Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. METHODS: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. RESULTS: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. CONCLUSIONS: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia.

Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia defined as onset before age of 13. Here we report on two unrelated cases diagnosed with both COS and alternating hemiplegia of childhood (AHC), and for whom two distinct pathogenic de novo variants were identified in the ATP1A3 gene. ATP1A3 encodes the α-subunit of a neuron-specific ATP-dependent transmembrane sodium-potassium pump. Using whole exome sequencing data derived from a cohort of 17 unrelated COS cases, we also examined ATP1A3 and all of its interactors known to be expressed in the brain to establish if variants could be identified. This led to the identification of a third case with a possibly damaging missense mutation in ATP1A3 and three others cases with predicted pathogenic missense variants in the FXYD gene family (FXYD1, FXYD6, and FXYD6-FXYD2 readthrough). FXYD genes encode proteins that modulate the ATP-dependant pump function. This report is the first to identify variants in the same pathway for COS. Our COS study illustrates the interest of stratifying a complex condition according to the age of onset for the identification of deleterious variants. Whereas ATP1A3 is a replicated gene in rare neuropediatric diseases, this gene has previously been linked with COS in only one case report. The association with rare variants in FXYD gene family is novel and highlights the interest of exploring these genes in COS as well as in pediatric neurodevelopmental disorders.

Borderline personality disorder and prior suicide attempts define a severity gradient among hospitalized adolescent suicide attempters.

BACKGROUND: Borderline personality disorder (BPD) and history of prior suicide attempt (SA) have been shown to be high predictors for subsequent suicide. However, no previous study has examined how both factors interact to modify clinical and suicide severity among adolescents. METHODS: This study presents a comprehensive assessment of 302 adolescents (265 girls, mean age = 14.7 years) hospitalized after a SA. To test clinical interactions between BPD and history of prior SA, the sample was divided into single attempters without BPD (non-BPD-SA, N = 80), single attempters with BPD (BPD-SA, N = 127) and multiple attempters with BPD (BPD-MA, N = 95). RESULTS: Univariate analyses revealed a severity gradient among the 3 groups with an additive effect of BPD on the clinical and suicide severity already conferred by a history of SA. This gradient encompassed categorical (anxiety and conduct disorders and non-suicidal-self-injury [NSSI]) and dimensional comorbidities (substance use and depression severity) and suicide characteristics (age at first SA). According to regression analyses, the BPD-MA group that was associated with the most severe clinical presentation also showed specific features: the first SA at a younger age and a higher prevalence of non-suicidal self-injury (NSSI) and anxiety disorders. The BPD-MA group was not associated with higher impulsivity or frequency of negative life events. CONCLUSIONS: Based on these findings and to improve youth suicide prevention, future studies should systematically consider BPD and the efficacy of reinforcing early interventions for anxiety disorders and NSSI.

Repeating a suicide attempt during adolescence: risk and protective factors 12 months after hospitalization.

Suicide attempts (SAs) are a public health concern in adolescence. A brief hospitalization is recommended, but access to inpatient wards is often not available. In addition, numerous risk factors for SA recurrence have been identified, but few studies have explored protective factors. Here, we aimed to assess the role of both risk and protective factors on SA relapse in a context of free access to inpatient services. We performed a prospective follow-up study of 320 adolescents who were hospitalized for an SA between January 2011 and December 2014 in France. Assessments at baseline included socio-demographics, clinical characteristics, temperament, reasons for living, spirituality, and coping. Patients were re-evaluated at 6 months and 12 months for depression severity and SA relapse. A total of 135 and 91 patients (78 girls, 12 boys, aged 13-17) were followed up at 6 and 12 months, respectively. At the 12-month follow-up, 28 (30%) subjects had repeated an SA. Adolescents who either had a history of SA or were receiving psychotropic treatment at baseline were at higher risk of recurrence. Several variables had a protective effect: (1) productive coping skills, namely, working hard and achieving, physical recreation, and seeking relaxing diversions; (2) a particular temperament trait, namely, cooperativeness; and (3) having experienced more life events. We also found a significant interaction: the higher the depression score during follow-up, the lower the protective effect of productive coping. Our findings confirm that a history of SA and seeking psychiatric care with medication are risk factors for SA relapse. However, productive coping strategies and cooperativeness are protective factors, and the improvement of such strategies as well as treatment of persisting depression should be a goal of psychotherapy treatment offered to suicidal adolescents.

