Family environment and polygenic risk in the bipolar high-risk context.

Background: The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD. Methods: Offspring of a parent with BD (oBD; n = 266) or no psychiatric disorders (n = 174), aged 12-21 at recruitment, participated in the US and Australia. Empirically-derived profiles of FE classified offspring by their perceived levels of familial cohesion, flexibility, and conflict. Offspring BD-PRS were derived from Psychiatric Genomics Consortium BD-GWAS. Lifetime DSM-IV bipolar disorders were derived from the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. We used a novel stepwise approach for latent class modeling with predictors and distal outcomes. Results: Fifty-two offspring were diagnosed with BD. For those with well-functioning FE (two-thirds of the sample), higher BD-PRS tracked positively with liability for BD. However, for those with high-conflict FEs, the relationship between BD-PRS and liability to BD was negative, with highest risk for BD observed with lower BD-PRS. In exploratory analyses, European-ancestry offspring with BD had elevated history of suicidal ideation in high-conflict FE compared to well-functioning-FE, and of suicide attempt with low-BD-PRS and high-conflict FE. Conclusions: The data suggest that the relationship of BD-PRS and offspring liability for BD differed between well-functioning versus high-conflict FE, potentially in line with a multifactorial liability threshold model and supporting future study of and interventions improving family dynamics.

Catatonia in Preadolescent Children.

OBJECTIVE: The aim of the study is to describe prepubescent catatonia in very young children, which is poorly documented in the current literature and, as a result, overlooked in medical settings. METHODS: We examined a convenience sample of 10 patients at an academic center who were younger than 12 years and met criteria for catatonia. After institutional review board approval, we extracted from the electronic medical records demographic and diagnostic information, comorbidity, developmental history, and laboratory testing. Bush Francis Catatonia Rating Scales at initial presentation and other symptomatology were gathered in addition to treatment received. Fifty percent of patients in this group were seen and diagnosed with catatonia at their presentation in an outpatient clinic, whereas the remaining 50% were diagnosed upon hospitalization, by the psychiatry consultation liaison team. RESULTS: All patients but one was diagnosed with a comorbid condition before the diagnosis of catatonia, including 70% with a previous diagnosis of autism spectrum disorder. Three patients had concurrent anti-N-methyl-D-aspartate receptor encephalitis, and one initially presented with seizures. All patients were treated for catatonia with lorazepam, and two patients additionally received electroconvulsive therapy. Regardless of the presence of early regression invariably associated with an autism spectrum diagnosis, secondary symptoms of regression were noted in each case at the time of diagnosing catatonia. CONCLUSIONS: Similar to previous observations in adolescents, prepubescent catatonia seems strongly associated with neurodevelopmental disorders, secondary regression, variability in presentation, and comorbidity with other neurological conditions. Delayed recognition of catatonia can hinder rapid and effective treatment in young children.

Maintenance Electroconvulsive Therapy Is an Essential Medical Treatment for Patients With Catatonia: A COVID-19 Related Experience.

Aim: Describe naturalistic clinical course over 14 weeks in a mixed adolescent and a young-adult patient group diagnosed with developmental delays and catatonia, when the frequency of maintenance electroconvulsive therapy (M-ECT) was reduced secondary to 2020 COVID-19 pandemic restrictions. Methods: Participants were diagnosed with catatonia, and were receiving care in a specialized clinic. They (n = 9), F = 5, and M = 4, ranged in age from 16 to 21 years; ECT frequency was reduced at end of March 2020 due to institutional restrictions. Two parents/caregivers elected to discontinue ECT due to concern for COVID-19 transmission. Majority (n = 8) were developmentally delayed with some degree of intellectual disability (ID). Observable symptoms were rated on a three point scale during virtual visits. Results: All cases experienced clinically significant decline. Worsening of motor symptoms (agitation, aggression, slowness, repetitive self-injury, stereotypies, speech deficits) emerged within the first 3 weeks, persisted over the 14 week observation period and were more frequent than neurovegetative symptoms (appetite, incontinence, sleep). Four participants deteriorated requiring rehospitalization, and 2 among these 4 needed a gastrostomy feeding tube. Conclusion: Moderate and severe symptoms became apparent in all 9 cases during the observation period; medication adjustments were ineffective; resuming M-ECT at each participant's baseline schedule, usually by week 7, resulted in progressive improvement in some cases but the improvement was insufficient to prevent re-hospitalization in 4 cases. In summary, rapid deterioration was noted when M-ECT was acutely reduced in the setting of COVID-19 related restrictions.

