Interactions between parenting styles, child anxiety, and oppositionality in selective mutism.

Selective mutism (SM) is a poorly understood condition, and debate continues regarding its etiology and classification. Research suggests that a genetic vulnerability may play a role in the development of the disorder which may be compounded by anxious and over-protective parenting. While previous studies supported the role of parenting styles in the development of SM, most of them examined child and parent factors in isolation. The current study examined how the interactions between child internalizing and externalizing behaviors (anxiety and oppositionality, respectively) and parenting styles (authoritative, permissive, and authoritarian) are associated with SM diagnosis. The study included 285 children aged 3-7 years (57.2% females), and their parents (66 children with SM and 219 typically developed children). Parents completed questionnaires about child social anxiety, oppositional behavior, SM severity, and their parenting style. Results showed that parents of children with SM reported lower levels of authoritative practices than those of typically developed children. We also found that child social anxiety and oppositionality moderated the effects of authoritative and authoritarian parenting practices on SM diagnosis. Our results suggest that child anxiety and oppositionality may explain the different susceptibility of children to adaptive and maladaptive parenting styles.

Mental health among children with long COVID during the COVID-19 pandemic.

A growing number of studies report that persons of all ages, infected with SARS-CoV-2, may experience long-term persistent symptoms, known as long COVID (LC) or post COVID-19 condition. This is one of the first studies examining the consequences of LC on children's mental health. In this case-control study, we compared select mental health aspects of 103 children diagnosed with LC to a control group of 113 children uninfected with SARS-COV-2; all 4-18 years old. Both groups were assessed via parents' questionnaires. In comparison to the control group, children with LC exhibited more memory difficulties. However, no group differences emerged in other functional aspects (connection with friends and engagement in physical activities), problems with concentration, or levels of emotional-behavioral problems (externalizing, internalizing, ADHD, and PTSD symptoms). We also found that children with LC had greater exposure to COVID-19-related stressors. Higher levels of parental worries regarding their children's functioning and economic difficulties at home significantly predicted higher levels of children's emotional-behavioral problems and were better predictors than the child's age, social functioning, or LC diagnosis.    Conclusion: LC was associated with impairments in some aspects of children's memory which may relate to academic functioning, but not with higher rates of emotional-behavioral problems, thus warranting interventional programs addressing school functioning and cognitive abilities in this population. Additionally, parents' economic stress and worries regarding their child's emotional adjustment during the pandemic, are important factors affecting pandemic-related emotional-behavioral problems among children, regardless of COVID-19 infection, that should be addressed. What is Known: • Children may have long COVID (LC) after being infected with SARS-COV-2. What is New: • LC may be associated to impairments in some aspects of children's memory, as reported by parents. • Parents' economic stress and worries concerning their children's emotional adjustment during the pandemic are associated with more distress in their children.

Neutrophil to-lymphocyte and platelet-to-lymphocyte ratios as biomarkers for suicidal behavior in children and adolescents with depression or anxiety treated with selective serotonin reuptake inhibitors.

BACKGROUND: Both the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) have been proposed as biomarkers of suicidal risk in adults with depression. We examined whether these ratios may be considered biomarkers for suicidal behavior in young patients with major depressive or anxiety disorders before treatment with selective serotonin reuptake inhibitors (SSRIs), or as biomarkers for the adverse event of SSRI-associated suicidality. METHODS: Children and adolescents meeting criteria for major depressive or anxiety disorder were recruited. Serum levels of three pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) were assessed; and NLR and PLR calculated, from blood samples collected at baseline and after 8 weeks treatment with SSRI. A Mann-Whitney test was performed to evaluate differences in NLR and PLR between children with and without a history of a suicide attempt prior to treatment. We compared hematological parameters before and after treatment, and between children who developed SSRI-associated suicidality versus children without treatment emergent suicidality. RESULTS: Among 91 children and adolescents (aged 13.9 ± 2.4 years), baseline NLR and PLR were significantly higher among those with a history of a suicide attempt versus those without such history. Statistically significant correlations were found for the suicide ideation subscale in the Columbia suicide severity rating scale with both baseline NLR and PLR. Baseline NLR and PLR were similar in children who did and did not develop SSRI-associated suicidality after 8 weeks. In the final logistic regression model (χ2 = 18.504, df = 4, p value = 0.001), after controlling for sex, depression severity and IL-6 levels, NLR was significantly associated with a past suicide attempt (ß = 1.247, p = 0.019; OR [95% CI] = 3.478 [1.230-9.841]), with a NLR cut-off value of = 1.76 (area under the curve = 0.75 (95% CI = 0.63-0.88, sensitivity = 73%, and specificity = 71%, p value = 0.003). CONCLUSIONS: High NLR and PLR values may be associated with suicidal behavior in depressed and anxious children and adolescents. NLR appears as a better predictor of suicide attempt than PLR, and thus may be a useful biomarker of suicidality in young patients with depression or anxiety.

