Childhood adversity and parenting behavior: the role of oxytocin receptor gene polymorphisms.

Previous research revealed experiences of childhood adversity (CA) to be related to less favorable parenting behavior. It can further be expected that maternal oxytocin receptor (OXTR) genes may influence parenting behavior and moderate relationships between CA and parenting behavior. Moreover, associations between the OXTR gene and plasma oxytocin (OT) have been discussed. The present study investigated main effects of the OXTR gene on parenting behavior and plasma OT of mothers, and moderating effects of the OXTR gene on the relationship between mothers' experiences of CA and parenting behavior. We relied on a sample of 193 mothers and their on average 8-year-old children. Maternal experiences of CA were assessed using a standardized interview. A questionnaire for the assessment of child abuse potential and observations of mother-child interaction were used as indicators of parenting behavior. For mothers, we analyzed three polymorphisms (rs53576, rs1042778, rs2254298) of the OXTR gene and plasma OT. Only the rs53576 was associated with mothers' parenting behavior, specifically with maternal sensitivity. The rs2254298 significantly moderated relations between mothers' experiences of CA and parenting behavior. Significant relations could be found only for mothers who were homozygous for the G allele. The G allele of the rs2254298 was further related to increased plasma OT levels. Our findings underline the importance of considering genetic variation when investigating consequences of CA and developing intervention programs that are adapted to an individual's needs.

Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016-March 2019.

PURPOSE OF REVIEW: This study was conducted in order to review randomized controlled trial (RCT) data published January 2016-March 2019 on long-acting injectable antipsychotics (LAIs) for schizophrenia. RECENT FINDINGS: Thirty-one RCTs (primary studies = 7; post hoc analyses = 24; n = 4738) compared LAIs vs. placebo (studies = 11, n = 1875), LAIs vs. oral antipsychotics (OAPs) (studies = 7, n = 658), and LAI vs. LAI (studies = 13, n = 2205). LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI. Regarding prevention of relapse and hospitalization, LAIs consistently outperformed placebo, being partly superior to OAPs, without relevant LAI-LAI differences. LAIs were comparable to OAPs regarding all-cause discontinuation, functioning, quality of life, and tolerability, being associated with higher patient satisfaction and service engagement. Recent meta-analyses yielded mixed results, but never favoring OAPs over LAIs. In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples.

Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities.

Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine's efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

Impact of Maternal Early Life Maltreatment and Maternal History of Depression on Child Psychopathology: Mediating Role of Maternal Sensitivity?

The study addresses the impact of maternal early life maltreatment (ELM) and maternal history of depression (HoD) on offspring's mental health. Maternal sensitivity was examined as a potential mediator explaining the relationship between maternal ELM, maternal HoD and child psychopathology. Participants were 194 mothers with and without HoD and/or ELM as well as their children between 5 and 12 years. Maternal sensitivity was assessed using the Emotional Availability Scales. Parent and teacher ratings were utilized to assess child psychopathology. Path analyses showed an indirect effect of maternal HoD on parents' ratings of child psychopathology with maternal sensitivity as mediating variable. In contrast, maternal ELM was directly linked to teachers' ratings of child psychopathology; this effect was not mediated by maternal sensitivity. Our results indicate that the impact of maternal HoD, maternal ELM, and maternal sensitivity on offspring psychopathology might vary depending on the context in which child psychopathology is assessed.

[Oxytocin and maltreatment potential : Influence of maternal depression, borderline personality disorder and experience of early childhood maltreatment]. / Oxytocin und Misshandlungspotenzial : Einfluss von mütterlicher Depression, Borderline-Persönlichkeitsstörung und frühkindlicher Misshandlungserfahrung.

