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Recent decades have seen substantial research on the biology of childhood aggression. Here, we review whether and how insights from biological research have contributed to more effective treatments for aggression, with a focus on parenting interventions. We also outline specific strategies for researchers to integrate biological and clinical approaches to refine or augment parenting-focused interventions moving forward. In particular, we (1) evaluate the ability of biological data to provide unique and treatment-relevant insights into the mechanisms of aggression, beyond behavioral data; (2) outline ways of incorporating biological measures directly into clinical practice and possible drawbacks; and (3) discuss the privileged position of biological evidence in the eyes of policymakers and the public, including the potential to drive change at the risk of promoting biological essentialism. To meaningfully advance parenting interventions for childhood aggression, clinical scientists must be thoughtful about the promises and possible pitfalls of integrating biological and implementation-oriented approaches. • Biological research on child aggression may contribute to future interventions. • We review evidence that biological research has helped refine theory and practice. • We discuss how to integrate biological measures directly into clinical practice. • We weigh the pros and cons of emphasizing biological aspects of child aggression. [ABSTRACT FROM AUTHOR]

Zebrafish are a dynamic research model in the domains of neuropsychopharmacology, biological psychiatry and behaviour. Working with larvae ≤4 days post-fertilisation (dpf) offers an avenue for high-throughput investigation whilst aligning with the 3Rs principles of animal research. The light/dark assay, which is the most widely used behavioural assay for larval neuropharmacology research, lacks experimental reliability and standardisation. This study aimed to formulate a robust, reproducible and standardised light/dark behavioural assay using 4 dpf zebrafish larvae. Considerable between-batch and inter-individual variability was found, which we rectified with a normalisation approach to ensure a reliable foundation for analysis. We then identified that 5-min light/dark transition periods are optimal for locomotor activity. We also found that a 30-min acclimation in the light was found to produce significantly increased dark phase larval locomotion. Next, we confirmed the pharmacological predictivity of the standardised assay using ethanol which, as predicted, caused hyperlocomotion at low concentrations and hypolocomotion at high concentrations. Finally, the assay was validated by assessing the behavioural phenotype of hyperactive transgenic (adgrl3.1 −/− ) larvae, which was rescued with psychostimulant medications. Our standardised assay not only provides a clear experimental and analytical framework to work with 4 dpf larvae, but also facilitates between-laboratory collaboration using our normalisation approach. • The light/dark assay establishes 4 dpf zebrafish as robust neuropsychopharmacology models. • Our unique normalisation analysis protocol facilitates researcher collaboration. • Predictable pharmacological effects were seen in 4 dpf larvae with ethanol exposure. • Hyperactive phenotypes of ADHD transgenic larvae were rescued with ATO and MPH. [ABSTRACT FROM AUTHOR]

• We found structural and functional abnormalities in misophonia. • Patients had larger right amygdala volumes. • Patients had stronger resting-state coupling between the amygdala and cerebellum. • Patients' ventral attention network was more connected within occipital cortex. • Misophonia involves dysfunction of emotional and attentional systems. Misophonia is a newly described condition in which specific ordinary sounds provoke disproportionately strong negative affect. Since evidence for neurobiological abnormalities underlying misophonia is scarce, we tested whether misophonia patients differed from healthy controls in grey matter volumes and resting-state functional connectivity. We collected structural magnetic resonance imaging and resting-state functional magnetic resonance imaging data from 24 misophonia patients and 25 matched controls. Compared to controls, voxel-based morphometry showed larger right amygdala volume in misophonia patients. Follow-up seed-based functional connectivity analysis of the amygdala showed a different pattern of connectivity with the cerebellum, driven by greater connectivity with the left amygdala. Additional data-driven independent component analysis showed greater connectivity within lateral occipital cortices and fusiform gyri in the ventral attention network. We propose that the amygdala enlargement may be associated with heightened emotional reactivity in misophonia. The higher connectivity between left amygdala and cerebellum might be linked to a tendency to exhibit reflex-like physical reactions to triggers. Higher attention network connectivity may reflect sensory enhancement of visual triggers or visual imagery related to trigger sounds. In sum, we found structural and functional abnormalities which implicate dysfunction of emotional and attentional systems in misophonia. [ABSTRACT FROM AUTHOR]