Social isolation in mice: behavior, immunity, and tumor growth.

The aim of this study was to investigate the behavioral, immunological, and neurological effects of long-term isolation in an animal model. Male C3H/eB mice wereraised in either social isolation or standard conditions for 6 weeks. At 10 weeks, each group was further divided into 3 sets. (A) Physical strength and behavior were evaluated with the grip strength, hot plate, staircase, and elevated plus-maze tests. Natural-killer cell activity and lymphocyte proliferation were measured. (B) Half the animals were subjected to electric shock with 3 reminders, and freezing time was evaluated at each reminder. Cortisone levels were evaluated after 16 weeks. (C)Mice were injected with 38 C-13 B lymphoma cells and followed for tumor size and survival. Strength evaluation yielded asignificantly lower body weight and grip strength in the socially isolated mice. Behavioral test results were similar in the two groups. The pattern of reactions to stress conditioning differed significantly, with the socially isolated mice showing an incline in freezing with each successive reminder, and the control mice showing a decline. The socially isolated mice had significantly attenuated tumor growth, with no significant difference in survival from control mice. There were no significant between-group differences in immunological parameters. In conclusion, social isolation serves as a model for chronic stress. It was associated with significant changes in stress conditioning reaction, resembling symptoms of post-traumatic stress disorder, and attenuated tumor development. No differences from controls were found in behavior tests, immune parameters, or survival after tumor cell inoculation.Lay summaryThis article explores biological and behavioral consequences of social isolation in a mice model. Our results show that social isolation leads to changes in the Hypothalamic-hypophyseal-adrenal axis, which in turn alter the response to stress. Additionally, social isolation was shown to impact tumor progression.

[THE PRODROME OF PSYCHOTIC DISORDERS].

INTRODUCTION: Psychotic disorders are associated with a severe functional decline and a significant impact on the quality of life. These disorders usually develop gradually, lasting days to months-years. The early phase of psychotic disorders is termed "pre-psychotic" or "prodromal". It is estimated that 30% of the individuals presenting with prodromal symptoms will develop psychosis in three years. This high-risk state is also known as "clinical high risk" (CHR), "ultra-high risk" (UHR), and "at-risk mental state" (ARMS). The diagnostic criteria of high-risk subjects include 3 groups: 1) genetic risk with a functional decline; 2) brief limited intermittent psychotic symptoms group (BLIPS); 3) subthreshold positive psychotic symptoms. In addition to the psychosis risk, these subjects suffer from distress, functional deterioration and psychiatric comorbidities that influence their quality of life. Therefore, many efforts are invested in early identification of the high-risk for psychosis subjects with the primary aim of using interventions to delay or prevent conversion to psychosis. Studies in the field have highlighted specific factors that predict the risk to develop psychosis and even developed predictive models. Interventions including cognitive-behavioral therapy, integrative psychological therapy and pharmacological therapy were found to be associated with postponing the conversion to psychosis. According to current guidelines, cognitive behavioral therapy is the first-choice intervention, and pharmacological interventions should be reserved for patients with comorbidities in need of stabilization of severe and progressive symptoms. Further prospective studies will allow a better identification of high-risk patients and enable the development of interventions for prevention and treatment of this population.

