Interpersonal functioning, support, and change in early-onset bipolar disorder: a transcendental phenomenological study of emerging adults.

BACKGROUND: Early-onset bipolar disorder (EOBD) diagnoses have increased, yet much remains to be understood about its phenomenology. Research and treatment models developed for adult-onset bipolar disorder have largely overlooked qualitative inquiries and adolescent developmental considerations that influence course of illness. AIM: The purpose of the current study was to obtain an understanding of the lived experience of interpersonal relationships and EOBD during adolescence through the retrospective report of emerging adults. METHODS: This study utilized a transcendental phenomenological design. A purposive sample of eight participants ages 18-25 participated in semi-structured interviews that explored the experience of interpersonal relationships and EOBD throughout adolescence. RESULTS: Participants described their experiences across three broad themes: managing and coping with EOBD; effect of EOBD on relationships; and change and uncertainty. Sub-themes include knowledge and denial of illness, involvement of others in treatment, support, difficulty maintaining social functioning, isolation and secrecy, and changes in relationships. CONCLUSIONS: Participants characterized adolescence as a period of constant, simultaneous challenges in symptom management, maintaining social functioning, and concurrent changes in family and peer relationships that provide interpersonal support. Future qualitative studies should explore the implications of normative social development and family functioning for the course of illness and treatment outcomes.

Familial aggregation analysis of cognitive performance in early-onset bipolar disorder.

We analysed the familial aggregation (familiality) of cognitive dimensions and explored their role as liability markers for early-onset bipolar disorder (EOBD). The sample comprised 99 subjects from 26 families, each with an offspring diagnosed with EOBD. Four cognitive dimensions were assessed: reasoning skills; attention and working memory; memory; and executive functions. Their familiality was investigated in the total sample and in a subset of healthy relatives. The intra-family resemblance score (IRS), a family-based index of the similarity of cognitive performance among family members, was calculated. Familiality was detected for the attention and working memory (AW) dimension in the total sample (ICC = 0.37, p = 0.0004) and in the subsample of healthy relatives (ICC = 0.37, p = 0.016). The IRS reflected that there are families with similar AW mean scores (either high or low) and families with heterogeneous scores. Families with the most common background for the AW dimension (IRS > 0) were selected and dichotomized in two groups according to the mean family AW score. This allowed differentiating families whose members had similar high scores than those with similar low scores: both patients (t = - 4.82, p = 0.0005) and relatives (t = - 5.04, p < 0.0001) of the two groups differed in their AW scores. AW dimension showed familial aggregation, suggesting its putative role as a familial vulnerability marker for EOBD. The IRS estimation allowed the identification of families with homogeneous scores for this dimension. This represents a first step towards the investigation of the underlying mechanisms of AW dimension and the identification of etiological subgroups.

Environmental Risk Factors for Bipolar Disorders and High-Risk States in Adolescence: A Systematic Review.

Background and objectives: A deeper comprehension of the role that environmental risk factors play in the development of adolescent Bipolar Disorder (BD), as well as in the evolution of high-risk states for BD, may entangle further prevention and treatment advances. The present systematic review is aimed at critically summarizing evidence about the role that environmental risk factors play in the development of BD in adolescence and their interaction with BD high-risk states. Materials and Methods: MEDLINE/Pubmed, Scopus and Web of Science datasets were systematically searched until 4 September 2020. Original studies that reported information about the role of environmental risk factors in the development of BD during adolescence, or assessing their influence on the development of psychopathology in high-risk states for BD, were considered for inclusion. Two blind researchers performed title/abstract, full-text screening, and hand-screening of relevant references. The risk of bias was assessed by means of the Newcastle-Ottawa Scale. Results: Fourteen studies were included in the review. Negative stressful life events, particularly sexual and physical abuse, but also emotional mistreatment, were associated with more severe psychopathology in adolescents with BD, as well as with higher risk for developing mood disorders in BD offspring. Similar findings were detected for familial environment-related features, such as parental rejection and low perceived care, while no univocal results were found when analyzing familial functioning. Conclusions: The present systematic review confirmed the relevant role that environmental risk factors, particularly negative stressful live events and family-related features, play in the development of BD psychopathology during adolescence. Future studies are expected to clarify possible further environmental factors that may be implicated in the development of BD during youth that may serve as target of prevention and early treatment strategies.

Adverse Childhood Experiences Among Inpatient Youths with Severe and Early-Onset Psychiatric Disorders: Prevalence and Clinical Correlates.