• "Physiometrics" refers to the measurement properties of biological variables. • Poor physiometrics decrease statistical power, effect sizes, and efficiency of research (financial, time, number of analyses, replicability). • Certain measurement properties germane to behavioral health research methods are reported less frequently for biological compared to psychological variables. • Internal consistency, dimensionality, method-specific variance, temporal stability, and temporal specificity are important considerations for interpreting and designing research. • Appreciation for physiometrics as consumers and producers of research can streamline the research to intervention pipeline. Biological psychiatry is a major funding priority for organizations that fund mental health research (e.g., National Institutes of Health). Despite this, some have argued that the field has fallen short of its considerable promise to meaningfully impact the classification, diagnosis, and treatment of psychopathology. This may be attributable in part to a paucity of research about key measurement properties ("physiometrics") of biological variables as they are commonly used in biological psychiatry research. Specifically, study designs informed by physiometrics are more likely to be replicable, avoid poor measurement that results in misestimation, and maximize efficiency in terms of time, money, and the number of analyses conducted. This review describes five key physiometric principles (internal consistency, dimensionality, method-specific variance, temporal stability, and temporal specificity), illustrates how lack of understanding about these characteristics imposes meaningful limitations on research, and reviews examples of physiometric studies featuring a variety of popular biological variables to illustrate how this research can be done and substantive conclusions drawn about the variables of interest. [ABSTRACT FROM AUTHOR]

The aberrant salience hypothesis proposes that striatal dopamine dysregulation causes misattribution of salience to irrelevant stimuli leading to psychosis. Recently, new lines of preclinical evidence on information coding by subcortical dopamine coupled with computational models of the brain's ability to predict and make inferences about the world (predictive processing) provide a new perspective on this hypothesis. We review these and summarize the evidence for dopamine dysfunction, reward processing, and salience abnormalities in people at clinical high risk of psychosis (CHR) relative to findings in patients with psychosis. This review identifies consistent evidence for dysregulated subcortical dopamine function in people at CHR, but also indicates a number of areas where neurobiological processes are different in CHR subjects relative to patients with psychosis, particularly in reward processing. We then consider how predictive processing models may explain psychotic symptoms in terms of alterations in prediction error and precision signaling using Bayesian approaches. We also review the potential role of environmental risk factors, particularly early adverse life experiences, in influencing the prior expectations that individuals have about their world in terms of computational models of the progression from being at CHR to frank psychosis. We identify a number of key outstanding questions, including the relative roles of prediction error or precision signaling in the development of symptoms and the mechanism underlying dopamine dysfunction. Finally, we discuss how the integration of computational psychiatry with biological investigation may inform the treatment for people at CHR of psychosis. [ABSTRACT FROM AUTHOR]

Background: Serious mental illnesses may be characterized by accelerated biological aging, and over the last years the research on the topic has been stimulated by studies exploring the molecular underpinnings of senescence.Methods: In the present manuscript we propose that measuring frailty, a general product of organismal ageing, through the "Frailty Index" (FI), a recently-emerged macroscopic indicator of functional status and biological age, adds an important marker to the measurements currently implemented in the study of accelerated biological age in psychiatric illnesses.Results: The FI quantifies functional negative health attributes and measures their cumulative effect, thus providing a useful estimate of the individual's biological age and risk profile. Recent studies in older adults have observed significant associations between FI and molecular measures of aging.Limitations: High FI values can be driven by causes different from aging per se, so FI may be a sensitive but not specific measure of biological aging.Conclusions: FI, which is extensively used in geriatrics and gerontology but it has rarely been used in relation to mental health, may be of relevance in the evaluation of age-related phenomena associated with psychiatric diseases. [ABSTRACT FROM AUTHOR]

Background: One third of people diagnosed with schizophrenia fail to respond adequately to antipsychotic medication, resulting in persisting disabling symptoms, higher rates of hospitalization and higher costs for society. In an effort to better understand the mechanisms behind resistance to antipsychotic treatment in schizophrenia, we investigated its potential relationship to the genetic architecture of the disorder.Methods: Patients diagnosed with a schizophrenia spectrum disorder (N = 321) were classified as either being treatment-resistant (N = 108) or non-treatment-resistant (N = 213) to antipsychotic medication using defined consensus criteria. A schizophrenia polygenic risk score based on genome-wide association studies (GWAS) was calculated for each patient and binary logistic regression was performed to investigate the association between polygenetic risk and treatment resistance. We adjusted for principal components, batch number, age and sex. Additional analyses were performed to investigate associations with demographic and clinical variables.Results: High levels of polygenic risk score for schizophrenia significantly predicted treatment resistance (p = 0.003). The positive predictive value of the model was 61.5% and the negative predictive value was 71.7%. The association was significant for one (p = 0.01) out of five tested SNP significance thresholds. Season of birth was able to predict treatment-resistance in the regression model (p = 0.05).Conclusions: The study indicates that treatment-resistance to antipsychotic medication is associated with higher polygenetic risk of schizophrenia, suggesting a link between antipsychotics mechanism of action and the genetic underpinnings of the disorder. [ABSTRACT FROM AUTHOR]