Increased circulatory IL-6 during 8-week fluoxetine treatment is a risk factor for suicidal behaviors in youth.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat anxiety and/or depression in pediatric populations. However, the response rates are low (approximately 50%). Moreover, SSRI use is frequently associated with adverse events (AE). Currently there are no available biomarkers for treatment response/AE. Identification of biomarkers predicting early response and/or AE could help maximize the benefit-risk ratio for the use of SSRIs, and accelerate matching of treatments to patients. Pro-inflammatory cytokines were proposed as potential biomarkers. METHOD: Ninety-two patients (35 boys and 57 girls) with major depressive disorder and/or anxiety disorders, aged 13.90 ±â€¯2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNFα, IL-6, and IL-1ß were measured by enzyme linked immunosorbent assays before and after FLX treatment. Clinical response and AE were measured using several clinical scales, including the Clinical Global Impression - improvement, Children's Depression Rating Scale-Revised, the Beck Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders, the Columbia suicide severity rating scale, and the Suicide Ideation Questionnaire. RESULTS: IL-6 levels increased after treatment only in the group of children who developed FLX-associated suicidality. CONCLUSION: An increase in IL-6 levels during treatment may be a risk factor for the emergence of FLX-associated suicidality (OR = 1.70). Further studies are necessary to clarify the role and mechanism(s) of this cytokine in the pathogenesis of this life-threatening AE.

Efficacy of Psychological Intervention for Children with Concurrent Posttraumatic Stress Disorder and Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common conditions following motor vehicle accidents (MVAs). Mild TBI and PTSD not only share similar features but may also coexist and interact. Nonetheless, research on psychotherapeutic interventions for PTSD in patients with a history of mTBI, particularly regarding pediatric populations, is limited. The present study compared the efficacy of the prolonged exposure treatment protocol for children and adolescents (PE-A) with PTSD and mTBI (n = 16) versus PTSD alone (n = 21); treatment commenced at least 3 months following an MVA. Emotional status and cognitive functioning were assessed pre- and postintervention using questionnaires and standardized neuropsychological tests. Participants from both groups benefitted from the intervention, as reflected in their emotional status via increased ratings of well-being and decreased ratings of PTSD, anxiety, depression, and postconcussive symptoms, η2 = .21-.50. Ratings of cognitive function also improved for cognitive flexibility, η2 = .30; executive function in everyday life, η2 = .27; and attention and inhibition, η2 = .16. Parental PTSD was the strongest predictor of improvement after intervention, sr2 = .35. Thus, it appears that PE-A is an effective intervention for children with MVA-related PTSD regardless of its comorbidity with mTBI.

Early changes in depression predict outcomes of inpatient adolescent anorexia nervosa.

PURPOSE: The aim of this study was to investigate the predictive value of early changes in depression levels during inpatient treatment of adolescent anorexia nervosa (AN). METHODS: Fifty-six adolescents (88% girls) aged 10-18 years (M = 15.35, SD = 2.23) diagnosed with AN were assessed at admission and 1 month following admission to an inpatient setting. Depression levels and eating disorder symptoms were reported at both assessments. Re-hospitalization within 12 months of discharge was documented using official national records. RESULTS: Whereas depression levels at baseline were found equivalent between subsequently re-hospitalized and non-re-hospitalized patients, at 1 month after admission patients who were later re-hospitalized had higher levels of depression compared to those who were not re-hospitalized. These differences remained significant after controlling for weight gain and anti-depressant medication intake. We additionally found that the proportion of boys in the non-re-hospitalized group was substantially larger than their proportion in the re-hospitalized group. CONCLUSIONS: Our results suggest that depression at the point of hospital admission may not be a reliable predictor of treatment outcomes, and highlight the risk of relapse in AN patients whose depression levels do not alleviate after a month of inpatient treatment. Clinicians should consider providing more adjusted and intensive attention to such patients in their efforts to facilitate remission. LEVEL OF EVIDENCE III: Well-designed cohort study.

[EXCORIATION (SKIN-PICKING) DISORDER].

