Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.

Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.

Calcitriol supplementation attenuates cisplatin-induced behavioral and cognitive impairments through up-regulation of BDNF in male rats.

Chemotherapy-induced cognitive impairment such as memory impairment and concentration problems are now extensively recognized as side effects of chemotherapy. These problems reduce the quality of life in patients. Therefore, the present study aims to examine the effects of calcitriol supplementation (100 ng/kg /day for five weeks) on cognitive impairment, behavioral deficits, and hippocampal brain-derived neurotrophic factor (BDNF) changes following cisplatin treatment (5 mg/kg/ once a week for five weeks). We also determined the impact of cisplatin and calcitriol administration on reaction time against the thermal stimulus and muscle strength. Our findings showed that cisplatin administration resulted in a significant increase in anxiety-like behaviors. Treatment of rats with cisplatin also impaired performance in the passive avoidance and novel object recognition tasks which are indicating cognitive deficits. Co-administration of calcitriol prevented the cisplatin-induced behavioral and cognitive impairments. Cisplatin exposure also resulted in enhanced reaction time to the thermal stimulus and decreased muscle ability. Besides, hippocampal BDNF levels were reduced in cisplatin-treated rats; however, calcitriol alleviated these effects of cisplatin and up-regulated BDNF mRNA in the hippocampus. In addition, calcitriol alone indicated a significant change in BDNF level compared to the control group. We conclude that increased hippocampal BDNF mediates the beneficial effects of calcitriol against neurotoxicity in cisplatin-exposed rats. However, further studies are required to explore the other mechanisms that mediate the beneficial effect of calcitriol.

Externalizing behavior in healthy young adults is associated with lower cortisol responses to acute stress and altered neural activation in the dorsal striatum.

The externalizing spectrum is characterized by disinhibition, impulsivity, antisocial-aggressive behavior as well as substance (mis)use. Studies in forensic samples and mentally impaired children suggested that higher rates of externalization are linked to lower cortisol stress responses and altered affect-related neural activation. In this fMRI-study, we investigated whether externalizing behavior in healthy participants is likewise associated with altered cortisol responses and neural activity to stress. Following a quasi-experimental approach, we tested healthy participants (N = 61, 31 males) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure. All participants were exposed to ScanSTRESS, a standardized psychosocial stress paradigm for scanner environments. In both groups, ScanSTRESS induced a significant rise in cortisol levels with the high externalization group showing significantly lower cortisol responses to stress than the low externalization group. This was mainly driven by males. Further, individual increases in cortisol predicted neural response differences between externalization groups, indicating more activation in the dorsal striatum in low externalization. This was primarily driven by females. In contrast, post-hoc analysis showed that hypothalamic-pituitary-adrenal axis hyporeactivity in males was associated with prefrontal and hippocampal activation. Our data substantiate that individuals from the general population high on externalization, show reduced cortisol stress responses. Furthermore, dorsal striatum activity as part of the mesolimbic system, known to be sensitive to environmental adversity, seems to play a role in externalization-specific cortisol stress responses. Beyond that, a modulating influence of gender was disclosed.

Social impairments in mice lacking the voltage-gated potassium channel Kv3.1.

Parvalbumin (PV)-expressing neurons have been implicated in the pathology of autism spectrum disorders (ASD). Loss of PV expression and/or reduced number of PV-expressing neurons have been reported not only in genetic and environmental rodent models of ASD, but also in post-mortem analyses of brain tissues from ASD vs. healthy control human subjects. PV-expressing neurons play a pivotal role in the maintenance of the balance between excitation and inhibition within neural circuits in part because of their fast-spiking properties. Their high firing rate is mostly regulated by the voltage-gated potassium channel Kv3.1. It is yet unknown whether disturbances in the electrophysiological properties of PV-expressing neurons per se can lead to behavioral disturbances. We assessed locomotor activity, social interaction, recognition and memory, and stereotypic behaviors in Kv3.1 wild-type (WT) and knockout (KO) mice. We then used Western Blot analyses to measure the impact of Kv3.1 deficiency on markers of GABA transmission (PV and GAD67) and neural circuit activity (Egr1). Deficiency in Kv3.1 channel is sufficient to induce social deficits, hyperactivity and stereotypic behaviors. These behavioral changes were independent of changes in GAD67 levels and associated with increased levels of PV protein in the prefrontal cortex and striatum. These findings reveal that a loss of PV expression is not a necessary factor to induce an ASD-like phenotype in mice and support the need for further investigation to fully understand the contribution of PV-expressing neurons to ASD pathology.