This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2 years) and 81 for a manic or mixed episode (average age 15.7 years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58 %) and from catatonia (57 %), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group.

Early interventions for youths at high risk for bipolar disorder: a developmental approach.

In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.

Verbal abuse, like physical and sexual abuse, in childhood is associated with an earlier onset and more difficult course of bipolar disorder.

OBJECTIVES: Physical or sexual abuse in childhood is known to have an adverse effect on the course of bipolar disorder, but the impact of verbal abuse has not been well elucidated. METHODS: We examined the occurrence and frequency (never to frequently) of each type of abuse in childhood in 634 US adult outpatients (average age 40 years). Patients gave informed consent and provided information about their age of onset and course of illness prior to study entry. RESULTS: Verbal abuse alone occurred in 24% of the patients. Similar to a history of physical or sexual abuse, a history of verbal abuse was related to an earlier age of onset of bipolar disorder and other poor prognosis characteristics, including anxiety and substance abuse comorbidity, rapid cycling, and a deteriorating illness course as reflected in ratings of increasing frequency or severity of mania and depression. CONCLUSIONS: A lasting adverse impact of the experience of verbal abuse in childhood is suggested by its relationship to an earlier age of onset of bipolar disorder, other poor prognosis factors, and a deteriorating course of illness. Verbal abuse is a common confound in comparison groups defined by a lack of physical or sexual abuse. Ameliorating the impact of verbal abuse on the unfolding course of bipolar disorder appears to be an important target of therapeutics and worthy of attempts at primary and secondary prophylaxis. Family-based treatments that focus on psychoeducation, enhancing intra-family communication, and coping skills may be particularly helpful.

Can diffusion tensor imaging have a diagnostic utility to differentiate early-onset forms of bipolar disorder and schizophrenia: A neuroimaging study with explainable machine learning algorithms.

BACKGROUND/AIM: Accurate diagnosis of early-onset psychotic disorders is crucial to improve clinical outcomes. This study aimed to differentiate patients with early-onset schizophrenia (EOS) from early-onset bipolar disorder (EBD) with machine learning (ML) algorithms using white matter tracts (WMT). METHOD: Diffusion tensor imaging was obtained from adolescents with either EOS (n = 43) or EBD (n = 32). Global probabilistic tractography using an automated tract-based TRACULA software was performed to analyze the fractional anisotropy (FA) of forty-two WMT. The nested cross-validation was performed in feature selection and model construction. EXtreme Gradient Boosting (XGBoost) was applied to select the features that can give the best performance in the ML model. The interpretability of the model was explored with the SHApley Additive exPlanations (SHAP). FINDINGS: The XGBoost algorithm identified nine out of the 42 major WMTs with significant predictive power. Among ML models, Support Vector Machine-Linear showed the best performance. Higher SHAP values of left acoustic radiation, bilateral anterior thalamic radiation, and the corpus callosum were associated with a higher likelihood of EOS. CONCLUSIONS: Our findings suggested that ML models based on the FA values of major WMT reconstructed by global probabilistic tractography can unveil hidden microstructural aberrations to distinguish EOS from EBD.

Reduced Cortical Thicknesses of Adolescents with Bipolar Disorder and Relationship with Brain-derived Neurotrophic Factor.

Background: Cortical thickness (CT) and brain-derived neurotrophic factor (BDNF) were widely investigated in bipolar disorder (BD). Previous studies focused on the association between the volume of subcortical regions and neurotrophic factor levels. Objective: In this study, we aimed to evaluate the association of the CT in youth with early-onset BD with BDNF levels as a potential peripheral marker of neuronal integrity. Method: Twenty-three euthymic patients having a clinical diagnosis of BD and 17 healthy subjects as an age-matched control group with neuroimaging and blood BDNF levels were found eligible for CT measurement. A structural magnetic resonance scan (MRI) and timely blood samples were drawn. Results: Youth with BD exhibited lower cortical thickness in caudal part of left (L) middle frontal gyrus, right (R) paracentral gyrus, triangular part of R inferior frontal gyrus, R pericalcarine region, R precentral gyrus, L precentral gyrus, R superior frontal gyrus and L superior frontal gyrus when compared to healthy controls. The effect sizes of these differences were moderate to large (d=0.67-0.98) There was a significant correlation between BDNF levels with caudal part of the R anterior cingulate gyrus (CPRACG) in adolescents with BD (r=0.49, p=0.023). Conclusion: As a special region for mood regulation, the CT of the caudal part of the R anterior cingulate gyrus had a positive correlation with BDNF. Regarding the key role of CPRACG for affective regulation skills, our results should be replicated in future follow-up studies, investigating a predictive neuroimaging biomarker for the early-onset BD.

