The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study.

BACKGROUND: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. METHODS: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. RESULTS: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. CONCLUSIONS: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.

Assessing the Outcomes of Patients with Severe SARS-CoV-2 Infection after Therapeutic Plasma Exchange by Number of TPE Sessions.

The high mortality risk in severe SARS-CoV-2 infections is tightly correlated to the extreme elevation of inflammatory markers. This acute accumulation of inflammatory proteins can be cleared using plasma exchange (TPE), commonly known as plasmapheresis, although the available data on performing TPE in COVID-19 patients is limited regarding the optimal treatment protocol. The purpose for this study was to examine the efficacy and outcomes of TPE based on different treatment methods. A thorough database search was performed to identify patients from the Intensive Care Unit (ICU) of the Clinical Hospital of Infectious Diseases and Pneumology between March 2020 and March 2022 with severe COVID-19 that underwent at least one session of TPE. A total of 65 patients satisfied the inclusion criteria and were eligible for TPE as a last resort therapy. Of these, 41 patients received 1 TPE session, 13 received 2 TPE sessions, and the remaining 11 received more than 2 TPE sessions. It was observed that IL-6, CRP, and ESR decreased significantly after all sessions were performed in all three groups, with the highest decrease of IL-6 in those who received >2 TPE sessions (from 305.5 pg/mL to 156.0 pg/mL). Interestingly, there was a significant increase in leucocyte levels after TPE, but there was no significant difference in MAP changes, SOFA score, APACHE 2 score, or the PaO2/FiO2 ratio. The ROX index was significantly higher among the patients who underwent more than two TPE sessions, with an average of 11.4, compared to 6.5 in group 1 and 7.4 in group 2, which increased significantly after TPE. Nevertheless, the mortality rate was very high (72.3%), and the Kaplan-Meier analysis identified no significant difference in survival according to the number of TPE sessions. TPE can be used as last resort salvage therapy that can be regarded as an alternative treatment method when the standard management of these patients fails. It significantly decreases the inflammatory status measured via IL-6, CRP, and WBC, as well as demonstrating an improvement of the clinical status measured via PaO2/FiO2, and duration of hospitalization. However, the survival rate does not seem to change with the number of TPE sessions. Based on the survival analysis, one session of TPE as last resort treatment in patients with severe COVID-19 proved to have the same effect as repeated TPE sessions of 2 or more.

Self-Harm in Children and Adolescents Who Presented at Emergency Units During the COVID-19 Pandemic: An International Retrospective Cohort Study.

OBJECTIVE: To compare psychiatric emergencies and self-harm at emergency departments (EDs) 1 year into the pandemic, to early pandemic and pre-pandemic, and to examine the changes in the characteristics of self-harm presentations. METHOD: This retrospective cohort study expanded on the Pandemic-Related Emergency Psychiatric Presentations (PREP-kids) study. Routine record data in March to April of 2019, 2020, and 2021 from 62 EDs in 25 countries were included. ED presentations made by children and adolescents for any mental health reasons were analyzed. RESULTS: Altogether, 8,174 psychiatric presentations were recorded (63.5% female; mean [SD] age, 14.3 [2.6] years), 3,742 of which were self-harm presentations. Rate of psychiatric ED presentations in March to April 2021 was twice as high as in March to April 2020 (incidence rate ratio [IRR], 1.93; 95% CI, 1.60-2.33), and 50% higher than in March to April 2019 (IRR, 1.51; 95% CI, 1.25-1.81). Rate of self-harm presentations doubled between March to April 2020 and March to April 2021 (IRR, 1.98; 95% CI, 1.68-2.34), and was overall 1.7 times higher than in March to April 2019 (IRR, 1.70; 95% CI, 1.44-2.00). Comparing self-harm characteristics in March to April 2021 with March to April 2019, self-harm contributed to a higher proportion of all psychiatric presentations (odds ratio [OR], 1.30; 95% CI, 1.05-1.62), whereas female representation in self-harm presentations doubled (OR, 1.98; 95% CI, 1.45-2.72) and follow-up appointments were offered 4 times as often (OR, 4.46; 95% CI, 2.32-8.58). CONCLUSION: Increased pediatric ED visits for both self-harm and psychiatric reasons were observed, suggesting potential deterioration in child mental health. Self-harm in girls possibly increased and needs to be prioritized. Clinical services should continue using follow-up appointments to support discharge from EDs. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Efficacy of Therapeutic Plasma Exchange in Severe Acute Respiratory Distress Syndrome in COVID-19 Patients from the Western Part of Romania.

