocation conditions. Group differences in the insula, sensorimotor cortex, supramarginal gyrus and visual processing regions were common among the checking, washing and disgust conditions. In the patient group, negative associations between OCS severity and activity in the supramarginal gyrus, inferior frontal gyrus, sensorimotor cortex, precuneus and visual processing regions were common among the provocation conditions. Tic severity was only associated with activity in the anterior cingulate cortex for the symmetry condition. Our findings implicate areas previously reported to be involved in OCD, as well as areas not typically implicated in OCD, suggesting that the neurobiological profile of TS+OCD is intermediate to pure TS and pure OCD.

Emotion regulation and intervention in adults with autism spectrum disorder: a synthesis of the literature

PurposeEmotion regulation is an ongoing multiprocess phenomenon and is a challenging developmental task to acquire in individuals with autism spectrum disorder (ASD) who have different neurobiological profiles and emotion regulation problems. The purpose of this paper is to review recent literature to understand the neurobiological and psychological perspective of emotion regulation in ASD, while converging themes of psychosocial interventions and existing best practices on emotion regulation within this heterogeneous population are reviewed and discussed in consideration of intellectual disability (ID).Design/methodology/approachReview of recent literature and common empirically supported interventions addressing emotional regulation implemented in individuals with and without ASD, and with and without ID were included in the electronic database search through PubMed, EBSChost, Science Direct, Wiley Online Library, GALE and SAGE. Search terms used included autism, ID, cognitive control, executive function, sensory processing/intervention, emotion regulation, cognitive behavior therapy, mindfulness, social stories, positive behavior support and behavior therapy.FindingsNeural systems governing emotion regulation can be divided into “top-down” and “bottom-up” processing. Prefrontal cortex, cognitive and attentional control are critical for effective emotion regulation. Individuals with ASD, and with ID show impairments in these areas have problems with emotion regulation. Targeted psychosocial intervention need to consider bottom-up and top-down processes of emotion regulation, and that standardized interventions require adaptations.Originality/valueThere are limited studies looking into understanding the neurobiological and psychological perspective of emotion regulation in ASD and linking them to interventions. This review highlights psychosocial interventions that are important for further research, investigation and development as treatment in this population is limited.

Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats.

Anxiety disorders are one of the most common mental disorders, and benzodiazepines (BDZs), acting on gamma-aminobutyric acid type A (GABA-A) receptor complex, represent the most common antianxiety medications in the world. However, chronic BDZ use elicits several adverse reactions. Reportedly, aromatherapy is safer for the management of anxiety. Bergamot essential oil (BEO) extracted from Citrus bergamia Risso et Poiteau fruit, like other essential oils, is widely used in aromatherapy to relieve symptoms of stress-induced anxiety. Interestingly, preclinical data indicate that BEO induces anxiolytic-like/relaxant effects in animal behavioural tasks not superimposable to those of benzodiazepine diazepam. To better elucidate the involvement of GABAergic transmission, the present study examines the effects of pretreatment with flumazenil (FLZ), a benzodiazepine site antagonist, on BEO effects using open-field task (OFT) in rats. The data yielded show that FLZ does not significantly affect behavioural effects of the phytocomplex. These results demonstrate the lack of overlapping between BEO and BDZ behavioural effects, contributing to the characterization of the neurobiological profile of the essential oil for its rational use in aromatherapy.

Distinct resting state functional connectivity abnormalities in hoarding disorder and major depressive disorder

Emerging research suggests that hoarding disorder (HD) is associated with abnormal hemodynamic activity in frontal brain regions. Prior studies have not examined intrinsic network connectivity in HD during unstructured “resting state” fMRI. Furthermore, it remains unclear whether previously observed HD abnormalities might be better explained by the presence of other disorders frequently comorbid with HD, such as major depressive disorder (MDD). The current study compared resting state functional connectivity in HD-only patients (n = 17), MDD-only patients (n = 8), patients with co-occurring HD and MDD (n = 10), and healthy control participants (n = 18). Using independent component analysis, we found that HD-only patients exhibited lower functional connectivity in a “task positive” cognitive control network, compared to the other three groups. The HD group also had greater connectivity in regions of the “task negative” default mode network than did the other groups. Findings suggest that HD is associated with a unique neurobiological profile, and are discussed in terms of recent neurological and neuropsychological findings and models in HD and related disorders.

Altered ability to access a clinically relevant control network in patients remitted from major depressive disorder.