Neuroimaging alterations associated with medication use in early-onset bipolar disorder: An updated review.

BACKGROUND: Pediatric bipolar disorder (PBD) is a severe disorder characterized by mood fluctuations starting at a young age. Several neuroimaging studies revealed a specific biological signature of PBD involving alterations in the amygdala and prefrontal regions. Considering the growing concerns regarding the effects of PBD treatments on developing brains, this review aims to provide an overview of the studies investigating the effect of mood stabilizers, antipsychotics, and anticonvulsants on neuroimaging findings in PBD. METHODS: We searched PubMed, Scopus, and Web of Science to identify all structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) studies exploring the effects of medications on neuroimaging findings in PBD. A total of 18 studies met our inclusion criteria (fMRI n = 11, sMRI n = 6, DTI n = 1). RESULTS: Although the findings varied highly across the studies, some investigations consistently indicated that medications primarily affect the prefrontal cortex and the amygdala. Moreover, despite some exceptions, the reported medication effects predominantly lean towards structural and functional normalization. LIMITATIONS: The reviewed studies differ in methods, medications, and fMRI paradigms. Furthermore, most studies used observational approaches with small sample sizes, minimizing the statistical power. CONCLUSIONS: Evidence suggests the potential of antipsychotics and mood stabilizers to modulate the neuroimaging findings in PBD patients, mostly normalizing brain structure and function in key mood-regulating regions.

Abnormal dynamic functional network connectivity in patients with early-onset bipolar disorder.

Objective: To explore the changes in dynamic functional brain network connectivity (dFNC) in patients with early-onset bipolar disorder (BD). Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 39 patients with early-onset BD and 22 healthy controls (HCs). Four repeated and stable dFNC states were characterised by independent component analysis (ICA), sliding time windows and k-means clustering, and three dFNC temporal metrics (fraction of time, mean dwell time and number of transitions) were obtained. The dFNC temporal metrics and the differences in dFNC between the two groups in different states were evaluated, and the correlations between the differential dFNC metrics and neuropsychological scores were analysed. Results: The dFNC analysis showed four connected patterns in all subjects. Compared with the HCs, the dFNC patterns of early-onset BD were significantly altered in all four states, mainly involving impaired cognitive and perceptual networks. In addition, early-onset BD patients had a decreased fraction of time and mean dwell time in state 2 and an increased mean dwell time in state 3 (p < 0.05). The mean dwell time in state 3 of BD showed a positive correlation trend with the HAMA score (r = 0.4049, p = 0.0237 × 3 > 0.05 after Bonferroni correction). Conclusion: Patients with early-onset BD had abnormal dynamic properties of brain functional network connectivity, suggesting that their dFNC was unstable, mainly manifesting as impaired coordination between cognitive and perceptual networks. This study provided a new imaging basis for the neuropathological study of emotional and cognitive deficits in early-onset BD.

Aberrant functional connectivity within and between brain networks in patients with early-onset bipolar disorder.