BACKGROUND: The "empathy hormone" oxytocin (OXT) is associated with social interaction and parent-child interaction. Mothers with mental stress factors, e.g., history of depression, borderline personality disorder or early life maltreatment in their own childhood often show distinct maternal behavior. The objectives of the study were (1) to examine the association between these three stress factors and maternal OXT within one analysis. (2) Moreover, OXT was tested as a potential mediator for the association between maternal experience of early childhood maltreatment and abuse potential against their own child. METHODS: Plasma OXT concentrations of 52 mothers during the follicular phase were collated (healthy control mothers n = 22, history of depression n = 23, borderline personality disorder n = 7). The maternal history of psychiatric disorders and experiences of early childhood maltreatment were examined via interviews. Regression and mediation analyses were applied to answer the research questions. RESULTS: Early childhood maltreatment was associated with reduced plasma OXT; however, maternal history of depression and borderline personality disorder were not related to OXT concentrations. In particular, having experienced parental antipathy in one's own childhood was associated with reduced OXT levels but OXT did not mediate the association between maternal early childhood experiences of maltreatment and abuse potential of their own child. CONCLUSION: In the present study alterations in plasma OXT concentrations were not associated with psychiatric disorders, such as a history of depression or borderline personality disorder but more with a potential etiological factor of these disorders, i.e. experience of maltreatment in their own childhood.

Affect Recognition, Theory of Mind, and Empathy in Preschool Children with Externalizing Behavior Problems-A Group Comparison and Developmental Psychological Consideration.

Preschool mental disorders are often associated with significant interpersonal problems, related to impaired affect recognition, theory of mind (ToM), and empathy. To date, these skills have not been studied together in preschoolers with externalizing behavior problems (EBPs). The aim of the present study was to investigate whether and to what extent preschool children with EBPs show impairments in affect recognition, ToM, and empathy. Preschoolers with EBPs, defined by current psychiatric treatment and T-scores ≥ 60 on the externalizing problem scale of the Child Behavior Checklist (CBCL/1½-5 or 6-18R) were compared to non-clinical controls (HCs), defined by no past and no current psychiatric treatment and T-scores < 60 on all CBCL broad-band scales. Groups were compared on affect recognition (NEuroPSYchological Assessment-II), affective ToM (Test of Emotion Comprehension), cognitive ToM (Extended Theory-of-Mind Scale), parent-reported emotional contagion, attention to others' feelings, and prosocial action (Empathy Questionnaire), IQ and language (Wechsler Preschool and Primary Scale of Intelligence-III Matrices, Active and Passive Vocabulary test), controlling for age, sex, and language abilities. Compared to 28 HCs, 22 preschoolers with EBPs (total sample meanage = 5.5 years +/- 0.8 years, range= 4.2-6.9 years, males 66%) had significantly greater impairments in cognitive ToM (p = 0.0012, η2 = 0.266), attention to others' feelings (p = 0.0049, η2 = 0.222), and prosocial action (p = 0.0070, η2 = 0.210), each representing strong effect sizes. EBPs were significantly related to cognitive domains, like prosocial action (r = -0.501), cognitive ToM (r = -0.425), and attention to others' feelings (r = -0.332), but not to affective domains of social cognition. Social cognitive development may be impaired as early as preschool age and should be promoted before the child starts school.

Magnitude and Correlates of Symptomatic, Global Illness, and Social Functioning Response; Out-of-Home Placement; and Length of Stay in 1,189 Consecutively Hospitalized Children and Adolescents With Mental Disorders.

Objective: To identify outcome predictors in hospitalized youth with mental disorders.Methods: This retrospective analysis of systematically recorded clinical parameters in youth hospitalized for psychiatric treatment in 2004-2015 assessed magnitude and correlates of symptom response (SR), global illness response (GIR), social functioning (SF), out-of-home placement (OOHP), and length of stay (LOS). Backward elimination regression analyses were performed to identify independent baseline correlates of each of the 5 outcomes, with R2 representing the variance explained by the independent correlates retained in the final model.Results: Across 1,189 youth (median age = 14.4 years; interquartile range = 11.6,16.1 years; range, 5-19 years; females = 61.5%), frequencies of coprimary outcomes were as follows: SR = 57.5% (statistically significant correlates = 13, R2 = 0.154), GIR = 30.0% (correlates = 5, R2 = 0.078), SF = 19.0% (correlates = 8, R2 = 0.207), OOHP recommendation = 35.2% (correlates = 13, R2 = 0.275), and mean ± SD LOS = 65.0 ± 37.5 days (correlates = 11, R2 = 0.219). In multivariable analyses, 11 factors were statistically significantly (P < .05) associated with > 1 poor outcome: 4 with 4 outcomes (disturbed social interaction, substance abuse/dependence symptoms; sole exception for both = LOS; disturbed drive/attention/impulse control, sole exception = OOHP; higher admission BMI percentile [but shorter LOS], sole exception = GIR), 3 with 3 outcomes (higher admission age [but good SF and shorter LOS], more abnormal psychosocial circumstances, more mental health diagnoses), and 4 with 2 outcomes (intelligence level [IQ] < 85, obsessive-compulsive disorder symptoms, disturbed social behavior, somatic findings). Additionally, 17 correlates were statistically significantly (P < .05) associated with 1 outcome, ie, SR = 6, OOHP = 5, LOS = 5, SF = 1.Conclusions: Higher admission BMI percentile, disturbed social interaction, disturbed drive/attention/impulse control, and substance abuse/dependence symptoms were independently associated with multiple poor outcomes in mentally ill youth requiring inpatient care. Knowledge of global and specific correlates of poor inpatient treatment outcomes may help inform treatment decisions.