Background and Objectives: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has surprised the medical world with its devastating effects such as severe acute respiratory distress syndrome (ARDS) and cytokine storm, but also with the scant therapeutic solutions which have proven to be effective against the disease. Therapeutic plasma exchange (TPE) has been proposed from the very beginning as a possible adjuvant treatment in severe cases. Our objective was to analyze the evolution of specific biological markers of the COVID-19 disease before and one day after a therapeutic plasma exchange session, how a change in these parameters influences the patient's respiratory status, as well as the impact of TPE on the survival rate. Materials and Methods: In this retrospective study, we include 65 patients with COVID-19 admitted to the intensive care unit department of our hospital between March 2020 and December 2021, and who received a total of 120 sessions of TPE. Results: TPE significantly reduced the following inflammation markers (p < 0.001): interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, ferritin, and erythrocyte sedimentation rate. This procedure significantly increased the number of lymphocytes and decreased D-dimers levels (p = 0.0024). TPE significantly improved the PaO2/FiO2 ratio (p < 0.001) in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 100). Survival was improved in intubated patients who received TPE. Conclusions: TPE involved the reduction in inflammatory markers in critical patients with COVID-19 disease and the improvement of the PaO2/FiO2 ratio in patients with severe ARDS and had a potential benefit on the survival of patients with extremely severe COVID-19 disease.

COVID-19 pandemic-related aspects and predictors of emotional and behavioural symptoms in youth with pre-existing mental health conditions: results from Georgia, Lithuania, Romania, Serbia, and Turkey.

OBJECTIVE: This study evaluated levels of and predictors of emotional and behavioral symptoms in youth with pre-existing mental health conditions over the early phase of the COVID-19 pandemic in 2020 across Georgia, Lithuania, Romania, Serbia, and Turkey. METHODS: The study included 421 children and adolescents aged 5 - 18 years with pre-existing mental health conditions and corresponding ongoing treatments. We used a parent- and/or child-report, which taps into a broad range of mental health symptoms and contextual factors thought to be particularly pertinent during periods of social restrictions. Data were collected simultaneously across the countries from May 2020 to August 2020. RESULTS: According to parents, 121 (33.1%) children had deteriorations in the overall quality of mental health over the COVID-19, 156 (43.1%) deteriorations in the quantity of mental health care received, while 82 (25.1%) mental health care received did not meet the needs. For 121 (49.8%) of children, there was worsening in the main presenting psychiatric symptom compared to January 2020, while for 64 (26.3%) there was some improvement. In total, 128 (43.9%) children reported worsened emotional and 118 (40.6%) behavioral symptoms. The COVID-related worry, parental emotional difficulties, and parent-child relationships emerged as the most relevant predictors for higher levels of emotional and behavioral difficulties. CONCLUSIONS: This study found that the COVID-19 pandemic has considerably changed the daily lives of some children with pre-existing mental health conditions, where almost every second child had deteriorations in overall mental health or worsening of psychiatric symptoms.

Posttraumatic stress disorder symptoms among trauma-exposed adolescents from low- and middle-income countries.

BACKGROUND: Exposure to traumatic events in childhood is associated with the development and maintenance of various psychiatric disorders, but most frequently with posttraumatic stress disorder (PTSD). The aim of this study was to evaluate the types of traumatic events experienced and the presence and predictors of PTSD symptoms among adolescents from the general population from ten low- and middle-income countries (LMICs). METHODS: Data were simultaneously collected from 3370 trauma-exposed adolescents (mean age = 15.41 [SD = 1.65] years, range 12-18; 1465 (43.5%) males and 1905 (56.5%) females) in Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, the Palestinian Territories, the Philippines, Romania, and Serbia, with Portugal, a high-income country, as a reference point. The UCLA PTSD Reaction Index for the DSM-5 (PTSD-RI-5) was used for the assessment of traumatic events and PTSD symptoms. RESULTS: The most frequently reported traumatic events were death of a close person (69.7%), witnessing violence other than domestic (40.5%), being in a natural disaster (34.4%) and witnessing violent death or serious injury of a close person (33.9%). In total, 28.5% adolescents endorsed two to three DSM-5 PTSD criteria symptoms. The rates of adolescents with symptoms from all four DSM-5 criteria for PTSD were 6.2-8.1% in Indonesia, Serbia, Bulgaria, and Montenegro, and 9.2-10.5% in Philippines, Croatia and Brazil. From Portugal, 10.7% adolescents fall into this category, while 13.2% and 15.3% for the Palestinian Territories and Nigeria, respectively. A logistic regression model showed that younger age, experiencing war, being forced to have sex, and greater severity of symptoms (persistent avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity) were significant predictors of fulfilling full PTSD criteria. CONCLUSIONS: Nearly every third adolescent living in LMICs might have some PTSD symptoms after experiencing a traumatic event, while nearly one in ten might have sufficient symptoms for full DSM-5 PTSD diagnosis. The findings can inform the generation of PTSD burden estimates, allocation of health resources, and designing and implementing psychosocial interventions for PTSD in LMICs.