Disturbance of the reciprocal-interaction between the OXTergic and DAergic systems in the CNS causes atypical social behavior in syntaxin 1A knockout mice.

Several studies have shown that oxytocin (OXT) modulates social behavior. Similarly, monoamines such as dopamine (DA) play a role in regulating social behavior. Previous studies have demonstrated that the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) protein syntaxin 1A (STX1A) regulates the secretion of OXT and monoamines, and that STX1A gene knockout (STX1A KO) mice exhibit atypical social behavior, such as deficient social recognition, due to reduced OXT release. In this study, we analyzed the neural mechanism regulating social behavior by OXT and/or DA using STX1A KO mice as a model animal. We found that OXT directly induced DA release from cultured DA neurons through OXT and V1a receptors. In STX1A KO mice, the atypical social behavior was partially improved by OXT administration, which was inhibited by D1 receptor blockade. In addition, the atypical social behavior in STX1A KO mice was partially improved by facilitation of DAergic signaling with the DA reuptake inhibitor GBR12909. Moreover, the amelioration by GBR12909 was inhibited by OXTR blockade. These results suggest that the reciprocal interaction between the DAergic and OXTergic neuronal systems in the CNS may be important in regulating social behavior.

Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

OBJECTIVES: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. METHODS: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. RESULTS: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. CONCLUSIONS: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

Between Temperament and Psychopathology: Examples from Neuropharmacological Challenge Tests in Healthy Humans.

BACKGROUND: This paper tries to demonstrate that the questionnaire-based continuum between temperament traits and psychopathology can also be shown on the biochemical level. A common feature is the incapacity to adapt to external demands, as demonstrated by examples of disturbed hormone cycles as well as neurotransmitter (TM) responses related to affective and impulse control disorders. METHODS: Pharmacological challenge tests performed in placebo-controlled balanced crossover experiments with consecutive challenges by serotonin (5-HT), noradrenaline (NA), and dopamine (DA) agonistic drugs were applied to healthy subjects, and individual responsivities of each TM system assessed by respective cortisol and prolactin responses were related to questionnaire-based facets of depressiveness and impulsivity, respectively. RESULTS: The depression-related traits "Fatigue" and "Physical Anhedonia" were characterized by low and late responses to DA stimulation as opposed to "Social Anhedonia," which rather mirrored the pattern of schizophrenia. Reward-related and premature responding-related impulsivity represented by high scores on "Disinhibition" and "Motor Impulsivity," respectively, as well as the questionnaire-based components of attention deficit hyperactivity disorder, "Cognitive" and "Motor Impulsivity," could be discriminated by their patterns of DA/NA responses. 5-HT responses suggested that instead of the expected low availability of 5-HT claimed to be associated with impulse control disorders, low NA responses indicated lack of inhibition in impulsivity and high NA responses in depression-related "Anhedonia" indicated suppression of approach motivation. CONCLUSIONS: In spite of the flaws of pharmacological challenge tests, they may be suitable for demonstrating similarities in TM affinities between psychopathological disturbances and respective temperament traits and for separating sub-entities of larger disease spectra.

G-protein coupled receptor 88 knockdown in the associative striatum reduces psychiatric symptoms in a translational male rat model of Parkinson disease.