Neurobiological models to explain vulnerability of major depressive disorder (MDD) are scarce and previous functional magnetic resonance imaging studies mostly examined “static” functional connectivity (FC). Knowing that FC constantly evolves over time, it becomes important to assess how FC dynamically differs in remitted‐MDD patients vulnerable for new depressive episodes. Using a recently developed method to examine dynamic FC, we characterized re‐emerging FC states during rest in 51 antidepressant‐free MDD patients at high risk of recurrence (≥2 previous episodes), and 35 healthy controls. We examined differences in occurrence, duration, and switching profiles of FC states after neutral and sad mood induction. Remitted MDD patients showed a decreased probability of an FC state (p < 0.005) consisting of an extensive network connecting frontal areas—important for cognitive control—with default mode network, striatum, and salience areas, involved in emotional and self‐referential processing. Even when this FC state was observed in patients, it lasted shorter (p < 0.005) and was less likely to switch to a smaller prefrontal–striatum network (p < 0.005). Differences between patients and controls decreased after sad mood induction. Further, the duration of this FC state increased in remitted patients after sad mood induction but not in controls (p < 0.05). Our findings suggest reduced ability of remitted‐MDD patients, in neutral mood, to access a clinically relevant control network involved in the interplay between externally and internally oriented attention. When recovering from sad mood, remitted recurrent MDD appears to employ a compensatory mechanism to access this FC state. This study provides a novel neurobiological profile of MDD vulnerability.

The Role of Behavioral Phenotypes on Impaired Driving Recidivism Risk and Treatment Response to Brief Intervention: A Preliminary Study.

Heterogeneity in the driving while impaired (DWI) offender population and modest outcomes from remedial programs are fueling interest in clarifying clinically significant DWI subtypes to better assess recidivism risk and target interventions. Our previous research identified 2 putative behavior phenotypes of DWI offenders with distinct behavioral, personality, cognitive, and neurobiological profiles: (i) offenders primarily engaging in DWI (pDWI); and (ii) offenders engaging in DWI and other traffic violations (MIXED). Here, we evaluate these phenotypes' clinical significance for prediction of recidivism and intervention targeting. DWI recidivists participating in a previous randomized controlled trial (N=184 comparing brief motivational interviewing (BMI) and an information and advice control condition (IA) were retrospectively classified as either pDWI (n=97) or MIXED (n=87). Secondary analyses then evaluated the effect of this phenotypic classification on self-reported 6- and 12-month alcohol misuse outcomes and documented 5-year DWI recidivism violations, and in response to either BMI or IA (i.e., pDWI-BMI, n=46; MIXED-BMI, n=45; pDWI-IA, n=51; MIXED-IA, n=42). Two hypotheses were tested: (i) MIXED classification is associated with poorer alcohol misuse outcomes and recidivism outcomes than pDWI classification; and (ii) pDWI paired with BMI is associated with better outcomes compared to MIXED paired with BMI. MIXED classification was associated with significantly greater risk of recidivism over the 5-year follow-up compared to pDWI classification. Moreover, the pDWI-BMI pairing was associated with significantly decreased recidivism risk compared to the MIXED-BMI pairing. Analyses of 6- and 12-month alcohol use outcomes produced null findings. The clinical significance of phenotypic classification for risk assessment and targeting intervention was partially supported with respect to recidivism risk. Prospective investigation of this and other behavioral phenotypes is indicated.

Can we use neuroimaging data to differentiate between subgroups of children with ADHD symptoms: A proof of concept study using latent class analysis of brain activity.

BackgroundMultiple pathway models of ADHD suggest that multiple, separable biological pathways may lead to symptoms of the disorder. If this is the case, it should be possible to identify subgroups of children with ADHD based on distinct patterns of brain activity. Previous studies have used latent class analysis (LCA) to define subgroups at the behavioral and cognitive level and to then test whether they differ at the neurobiological level. In this proof of concept study, we took a reverse approach. We applied LCA to functional imaging data from two previously published studies to explore whether we could identify subgroups of children with ADHD symptoms at the neurobiological level with a meaningful relation to behavior or neuropsychology.MethodsFifty-six children with symptoms of ADHD (27 children with ADHD and 29 children with ASD and ADHD symptoms) and 31 typically developing children performed two neuropsychological tasks assessing reward sensitivity and temporal expectancy during functional magnetic resonance imaging. LCA was used to identify subgroups with similar patterns of brain activity separately for children with ADHD-symptoms and typically developing children. Behavioral and neuropsychological differences between subgroups were subsequently investigated.ResultsFor typically developing children, a one-subgroup model gave the most parsimonious fit, whereas for children with ADHD-symptoms a two-subgroup model best fits the data. The first ADHD subgroup (n = 49) showed attenuated brain activity compared to the second subgroup (n = 7) and to typically developing children (n = 31). Notably, the ADHD subgroup with attenuated brain activity showed less behavioral problems in everyday life.ConclusionsIn this proof of concept study, we showed that we could identify distinct subgroups of children with ADHD-symptoms based on their brain activity profiles. Generalizability was limited due to the small sample size, but ultimately such neurobiological profiles could improve insight in individual prognosis and treatment options.