Background: ECT is the most effective treatment of major depressive episode (MDE) but remains a neglected treatment. The French Society for Biological Psychiatry and Neuropsychopharmacology aimed to determine whether prescribing practice of ECT followed guidelines recommendations.Methods: This multicenter, retrospective study included adult patients with major depressive disorder (MDD) or bipolar disorder (BD), who have been treated with ECT for MDE. Duration of MDE and number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests.Results: Seven hundred and forty-five individuals were included. The mean duration of MDE before ECT was 10.1 months and the mean number of lines of treatment before ECT was 3.4. It was significantly longer for MDD single episode than recurrent MDD and BD. The presence of first-line indications for using ECT was significantly associated to shorter duration of MDE (9.1 vs 13.1 months, p<0.001) and lower number of lines of treatment before ECT (3.3 vs 4.1, p<0.001).Limitations: This is a retrospective study and not all facilities practicing ECT participated that could limit the extrapolation of the results.Conclusion: Compared to guidelines, ECT was not used as first-line strategy in clinical practice. The presence of first-line indications seemed to reduce the delay before ECT initiation. The improvements of knowledge and access of ECT are needed to decrease the gap between guidelines and clinical practice. [ABSTRACT FROM AUTHOR]

• Signature is a unique longitudinal dataset of psychiatric patients and controls. • We describe the baseline characteristics of the Signature patient cohort. • We provide a review of studies published using the Signature dataset. The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit. [ABSTRACT FROM AUTHOR]

Le syndrome de Klinefelter (47,XXY) constitue l'aneuploïdie des chromosomes sexuels la plus fréquente chez l'Homme (1 sur 650, 0,1 à 0,2 % de la population masculine). En raison d'une grande variabilité phénotypique, le syndrome est largement sous-diagnostiqué (moins de 25 % des sujets atteints diagnostiqués). Le profil neurocognitif est plus stable et spécifique. Dans la littérature, un quotient intellectuel total normal ou bas, associé à un quotient intellectuel verbal plutôt faible, des difficultés d'adaptation sociale et un taux élevé de comorbidités psychiatriques, incluant une agressivité précoce, sont classiquement décrits. Au Danemark, un risque plus élevé de commettre un crime sexuel et un incendie volontaire (comparativement à un sujet contrôle) a été récemment démontré. Un certain nombre de cas cliniques isolés, relatifs à des patients institutionnalisés, suggèrent la présence d'un sous-type « médico-légal » de patients Klinefelter. À l'heure actuelle, il existe peu de données robustes et exploitables en ce sens. Le syndrome de Klinefelter présente des spécificités neuropsychologiques, neurobiologiques et neuro-anatomiques bien documentées, qui peuvent être utiles à la compréhension de la psychopathologie des symptômes comorbides. Certains auteurs utilisent également les caractéristiques génétiques et épigénétiques des aneuploïdies des chromosomes sexuels afin de clarifier les liens génotype-phénotype. Avec nos collègues belges du CRDS (Centre de Recherche en Défense Sociale, Tournai, Belgique), nous recrutons actuellement des patients Klinefelter hospitalisés parmi la population médico-légale, afin d'évaluer leurs traits psychopathiques avec l'échelle de Hare (PCL-R). Nos premiers résultats (n = 3) confirment que l'échelle est utile à la caractérisation objective phénotypique clinique de la population. Nous avons mis en évidence deux diagnostics doubles « Klinefelter-psychopathe » (score de PCL total > = à 30/40). De façon plus intéressante, l'analyse dimensionnelle supporte notre hypothèse d'une prévalence importante du « profil explosif » relativement aux autres profils de psychopathie. Le présent article résume les arguments contextuels, historiques et actuels ayant motivé notre projet de recherche. Il discute certains des avantages offerts par l'étude de patients Klinefelter préalablement évalués à l'échelle de Hare, comme la lutte contre la stigmatisation et la discrimination, la meilleure compréhension de la psychopathologie et du rôle développemental complexe des facteurs biologiques, psychologiques et sociaux, pour chacune de ces deux entités cliniques. Klinefelter syndrome (KS) (47,XXY) is the most common aneuploidy (1/650) of sexual chromosome among male (0,1 à 0,2 % of male population) (Hong and Reiss, 2014). Because its large physical phenotypic variability (high tall, sparse hairiness, gynecomastia), this syndrome is largely underdiagnosed (less than 25 % of affected persons) (Samango-Sprouse et al., 2018). Nevertheless, cognitive variability is smaller. Normal to low average total IQ, low verbal IQ, social problems and high levels of psychiatric comorbidities including early aggressiveness are commonly described (Hong and Reiss, 2014). In Denmark, higher risks of committing sexual crime and arson (compared to criminal controls) was recently reported (Stochholm et al., 2012). Quite a few clinically relevant cases reports scattered in the literature, suggests the presence of a pattern of a specific subtype of KS inpatients among forensic population (Bénézech, 1975). However, very few studies provide quantitative or qualitative pertaining to robust results. KS well-documented neurobiological (van Rijn, 2018) (e.g. low levels of testosterone), neuropsychological (Bénézech, 1975; Hong and Reiss, 2014; Samango-Sprouse et al., 2018; Savic, 2012; Seara-Cardoso et al., 2016; Senon, 2005; Stochholm et al., 2012; van Rijn, 2018; van Rijn et al., 2008; van Rijn et al., 2018; van Rijn et al., 2014; van Rijn et al., 2012) [29] (e.g. alterations of both complex cerebral — attention, empathy — and behavioral regulation functions - inhibition, mental flexibility, emotional response modulation, control of own actions) and neuroanatomical (Hong and Reiss, 2014; Itti et al., 2003; Savic, 2012; van Rijn et al., 2008; van Rijn et al., 2012) [29] (e.g. limbic system and temporal lobe abnormal volume, hemispheric specialization shortcoming) features may be helpful to understand comorbid symptoms psychopathology. Numbers of recent studies conduct on KS pediatric or adult population provide interesting results on conduct, anxiety, psychotic and autism spectrum disorders. In addition, some authors use genetic and epigenetic specific features of sex chromosome aneuploidies (e.g. X genes neurodevelopmental role; imprinting) in order to clarify genotype-phenotype links of comorbid symptoms (Bruining et al., 2011; Zitzmann et al., 2004;). With Belgian colleagues from the Social Defense Research Center (CRDS, Tournai, Belgium), we are currently recruiting KS inpatients from security hospitals or psychiatric units in Belgium and France. We aim to assess psychopathic traits with the Psychopathy Checklist Revised (PCL-R, Hare) (Hare, 2003). Our first results concerning 3 KS males outline that PCL-R is useful for the characterization of clinical phenotype among KS forensic sample. While three of them present psychopathic traits, two of them present categorical double diagnose "psychopathy-KS" (total PCL-R score > = 30/40 (Delannoy et al., 2017)). Moreover, dimensional analysis support our hypothesis of a higher prevalence of "explosive profile" in comparison to other psychopathic profiles in our sample (Delannoy et al., 2017). The present article summarizes historic background (e.g. "psychopathy" disappearance of mental disorder reference classification schemes, "crime chromosome" (Bénézech, 1975)) and current context argues (e.g. French psychiatrists court experts widely refer to psychopathy concept despite a lack of consensual definition (Senon, 2005), weak knowledge and training of PCL-R and its related biopsychological recent findings (Blair, 2013; de Oliveira-Souza et al., 2008; Dotterer et al., 2017; Glenn and Raine, 2014; Hosking et al., 2017; Korponay et al., 2017; Pham, 1995; Pham, 2005; Raine, 2008; Raine et al., 2003); stigma and discrimination apprehensions of KS and psychopath) that motivate our research project. Finally, we discuss the advantages of our research protocol on KS participants assessed with PCL-R, such as tackling stigma and discrimination, better understanding psychopathology, and clarifying murky interactions of biological, psychological and social factors entangled in the development of these two fascinating troubles. [ABSTRACT FROM AUTHOR]