External locus-of-control partially mediates the association between cumulative trauma exposure and posttraumatic stress symptoms among adolescents from diverse background.

Locus of control (LOC) is a modifiable mediator of symptoms of posttraumatic stress disorder (PTSD) among traumatized individuals and a potential target of intervention. Compared with studies involving adults, the potential mediation effect of LOC on PTSD symptoms among trauma-exposed children and adolescents is relatively under-explored. This study, therefore, assessed the mediation effects of LOC on the association between lifetime cumulative trauma and PTSD symptoms among a large cohort of adolescents from different cultural background.Cross-sectional study.LOC was determined using the Multi-Dimension Locus of Control Scale; Posttraumatic stress symptoms using the UCLA PTSD Reaction Index; and other significant negative life events using the Life Events Checklist.Among 3826 adolescents who completed the study, external LOC explained 24% of variance (R2 = .24; F2,3823 = 619.01; p < .01) in PTSD symptoms and had significant indirect effect on the relationship between self-reported cumulative traumatic event exposure and PTSD symptoms (ß = .14; 95% BC CI [.10, .20]). Moderated mediation results showed significant potentiation of the moderation effects among older adolescents; boys; and those from more affluent families.The study further strengthened the hitherto limited evidence that external LOC partially mediate the relationship between cumulative trauma exposure and PTSD symptoms among adolescents.

The role of personality dimensions and trait anxiety in increasing the likelihood of suicide ideation in women during the perinatal period.

INTRODUCTION: Increasing amount of data reveal that suicide risk is a real phenomenon among perinatal women, determined by several other psychopathological conditions with depression being just one of them. This study aimed to investigate the role of personality dimensions on the occurrence of suicide ideation during the perinatal period. METHODS: A longitudinal prospective study was performed in pregnant women who were monitored at university-based obstetrical care units in our county. Recruited women were reassessed between 6 and 8 weeks into their postnatal period. Trait and state anxiety, five-factor based dimensions of personality, and depressive symptoms were assessed using established psychometric measures. Appropriate statistical analyses were conducted, depending on the distribution of variables. RESULTS: Significant levels of state anxiety (33.7% vs. 15.5%), depressive symptoms (19.8% vs. 8.5%), and suicide risk (13.9% vs. 6.3%) have halved in the postnatal period compared to the antenatal assessment. A lower level of education was associated with the presence of postnatal suicide ideation (p = .041), while an unemployed professional status was more frequent in pregnant women presenting antenatal suicide ideation (p = .021). Trait anxiety was predictive for the appearance of suicide ideation within the entire perinatal period assessed (p < .001 and p = .007, respectively). Agreeableness and conscientiousness predicted antenatal suicide ideation (p = .033 and p = .032, respectively). DISCUSSIONS: Different dimensions of personality may play a contributing role in the development of suicide ideation in perinatal women. Consequently, personality dimensions and trait anxiety, not only depressive symptoms, should be investigated when attempting to identify perinatal women at risk of suicide.

De novo 8p21.3→ p23.3 Duplication With t(4;8)(q35;p21.3) Translocation Associated With Mental Retardation, Autism Spectrum Disorder, and Congenital Heart Defects: Case Report With Literature Review.