Hippocampal subfields alterations in adolescents with post-traumatic stress disorder.

Reexperiencing symptoms in adolescent Post-Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high-resolution MRI images in 15 adolescents (13-18 years old) with PTSD and 24 age-matched healthy controls. The volume of the region CA2-3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2-3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale-Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2-3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.

Functional brain alterations during self-reference processing in adolescents with sexual abuse-related post-traumatic stress disorder: A preliminary report.

We proposed to explore the functional brain changes during a self-reference processing (SRP) task in adolescents with sexual abuse-related post-traumatic stress disorder (N = 10), compared with healthy adolescents (N = 10). While patients showed no behavioral disturbances in (SRP), they exhibited changes in activity and connectivity in regions involved in emotional regulation (amygdala and dorsal prefrontal cortex) and semantic memory (temporal and ventrolateral prefrontal regions). These preliminary results suggest that these alterations may have an effect on self-esteem which may contribute to a possible retention and impairment of symptoms in adulthood.

[Pregnancy and motherhood in adolescence]. / Grossesse et maternité à l'adolescence.

Adolescence and pregnancy are two periods which involve major psychological and identity changes. Teenage pregnancies are often considered to be a result of a confusion between these periods. The circumstances of teenage pregnancies and early motherhood are diverse and sit within the wider context of the psychopathology of adolescence, the heterogeneity of family configurations and evolutions in society.

French version of the Brief Infant-Toddler Social and Emotional Assessment questionnaire-BITSEA.

OBJECTIVE: The aim of the present study was to examine the psychometric properties of the French version of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). METHODS: The sample consisted of 589 low-risk infants aged 12-36 months and their parents. Parents completed the BITSEA, the Child Behavior Checklist 1½-5 (CBCL - 18 months to 5 years version), and the Parenting Stress Index - Short Form (PSI-SF). RESULTS: Multitrait-multimethod and confirmatory factor analyses revealed adequate psychometric properties for the French version of the BITSEA. Scores on the BITSEA Problem scale were positively correlated to all CBCL and PSI-SF subscales, whereas negative correlations were found between BITSEA Competence scale and CBCL and PSI-SF subscales. The BITSEA Problem score significantly increased with level of parental worry, examined through a single-item question that is part of the BITSEA. CONCLUSION: Findings support the validity of the French version of the BITSEA. However, additional work on the clinical validity of the BITSEA, including with at-risk children, is warranted.

Hard-to-treat or hard-to-catch? Clinical features and therapeutic outcomes of help-seeking foster care youths with mood disorders.

Introduction: The high level of emotional problems in youths placed in foster care contrasts with the limited use of evidence-based treatments. This study aims to better characterize the clinical features and therapeutic outcomes of foster care youths with mood disorders. Methods: A secondary analysis of data collected in the context of a French-Canadian clinical research network on pediatric mood disorders in four sites was conducted to compare three groups of patients with depressive or bipolar disorder: those without exposure to child welfare intervention (WCWI, n = 181), those who received non-placement psychosocial intervention (NPI, n = 62), and those in placement interventions (PI, n = 41). Results: We observed a very high rate of academic problems in patients in the groups NPI/PI compared to those in the WCWI group. Patients in the PI group had more disruptive behavioral disorders (OR = 6.87, 95% CI [3.25-14.52]), trauma-related disorders (OR = 3.78, 95% CI [1.6-8.94]), and any neurodevelopmental disorders (OR = 2.73, 95% CI [1.36-5.49]) compared to the other groups (NPI/WCWI). Among inpatients, the Clinical Global Impression-Improvement scale and the change in the Children Global Assessment Scale during the hospital stay did not differ across the three groups. We observed a higher prescription rate of antipsychotics in the PI group compared to the NPI/WCWI groups, but no significant difference for antidepressants and mood stabilizers. Discussion: These findings support the view that, when provided with dedicated support, fostered inpatient youths can improve in a range comparable to other inpatients. Undetected neurodevelopmental disorders and academic problems are likely important contributors of the burden of mood disorders in these youths.

Impact of the Timing of Maternal Peripartum Depression on Infant Social and Emotional Development at 18 Months.