Background: In addition to motor disability, another characteristic feature of Parkinson disease is the early appearance of psychiatric symptoms, including apathy, depression, anxiety and cognitive deficits; treatments for these symptoms are limited by the development of adverse effects such as impulse-control disorders. In this context, we investigated the orphan G protein-coupled receptor 88 (GPR88) as a novel therapeutic target. Methods: We used lentiviral-mediated expression of specifically designed microRNA to knock down Gpr88 in a translational male rat model of early Parkinson disease obtained by dopamine loss in the dorsolateral striatum as a result of 6-hydroxydopamine lesions. We evaluated the impact of Gpr88 knockdown on the Parkinson disease model using behavioural, immunohistochemical and in situ hybridization studies. Results: Knockdown of Gpr88 in associative territories of the dorsal striatum efficiently reduced alterations in mood, motivation and cognition through modulation of the regulator of the G-protein signalling 4 and of the truncated splice variant of the FosB transcription factor. Knockdown of Gpr88 also reduced allostatic changes in striatal activity markers that may be related to patterns observed in patients and that provide support for an "overload" hypothesis for the etiology of the psychiatric symptoms of Parkinson disease. Limitations: Behavioural tests assessing specific cognitive and motivational parameters are needed to further characterize the effects of the lesion and of Gpr88 knockdown in early-stage and advanced Parkinson disease models, presenting more extensive dopamine loss. Additional studies focusing on the direct and indirect striatal output pathways are also required, because little is known about the signalling pathways regulated by GPR88 in different striatal cell types. Conclusion: GPR88 may constitute a highly relevant target for the treatment of the psychiatric symptoms of Parkinson disease.

Psychological and Sociodemographic Variables related to Cortisol in Hair in Spanish Healthy Population.

Some recent researches have shown the important role of hair cortisol as a retrospective biomarker of chronic stress. The aim of this research was to investigate the relationship between hair cortisol levels and sociodemographic and psychological variables, such as perceived stress levels and psychopathological symptoms on a Spanish population. The sample consisted of 347 healthy people, 230 women and 117 men, with an average age of 33.39 years (SD = 12.63). Hair cortisol levels were measured by obtaining a hair sample. In addition, a psychological assessment composed by: Analogic-Visual Stress Scale, Perceived Stress Scale (PSS), Symptom Checklist 90 Revised (SCL-90-R) and the assessment of vital stressful events suffered, was carried out. The mean cortisol level was 108.93 pg/mg (SD = 66.43) in men, and 120.38 pg/mg (SD = 87.26) in women. The linear hierarchical regression showed that Analogic-Visual Stress Scale and perceived stress levels were related with higher hair cortisol levels (R2 = .032; t = 2.21; p = .029). Due to the relationship between daily stress levels, Analogic-Visual Stress Scale, anxiety sub-scale of SCL 90-R and perceived stress levels with hair cortisol levels, we conclude that there is a relation between perceived yourself stressed and the physiological levels.

Endocannabinoid concentrations in hair and mental health of unaccompanied refugee minors.

Altered activity of the endocannabinoid (EC) system has been linked to dysregulated stress-reactivity and the development of trauma-related psychopathology. The EC system, with its main components anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and other N-acyl-ethanolamides, is considered to be a buffer system that protects against the negative effects of traumatic experiences on mental health. Recently, the use of hair analyses, a method to gain information on long-term cumulative system activity, has been introduced to the study of ECs. Here, we seek to extend current knowledge on the potential use of hair EC concentrations as a marker of trauma-related psychological symptoms as well as psychological resources. Ninety-one male URM from Syria and Afghanistan (mean age = 17.4 years) living in group homes of the Child Protection Services in Leipzig, Germany, completed assessments on traumatic life events (TLE), PTSD symptoms, depression, anxiety and somatic symptoms as well as on self-efficacy and prosocial behavior. Scalp-near 3 cm hair segments were obtained and EC concentrations quantified using liquid chromatography tandem mass spectrometry. Analyses revealed relatively week and inconsistent associations of hair ECs and psychological symptoms, with only a positive correlation between 2-AG and depression. Concerning prosocial behavior and self-efficacy positive relationships were found with oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA). Our findings add data concerning the utility of hair EC analyses for PNE research but on a whole fail to reveal a clear association pattern between hair ECs and mental health in URM.