Duplications of chromosome 8p lead to rare genetic conditions characterized by variable phenotypes. 8p21 and 8p23 duplications were associated with mental retardation but only 8p23 duplication was associated with heart defects. 8p22→ p21.3 duplications were associated with an autism spectrum disorder in several cases. We present a rare case with a de novo duplication of the entire 8p21.3→ p23.3 region, documented by karyotype, FISH, and array CGH, with t(4;8)(q35;p21.3) translocation in a 7 years-old girl. She was referred for genetic counseling at the age of 20 months due to mild dysmorphic facial features, psychomotor retardation, and a noncyanotic heart defect. Another examination carried out at the age of 5 years, enabled the diagnosis of autism spectrum disorder and attention deficit hyperactivity disorder. Upon re-examination after two years she was diagnosed with autism spectrum disorder, attention deficit hyperactivity disorder, liminal intellect with cognitive disharmony, delay in psychomotor acquisitions, developmental language delay, an instrumental disorder, and motor coordination disorder. Cytogenetic analysis using GTG technique revealed the following karyotype: 46,XX,der(4),t(4;8)(q35;p21.3). The translocation of the duplicated 8pter region to the telomeric region 4q was confirmed by FISH analysis (DJ580L5 probe). Array CGH showed: arr[GRCh37]8p23.3p21.3(125733_22400607) × 3. It identified a terminal duplication, a 22.3 Mb copy number gain of chromosome 8p23.3-p21.3, between 125,733 and 22,400,607. In this case, there is a de novo duplication of a large chromosomal segment, which was translocated to chromosome 4q. Our report provides additional data regarding neuropsychiatric features in chromosome 8p duplication. The phenotypic consequences in our patient allow clinical-cytogenetic correlations and may also reveal candidate genes for the phenotypic features.

UCLA PTSD reaction index for DSM-5 (PTSD-RI-5): a psychometric study of adolescents sampled from communities in eleven countries.

Background: Children and adolescents are often exposed to traumatic events, which may lead to the development of posttraumatic stress disorder (PTSD). It is therefore important for clinicians to screen for potential symptoms that can be signs of PTSD onset. PTSD in youth is a worldwide problem, thus congruent screening tools in various languages are needed. Objective: The aim of this study was to test the general psychometric properties of the Traumatic Stress Disorder Reaction Index for children and adolescents (UCLA PTSD) Reaction Index for DSM-5 (PTSD-RI-5) in adolescents, a self-report instrument intended to screen for trauma exposure and assess PTSD symptoms. Method: Data was collected from 4201 adolescents in communities within eleven countries worldwide (i.e. Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, Palestine-Gaza, Philippines, Portugal, Romania, and Serbia). Internal consistency, discriminant validity, and a confirmatory factor analysis of a four-factor model representing the main DSM-5 symptoms of the PTSD-RI-5 were evaluated. Results: The PTSD-RI-5 total score for the entire sample shows very good reliability (α = .92) as well as across all countries included (α ranged from .90 to .94). The correlations between anxiety/depressive symptoms and the PTSD-RI-5 scores were below .70 indicating on good discriminant validity. The four-factor structure of the scale was confirmed for the total sample and data from six countries. The standardized regression weights for all items varied markedly across the countries. The lack of a common acceptable model across all countries prevented us from direct testing of cross-cultural measurement invariance. Conclusions: The four-factor structure of the PTSD-RI-5 likely represents the core PTSD symptoms as proposed by the DSM-5 criteria, but there could be items interpreted in a conceptually different manner by adolescents from different cultural/regional backgrounds and future cross-cultural evaluations need to consider this finding.