Assessment and Diagnostic Classification Using DC:0-5 in Early Childhood Mental Health Clinics: The Protocol for the Developmental Psychiatry Diagnostic Challenges Study (DePsy).

Mental health problems in early childhood are common, but there is a lack of psychiatric research on this age group. DC:0-5 is a multiaxial classification system for mental disorders in early childhood, providing a framework for standardizing clinical practice and research. However, research on the validity of DC:0-5 is scarce. The Developmental Psychiatry Diagnostic Challenges Study (DePsy) is a multi-site, prospective clinical study including six German early childhood mental health (ECMH) clinics. The main objective of the study is to contribute to the validation of Axis I and Axis II of DC:0-5. A second aim of the study is to describe the population of the participating clinics regarding diagnoses, family context, and treatment outcomes. Additionally, the impact of environmental risk factors, including parental Adverse Childhood Experiences (ACEs) and media use, on child psychopathology and caregiver-child relationships will be examined. Over two years, patients aged 0.0-5.9 years old will be enrolled in the study. Assessments include ICD-10 and DC:0-5 diagnoses, developmental tests, video-based observations of caregiver-child interactions, and questionnaires on child psychopathology, media use, parental stress, and treatment satisfaction. Study results will promote the standardization of assessment and treatment in ECMH clinics aiming to improve the development of patients and their families.

Early life maltreatment and depression: Mediating effect of maternal hair cortisol concentration on child abuse potential.

INTRODUCTION: Maternal early life maltreatment (ELM) and history of depression can bear a risk for adverse development in the child. One neurobiological pathway for the transmission of both maternal ELM and remitted depression (MDD) might be altered maternal cortisol levels. In the present study, we examine (1) main and interacting effects of maternal ELM and remitted MDD on hair cortisol concentration (HCC) in mothers, whether (2) maternal HCC explains the association between maternal ELM or remitted MDD and maternal child abuse potential, and (3) whether maternal child abuse potential as well as maternal HCC are associated with maternal report of child well-being. METHODS: The current study involved 127 mother-child dyads. Maternal history of ELM and psychopathology were assessed via the Mini International Neuropsychiatric Interview (M.I.N.I.) and Childhood Experience and Care (CECA) interview. The Child Abuse Potential Inventory (CAPI) was used to assess maternal child abuse and neglect potential. We applied the Kidscreen-27 parent report to study child well-being. To assess HCC, hair strands were taken from the mothers. To test the research questions, a two-factorial analysis of covariance, mediation analysis using ordinary least squares regressions with bootstrapping, and Pearson correlations were calculated. RESULTS: Mothers with ELM had significantly increased HCC. There was no effect of remitted MDD on HCC, nor an interaction effect of both factors. HCC was a significant mediator of the association between maternal ELM and maternal child abuse potential. Maternal child abuse potential as well as HCC were significantly associated with reduced child well-being. DISCUSSION: Our data suggest that adverse experiences in childhood are associated with altered HPA-axis functioning reflected in increased levels of HCC. HPA-axis activity is not altered in mothers with remitted MDD. From a clinical point of view, one might speculate that the partially mediating effect of maternal HCC could indicate a starting point in the prevention of the intergenerational cycle of abuse.

Hair cortisol moderates the association between obstetric complications and child wellbeing.