Disaster-related prenatal maternal stress predicts HPA reactivity and psychopathology in adolescent offspring: Project Ice Storm.

BACKGROUND: Prenatal stress has been associated with adverse outcomes in offspring, including elevated risk of psychopathology. Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been posited as a biological mechanism underlying such consequences. The present study aimed to examine whether dysregulation of the offspring HPA axis mediates the relationship between prenatal stress exposure and adolescent psychopathology. METHODS: Five months after the Quebec ice storm of 1998, women who had been pregnant at the time of the storm completed questionnaires about their objective hardship and subjective distress from the disaster. A total of 45 of their children, exposed to the ice storm in utero, participated at 13 years of age. Adolescents completed the Trier Social Stress Test while providing salivary samples to measure circulating cortisol levels. Maternal report of adolescent behaviors was assessed with the Child Behavior Checklist. RESULTS: Results from the study found that greater objective hardship was associated with elevated offspring cortisol reactivity at 13 years of age. Furthermore, greater subjective distress was associated with greater externalizing behaviors. While lower cortisol reactivity predicted greater externalizing behaviors, it did not mediate the association between maternal objective hardship or subjective distress and offspring externalizing or internalizing behaviors. CONCLUSIONS: Findings suggest that objective hardship in pregnancy has long-term implications for offspring HPA axis functioning, which is also associated with externalizing behaviors. While dysregulation of the offspring HPA axis did not mediate the association between prenatal stress and offspring psychopathological symptoms, further research is warranted to investigate programming of alternative biological systems.

Rx risk or resistance? Psychotropic medication use in relation to physiological and psychosocial functioning of psychiatric hospital workers.

To avoid methodological biases, psychoneuroendocrine studies have generally excluded psychotropic medication users. In workplace stress research, this has limited our ability to understand how psychotropic medication use affects many stress-related measures of interest. In this exploratory study, the effects of psychotropic medication use on stress physiology, occupational stress, and mental health were measured in a sample of healthy adult psychiatric hospital workers (N = 203, 70 % women). Diurnal cortisol was assessed on two non-consecutive work-days at five time-points (e.g., awakening, thirty minutes after awakening, 2 P M, 4 P M and bedtime). Cortisol reactivity was assessed by exposing participants to the Trier Social Stress Test. An allostatic load index was constructed using 19 neuroendocrine, immune, cardiovascular, and metabolic biomarkers. Occupational stress (e.g., job strain, effort-reward imbalance) and psychiatric symptoms (e.g., depression, burnout) were assessed with well-validated self-reports. Results showed that psychotropic medication use had no significant effects on diurnal cortisol profiles; however, psychotropic users had significantly decreased cortisol reactivity to the Trier Social Stress Test and higher allostatic load. Psychotropic users also had decreased effort-reward imbalance, but not job strain. Depressive symptoms did not differ between psychotropic medications users and non-users; however, burnout symptoms were higher among psychotropic medication users than non-users. Taken together, our findings do not warrant the systematic exclusion of psychotropic medication users from psychoneuroendocrine studies if insights into individual differences are sought among workers and other populations exposed to elevated stress.

Stress Response in Suicide Attempters with Borderline Personality Disorder: The Role of Behavioral Problems in Childhood.

Objective: Suicidal individuals are a heterogeneous population and may differ in systematic ways in their responsiveness to stress. The primary aim of the present study was to identify whether a different pattern of physiological stress response exists among adult suicide attempters with a history of behavioral problems during childhood and adolescence, which earlier studies have related to both decreased activity of the HPA axis and to suicidal behaviors. Method: Seventy-eight participants with Borderline Personality Disorder were assessed using the SCID-II, and completed self-report measures assessing their history of suicide attempts, history of aggressive behaviors, depressive symptoms, history of lifetime abuse and demographics. Participants' cortisol reactivity was assessed using the Trier Social Stress Test. Results: Analyses indicated that suicide attempters with a history of behavioral problems in youth (n = 30) had a significantly lower response to stress than both suicide attempters without such a history (n = 26) and non-attempters (n = 22), when controlling for lifetime history of abuse. The groups did not differ in basal cortisol. Conclusions: These findings suggest a unique subtype of suicide attempter among those with Borderline Personality Disorder, characterized by a blunted physiological stress response.