The study assessed how the timing of maternal perinatal depressive symptoms affects infant socio-emotional characteristics at age 18 months. The study was a longitudinal cohort study that included six assessment points from the third trimester of pregnancy up to age 18 months (±1 month). Assessment of mothers included the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory, while assessments of infant included the Infant Toddler Social and Emotional Assessment (ITSEA) at 18 months. Mothers were categorized into one of the following groups: mothers who presented postnatal depression only (n = 19); mothers who presented both prenatal and postnatal depression (n = 14), and mothers who never showed perinatal depression symptoms (n = 38). Mothers who presented both prenatal and postnatal depression showed significantly higher levels of depressive score, reactivity to stress and level of anxiety trait compared to mothers of the two other groups. Infants of prenatally and postnatally depressed mothers had higher scores on the internalizing subscore of the ITSEA. The number of depression episodes during the study period was positively correlated with the externalizing and internalizing subscores of the ITSEA. These findings support the need to provide specific screening to identify women with prenatal depression.

Panda Unit, a Mother-Baby Unit Nested in a Neonatal Care Service.

The PANDA unit is a full-time mother-baby hospitalization unit based on an original model of care for vulnerable dyads. It is located within a neonatal unit allowing tripartite care (perinatal psychiatry, neonatology and post-natal care). It thus differs from traditional mother-baby units in its close links with the other perinatal care actors, allowing comprehensive health and mental health care in the immediate post-partum period. Patients admitted to the Panda Unit may have been referred during the antenatal period or taken into care in an emergency if the mother's clinical condition requires it, in the aftermath of childbirth. During their stay, the dyads are evaluated daily by a perinatal psychiatrist. This includes assessment of maternal clinical state, the newborn's development and the quality of mother-infant interactions. During the first 6 months of use, 24 dyads have benefited from PANDA care. Three women among 5 were admitted during the antenatal period and almost one-third were aged under 21. The first primary diagnosis during the antepartum was major depressive disorder, two-fold that of personality disorder or bipolar disorder alone. At the end of PANDA stay, close to 3 women among 4 were back to their home with their child, and an out-of-home placement was mandated for 4 infants. PANDA unit is a step toward continuous and comprehensive integrative care. The mother and baby do not leave the maternity ward, and management of mother, baby, and their interactions can start immediately after birth. Considering the importance of the first months of life in the establishment of fundamental links and bonding, PANDA offers an innovative opportunity for what we hope will be both therapeutic and preventive for at-risk dyads. The detection, and ultimately prevention and management of risk of abuse and neglect is another major challenge that this unit hopes to address from the very beginning.

Gender Differences Related to Spirituality, Coping Skills and Risk Factors of Suicide Attempt: A Cross-Sectional Study of French Adolescent Inpatients.

Background: Suicide attempts in adolescence represent a major public health concern, since these behaviors are associated with psychosocial burden and an increased risk of suicide. This cross-sectional study aimed to explore possible gender differences related to protective and risk factors in adolescents who have attempted suicide. Methods: Participants were French adolescents hospitalized for attempt suicide in five French pediatric departments. The participants were evaluated on 12 instruments measuring individual risk and protective factors. Results: Our sample included 320 adolescents aged 13-17 years (M = 14.43, SD = 1.29), of whom 82% were female and 35% were repeat attempters. Boys had greater difficulties at school and used more lethal means such as strangulation. We failed to find any differences between the two groups as regards the main Axis I psychiatric diagnoses. Boys tend to use more non-productive coping skills such as tension reduction or wishful thinking and girls use more reference to other strategies such as seeking social support. Although spirituality scores were low overall sample, they were significantly higher among girls. Conclusions: In the end, we find little difference between the two groups in terms of risk factors. However, we have shown gender differences in spirituality and some coping strategies. These results should be taken into consideration when designing suicide prevention programs.

Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series.

Despite its drastic efficacy in resistant psychiatric disorders, clozapine remains rarely used in youth due to its side effects. Clozapine plasma level is determined through its metabolism involving several isoforms of cytochromes 450 (CYP450) family. Isoform CYP1A2 appears as a limiting enzyme involved in the metabolism of clozapine, while isoforms 2C19, 2D6, 3A4, and 3A5 also contribute in a minor way. Clozapine efficacy is limited by a significant inter-patient variability in exposure according to CYP's polymorphisms. Clozapine plasma levels may be increased with CYP inhibitors such as fluvoxamine. This drug is a potent enzymatic inhibitor of CYP1A2 and, to a lesser extent, of CYP3A4 and CYP2D6. Hence, in case of CYP's polymorphisms in youth, the use of fluvoxamine as add-on to clozapine could help in reaching clinical and biological efficacy and allowing lower clozapine dosage and a better tolerance profile as it has already been described in adults. We report four pediatric cases with severe psychiatric disorders underlying our experience with CYP polymorphism explorations and the use of fluvoxamine as add-on to clozapine. Our four patients clinically improved after the introduction of fluvoxamine, enhancing clozapine metabolism and therefore the clozapine plasma level within therapeutic range. Despite the interesting results of fluvoxamine, we report a severe issue of tolerance for one patient, emphasizing the need for caution regarding possible drug interactions when fluvoxamine is considered. Hence, we propose a detailed step-by-step multidisciplinary protocol.