OBJECTIVE: This study used independent component analysis (ICA) to investigate the connectivity patterns of resting-state functional large-scale brain networks in patients with early-onset bipolar disorder (BD). METHODS: ICA was used to extract brain functional network components from 43 early-onset BD patients and 21 healthy controls (HCs). Then, the functional connectivity (FC) and functional network connectivity (FNC) within and between the independent brain networks was calculated, and the correlation between the connectivity changes and neuropsychological scale was evaluated. RESULTS: Compared with HCs, FC increased in the right hippocampus and inferior temporal gyrus, and left triangular inferior frontal gyrus of the anterior default mode network (aDMN); right median cingulate and paracingulate gyri, and inferior parietal lobule of the posterior DMN (pDMN); and right precentral and postcentral gyrus of the sensorimotor network (SMN) in early-onset BD patients. However, FC decreased in the left superior frontal gyrus of the aDMN, left paracentral lobule of the SMN, and left lingual gyrus and calcarine of the visual network in early-onset BD patients. There was no significant correlation between FC values of differential brain regions within resting-state networks (RSNs) and neuropsychological scores (uncorrected p > 0.05). In addition, the FNC among the pDMN-auditory network, pDMN-visual network, left frontoparietal network (lFPN)-visual network, lFPN-aDMN and dorsal attention network-ventral attention network (DAN-VAN) were increased in early-onset BD patients. The zFNC of the pDMN-visual network was positively correlated with the anxiety/somatization score (r = 0.5833, p < 0.0001) and sleep disorders (r = 0.6150, p < 0.0001). The zFNC of the lFPN-aDMN was positively correlated with despair (r = 0.4505, p = 0.004 × 10 < 0.05 after Bonferroni correction). The zFNC of the DAN-VAN was positively correlated with cognitive impairment (r = 0.4598, p = 0.0032 × 10 < 0.05 after Bonferroni correction). The zFNC of the DAN-VAN showed a positive correlation trend with the Hamilton Depression Scale (HAMD) total score (r = 0.4404, p = 0.005 × 10 = 0.05 after Bonferroni correction). CONCLUSIONS: Patients with early-onset BD showed changes in a wide range of neural functional networks, involving changes in executive control, attention, perceptual regulation, cognition and other neural networks, which may provide new imaging evidence for understanding the pathogenesis of early-onset BD and for therapeutic intervention targets.

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.

Evaluation and treatment of older-age bipolar disorder: a narrative review.

OBJECTIVES: This narrative review aims to synthesize information from the literature regarding older-age bipolar disorder (OABD) in order to provide up-to-date information on this important illness. METHODS: We searched Ovid (Medline, Embase and PsychInfo) on October 1, 2020, using the keywords "bipolar disorder", "older adults" and "elderly" to identify relevant articles on OABD. Additionally, the bibliography of identified articles was reviewed for pertinent studies. DISCUSSIONS: OABD is a term that is used to describe bipolar disorder (BD) occurring amongst individuals ≥50 years of age. Evidence indicates that OABD accounts for a quarter of all cases of BD. When compared to individuals with early-onset BD, individuals with OABD have a greater association with cerebrovascular disease and other neurological disorders, less family history of mood disorders, and utilize almost four times the total amount of mental health services. In addition, they are four times more likely to have psychiatric hospitalizations when compared to age-matched controls. Despite a dearth of controlled studies on the use of pharmacotherapy amongst individuals with OABD, available evidence from mixed-age studies indicates the efficacy of commonly used medications in individuals with early-onset BD. Additionally, psychosocial treatments have been found to be effective as adjunctive management strategies amongst individuals with OABD. Furthermore, electroconvulsive therapy may be effective in the treatment of refractory cases of OABD. CONCLUSIONS: There is a great need for an improved understanding of the phenomenology and neurobiology of OABD. Additionally, research into effective treatments for this serious psychiatric disorder will mitigate the suffering of individuals with OABD.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration.

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Efficacy and Safety of Lurasidone in Children and Adolescents: Recommendations for Clinical Management and Future Research.

Lurasidone is a novel azapirone derivative and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5- HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acted on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Administered with food or within 30 minutes from a meal, it presents sufficient bioavailability and does not interact with most of the other drugs during metabolism. With little effects on hormones and weight gain, potential procognitive profile due to its 5-HT7 antagonism, and reduced extrapyramidal side effects, lurasidone could be a good choice in terms of both effectiveness and tolerability, particularly for patients headed towards a long-term treatment. This article aims to summarize the available scientific evidence from the literature on the use of lurasidone in children and adolescents and to provide recommendations for clinical management and future research.

Association between CRP genetic diversity and bipolar disorder comorbid complications.

BACKGROUND: Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD. METHODS: 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3'-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders. RESULTS: We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004). CONCLUSIONS: Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.

Early-Onset Bipolar Disorder: Characteristics and Outcomes in the Clinic.