Antecedentes: Los niños y adolescentes a menudo están expuestos a eventos traumáticos, que pueden llevar al desarrollo de un trastorno de estrés postraumático (TEPT). Por lo tanto, es importante que los médicos examinen los posibles síntomas que pueden ser signos del inicio de un TEPT. Este trastorno en jóvenes es un problema global, por lo que se necesitan herramientas de detección congruentes en varios idiomas.Objetivo: El objetivo de este estudio fue probar en adolescentes las propiedades psicométricas generales del Índice de Reacción TEPT de la UCLA para el DSM-5 (PTSD-RI-5), que es un instrumento de auto-reporte destinado a evaluar la exposición al trauma y evaluar los síntomas de PTSD.Método: Los datos se recopilaron de 4201 adolescentes en comunidades dentro de once países alrededor del mundo (es decir, Brasil, Bulgaria, Croacia, Indonesia, Montenegro, Nigeria, Palestina-Gaza, Filipinas, Portugal, Rumania y Serbia). Se evaluó la consistencia interna, la validez discriminante y un análisis factorial confirmatorio de un modelo de cuatro factores que representa los principales síntomas del DSM-5 del PTSD-RI-5Resultados: La puntuación total de PTSD-RI-5 para toda la muestra reveló una muy buena confiabilidad (α = .92), así como en todos los países incluidos (α varió de .90 a .94). Las correlaciones entre los síntomas de ansiedad/depresión y las puntuaciones del PTSD-RI-5 fueron inferiores a .70, lo que indica una buena validez discriminante. La estructura de cuatro factores de la escala se confirmó para la muestra total y los datos de seis países. Las ponderaciones de regresión estandarizada variaron notablemente para todos los ítems en todos los países. La falta de un modelo aceptable común en todos los países nos impidió realizar pruebas directas de invariancia de medición intercultural.Conclusiones: La estructura de cuatro factores del PTSD-RI-5 probablemente representa los síntomas centrales del TEPT según lo propuesto por los criterios del DSM-5, pero podría haber elementos interpretados de manera conceptualmente diferente por adolescentes con diferentes orígenes culturales/regionales, y futuras evaluaciones interculturales deben considerar este hallazgo.

Impact of the CYP2D6 phenotype on hyperprolactinemia development as an adverse event of treatment with atypical antipsychotic agents in pediatric patients.

BACKGROUND: Treatment with atypical antipsychotics is today the election therapy for different types of psychosis, but there is a high incidence of endocrine and metabolic disturbances. One of the major enzymes involved in the metabolism of antipsychotics is CYP2D6. Depending on the existing CYP2D6 alleles, the metabolic capacity of the enzyme may vary from very low to very high, so that patients can be grouped into four phenotypic groups: slow, intermediate, extensive (normal), and fast metabolizers. AIM OF THE STUDY: The aim of the study is to find a relationship between the individual intervariability of CYP2D6 and the incidence of hyperprolactinemia as side effect of atypical antipsychotics. RESULTS: A total of 81 patients with schizophrenia or bipolar disorders, median age 15.74 ± 4 years, were enrolled in the study and prescribed the following atypical antipsychotics: risperidone, aripiprazole, and olanzapine. They were evaluated at 6, 12, and 18 months after the initiation of treatment. Using the TaqMan Genotyping Assay, it has been identified the presence of the CYP2D6*4 allele in 28 patients, representing 34.56% of the total of 81 patients in the study, and CYP2D6*3 allele was identified in 15 patients and the presence of CYP2D6*41 to 11 patients. The allele CYP2D6*5 has not been present to the study patients. The study group has 44 patients which are extensive metabolizers (54%), 34 intermediate metabolizers (42%), and 3 poor (slow) metabolizers (4%). CONCLUSIONS: For the slow and intermediate metabolizers, atypical antipsychotics determined a significant increase of prolactinemia with high risk of adverse events.

The utility of indirect imagistic signs in the diagnosis of anterior cruciate ligament ruptures.

We conducted a retrospective study, between 2013 and 2018. The study was conducted by analyzing the comparative imaging of two groups of patients. The two groups comprise 42 patients, 14 women and 28 men aged between 17 and 70 years old, to whom objective variables of statistical relevance were tracked. The results of this study show that there is a significant correlation between an angle value of less than 45° and the rupture of the anterior crossed ligament.

Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Integrative clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological correlations in depressive and anxiety disorders.

We approach the theme of modern treatment strategies, based on clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological integrative correlations in the management of depressive and comorbid anxiety disorders. We target to evaluate the efficacy of the pharmacogenetic testing and the evolution, functioning of patients in correlation with specific neurobiological, neuroimagistic and neuroendocrinological markers. Our research was conducted between 2010-2016 on 80 children and adolescents with depressive and comorbid anxiety disorders - 40 children (G1 group), who benefited in choosing the pharmacotherapy from pharmacogenetic testing and 40 children without testing (G2 group). Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the CDRS (Children's Depression Rating Scale) total scores, in the CGI-S÷I (Clinical Global Impression - Severity÷Improvement), CGAS (Children's Global Assessment Scale) and through the change of the relevant neurobiological markers and MR spectroscopy metabolites. We evaluated the side effects through the PAERS (Pediatric Adverse Events Rating Scale)-Clinician. Our results show statistically significant differences of the clinical scores between the studied groups: for those subjects who benefited of pharmacogenetic testing, the CDRS, the global functioning scores prove a higher clinical improvement, a better compliance and lower PAERS side effects scores and also improvement concerning the MR spectroscopy dosed metabolites values. Our research was a proof sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological, neuroimagistic and neuroendocrinological markers for a personalized therapy in depressive disorders.