There is considerable variability in the severity of bipolar disorder, e.g., in terms of the frequency of inpatient episodes. The long-term progression also differs, where some patients are sensitised with progressively shorter healthy intervals. Little is known about the proportion of patients being sensitised, their clinical characteristics, and biological underpinnings. We analysed long-term progression of bipolar disorder in relation to clinical characteristics (N = 3074), serum biomarkers (N = 745), and genetic variants (N = 1401) in a cohort of Swedish bipolar disorder patients. We took advantage of the National Patient Register, providing reliable data on 35,973 psychiatric inpatient care episodes in Sweden since 1973. First, one third of the cohort cluster together with a maximum of one inpatient episode per year, while the remaining two thirds had >1 episode per year. These groups did not differ with respect to clinical features or biomarkers. Second, among patients with at least five inpatient episodes (defined as severely ill), we find one group with progressively shorter cycle-lengths (one fifth of the total cohort, N = 550). Compared with those with a stable or recuperant trajectory, these patients featured lower functioning, more antidepressant treatment, as well as reduced levels of inflammatory markers in serum. Third, sensitisation was associated with a common genetic variant near the calcium channel gene CACNA2D3 at genome-wide significance. These results suggest the potential for translational research aimed at preventive actions. [ABSTRACT FROM AUTHOR]