Adolescents Engaged in Radicalisation and Terrorism: A Dimensional and Categorical Assessment.

Since 2010 and the founding of the Islamic State, the radicalisation phenomenon in Europe has involved more adolescents and converts to Islam than in previous Islamist terrorist group movements (e.g., Al-Qaeda). In most cases, these adolescents are "homegrown terrorists," a challenging difference, as they are in confrontation with their home and societal environment. As a new and emerging phenomenon, radicalisation leads to many questions. Are empathic capacities altered? Are they presenting psychiatric pathologies or suicidal tendencies that explain why they put themselves in serious dangers? Are they just young delinquents who simply met a radical ideology? In January 2018, by special Justice Department authorisation, we contacted all minors (N = 31) convicted in France for "criminal association to commit terrorism." We assessed several sociodemographic, clinical and psychological variables, including empathy and suicidality, in half of them (N = 15) and compared them with 101 teenagers convicted for non-terrorist delinquency who were placed in Closed Educational Centres (CEC). The results show that adolescents engaged in radicalisation and terrorism do not have a significant prevalence of psychiatric disorders, suicidal tendencies or lack of empathy. It also appears that they have different psychological profiles than delinquent adolescents. "Radicalised" adolescents show better intellectual skills, insight capacities and coping strategies. In addition, the manifestation of their difficulties is less externalised than adolescents from the CEC, having committed very few delinquent acts.

Specificity and wealth of autobiographical memories in restrictive and mixed anorexic patients.

The reduced specificity of positive and negative autobiographical memories observed in anorexic (AN) patients may reflect a global disturbance in their emotional information processing. However, their emotional difficulties may differ according to the subtype of AN, implying possible differences in the manifestation of autobiographical memory impairments. The aims of the study were (1) to confirm the autobiographical memory deficits in AN patients in terms of specificity and wealth of memories, and (2) to compare autobiographical deficits according to the AN subtype: restrictive type (AR) or binge/purging type (AB). Ninety-five non-clinical (NC) individuals and 95 AN patients including 69 AR and 22 AB patients were administered the Williams' and Scott's Autobiographical Memory Test. The results confirmed a lack of specificity regardless of emotional valence in the overall AN patient group without any distinction of subtype, which was linked to the number of hospitalizations. When the AN subtype was considered, AR patients demonstrated reduced specificity for negative memories only, suggesting differences in emotional functioning or in the mechanisms underlying reduced specificity between AR and AB patients. Furthermore, the overall AN group demonstrated lower variability and complexity in their memory content than the NC group. However, this difference in the complexity of recalled memories was only found in response to negative cues. When AN subtypes were considered, AR patients showed fewer complex memories than NC individuals. Beyond a reduced specificity, AN patients also depict a poverty in the range of event recall and a difficulty in developing narrative content. The clinical implications of such autobiographical memory deficits need to be further investigated.

Psychiatric autoimmune conditions in children and adolescents: Is catatonia a severity marker?