A rare case of Meckel-Gruber syndrome.

Meckel-Gruber syndrome (MKS) is a lethal, autosomal recessive transmitted anomaly, characterized by the ultrasound triad: occipital meningoencephalocele, bilateral polycystic kidney, postaxial polydactyly. The incidence is between 1÷13 250 and 1÷140 000 live births, being a rare anomaly. We report a MKS case of feminine gender diagnosed on two ultrasound findings (bilateral polycystic kidney, occipital meningoencephalocele). This case highlights the presence of MKS in a young female without family history.

Health-related quality of life in patients with hallux valgus.

BACKGROUND AND AIMS: No deformity of the forefoot occurs more frequently than hallux valgus (HV), which is considered to be medial deviation of the first metatarsal and lateral deviation and rotation of the hallux, either with or without medial soft tissue enlargement of the metatarsal head. The HV deformity can lead to painful motion of the joint or difficulty in daily joint activity that often requires surgical correction. The aims of this study were to investigate the levels of foot pain and quality of life of patients with HV before and after surgery. Our study is focusing on imagistic investigations in HV, clinical aspects, specific treatment, foot pain levels, quality of life and general health before and after surgery. PATIENTS, MATERIALS AND METHODS: Our research was conducted in the period 2010-2015. We recruited 56 patients, 35 women and 21 men, age range 20 to 76 years, mean age 44.4 years, with HV (radiographic HV angle 25-40 and >40). We applied Visual Analogue Scales (VAS) for the foot pain and the Euro Quality of Life - five dimensions health questionnaire (EQ-5D). RESULTS: The results show statistically significant differences concerning the foot pain levels in VAS and also pain/discomfort, mobility and anxiety÷depression in the EQ-5D subscale in HV before and after surgery. The results prove high improvement of the scores of foot pain, discomfort, mobility and anxiety÷depression after surgery. Concerning the participation in usual activities and the self-care, the obtained results were not statistically significant. CONCLUSIONS: Our research was a proof that the surgery in HV represents a fruitful pathway of intervention and care and shows a high rate of success, favorable outcomes and improvement in quality of life of the patients.

The effect of neurobiological changes in the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations with EEG and neuroimagistic abnormalities.

Relatively little research has been conducted on quantitative electroencephalography (QEEG) activity in patients with psychosis÷schizophrenia, especially in populations at-risk for the illness. Further studies are needed, in order to offer a possible endophenotypic marker of the cerebral functioning, associated with psychosis÷schizophrenia, in correlation with the neuroimaging, the neurocognitive, biochemical, molecular genetic tests, clinical aspects and the EEG activity from the same subjects. The aim was to investigate the role the QEEG abnormalities play in the etiology of psychosis÷schizophrenia, whether it can provide an endophenotype for psychosis and to make some correlations with the results obtained through magnetic resonance (MR) spectroscopy, for proper early detection and intervention. The prospective research was performed in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania, involving 55 children with schizophrenia or ultra high-risk (UHR) for psychosis (groups 1, 2, 3 and 4) and 55 children as healthy controls (group 5). Groups 1 and 2 (28 children) are diagnosed with schizophrenia, groups 3 and 4 are UHR for psychosis (27 children), and group 5 represents healthy controls. Groups 1 and 3 had convulsive seizures in their personal history. We noticed: through the QEEG, numerous patterns of theta and delta activity, the diminished amplitude of the alpha band waves and the diminished alpha activity; also, the onset of psychosis was earlier at those presenting convulsive seizures in their personal history (groups 1 and 3); also, specific neuroimagistic abnormalities and modifications. The cerebral lesions, appearing during the development, raise the liability for schizophrenia. The high-risk for schizophrenia is correlated with the personal history of epilepsy, as well as with the family risk for psychosis.

The prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories.