The role of oxytocin on self-serving lying.

INTRODUCTION: The effects of intranasal administration of the neuropeptide oxytocin on social cognition and behavior are highly specific. Potentially situational and personal variables influence these effects. The aim of the present study was to investigate effects of oxytocin administration on self-serving lying, including situational effects. METHODS: A total of 161 adult males participated in a randomized double-blind placebo-controlled between-subject intranasal oxytocin administration (24 international units) study. Self-serving lying was assessed using three subsequent rounds of the die-in-a-cup paradigm, in which different degrees of lying can be implemented by the participants that can be determined on group level. RESULTS: Oxytocin administration seemed to promote self-serving lying, particularly in the third (last) round and only to a certain degree (not to the maximum possible). CONCLUSIONS: Our findings demonstrate that oxytocin administration can promote self-serving lying when given repeated opportunities to lie. Moreover, exploratory results presented in the Supplementary Material indicate that the sensitivity to the effects of intranasal oxytocin in this domain might be moderated by individual differences in the oxytocin receptor gene.

How interindividual differences shape approach-avoidance behavior: Relating self-report and diagnostic measures of interindividual differences to behavioral measurements of approach and avoidance.

Responding to stimuli in ambiguous environments is partially governed by approach-avoidance tendencies. Imbalances in these approach-avoidance behaviors are implicated in many mental disorders including anxiety disorders, phobias and substance use disorders. While factors biasing human behavior in approach-avoidance conflicts have been researched in numerous experiments, a much-needed comprehensive overview integrating those findings is missing. Here, we systematically searched the existing literature on individual differences in task-based approach-avoidance behavior and aggregated the current evidence for the effect of self-reported approach/avoidance traits, anxiety and anxiety disorders, specific phobias, depression, aggression, anger and psychopathy, substance use and related disorders, eating disorders and habits, trauma, acute stress and, finally, hormone levels (mainly testosterone, oxytocin). We highlight consistent findings, underrepresented research areas and unexpected results, and detail the amount of controversy between studies. We discuss potential reasons for ambiguous results in some research areas, offer practical advice for future studies and highlight potential variables such as task-related researcher decisions that may influence how interindividual differences and disorders drive automatic approach-avoidance biases in behavioral experiments.

Lifelong consequences of brain injuries during development: From risk to resilience.

Traumatic brain injuries in children represent a major public health issue and even relatively mild injuries can have lifelong consequences. However, the outcomes from these injuries are highly heterogeneous, with most individuals recovering fully, but a substantial subset experiencing prolonged or permanent disabilities across a number of domains. Moreover, brain injuries predispose individuals to other kinds of neuropsychiatric and somatic illnesses. Critically, the severity of the injury only partially predicts subsequent outcomes, thus other factors must be involved. In this review, we discuss the psychological, social, neuroendocrine, and autonomic processes that are disrupted following traumatic brain injury during development, and consider the mechanisms the mediate risk or resilience after traumatic brain injury in this vulnerable population.

Disturbed neurotransmitter homeostasis in ether lipid deficiency.