INTRODUCTION: Excoriation (Skin-Picking) disorder is a clinically recognized condition which was recently included in the Diagnostic and Statistical manual of the American Psychiatric Association (DSM) - fifth edition, as OCD (obsessive compulsive disorder) related disorder. The disorder's official status has been achieved due to its high frequency and unique clinical picture involving both mental and physical impairment. In this article, we would like to present a concise review of the literature together with an illustrative case. Epidemiological surveys show a prevalence of 3% to 5% for the general population, with heterogeneous gender and age distribution. In recent years the disorder has been categorized under the family of BFRB's (Body Focused Repetitive Behaviours). However, there are some elements associated with movement suppression and tic disorders, as well as disorders belonging to obsessive-compulsive spectrum. The treatment of this disorder may be pharmacological and/or psychological. There is some evidence for the benefit of some SSRI (Selective Serotonin Reuptake Inhibitors) agents as well as for N-Acetyl-Cysteine. Various psychological treatments have been investigated and some of them have proven to be effective. These include cognitive behavioural protocols, some of which have been developed specifically for this disorder.

A study of sensory dysregulation in children with tic disorders.

Disrupted somatosensory processing characterized by over- or under- responsiveness to environmental stimuli plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. These dysfunctional somatosensory processes have been conceptualized as an entity termed somatosensory dysregulation (SMD). Since Tourette syndrome (TS) is a prototypical example of developmental psychopathological disorder, we hypothesised that SMD would be a feature found in children suffering from the disorder. Ninety-two subjects representing consecutive admissions to a tertiary paediatric Tourette syndrome clinic were admitted to the study. Comorbid conditions included ADHD, depression, anxiety disorder, and OCD. For purposes of the study, patients completed a battery of self-, caregiver-, and clinician-rated psychological instruments measuring TS core symptoms and comorbidities and quality of life. Sensory modulation was measured by self-report and by objective measures such as stimulation with Von Frey filaments. Almost 50% of the cohort had no SMD. Of the remainder, 14 (15%) had suspected SMD and 32 (34.8%) had SMD. SMD was significantly more common and severe when there were comorbidities. The presence of SMD was associated with more severe impairments in quality of life and less participation in daily activities. The SMD, as measured by subjective measures but not by objective, is probably more associated with central processing rather than peripheral perception.

Gender Differences in Neurocognitive Performance Among Children With Posttraumatic Stress Disorder and Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are frequent sequelae after motor vehicle accidents (MVAs). These two pathologies often have overlapping neurocognitive deficits across several domains, such as attention, memory, and executive functions. The present study was an effort to examine the contribution of gender to these overlapping symptoms. To this end, psychodiagnostic and neuropsychological data were collected on 61 children and adolescents 3 months following MVA. All participants were diagnosed with PTSD, and about half (n = 33) also received a diagnosis of mTBI. Analyses of variance revealed significant interactions between gender and mTBI (ηp2=.15), such that girls with mTBIs preformed significantly worse than noninjured girls on measures of executive functions (Cohen's d = 3.88) and sustained attention (Cohen's d = 3.24). Boys, on the other hand, did not differ significantly on any of those measures, irrespective of TBI injury status. Similarly, comparisons to the normative population revealed that, whereas boys showed impaired neurocognitive performances regardless of TBI status, impaired performances in girls were limited to those cases in which the girls were comorbid for PTSD and mTBI. It appears then that whereas PTSD alone might explain boys' reduced neurocognitive performance, among girls the comorbidity of PTSD and mTBI is required to account for performance deficits.

Inpatient weight curve trajectory as a prognostic factor among adolescents with anorexia nervosa: a preliminary report.

OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN. METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1 year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV). RESULTS: Logistic regression indicated that negative cubic variation rates (NCV) predicted re-hospitalization. PFTW was found only marginally significant. CONCLUSION: Variations in weight restoration during inpatient treatment may be used to identify patients at risk for relapse. NCV can alert clinicians to initiate early relapse prevention interventions before discharge. Level of Evidence Level III, cohort study.

Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders.

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dß, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ 2 = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dß CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ 2 = 8.99, df = 2, p = 0.011). The 5-HTR1Dß CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dß polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.

The relationship between self-injurious behavior and self-disclosure in adolescents with eating disorders.

PURPOSE: The aim of the current study is to examine the association between self disclosure and self-injurious behaviors among adolescent patients diagnosed with an eating disorder. METHODS: Sixty three female patients who fulfilled the DSM-IV diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia, binge eating disorder and eating disorders not otherwise specified). Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82). Participants completed self- report questionnaires about eating disorders, self-disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS: 82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative relationship was found between general disclosure to parents and self-injurious behaviors indicating that patients who generally self-disclose to their parents (on different topics, apart from suicidal ideation) engage less frequently in self-injurious behaviors. In addition, the more patients self-disclose their suicidal ideation to others, the more they tend to self-injure. CONCLUSION: Self-disclosure to parents on any topic may buffer against self-injurious behaviors and therefore it is important to work with adolescents suffering from eating disorders on effective self disclosure. In addition, self-disclosure about suicidal ideation to others by adolescents suffering from eating disorders should always be taken seriously, since it may be related to self-injurious behaviors.