We approach an integrated, multidisciplinary, innovative research-action model in children and adolescents with psychosis and ultra high-risk categories. Our main focus was: to investigate the prognostic and clinical significance of neuroimagistic and neurobiological vulnerability markers in correlation with the molecular pharmacogenetic testing in psychoses and ultra high-risk categories; the dynamic evaluation of the clinical evolution for the studied groups in correlation with specific neurobiological and neuroimagistic variables and markers. Our research was conducted in the period 2009-2015 on 87 patients, children and adolescents with psychosis (42 took treatment after pharmacogenetic testing, 45 without) and 65 children with ultra high-risk (UHR) for psychosis - 32 benefited of pharmacotherapy after pharmacogenetic testing and 33 without. Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the Positive and Negative Syndrome Scale (PANSS) total scores, in the Clinical Global Impression of Severity and Improvement (CGI-S÷I), Children's Global Assessment Scale (CGAS) and through the change registered for the relevant neurobiological markers and MR spectroscopy metabolites, from baseline until endpoint in different timepoints. Our results, showed statistically significant differences of the clinical scores between the studied groups. Our research was a proof, sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological and neuroimagistic markers for a personalized, tailored therapy for psychotic patients and neuro-psychiatric UHR categories, as a fruitful pathway of intervention and care.

-759C÷T polymorphism of the HTR2C gene is not correlated with atypical antipsychotics-induced weight gain, among Romanian psychotic patients.

We aim to investigate whether the -759C÷T polymorphism in 5-HTR2C gene was associated with weight change and hyperinsulinemia in Romanian pediatric patients with schizophrenia and bipolar disorders. The patients under investigation were enrolled between 2009 and 2014. A total of 81 schizophrenic and bipolar-disorder patients, aged between nine to 20 years (median age 15.74±4 years), who were following an atypical antipsychotic treatment (Risperidone, Aripiprazole, Olanzapine), were enrolled from University Hospital for Child and Adolescent Psychiatry and Neurology from Timisoara, Romania. The outcomes that we measured were the changes in Body Mass Index (BMI) from baseline to different time points: three months, six months, 12 months and 18 months, and the change in insulinemia over time, after atypical antipsychotic treatment. After carrying out the 5-HTR2C 759C÷T polymorphism identification, we found that 22 patients presented the -759C÷T polymorphism in 5-HTR2C gene. Between the patients exhibiting the 5-HTR2C -759C÷T polymorphism and the patients having the wild type alleles, there was no significant statistical difference in changes of BMI from baseline to endpoints that indicates the lack of the protective effect of the T allele against atypical antipsychotics-induced weight gain. Interestingly, we found a statistically significant association between insulinemia and T alleles' carriers, after 18 months of treatment with the above-mentioned antipsychotics. Taking into consideration that atypical antipsychotics have been associated with elevated insulin levels and insulin resistance, maybe in the future the -759C÷T polymorphism would find a role in the development of a more complex algorithm for prediction of diabetes mellitus risk, in patients taking atypical antipsychotics.

Molecular study of weight gain related to atypical antipsychotics: clinical implications of the CYP2D6 genotype.

Atypical antipsychotics, especially some of them, influence cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of atypical antipsychotics in children and adolescents, their metabolic and endocrine adverse effects are of particular concern especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on atypical antipsychotics adverse effects include CYP2D6 polymorphisms. Our study, performed in 2009-2014, with a two-year enrolment period during which we recruited children and adolescents with a diagnosis of schizophrenia or bipolar disorder on treatment with the antipsychotics (Risperidone, Aripiprazole or Olanzapine), included 81 patients, aged between 9 and 20 years, median age being 15.74 years. The gender percentage was 54% girls/46% boys. The CYP2D6 genotyping was performed after enrolment of the last patient. Based on the CYP2D6 genotype, three activity groups were identified and compared and we found that the patients with wt/*4 genotype, intermediary metabolizer (carrier of one functional and one non-functional allele) have significantly higher weight gain values than the patients who did not exhibit allele *4. The CYP2D6 genotype in children and adolescents with schizophrenia and bipolar disorder, proved to be a good predictor for the response to atypical antipsychotics and the side effects registered. The significant correlations between the CYP2D6 polymorphisms and the weight gain/BMI (body mass index) increase, as major side effects induced by antipsychotics proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk individuals.