OBJECTIVE: To assess patient characteristics and clinician-rated outcomes for children diagnosed with early-onset bipolar disorder in comparison to a depressive disorders cohort from a single clinic site. To assess predictors of bipolar treatment response. METHODS: Medical records from 714 consecutive pediatric patients evaluated and treated at an academic tertiary child and adolescent psychiatry clinic between 2006 and 2012 were reviewed. Charts of bipolar children (n = 49) and children with depressive disorders (n = 58) meeting study inclusion/exclusion criteria were compared on variables assessing clinical characteristics, treatments, and outcomes. Outcomes were assessed by using pre- and post-Clinical Global Impressions (CGI)-Severity and Children's Global Assessment Scale (CGAS) scores, and a CGI-Improvement score ≤2 at final visit determined responder status. Bipolar outcome predictors were assessed by using multiple linear regression. RESULTS: Clinic prevalence rates were 6.9% for early-onset bipolar disorder and 1.5% for very early-onset bipolar disorder. High rates of comorbid diagnoses, symptom severity, parental stress, and child high-risk behaviors were found in both groups. The bipolar cohort had higher rates of aggression and higher lifetime systems of care utilization. The final CGI and CGAS outcomes for unipolar depression patients differed statistically significantly from those for the bipolar cohort, reflecting better clinical status and more improvement at outcome for the depression patients. Both parent-reported Child Behavior Checklist total T-score at clinic admission and the number of lifetime systems-of-care for the child were significantly and inversely associated with improvement for the bipolar cohort. CONCLUSIONS: Early-onset bipolar disorder is a complex and heterogeneous psychiatric disorder. Evidence-based treatment should emphasize psychopharmacology with adjunctive family and individual psychotherapy. Strategies to improve engagement in treatment may be especially important. Given high rates of high-risk behaviors in these youth, regular mental health follow-up to assess safety is important. Additional evidence-based treatments for pediatric bipolar disorder are needed.

First Manic Episode in an 11 Year-old Girl.

OBJECTIVE: We present the case of an 11 year-old girl admitted to the Centre hospitalier universitaire de Sherbrooke for a first manic episode. METHOD: Differential diagnoses of adjustment disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder were considered but eliminated. RESULTS: No organic etiology was detected. Her condition rapidly remitted with aripiprazole 3mg. After her discharge, she suffered a relapse due to instability of her living conditions and was rehospitalized. CONCLUSION: Mania is a difficult diagnosis in youths due to its nonspecific symptoms, rare prepubertal occurrence, and diagnostic complexity. Despite ongoing research, there is little conclusive information on the impact of psychosocial stressors on the evolution of early-onset bipolar disorder.

OBJECTIF: Nous présentons le cas d'une fillette de 11 ans hospitalisée au Centre hospitalier universitaire de Sherbrooke pour un premier épisode de manie. MÉTHODE: Les diagnostics différentiels du trouble d'adaptation, du trouble de déficit de l'attention avec hyperactivité, du trouble oppositionnel avec provocation et du trouble des conduites ont été envisagés mais rejetés. RÉSULTATS: Aucune étiologie organique n'a été détectée. La rémission de son affection a été rapide avec 3 mg d'aripiprazole. Après son congé, elle a souffert d'une rechute attribuable à l'instabilité de ses conditions de vie et a été réhospitalisée. CONCLUSION: La manie est un diagnostic difficile chez les adolescents en raison de ses symptômes non spécifiques, d'une rare occurrence pré-pubère, et de la complexité diagnostique. Malgré la recherche en cours, il y a peu d'information concluante sur l'effet des stresseurs psychologiques sur l'évolution du trouble bipolaire d'apparition précoce.

Reconsideration of bipolar disorder as a developmental disorder: importance of the time of onset.

Bipolar disorder is a multifactorial psychiatric disorder with developmental and progressive neurophysiological alterations. This disorder is typically characterized by cyclical and recurrent episodes of mania and depression but is heterogeneous in its clinical presentation and outcome. Although the DSM-IV-TR criteria identify several features that are of phenomenological relevance, these are of less utility for defining homogeneous subgroups, for analyses of correlations with biomarkers or for directing focused medication strategies. We provide a comprehensive review of existing evidence regarding to age at onset in bipolar disorder. Eight admixture studies demonstrate three homogeneous subgroups of patients with bipolar disorder identified according to age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years. It is suggested that the early-onset subgroup has specific clinical features and outcomes different from those of the other subgroups. Early-onset subgroup may be considered a more suitable clinical phenotype for the identification of susceptibility genes with recent data demonstrating associations with genetic variants specifically in this subgroup. The use of age at onset as a specifier may also facilitate the identification of other biological markers for use in brain imaging, circadian, inflammatory and cognitive research. A key challenge is posed by the use of age at onset in treatment decision algorithms, although further research is required to increase the evidence-base. We discuss three potential benefits of specifying age at onset, namely: focused medication strategies, the targeted prevention of specific comorbid conditions and decreasing the duration of untreated illness. We argue that age at onset should be included as a specifier for bipolar disorders.