LET's CONNECT Community Mentorship Program for Adolescents with Peer Social Problems: A Randomized Intervention Trial.

This study examined the effectiveness of LET's CONNECT (LC), a community mentorship program based on the positive youth development model. Participants were 218 youth (66.5% girls), ages 12 to 15, who reported peer victimization, bullying perpetration, and/or low social connectedness. These youth were randomized to LC or the control group (community resource information). The LC program linked youth to community mentors who connected with youth and facilitated their involvement in social growth activities across a 16-month period. Outcomes were assessed at 6 and 16 months with self-report measures of social and community connectedness, thwarted belongingness, depression, self-esteem, and suicidal ideation and behavior. In intent-to-treat analyses, LC was associated with modest positive effects for social connectedness, self-esteem, and depression. It had no effects on suicidal ideation or behavior. Results suggest that LC has the potential to positively impact the developmental trajectories of youth dealing with the interpersonal challenges of victimization, bullying perpetration, or low social connectedness. LC implementation challenges and directions for further research are also discussed.

Bipolar Disorder and Psychosis in Autism.

Autism seldom occurs in its pure form. Often labeled as behavioral disorders or psychological reactions, comorbid psychiatric disorders are common. Bipolar disorder is one of the most common psychiatric disorders that occur in persons with autism across their life spans. It can be comorbid with and mistaken for several other conditions. Similarly, psychosis occurs in several psychiatric disorders. Schizophrenia is the prototype psychotic disorder that has a close but controversial relationship with autism. Assessment and treatment of bipolar disorder and psychosis should be based on their individual characteristics, family dynamics, and community resources.

Catatonia in Patients with Autism Spectrum Disorder.

Catatonia was first described by Karl Ludwig Kahlbaum in 1874, occurring in association with other psychiatric and medical disorders. However, in the nineteenth century the disorder was incorrectly classified as a subtype of schizophrenia. This misclassification persisted until the publication of DSM-5 in 2013 when important changes were incorporated. Although the etiology is unknown, disrupted gamma-aminobutyric acid has been proposed as the underlying pathophysiological mechanism. Key symptoms can be identified under 3 clinical domains: motor, speech, and behavioral. Benzodiazepines and electroconvulsive therapy are the only known effective treatments. Timely recognition and treatment have important outcome, and sometimes lifesaving, implications.

Bipolar Disorder and Psychosis in Autism.

Autism seldom occurs in its pure form. Often labeled as behavioral disorders or psychological reactions, comorbid psychiatric disorders are common. Bipolar disorder is one of the most common psychiatric disorders that occur in persons with autism across their life spans. It can be comorbid with and mistaken for several other conditions. Similarly, psychosis occurs in several psychiatric disorders. Schizophrenia is the prototype psychotic disorder that has a close but controversial relationship with autism. Assessment and treatment of bipolar disorder and psychosis should be based on their individual characteristics, family dynamics, and community resources.

Catatonia in Patients with Autism Spectrum Disorder.

Catatonia was first described by Karl Ludwig Kahlbaum in 1874, occurring in association with other psychiatric and medical disorders. However, in the nineteenth century the disorder was incorrectly classified as a subtype of schizophrenia. This misclassification persisted until the publication of DSM-5 in 2013 when important changes were incorporated. Although the etiology is unknown, disrupted gamma-aminobutyric acid has been proposed as the underlying pathophysiological mechanism. Key symptoms can be identified under 3 clinical domains: motor, speech, and behavioral. Benzodiazepines and electroconvulsive therapy are the only known effective treatments. Timely recognition and treatment have important outcome, and sometimes lifesaving, implications.

Electroconvulsive Therapy for the Treatment of Severe Mood Disorders During Adolescence: A Retrospective Chart Review.