Intense anger and anger-related aggression are frequently reported by patients with borderline personality disorders (BPD). Recent results suggest that anger-related aggression and its control is associated with a complex interplay of different neural systems in BPD. To further investigate this, we complement standard activation and seed-based connectivity analyses by examining whole-brain changes in functional connectivity during anger and reactive aggression in BPD. We reanalyzed functional MRI data from 33 women with BPD, all of them fulfilling BPD criterion 8, "anger proneness", according to DSM-IV, and 30 healthy women. Subjects performed a script-driven imagery task consisting of four phases: baseline, anger-induction by a narrative of interpersonal rejection, a narrative of directing physical aggression towards others, and relaxation. We used a data-driven, spatially constrained spectral clustering approach to parcellate the brain into 200 regions. For each script-phase and subject, we computed the full connectivity matrix using wavelet coefficient correlations in the 0.05–0.10 Hz range. We calculated the individual increase in connectivity from baseline to the anger-induction and physical aggression phases by subtracting the corresponding connectivity matrices per subject, as well as the increase and decrease from the anger-induction to the aggression phase. We then applied permutation-based sampling to determine a combined threshold on the strength of individual connections and the size of the discovered networks for these difference matrices. We discovered a single, large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. This network consisted of regions in the anterior and posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, superior and middle temporal gyrus, hippocampus, insula, ventrolateral and dorsolateral prefrontal cortex, superior parietal lobe, thalamus, precentral and postcentral gyrus, caudate, pallidum, cerebellum, middle occipital lobe, lingual gyrus, calcarine sulcus, and fusiform gyrus. Hub regions with highest node centrality were found in the right caudate and left thalamus. We found no significant differences for the increase of connectivity from baseline to anger-induction, as well as for the increase or decrease from the anger-induction to the aggression phase. We identified a large network showing a significantly stronger increase in connectivity from baseline to the aggression phase in female patients with BPD compared to healthy women. The regions constituting this network belong to four previously described functional networks: The frontoparietal cognitive control network, the extended default mode network, the visual system, and the motor system. This stronger increase in connectivity between regions of different functional brain systems associated with cognitive control of behavior, socio-affective and self-referential thinking, as well as salience processing and emotion regulation, visual perception, and action is mediated via hubs in the thalamus and caudate, i.e., core components of the thalamocorticostriatal motor loop essential for action selection and initiation. These findings suggest increased interaction of prefrontal cognitive control processes with thalamocorticostriatal action-selection processes in female patients with BPD during the processing of aggressive action impulses, which are facilitated by states of high emotional salience and associated processes of self-referential and social processing, and ineffective emotion regulation. • Female borderline patients show distinct functional network dynamics. • A large brain network increases connectivity during imagined aggression. • It includes parts of the motor system, cognitive control, and default-mode networks. • Network hubs are located in the caudate and thalamus. [ABSTRACT FROM AUTHOR]

To systematically review findings of GWAS in schizophrenia (SZ) and in bipolar disorder (BD); and to interpret findings, with a focus on identifying independent replications. PubMed search, selection and review of all independent GWAS in SZ or BD, published since March 2011, i.e. studies using non-overlapping samples within each article, between articles, and with those of the previous review (Li et al., 2012). From the 22 GWAS included in this review, the genetic associations surviving standard GWAS-significance were for genetic markers in the regions of ACSL3/KCNE4 , ADCY2 , AMBRA1, ANK3, BRP44, DTL, FBLN1, HHAT, INTS7, LOC392301, LOC6 45434/NMBR , LOC729457, LRRFIP1, LSM1, MDM1, MHC, MIR2113/POU3F2, NDST3, NKAPL, ODZ4, PGBD1, RENBP, TRANK1, TSPAN18, TWIST2, UGT1A1/HJURP, WHSC1L1/FGFR1 and ZKSCAN4. All genes implicated across both reviews are discussed in terms of their function and implication in neuropsychiatry. Taking all GWAS to date into account, AMBRA1 , ANK3 , ARNTL , CDH13 , EFHD1 (albeit with different alleles), MHC , PLXNA2 and UGT1A1 have been implicated in either disorder in at least two reportedly non-overlapping samples. Additionally, evidence for a SZ/BD common genetic basis is most strongly supported by the implication of ANK3 , NDST3 , and PLXNA2. [ABSTRACT FROM AUTHOR]

Positive life experiences are potentially-rewarding events and behaviors, such as social and romantic interactions, experiences of relaxation and physical comfort, time spent in nature, and other leisure activities. To date, there is limited evidence linking positive life experiences to long-term health outcomes. The current study used data from N = 1243 participants in the Midlife Development in the US Study Biomarker Project to examine whether greater frequency of a range of different positive experiences and greater level of enjoyment of these experiences was linked to survival over a 12- to-16-year period in Cox proportional hazards models. The potential mediating roles of positive affect, depression, perceived stress, and an allostatic load index of physiological dysregulation in these associations were also examined. Greater frequency of positive experiences and greater enjoyment of positive experiences were both associated with a reduced hazard of mortality over the 12- to 16-year period. Models assessing a single mediator showed that both associations were mediated by decreased depression and decreased perceived stress, but not by positive affect or allostatic load. In supplementary multi-mediation models, depression was the only significant mediator of the frequency-survival and enjoyment-survival associations. Positive life experiences may confer long-term survival benefits, partially through lessening depressive symptomatology. • Positive life experiences may confer health and survival benefits. • Greater frequency of positive experiences was linked to long-term survival. • Greater enjoyment flowing from positive experiences conferred a survival benefit. • Lower depression and perceived stress may link positive experiences to survival. [ABSTRACT FROM AUTHOR]