The impact of comorbid depressive and anxiety disorders on severity of anorexia nervosa in adolescent girls.

We examined the impact of comorbid depression and anxiety disorders on the severity of anorexia nervosa (AN) in adolescent girls. Adolescent girls with AN (N = 88) were divided into one group with and another group without comorbid disorders, and selected subjective and objective measures of illness severity were compared between the two groups. The comorbid group had significantly higher scores than the noncomorbid group for all four subscales and total scores of the Eating Disorders Examination as well as for all Eating Disorders Inventory-2 subscales, except for bulimia. The comorbid group also had significantly more suicide attempts and hospitalizations compared with the noncomorbid group. There were no significant group differences for the lowest ever body mass index, duration of AN symptoms, and age at AN onset. Our findings suggest that AN with comorbid depression and anxiety disorder is a more severe clinical variant of the disorder, especially with respect to severity of psychological symptoms and suicide risk.

Selective mutism in immigrant families: An ecocultural perspective.

Although the diagnosis of selective mutism (SM) is more prevalent among immigrant children, the link between the disorder and an immigration background has been elusive. Guided by ecocultural models of development, the current study aimed to construct a theory-based description of SM while considering individual, family, and contextual risk factors. Participants were 78 children with SM (38.4% with an immigration background), and 247 typically developed children (18.2% with an immigration background). Consistent with previous studies, our results suggest that anxiety was the most important predictor of SM symptoms, above and beyond immigration background. Immigration, especially if coupled with bilingual status and low family income, predicted increased levels of SM symptoms. Identifying multi-level predictors of SM may help researchers and clinicians to improve early identification and treatment of SM in culturally and linguistically diverse children.

Psychosocial Correlates of Suicidal Ideation and Behavior in Adolescents and Preadolescent Children Discharged from an Emergency Department in Israel.

OBJECTIVES: Adolescent suicidal behavior is highly prevalent in pediatric psychiatric emergency departments, and there is a growing occurrence of such behavior among preadolescent children. This study aims to examine the psychosocial factors associated with nonfatal suicidal behaviors in children (<12 years old) and adolescents (aged 12-18), to gain insight into unique and shared characteristics of suicidal behavior across these two age groups. METHOD: This study investigates the psychosocial characteristics associated with suicidal ideation and behaviors in an emergency department sample of 183 children and adolescents aged 7-18 years in Israel. Participants completed a diagnostic interview, and self-report and parent-report questionnaires of psychosocial measures. Cross-sectional correlational and regression analyses were used to determine significant correlates of suicidal outcomes within the two age groups. RESULTS: Among adolescents, females exhibited a higher prevalence of suicidal thoughts and behaviors, while in children, both boys and girls showed similar rates. Depression correlated with suicidal ideation for both adolescents and children. In children, anxiety and conduct symptoms were associated with suicidal behavior, whereas in adolescents, suicidal behavior was associated with depression and anxiety. CONCLUSIONS: The present findings contribute to the growing understanding of factors associated with suicidal thoughts and behaviors among children in comparison to adolescents. These findings underscore the importance of targeting specific risk factors when developing assessment and intervention strategies tailored to the two age groups.

Suicidal thoughts and behaviors were more common in female adolescents, but similar for boys and girls in children.Different correlates were found for suicidal behavior in children compared to adolescents.This study emphasizes the need for age-specific tailored assessment and intervention.

Barriers to Adolescents' Adherence to Medical Advice after Metabolic Bariatric Surgery: A Statistical Analysis.