Objective: Electroconvulsive therapy (ECT) is a well-recognized treatment of refractory mood disorders in adults. However, relatively little is known about its use for similar conditions in adolescents. Based on a chart review, we describe its use and outcome in a sample of adolescents with severe, refractory mood disorders (unipolar or bipolar disorder) hospitalized in an academic medical center. Methods: The sample was drawn from referrals to an adolescent psychiatry service. After obtaining approval from the ethics board, medical records of 54 adolescents with refractory mood disorder were examined. Participants (males 24, females 30; mean age 15.8 ± 1.5 years) had received their first course of ECT before the age of 18 years during the period 1996-2010. Response to treatment was examined after the initial treatment and during a 1-year follow-up. Results: Following the index course of ECT (mean number of treatments = 13.7 ± 6.3), a 52.8% response rate (defined as a Clinical Global Impressions [CGI] score ≤2) was noted, while 15.1% achieved remission (CGI = 1). The response rate was 82.4% after a 1-year follow-up with a remission rate of 23.5%. The Children's Depression Rating scores declined significantly from pre-ECT to the end of the index course (70.7 ± 16.4 to 52.5 ± 18; p ≤ 0.00). A reduction in suicidal ideation and self-injurious behaviors along with increased school attendance was noted. Cognition, monitored by the Mini-Mental State Examination, did not decline significantly. Minor side effects were limited to the day of the treatment. Prolonged seizures (>2 minutes) were common during ECT (74% of subjects experienced one or more). The only side effect noted at the 1-year follow-up was self-reported memory loss involving events during and around the index treatment course. Conclusions: In this severely impaired sample of adolescents, ECT was found to decrease suicidal behavior, reduce depressive symptoms, and improve overall functioning, as indexed by school attendance at follow-up after 1 year. Prospective studies using large samples are needed to determine its effectiveness and safety in refractory mood disorders in adolescents.

Efficacy and Safety of Electroconvulsive Therapy in Adolescents: A Retrospective Chart Review Study From Turkey.

OBJECTIVE: The aim of this study was to report the efficacy and safety of electroconvulsive therapy (ECT) in manic, depressed, psychotic, and catatonic adolescent patients. METHODS: Medical records of 78 adolescents who had received ECT in Department of Psychiatry, Gaziantep University Medical Faculty, during 2011 to 2017 were reviewed. Sixty-two subjects in this sample were identified to have complete records and met the study inclusion criteria. RESULTS: The mean ± SD age of subjects was 17.11 ± 1.04 years and female sex was 53.2% (n = 33). Primary the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision or the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnoses were bipolar mood disorders (n = 33, 53.2%), major depressive disorder (n = 16, 25.8%), schizophrenia (n = 8, 12.9%), and schizoaffective disorders (n = 5, 8.1%). Electroconvulsive therapy was significantly effective in treating manic, depressive, psychotic, and catatonia symptoms as evidenced by significant differences in pretreatment and posttreatment scores in outcome measures including Hamilton Depression Rating Scale, Young Mania Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression-Severity Scale (P < 0.001). Presence of comorbidity adversely affected treatment response (P = 0.001). However, ECT was also effective in those with comorbid diagnoses (P < 0.001). Depressive symptoms in patients with bipolar depression responded better than those with unipolar depression (P = 0.012). Electroconvulsive therapy was generally safe with subjective memory complaints (85%), headache (69%), and prolonged seizure (8%) as the reported adverse effects possibly related to ECT. Four subjects (6%) developed a manic switch during ECT. CONCLUSIONS: Electroconvulsive therapy is an effective and a safe treatment option in adolescent patients with severe and resistant psychopathology. Although comorbidity may decrease treatment response, ECT seems to be effective even in the presence of multiple psychiatric diagnoses.

Patterns and predictors of family environment among adolescents at high and low risk for familial bipolar disorder.

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12-21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two 'conflict classes' perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics.

Salivary melatonin onset in youth at familial risk for bipolar disorder.

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability.

LET's CONNECT community mentorship program for youths with peer social problems: Preliminary findings from a randomized effectiveness trial.

This study examined the effectiveness of LET's CONNECT (LC), a community mentorship program for youths who report peer social problems, which is based on a positive youth development framework. Participants were 218 youths (66.5% girls), aged 12 to 15 years, who were recruited from an urban medical emergency department and screened positive for bullying victimization, bullying perpetration, and/or low social connectedness. Youths were randomized to LC (n = 106) or the control condition (n = 112). Six-month outcomes were assessed with self-report measures of youth social connectedness, community connectedness, thwarted belongingness, depression, self-esteem, and suicidal ideation. LC was associated with a significant increase in only one of these outcomes, social connectedness (effect size = 0.4). It was associated consistently with trend-level positive changes for thwarted belongingness (decreased), depression (decreased), community connectedness, and self-esteem (effect sizes = 0.2). There was no effect on suicidal ideation (effect size = 0.0), and although not a primary outcome, eight youths in the LC condition and seven youths in the control condition engaged in suicidal behavior between baseline and follow-up. Although LC effect sizes are consistent with those from previous studies of community mentorship, there were multiple challenges to LC implementation that affected dosage and intervention fidelity, and that may account for the lack of stronger positive effects.