Highlights • Evidence for brain systems specialized in defensive behavior in fish are reviewed. • Telencephalic and habenular circuits represent a "high road" for defensive behavior. • Hypothalamic circuits organize neuroendocrine and neurovegetative outputs. • The optic tectum mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Abstract Defensive behavior is a function of specific survival circuits, the "aversive brain system", that are thought to be conserved across vertebrates, and involve threat detection and the organization of defensive responses to reduce or eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic subnuclei and midbrain circuits. The increased interest in teleost fishes as model organisms in neuroscience created a demand to understand which brain circuits are involved in defensive behavior. Telencephalic and habenular circuits represent a "forebrain circuit" for threat processing and organization of responses, being important to mounting appropriate coping responses. Specific hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but are the less well-studied in fish. A "midbrain circuit" is represented by projections to interneurons in the optic tectum which mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Threatening stimuli (especially visual stimuli) can bypass the "high road" and directly activate this system, initiating escape responses. Increased attention to these circuits in an evolutionary framework is still needed. [ABSTRACT FROM AUTHOR]

Abstract Depression is a wide-spread, debilitating psychiatric disorder. Mainly rodent-based, experimental animal models of depression are extensively used to probe the pathogenesis of this disorder. Here, we emphasize the need for innovative approaches to studying depression, and call for a wider use of novel model organisms, such as the zebrafish (Danio rerio), in this field. Highly homologous to humans and rodents, zebrafish are rapidly becoming a valuable tool in translational neuroscience research, but have only recently been utilized in depression research. Multiple conceptual and methodological problems, however, arise in relation to separating putative zebrafish depression-like states from motor and social deficits or anxiety. Here, we examine recent findings and the existing challenges in this field, to encourage further research and the use of zebrafish as novel organisms in cross-species depression modeling. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders, characterized by early-onset deficits in social behavior and communication across multiple contexts, together with restricted, repetitive patterns of behavior, interests, or activities. ASD is among the most heritable neuropsychiatric conditions with heritability estimates higher than 80%, and while available evidence points to a complex set of genetic factors, the SHANK (also known as ProSAP) gene family has emerged as one of the most promising candidates. Several genetic Shank mouse models for ASD were generated, including Shank1 knockout mice. Behavioral studies focusing on the Shank1 knockout mouse model for ASD included assays for detecting ASD-relevant behavioral phenotypes in the following domains: (I) social behavior, (II) communication, and (III) repetitive and stereotyped patterns of behavior. In addition, assays for detecting behavioral phenotypes with relevance to comorbidities in ASD were performed, including but not limited to (IV) cognitive functioning. Here, we summarize and discuss behavioral and neuronal findings obtained in the Shank1 knockout mouse model for ASD. We identify open research questions by comparing such findings with the symptoms present in humans diagnosed with ASD and carrying SHANK1 deletions. We conclude by discussing the implications of the behavioral and neuronal phenotypes displayed by the Shank1 knockout mouse model for the development of future pharmacological interventions in ASD. [ABSTRACT FROM AUTHOR]

Changes in sleep-EEG after endocrine stimulation tests in patients with schizophrenia include reduced sleep efficiency, prolonged sleep latency and increased awaking after sleep onset Findings on sleep associated growth hormone (GH) secretion were ambiguous. The aim of this study was to elucidate the sleep-endocrine activity especially in the GH system of patients with schizophrenia after repeated administration of GHRH. The effect of repetitive injections of 4 × 50 μg GHRH between 22.00 and 01.00 h on sleep endocrine parameters was investigated in 9 patients diagnosed for schizophrenia. Patients did not receive any medication for one week. Concentrations of ACTH, cortisol, prolactin and GH were determined. Patients spent three consecutive nights in the sleep laboratory. Blood was taken every 20min. Results were compared with matched healthy controls. A non-significant prolonged sleep onset latency and increased time awake was found in patients compared to controls. Sleep stage 2 was significantly reduced in patients. No significant difference in ACTH and cortisol was detected, whereas the GH secretion in patients following GHRH stimulation was significantly elevated compared to controls. Our results in drug free patients confirm already known changes in sleep-EEG in these patients. The GH response to GHRH-stimulation indicates a different regulatory sensitivity of the system between daytime and night-time. [ABSTRACT FROM AUTHOR]