Obstetric complications (OC) may have implications for later health outcomes. However, there is a lack of research examining the association between OC and behavior problems or quality of life (HRQoL). We aimed to close this gap and further investigate functioning of the hypothalamus-pituitary-adrenal (HPA)-axis as a potential physiological vulnerability moderating the association between OC and behavior problems and HRQoL. We investigated 232 mothers and their five to 12-year-old children. Presence of OC during the pre-, peri-, and postnatal phases was determined by interviewing mothers. Children's behavior problems (CBCL, TRF) and HRQoL (Kidscreen rated by mothers and children) were assessed. Children gave 3 cm strands of hair for analysis of hair cortisol (HC). Structural equation modeling analyses with a latent variable of child outcome ("distress"), OC as predictor and HC as a potential moderator were conducted. OC significantly predicted distress (ß = .33, p < .01). The model showed a good fit to the data: χ2(14)=15.66, p < .33, CFI=.99, TLI=.99, RMSEA=.02, 90 %CI [.00, .06], SRMR=.04. In addition, HC moderated the association between OC and distress (ß=-.32, p < .01). The moderation model also showed a good fit: χ2(14) =7.13, p = .93, CFI=1.00, TLI=1.06, RMSEA=.00, 90 %CI [.00, .02], SRMR=.03. Results indicated that the association between OC and distress was significant only when children had low HC-levels. This was also the case for both externalizing and internalizing behavior problems. Our results underline the notion of OC as a risk factor for child behavior problems and wellbeing and point to an important role of the children's physiological set-up such as HPA-functioning.

Link between children's hair cortisol and psychopathology or quality of life moderated by childhood adversity risk.

The hypothalamus-pituitary-adrenal axis (HPAA) and its end product, the glucocorticoid cortisol, has been shown to be associated with psychopathology. Determining cortisol concentrations in hair (HCC) allows the investigation of long-term HPAA-activity. There is a significant scarcity of studies investigating the link between HCC and psychopathology and quality of life in child and adolescent samples. In addition, as the HPAA constitutes a feedback system enabling adaption to environmental demands, it is important to consider the socio-environmental context that the children grow up in. We therefore investigated the associations between child HCC and psychopathology/quality of life and compared these links in two groups of five to 12-year-olds: children living with mothers who report experiences of early life maltreatment (ELM) (high-risk group) and children whose mothers did not report any ELM (low-risk group). We expected that, under conditions of a high-risk environment, elevated HPAA-functioning would be associated with low levels of psychopathology and high levels of quality of life in children. Under low-risk conditions, elevated HPAA-functioning would be associated with high levels of psychopathology and low levels of quality of life in children. For the complete sample of N = 130 children, three-months HCC did not significantly predict child psychopathology or quality of life. However, there was a significant moderating effect of group membership: In the high-risk group, high levels of HCC were significantly associated with high levels of self-reported quality of life. In the low-risk group, there was no association between HCC and self-reported quality of life. For child psychopathology, in the low-risk group, high levels of HCC were significantly associated with high levels of teacher reported behavior problems, whereas in the high-risk group, the association did not reach significance. Our results underline the importance of accounting for the social environment children grow up in when investigating the link between HCC and child psychopathology and quality of life.

Effects of maternal history of depression and early life maltreatment on children's health-related quality of life.

BACKGROUND: There is a well-established link between maternal depression and child mental health. Similar effects have been found for maternal history of early life maltreatment (ELM). However, studies investigating the relationship of children's quality of life and maternal depression are scarce and none have been conducted for the association with maternal ELM. The aim of the present study was to investigate the effects of maternal history of ELM and depression on children's health-related quality of life and to identify mediating factors accounting for these effects. METHODS: Our study involved 194 mothers with and without history of depression and/or ELM and their children between five and 12 years. Children's health-related quality of life was assessed by maternal proxy- and child self-ratings using the KIDSCREEN. We considered maternal sensitivity and maternal parenting stress as potential mediators. RESULTS: We found an effect of maternal history of depression but not of maternal history of ELM on health-related quality of life. Maternal stress and sensitivity mediated the effects of maternal depression on child global health-related quality of life, as well as on the dimensions Autonomy & Parent Relation, School Environment (maternal and child rating), and Physical Wellbeing (child rating). LIMITATION: Due to the cross-sectional design of the study, causal interpretations must be made with caution. Some scales yielded low internal consistency. CONCLUSIONS: Maternal impairments in areas of parenting which possibly developed during acute depression persist even after remission of acute affective symptoms. Interventions should target parenting stress and sensitivity in parents with prior depression.