Circuit Mechanisms of Reward, Anhedonia, and Depression.

Pleasure and motivation are important factors for goal-directed behavior and well-being in both animals and humans. Intact hedonic capacity requires an undisturbed interplay between a number of different brain regions and transmitter systems. Concordantly, dysfunction of networks encoding for reward have been shown in depression and other psychiatric disorders. The development of technological possibilities to investigate connectivity on a functional level in humans and to directly influence networks in animals using optogenetics among other techniques has provided new important insights in this field of research.In this review, we aim to provide an overview on the neurobiological substrates of anhedonia on a network level. For this purpose, definition of anhedonia and the involved reward components are described first, then current data on reward networks in healthy individuals and in depressed patients are summarized, and the roles of different neurotransmitter systems involved in reward processing are specified. Based on this information, the impact of different therapeutic approaches on reward processing is described with a particular focus on deep brain stimulation (DBS) as a possibility for a direct modulation of human brain structures in vivo.Overall, results of current studies emphasize the importance of anhedonia in psychiatric disorders and the relevance of targeting this phenotype for a successful psychiatric treatment. However, more data incorporating these results for the refinement of methodological approaches are needed to be able to develop individually tailored therapeutic concepts based on both clinical and neurobiological profiles of patients.

Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders

Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.

Polygenic pleiotropy and potential causal relationships between educational attainment, neurobiological profile, and positive psychotic symptoms

Event-related potential (ERP) components have been used to assess cognitive functions in patients with psychotic illness. Evidence suggests that among patients with psychosis there is a distinct heritable neurophysiologic phenotypic subtype captured by impairments across a range of ERP measures. In this study, we investigated the genetic basis of this “globally impaired” ERP cluster and its relationship to psychosis and cognitive abilities. We applied K-means clustering to six ERP measures to re-derive the globally impaired (n = 60) and the non-globally impaired ERP clusters (n = 323) in a sample of cases with schizophrenia (SCZ = 136) or bipolar disorder (BPD = 121) and healthy controls (n = 126). We used genome-wide association study (GWAS) results for SCZ, BPD, college completion, and childhood intelligence as the discovery datasets to derive polygenic risk scores (PRS) in our study sample and tested their associations with globally impaired ERP. We conducted mediation analyses to estimate the proportion of each PRS effect on severity of psychotic symptoms that is mediated through membership in the globally impaired ERP. Individuals with globally impaired ERP had significantly higher PANSS-positive scores (β = 3.95, P = 0.005). The SCZ-PRS was nominally associated with globally impaired ERP (unadjusted P = 0.01; R2 = 3.07%). We also found a significant positive association between the college-PRS and globally impaired ERP (FDR-corrected P = 0.004; R2 = 6.15%). The effect of college-PRS on PANSS positivity was almost entirely (97.1%) mediated through globally impaired ERP. These results suggest that the globally impaired ERP phenotype may represent some aspects of brain physiology on the path between genetic influences on educational attainment and psychotic symptoms.

S.03.02 - Clinical heterogeneity in major depressive disorder

S.03.02 - Clinical heterogeneity in major depressive disorder

Relationships of Alpha, Beta, and Theta EEG Spectra Properties with Aggressive and Nonaggressive Antisocial Behavior in Children and Adolescents

Abstract We investigated potential correlations between underlying electroencephalogram (EEG) spectral power and aggressive or nonaggressive antisocial behavior. Frontal and parietal EEG spectral properties were calculated for 3 different ranges (theta, 4–8 Hz; alpha, 8–10.5 Hz; and beta, 10.5–30 Hz) in 900 twins in an open-eyed resting state during 2 stages of development: ages 9–10 and ages 14–15. In multilevel regression modeling, relationships emerged between EEG spectral power properties and measures of antisocial behavior at age 14–15 years but not at the concurrent age of 9–10 years, providing support for neurodevelopmental underpinnings for adolescent-onset antisocial behavior. For boys, frontal alpha power, frontal beta power, and parietal beta power were correlated with aggressive antisocial behavior. For girls, parietal alpha power was anticorrelated with nonaggressive antisocial behavior, raising questions about differing neurobiological profiles for antisocial behavior between sexes. These results also support a distinction between aggressive and nonaggressive antisocial behavior.