Background Psychological interventions are an important but often overlooked adjunctive treatment option for patients with rheumatoid arthritis. Findings from systematic reviews of psychological interventions for this patient group are conflicting. A systematic review of reviews can explain inconsistencies between studies and provide a clearer understanding of the effects of interventions. Objectives To: 1) determine the effectiveness of psychological interventions in improving biopsychosocial outcomes for adults with rheumatoid arthritis, 2) determine the relationship between the intensity of the psychological interventions (number of sessions, duration of sessions, duration of intervention) on outcomes, and 3) assess the impact of comparator group (usual care, education only) on outcomes. Design We conducted a systematic review of reviews using the following inclusion criteria: 1) randomised controlled trials of psychological interventions (including cognitive behavioural therapy, supportive counselling, psychotherapy, self-regulatory techniques, mindfulness-based cognitive therapy and disclosure therapy) provided as an adjunct to medication, 2) included rheumatoid arthritis patients aged ≥ 18 years, 3) reported findings for at least 1 of the primary outcomes: pain, fatigue, psychological status, functional disability and disease activity and 4) were published in English between January 2000 and March 2015 (updated January 2018). Data sources We searched in MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects. Reference lists were searched for additional reviews. Review methods Study selection and 50% of the quality assessments were performed by two independent reviewers. Methodological quality was measured using the Assessment of Multiple Systematic Reviews checklist. Data extraction was conducted by one reviewer using a predesigned data extraction form. Results Eight systematic reviews met inclusion criteria (one review was excluded due to its low-quality score). Small post intervention improvements in patient global assessment, functional disability, pain, fatigue, anxiety and depression were observed. The effect on coping, self-efficacy and physical activity was greater. Improvements in depression, coping and physical activity were maintained (8.5–14 months). Interventions delivered over a longer period with a maintenance component appeared more effective. Attention, education, and placebo control groups produced some improvements but not as large as those produced by the psychological interventions. Conclusions Psychological interventions result in small to moderate improvements in biopsychosocial outcomes for patients with rheumatoid arthritis in addition to those achieved by standard care. Several priorities for future research were identified, including determining the cost effectiveness of non-psychologically trained health professionals delivering psychological interventions. [ABSTRACT FROM AUTHOR]

Background: Suicidal behavior has been associated with maladaptive strategies for emotion regulation; however, limited research has explored this association after controlling for diagnosis. This study aims to explore this connection across diagnoses. We hypothesized that patients who reported greater difficulty with emotion regulation would be more likely to have made suicide attempts.Method: Participants included 1046 psychiatric outpatients. Diagnoses and information about suicide history were determined using semi-structured interviews. Patients also completed the Difficulties in Emotion Regulation Scale (DERS). Analyses were conducted to determine the relationships between emotion regulation difficulties and lifetime suicide attempts.Results: Emotion regulation difficulties did not independently predict suicidal behavior. After controlling for the contribution of emotion dysregulation on lifetime suicide attempts, diagnoses of borderline personality disorder and posttraumatic stress disorder were the only disorders independently associated with a history of suicidal behavior.Limitations: The generalizability of our findings may be limited based on the sample's demographic characteristics and low base rate of suicide attempts. This study was cross-sectional in nature; therefore, the predictive capacity of either DERS scores or psychiatric diagnoses in terms of future suicidal behavior could not be determined.Conclusions: The independent effect of emotion dysregulation on suicidal behavior was negated after controlling for psychiatric diagnosis. Individuals with certain disorders tend to make suicide attempts for reasons that are distinct from emotion dysregulation, whereas emotion dysregulation may be at the core of suicidality for individuals with other clinical presentations. [ABSTRACT FROM AUTHOR]

The search for biomarkers has been a leading endeavor in biological psychiatry. To analyze its evolution over the years, we performed a systematic review to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main features of studies proposing them as biomarkers and (c) whether their patterns of variation are similar across disorders. Of the six molecules most commonly studied as plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across diagnoses. An analysis of this literature showed that, while 66% of studies compared patients and controls, only 34% were longitudinal, and only 10% presented a measure of diagnostic or prognostic efficacy. Meta-analyses showed variation in the levels of these molecules to be robust across studies, but similar among disorders, suggesting them to reflect transdiagnostic systemic consequences of psychiatric illness. Based on this, we discuss how current publication practices have led to research fragmentation across diagnoses, and suggest approaches to face this issue. [ABSTRACT FROM AUTHOR]

Objectives: Recent research indicates that Heart Rate Variability (HRV) is affected in Bipolar Disorders (BD) patients. To determine whether such alterations are a mere expression of the current mood state or rather contain longitudinal information on BD course, we examined the potential influence of states adjacent in time upon HRV features measured in a target mood state.Methods: Longitudinal evaluation of HRV was obtained in eight BD patients by using a wearable monitoring system developed within the PSYCHE project. We extracted time-domain, frequency-domain and non-linear HRV-features and trained a Support Vector Machine (SVM) to classify HRV-features according to mood state. To evaluate the influence of adjacent mood states, we trained SVM with different HRV-feature sets: 1) belonging to each mood state considered alone; 2) belonging to each mood state and normalized using information from the preceding mood state; 3) belonging to each mood state and normalized using information from the preceding and subsequent mood states; 4) belonging to each mood state and normalized using information from two randomly chosen states.Results: SVM classification accuracy within a target state was significantly greater when HRV-features from the previous and subsequent mood states were considered.Conclusions: Although preliminary and in need of replications our results suggest for the first time that psychophysiological states in BD contain information related to the subsequent ones. Such characteristic may be used to improve clinical management and to develop algorithms to predict clinical course and mood switches in individual patients. [ABSTRACT FROM AUTHOR]