Plasmalogens, the most prominent ether (phospho)lipids in mammals, are structural components of most cellular membranes. Due to their physicochemical properties and abundance in the central nervous system, a role of plasmalogens in neurotransmission has been proposed, but conclusive data are lacking. Here, we targeted this issue in the glyceronephosphate O-acyltransferase (Gnpat) KO mouse, a model of complete deficiency in ether lipid biosynthesis. Throughout the study, focusing on adult male animals, we found reduced brain levels of various neurotransmitters. In the dopaminergic nigrostriatal tract, synaptic endings but not neuronal cell bodies were affected. Neurotransmitter turnover was altered in ether lipid-deficient murine as well as human post-mortem brain tissue. A generalized loss of synapses did not account for the neurotransmitter deficits, since the levels of several presynaptic proteins appeared unchanged. However, reduced amounts of vesicular monoamine transporter indicate a compromised vesicular uptake of neurotransmitters. As exemplified by norepinephrine, the release of neurotransmitters from Gnpat KO brain slices was diminished in response to strong electrical and chemical stimuli. Finally, addressing potential phenotypic correlates of the disturbed neurotransmitter homeostasis, we show that ether lipid deficiency manifests as hyperactivity and impaired social interaction. We propose that the lack of ether lipids alters the properties of synaptic vesicles leading to reduced amounts and release of neurotransmitters. These features likely contribute to the behavioral phenotype of Gnpat KO mice, potentially modeling some human neurodevelopmental disorders like autism or attention deficit hyperactivity disorder.

Maternal depression impacts child psychopathology across the first decade of life: Oxytocin and synchrony as markers of resilience.

BACKGROUND: While maternal depression is known to carry long-term negative consequences for offspring, very few studies followed children longitudinally to address markers of resilience in the context of maternal depression. We focused on oxytocin (OT) and mother-child synchrony - the biological and behavioral arms of the neurobiology of affiliation - as correlates of resilience among children of depressed mothers. METHOD: A community birth-cohort was recruited on the second postbirth day and repeatedly assessed for maternal depression across the first year. At 6 and 10 years, mothers and children underwent psychiatric diagnosis, mother-child interactions were coded for maternal sensitivity, child social engagement, and mother-child synchrony, children's OT assayed, and externalizing and internalizing problems reported. RESULTS: Exposure to maternal depression markedly increased child propensity to develop Axis-I disorder at 6 and 10 years. Child OT showed main effects for both maternal depression and child psychiatric disorder at 6 and 10 years, with maternal or child psychopathology attenuating OT response. In contrast, maternal depression decreased synchrony at 6 years but by 10 years synchrony showed only child disorder effect, highlighting the shift from direct to indirect effects as children grow older. Path analysis linking maternal depression to child externalizing and internalizing problems at 10 years controlling for 6-year variables indicated that depression linked with decreased maternal sensitivity and child OT, which predicted reduced child engagement and synchrony, leading to higher externalizing and internalizing problems. OT and synchrony mediated the effects of maternal depression on child behavior problems and an alternative model without these resilience components provided less adequate fit. CONCLUSIONS: Maternal depression continues to play a role in children's development beyond infancy. The mediating effects of OT and synchronous, mutually regulated interactions underscore the role of plasticity in resilience. Results emphasize the need to follow children of depressed mothers across middle childhood and construct interventions that bolster age-appropriate synchrony.

Molecular Imaging of Opioid System in Idiopathic Parkinson's Disease.

Opioid receptors are localized throughout peripheral and central nervous system and interact with endogenous opioid peptides and drugs including heroin, synthetic opioids, and pain relievers (codeine, morphine). If several opioid PET tracers exist for preclinical studies, only a few have been used in human. Some tracers are selective for one subtype of opioid receptors (e.g., [11C]CAF (carfentanil) for µ receptor) while others are not ([11C]DPN (diprenorphine)). As shown by imaging studies, the opioid system is involved in pain processing, but also in addiction, neuropsychiatric manifestations (harm avoidance, sadness, novelty seeking behavior), feeding and food disorders and, finally, movement disorders and levodopa-induced dyskinesias. However, no imaging study has analyzed the potential dysfunction of opioid system in pain manifestations in Parkinson's disease. In addition, the involvement of opioid system in impulse control disorders and neuropsychiatric manifestations has never been studied in Parkinson's disease. Thus, there is an urgent need to understand the impact of opioid system dysfunctions in Parkinson's disease.