Neurobiological Correlates and Predictors of Two Distinct Personality Trait Pathways to Escalated Alcohol Use

BackgroundThe delineation of the behavioral neurobiological mechanisms underlying the heterogeneous pathways for alcohol use disorders (AUDs) is ostensibly imperative for the development of more cost-effective treatments predicated on better understanding of this complex psychopathology. Methods1) Forty-eight high anxiety sensitive (HAS) and high sensation seeking (HSS) psychopathology-free emerging adults (mean (SD) age: 20.4 (1.9) years) completed a Face Emotion Processing Task and a social stress paradigm (Montreal Imaging Stress Task) during functional magnetic resonance imaging sessions with and without alcohol ingestion (1ml/kg of 95% USP alcohol, p.o.). Drug and alcohol use was reassessed during follow-up interviews 2–3years later. OutcomesThe effects of alcohol (versus placebo) ingestion depended upon the task and risk group. In response to negative (versus neutral) faces, alcohol diminished amygdala (AMYG) activations in HAS but not HSS subjects. In response to psychosocial evaluative stress, alcohol enhanced activations of the medial orbitofrontal cortex (mOFC), perigenual anterior cingulate cortex, and nucleus accumbens in HAS male subjects (HASMS), but decreased mOFC activity in HSS male subjects (HSSMS). At follow-up, a greater alcohol versus placebo differential for threat-related AMYG activations predicted escalating drinking and/or illicit drug use among HAS but not HSS participants, whereas a greater differential for mOFC activations during acute social stress predicted escalating substance use among HSS but not HAS participants. InterpretationThis double dissociation provides evidence of distinct neurobiological profiles in a priori identified personality trait-based risk groups for AUDs, and links these signatures to clinically relevant substance use outcomes at follow-up. AUD subtypes might benefit from motivationally and personality-specific ameliorative and preventative interventions.

Frontotemporal dementia: latest evidence and clinical implications.

Frontotemporal dementia (FTD) describes a cluster of neurocognitive syndromes that present with impairment of executive functioning, changes in behavior, and a decrease in language proficiency. FTD is the second most common form of dementia in those younger than 65 years and is expected to increase in prevalence as the population ages. This goal in our review is to describe advances in the understanding of neurobiological pathology, classification, assessment, and treatment of FTD syndromes. PubMed was searched to obtain reviews and studies that pertain to advancements in genetics, neurobiology, neuroimaging, classification, and treatment of FTD syndromes. Articles were chosen with a predilection to more recent preclinical/clinical trials and systematic reviews. Recent reviews and trials indicate a significant advancement in the understanding of molecular and neurobiological clinical correlates to variants of FTD. Genetic and histopathologic markers have only recently been discovered in the past decade. Current therapeutic modalities are limited, with most studies reporting improvement in symptoms with nonpharmacological interventions. However, a small number of studies have reported improvement of behavioral symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. Stimulants may help with disinhibition, apathy, and risk-taking behavior. Memantine and cholinesterase inhibitors have not demonstrated efficacy in ameliorating FTD symptoms. Antipsychotics have been used to treat agitation and psychosis, but safety concerns and side effect profiles limit utilization in the general FTD population. Nevertheless, recent breakthroughs in the understanding of FTD pathology have led to developments in pharmacological interventions that focus on producing treatments with autoimmune, genetic, and molecular targets. FTD is an underdiagnosed group of neurological syndromes comprising multiple variants with distinct neurobiological profiles and presentations. Recent advances suggest there is an array of potential novel therapeutic targets, although data concerning their effectiveness are still preliminary or preclinical. Further studies are required to develop pharmacological interventions, as there are currently no US Food and Drug administration approved treatments to manage FTD syndromes.

A comprehensive neuroimaging review of PCL-R defined psychopathy

Abstract Neurobiological theories of psychopathy typically include abnormalities in paralimbic circuits, and a neurobiological profile of paralimbic dysfunction in increasingly invoked in applied legal settings. The current study systematically evaluated whether sMRI and fMRI findings in PCL-R defined psychopaths suggest paralimbic dysfunction. Our review indicates diffuse and variable neural correlates of psychopathy, with numerous issues complicating the interpretation of these heterogeneous data. Our review also extends previous discussions concerning how this heterogeneity may be related to sample characteristics, methodological variations, and statistical analyses. To elucidate the neural correlates of psychopathy, researchers may need to clarify the relationship between psychopathy and co-occurring conditions (such as substance use disorders) both conceptually and methodologically. Our review also indicates that caution is warranted when introducing these data in applied contexts.