Background Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. Methods We examined the association of epigenetic age and immune cell aging with sleep in the Women’s Health Initiative study ( N = 2078; mean 64.5 ± 7.1 years of age) with assessment of insomnia symptoms (restlessness, difficulty falling asleep, waking at night, trouble getting back to sleep, and early awakenings), sleep duration (short sleep 5 hours or less; long sleep greater than 8 hours), epigenetic age, naive T cell (CD8+CD45RA+CCR7+), and late differentiated T cells (CD8+CD28–CD45RA–). Results Insomnia symptoms were related to advanced epigenetic age ( β ± SE = 1.02 ± 0.37, p = .005) after adjustments for covariates. Insomnia symptoms were also associated with more late differentiated T cells ( β ± SE = 0.59 ± 0.21, p = .006), but not with naive T cells. Self-reported short and long sleep duration were unrelated to epigenetic age. Short sleep, but not long sleep, was associated with fewer naive T cells ( p < .005) and neither was related to late differentiated T cells. Conclusions Symptoms of insomnia were associated with increased epigenetic age of blood tissue and were associated with higher counts of late differentiated CD8+ T cells. Short sleep was unrelated to epigenetic age and late differentiated cell counts, but was related to a decline in naive T cells. In this large population-based study of women in the United States, insomnia symptoms are implicated in accelerated aging. [ABSTRACT FROM AUTHOR]

Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex ® (Bio-Rad) and the electro-chemiluminescence-based V-plex ® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age- and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX ® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX ® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX ® platform. Furthermore, the V-PLEX ® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1β, PDGF-BB, TNF, TNF-β and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry. [ABSTRACT FROM AUTHOR]

Since its inception, the concept of “secondary psychopathy” has been contrasted with primary psychopathy on the grounds of neuroticism, affect instability, and anxiety. Nonetheless, while the etiology of primary psychopathy, and its various possible expressions, has received ample attention, secondary psychopathy has been largely neglected and only discussed in cluster-analytic studies. This paper seeks to fill that caveat by delineating the continuum on which secondary psychopathic individuals may be set apart and exploring potential sources of within group homogeneity and heterogeneity. While secondary psychopathic individuals share a number of etiological antecedents (attachment problems, childhood maltreatment, neurobiological dysfunctions) they can vary on different temperamental predispositions and specific types of maltreatment experienced in childhood (neglect/abuse vs. trauma/abuse, low vs. high prefrontal catecholaminergic activity), thus creating the heterogeneity observed in this group. Secondary psychopathic individuals may be situated on a continuum that spans from attentional hyposensitivity and cognitive distractibility on the far left side, associated with deficient prefrontal catecholamine activity and childhood neglect/abuse, ultimately culminating in more detached expressions of secondary psychopathy (callousness, hedonism, and low worrying), to attentional hypersensitivity and cognitive rigidity on the far right side, associated with non-optimally high levels of catecholamine activity and childhood relational trauma/abuse leading to more unstable expressions of secondary psychopathy (hostility, neuroticism, instability, and worrying). [ABSTRACT FROM AUTHOR]

We have seen an era of explosive progress in translating neurobiology into etiological understanding of mental disorders for the past 10–15 years. The discovery of Disrupted-in-schizophrenia 1 ( DISC1 ) gene was one of the major driving forces that have contributed to the progress. The finding that DISC1 plays crucial roles in neurodevelopment and synapse regulation clearly underscored the utility and validity of DISC1-related biology in advancing our understanding of pathophysiological processes underlying psychiatric conditions. Despite recent genetic studies that failed to identify DISC1 as a risk gene for sporadic cases of schizophrenia, DISC1 mutant mice, coupled with various environmental stressors, have proven successful in satisfying face validity as models of a wide range of human psychiatric conditions. Investigating mental disorders using these models is expected to further contribute to the circuit-level understanding of the pathological mechanisms, as well as to the development of novel therapeutic strategies in the future. [ABSTRACT FROM AUTHOR]

The pathophysiology of cognitive deficits in schizophrenia may involve the neuroinflammation mediated by cytokines. This study examined the IL-18 levels, the cognitive function, and their association in schizophrenia. We recruited 70 chronic patients and 75 normal controls and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and IL-18 levels. Positive and Negative Syndrome Scale (PANSS) was assessed in chronic patients. IL-18 levels were increased in chronic patients as compared to normal controls (p < 0.01). RBANS total score and the subscales of immediate memory and delayed memory were lower in patients than controls (all p < 0.001). In patients, IL-18 levels were positively associated with RBANS total score and the subscales of immediate and delayed memory (all p < 0.05). Multiple regression analysis further confirmed that IL-18 was an independent contributor to RBANS total score and the aforementioned two indexes (all p < 0.05). Our data demonstrate that immune responses may play an important role in cognitive deficits in schizophrenia and the abnormal levels of IL-18 reflecting the disturbed balance of proinflammatory and anti-inflammatory mechanisms may be relevant to cognitive deficits of this disorder. [ABSTRACT FROM AUTHOR]