Background: Adolescent obesity has markedly increased worldwide, and metabolic bariatric surgery is an effective treatment option. A major predictor of the outcomes of this procedure is adherence to post-surgery lifestyle changes and medical recommendations. While adolescents generally have more difficulty adhering to medical advice than adults, their failure to do so could adversely affect their physical and psychological health, the cost-effectiveness of medical care, and the results of clinical trials. To our knowledge, this is the first attempt to identify the characteristics associated with the adherence of adolescents and their families to medical advice after bariatric surgery. Methods: We investigated potential variables influencing adherence to medical advice in adolescents diagnosed with severe obesity enrolled in a nutritional and behavior-oriented bariatric program-a 3-month pre-surgical outpatient intervention and a 6-month post-surgical follow-up. The program monitored weight, program attendance, diet compliance, lifestyle changes, and daily activities. All participants and parents completed a standard battery of questionnaires, provided demographic information, and participated in a semi-structured interview about their lifestyle. Results: The study group consisted of 47 adolescents: 34 girls and 13 boys, aged 13-18 years. Over time, three groups emerged with different degrees of adherence-high, low, and delayed low adherence. The analyses showed that adolescents' depression, autonomy, and independence from their family had strong, significant effects on adherence across the groups. Conclusions: Using adherence typologies, practitioners may be able to identify, predict, and tailor interventions to improve adolescent adherence to post-surgery recommendations. Parents have an important role in ensuring that adolescents undergoing metabolic bariatric surgery follow medical advice after the procedure.

Association between a common CYP17A1 haplotype and anxiety in female anorexia nervosa.

Dehydroepiandrosterone (DHEA), the main brain neurosteroid, has been implicated in various psychiatric disorders especially those including gender differences. We studied genetic variability in the DHEA-producing enzyme CYP17A1 in relation to anorexia nervosa (AN) susceptibility and AN-related co-morbidities. We performed analysis of 100 Israeli AN family trios accounting for CYP17A1 haplotypes characteristic of populations of European origin and studied genotype-phenotype relationships using correlation analyses and transmission disequilibrium test. Although our analysis revealed no evidence of association between CYP17A1 and AN per se, it revealed an association between specific CYP17A1 haplotypes and AN co-morbidity, specifically anxiety. We found that a common CYP17A1 haplotype (H1) was associated with higher anxiety in AN patients (Clinical Global Impression; CGI-anxiety ≥4). Moreover, H1 homozygotes were at higher risk for expressing high CGI-anxiety levels (OR = 3.7), and H1 was preferentially transmitted to AN patients with high CGI-anxiety levels (P = 0. 037). We suggest that CYP17A1 H1 haplotype may contribute to genetic predisposition to higher CGI-anxiety levels in AN patients and that this predisposition may be mediated by reduced CYP17A1 enzymatic activity and corresponding lower DHEA production.

[Formula: see text]Persistent post-concussion symptoms in children: pre-injury social difficulties and acute stress reaction as risk factors.

Following mild traumatic brain injury (mTBI) children usually experience one or more somatic, cognitive, and/or emotional-behavioral post-concussion symptoms (PCS). PCS may be transient, however for some children, persistent post-concussion symptoms (PPCS) might linger for months or years. Identifying risk factors for PPCS may allow earlier interventions for patients at greater risk. We examined pre-injury social difficulties and acute stress reaction as risk factors to PPCS in children. Participants were 83 children (aged 8-16) with mTBI. In a prospective follow-up, pre-injury social difficulties, 24-hours post-concussion symptoms, and acute stress reactions were tested as predictors of one-week and four-months PCS reports. Parents' reports, self-reports, and neurocognitive tests were employed. One-week PCS level was associated with acute stress, and not with 24-hours post-concussion symptoms or pre-injury social difficulties. Four-months PCS level was predicted by pre-injury social difficulties and 24-hours post-concussion symptoms, with no contribution of acute stress. Interestingly, less symptoms at 24-hour from injury were associated with a higher level of PCS at four months. Cognitive functioning at four months was predicted by acute stress, with no contribution of 24-hours post-concussion symptoms or pre-injury social difficulties. Cognitive functioning did not differ between children with and without PPCS. In conclusion, non-injury, socio-emotional factors (pre-injury social difficulties, acute stress) should be considered, alongside injury-related factors, in predicting recovery from mTBI. Pre-injury social difficulties and stress reaction to the traumatic event might pose an emotional burden and limit one's social support during recovery, thus require clinical attention in children following mTBI.