OBJECTIVES: Patients with autoimmune encephalitis (AE) are likely to exhibit an acute onset of severe psychiatric features, including psychosis and/or catatonia. Based on the high prevalence of catatonia in AE and our clinical experience, we hypothesized that catatonia might be a marker of severity requiring more aggressive treatment approaches. METHODS: To reach a sufficient number of cases with brain-autoimmune conditions, we pooled two samples (N = 58): the first from the French National Network of Rare Psychiatric diseases and the second from the largest Italian neuro-pediatrics center for encephalopathies. Autoimmune conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. We retrospectively compared patients with and without catatonia for psychiatric and non-psychiatric clinical features, biological and imaging assessments, type of immunotherapy used and outcomes. RESULTS: The sample included 25 patients (43%) with catatonia and 33 (57%) without catatonia. Forty-two patients (72.4%) had a definite AE (including 27 anti-NMDA receptor encephalitis) and 16 (27.6%) suspected autoimmune encephalitis. Patients with catatonia showed significantly more psychotic features [18 (72%) vs 9 (27.3%), p < 0.001)] and more movement disorders [25 (100%) vs 20 (60.6%), p < 0.001] than patients without catatonia. First line (corticoids, immunoglobulin and plasma exchanges) and second line (e.g., rituximab) therapies were more effective in patients with catatonia, with 24 (96%) vs 22 (66.7%) (p = 0.006) and 17 (68%) vs 9 (27.3%) (p = 0.002), respectively. However, those with catatonia received more combinations of first and second line treatments and had more relapses during outcomes. CONCLUSION: Despite its exploratory design, the study supports the idea that autoimmune catatonia may be a marker of severity and morbidity in terms of initial presentation and relapses, requiring the need for early and aggressive treatment.

Phenomenology, psychopathology, and short-term therapeutic outcome of 102 infants aged 0 to 12 months consecutively referred to a community-based 0 to 3 mental health clinic.

Infants ages 0 to 1 year consecutively referred for psychiatric treatment during the year 2005 were followed, and variables associated with diagnosis and short-term outcome were assessed. Infants were evaluated using the Psychiatric Infant Navigator Chart and Evaluation that includes nosological diagnoses [Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, (DC 0-3), Zero to Three, 1994] as well as risk and protective factors, treatment procedure, and outcomes. Seventy-six percent of the infants had an Axis I diagnosis, with anxiety disorders and a mixed disorder of emotional expressiveness being the most frequent. Twenty-five percent had an Axis II diagnosis. Multiple correspondence analyses showed that two dimensions corresponding grossly to DC 0-3 Axes I and II emerged. They emphasized three clinical profiles characterized by (a) good infant functioning, parent's awareness of their own difficulties, and a good outcome; (b) moderate child symptoms, overinvolved relating, and a good/intermediate outcome; (c) severe child symptoms, underinvolved relating, and a less favorable short-term outcome, signaling the risk for developmental disorders. Among the associated risk factors were cumulative parental stress, maternal psychopathology, and family dysfunction. Clinical implications of these findings indicated that infants under the age of 1 year who are referred for mental health evaluation and intervention are a heterogeneous group in terms of both severity and prognosis. Clinicians should differentiate subgroups of young children to detect those infants at risk for persistent psychopathology.

Use of Prazosin for Pediatric Post-Traumatic Stress Disorder With Nightmares and/or Sleep Disorder: Case Series of 18 Patients Prospectively Assessed.

OBJECTIVES: Few studies have investigated pharmacologic treatment for pediatric post-traumatic stress disorder (PTSD). Prazosin, an alpha-1 adrenergic receptor antagonist, has been studied and demonstrated to be efficacious in an adult population for PTSD related sleep disturbances; however, in the pediatric population, data is limited to case reports and retrospective case series. This study prospectively assessed the safety and effects of Prazosin on PTSD symptoms in a pediatric sample. METHODS: Since 2016, 18 patients with PSTD under the age of 15 admitted in a child and adolescent psychiatric unit were challenged with prazosin as part of a treatment protocol. PTSD symptoms and adverse effects were collected weekly and prospectively assessed each month with validated clinical scales. All data were retrospectively analyzed. This treatment protocol and the evaluation of clinical data were approved by our Ethical committee for research on preexisting data at the University Teaching Hospital of Rouen. RESULTS: Among the 18 patients (10 girls and 8 boys), 13 (72%) had experienced sexual abuse and 5 (28%) family violence. After 1 month of treatment with a mean prazosin dose of 2.16 ( ± 0.6) mg/day, the CGI-S score significantly decreased from 5.3 ( ± 0.9) to 2.9 ( ± 0.7) (improvement of 43%). The mean total UCLA-PTSD-RI score significantly decreased 11.4 points ( ± 5.4) during the first week and 37.9 ( ± 16) during the first month, leading to an improvement of 20% and 67%, respectively. The improvement was significant irrespective of trauma exposure or sex. No adverse effects were reported except for one patient (hypotension). CONCLUSION: Consistent with prior case reports and retrospective reviews, our retrospective analysis of data prospectively and systematically assessed among 18 patients suggests that prazosin is well-tolerated and associated with improvement in symptoms for pediatric PTSD.