Experience, Knowledge, and Attitudes of Child and Adolescent Psychiatrists in Belgium Toward Pediatric Electroconvulsive Therapy.

OBJECTIVE: The purpose of the present study was to ascertain the experience, knowledge, and attitudes of child and adolescent psychiatrists toward the use of ECT (electroconvulsive therapy) in children and adolescents in Belgium. METHODS: A questionnaire was mailed to all the members of the Flemish and Walloon Association of Child and Adolescent Psychiatrists. RESULTS: Thirty-five percent (n = 151) of the psychiatrists responded to the questionnaire. Sixty-seven percent (n = 101) rated their knowledge about ECT in children and adolescents as nil or negligible. Only one percent (n = 2) estimated their knowledge to be advanced. Fifteen percent (n = 22) were aware of a minor treated with ECT. Ten (n = 16) and thirty-one percent (n = 47) believed that ECT is a safe treatment for children and adolescents, respectively. Only six percent (n = 10) would recommend ECT for a major psychiatric disorder in a child, whereas thirty-eight percent (n = 58) for an adolescent. Fifty-three percent (n = 71) regarded ECT as a treatment of last resort. A significant correlation was identified between knowledge and attitudes toward the use of ECT in minors. Respondents with some or advanced knowledge perceived ECT as a safer and a more effective treatment option than those with negligible knowledge. Most (91%, n = 138) of the child and adolescent psychiatrists are enthusiastic to learn more about the use of ECT in minors. CONCLUSIONS: Flemish and Walloon child and adolescents psychiatrists have very little experience with using ECT in minors. They self-estimated their knowledge as negligible but are keen to learn more about this treatment option. The lack of knowledge likely explains the rare use of ECT in Belgium for children and adolescents with serious psychiatric disorders.

A Follow-up Study of Electroconvulsive Therapy in Children and Adolescents.

OBJECTIVES: Electroconvulsive therapy (ECT) is an effective and a safe treatment for several severe psychiatric disorders across the age span. However, its use remains controversial and highly stigmatized especially among patients under 18 years. In this study, we examined current symptoms, attitudes, perception, and functioning of patients treated with ECT when they were less than 18 years old. METHODS: Participants had received ECT before age 18, between 1989 and 2015, at a tertiary medical center. Institutional review board-approval was obtained, and study documents (cover letter, consent, self-ratings scales for depression, anxiety, global functioning, and suicidality) were mailed. RESULTS: Based on self-rated depression, 59.1% (13/22) participants indicated mild or no depression; 65% (13/20) reported mild or no anxiety; the majority, 84.3% (16/19) perceived ECT as having improved their overall illness; and 27.3% (6/22) among the respondents reported no clinical impairment on a global functioning scale, whereas 72.7% (16/22) reported significant or severe impairment. Despite reports of ongoing impaired global functioning among some participants, adequate academic performance (83.3%, 5/6) and mild or no suicidality (78.3%, 18/23) were endorsed by the majority reported. CONCLUSIONS: The majority of participants who had received ECT before age 18 years reported mild or absence of depression and anxiety on self-rated follow-up measures after treatment with ECT. Most notably, the majority reported absence of suicidality and adequate academic performance. A number of respondents, however, continued to endorse global impairment, which may be a reflection of their baseline severe illness, which had warranted treatment with ECT.

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts.

OBJECTIVE: Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). METHOD: Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. RESULTS: After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). CONCLUSION: BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.

Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk?

BACKGROUND: Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized. METHODS: We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006-2011. Youth offspring/relatives ("Relatives of BD probands;" n=267; mean age=16.8years; ±2.9S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands ("relatives of control probands;" n=149; mean age=17.4years; ±2.9S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes. RESULTS: Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p=0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR=2.80-3.17; p<0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves. CONCLUSION: Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population.