Michael Strober

• University of California, Los Angeles

Background: People with anorexia nervosa (AN) commonly exhibit elevated anxiety and atypical reward responsiveness. To examine multivariate neural patterns associated with reward and the impact of anxiety on reward, we analyzed fMRI data from a monetary reward task using representational similarity analysis, a multivariate approach that measures t...

This study represents the first large-scale investigation of rare (<1% population frequency) copy number variants (CNVs) in anorexia nervosa (AN). Large, rare CNVs are reported to be causally associated with anthropometric traits, neurodevelopmental disorders, and schizophrenia, yet their role in the genetic basis of AN is unclear. Using genome-wid...

People with anorexia nervosa (AN) commonly exhibit elevated anxiety and atypical reward responsiveness. To examine multivariate neural patterns associated with reward and the impact of anxiety on reward, we analyzed fMRI data from a monetary reward task using representational similarity analysis, a multivariate approach that measures trial-by-trial...

Objective Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN. Method Adolescent gi...

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis o...

Anorexia nervosa (AN) is characterized by low body weight, fear of gaining weight, and distorted body image. Anxiety may play a role in the formation and course of the illness, especially related to situations involving food, eating, weight, and body image. To understand distributed patterns and consistency of neural responses related to anxiety, w...

Background: Behavioural features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN. Method...

Objectives: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder. Methods: 394 youth with bipolar disorder who completed >2 follow-up assessments (median follow-up length=13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide a...

Background Behavioural features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN. Methods...

Background Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedoni...

Background : To identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course. Methods : 82 youths with BD with persistent poor mood symptomatology (“predominantly ill course”) were compared to 70 youths with BD who at intake had...

Background Childhood abuse negatively impacts the course of Bipolar Disorder (BD). Yet, no study has examined risk factors associated with prospectively evaluated physical/sexual abuse, specifically, those preceding first abuse among BD youth. We investigate past/intake/follow-up factors preceding first physical/sexual abuse among BD youth. Method...

Background Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genom...

Background : The ability to predict an individual's risk of mood episode recurrence can facilitate personalized medicine in bipolar disorder (BD). We sought to externally validate, in an adult sample, a risk calculator of mood episode recurrence developed in youth/young adults with BD from the Course and Outcome of Bipolar Youth (COBY) study. Meth...

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults a...

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared AN and BDD in brain activation and connectivity in relevant networks when viewing images of others' bodies and tested their relationship...

Suicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide...

Background Pediatric bipolar disorders are often characterized by disruptions in cognitive functioning, and exposure to child maltreatment (e.g., physical and sexual abuse) is associated with a significantly poorer course of illness. Although clinical and developmental research has shown maltreatment to be robustly associated with poorer cognitive...

Background Youth with bipolar disorder (BD) are at high risk for suicidal thoughts and behaviors and frequently experience interpersonal impairment, which is a risk factor for suicide. Yet, no study to date has examined the longitudinal associations between relationship quality in family/peer domains and suicidal thoughts and behaviors among youth...

Objective: Despite substantial literature on sex differences in adults with bipolar disorder (BD), little is known about this topic in youth; this study examines sex differences in mood symptomatology and psychiatric comorbidity in prospectively followed youth with BD. Methods: A subsample of the Course and Outcome of Bipolar Youth study (N = 37...

As current psychosocial and pharmacological interventions show limited efficacy in the treatment of anorexia nervosa (AN), interest in the potential value of neurosurgical intervention and neuromodulation in managing severe and enduring illness has grown. We conducted a systematic review of 20 trials of neurosurgical and neuromodulatory treatments...

Background: Exposure to severe Traumatic Events (TEs) has been associated with poor course and outcomes among individuals with Bipolar Disorder (BD). However, there is limited research on TEs among youth with BD, and few studies are longitudinal. This study prospectively followed a large sample of BD youth, examining the associations of lifetime TE...

Objectives Compare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5). Methods Participants from the parent Course and Outcome of Bipolar Youth study (N...

Objectives : Few studies have examined domain-specific psychosocial functioning in Bipolar Disorder (BD) youths. This prospective study examines 1) Interpersonal Relationships with Family; 2) Interpersonal Relationships with Friends; 3) School/Work; 4) Recreation; 5) Life Satisfaction, in BD youths. Method : A Course and Outcome of Bipolar Youth s...

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared brain activation and connectivity in relevant networks when viewing images of others bodies and tested their relationships with clinical...

Objective: With each recurrence the prognosis of bipolar disorder (BD) worsens, indicating the need to identify the factors associated with increased recurrence risk. The course of BD is heterogenous and although risk factors for recurrence for the group as a whole have been reported in the literature, identification of risk factors for a specific...

Objectives: To compare the longitudinal clinical course of youths with bipolar spectrum disorders (BD) with lifetime (past,intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. Method:...

Objective: Lithium (LI) is the mainstay for bipolar disorder (BD) treatment in adults, but evidence in youth is limited. We used data from the Course and Outcome of Bipolar Youth (COBY) study to assess whether LI vs. other mood stabilizing medication (OMS) was associated with improved outcomes, including mood symptoms and suicidality. Method: CO...

Objectives: Examine how relationship quality in family and peer domains are associated with suicidal ideation (SI) in youth with Bipolar Disorder (BP). Methods: 404 Course and Outcome of Bipolar Youth study participants were assessed for psychiatric disorders and SI at intake, and family/peer relationships the month after intake. Multivariate logis...

Objective Long‐term outcome studies of anorexia nervosa (AN) have demonstrated that up to 20% of cases will follow an unremitting course despite many attempts at symptom‐based treatments. The objectives of this study are to identify in a younger age group with AN whether persistent illness can be identified early and prevented. Methods An extensiv...

Objective This study examined a hypothesized pathway by which interoceptive dysfunction accounted for associations between personality features (harm avoidance, self‐directedness, and perfectionism) and anorexia nervosa (AN) severity (indicated by drive for thinness, eating disorder‐related preoccupations and rituals, and body mass index). Method...

Objectives: In a sample of participants diagnosed with Bipolar Disorder (BD) in youth, we aim: (1) to examine longitudinal psychosocial functioning; (2) to determine whether psychosocial impairment remains in those who remitted from mood disorders during later periods of follow-up; (3) to examine predictors of psychosocial impairment despite sympt...

Background: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN as well as ancestrally matched controls. We p...

Individuals with anorexia nervosa (AN) typically display anxious traits prior to the onset of food avoidance and weight loss that characterize the disorder. Meal associated anxiety is an especially common clinical feature in these patients, and heightened sensitivity to sympathetically mediated interoceptive sensations has also been observed. Howev...

Objective: Youth with subthreshold mania are at increased risk of conversion to bipolar disorder (BP) I/II. Predictors for conversion have been published for the group as a whole. However, risk factors are heterogeneous, indicating the need for personalized risk assessment. Method: One hundred forty youth with BP not otherwise specified (BP-NOS;...

Phillipou et al. recently comment on our theoretical article (Feusner, Deshpande, & Strober, 2017). Their remarks have expanded upon what we were able to outline in this relatively brief conceptual paper, and we believe that this discourse is helpful to the field. There are several points that we would like to make in response to their letter: The...

Objective Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. Method In path analyses (N = 732 women with either current AN or...

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) share distorted perceptions of appearance with extreme negative emotion, yet the neural phenotypes of emotion processing remain underexplored in them, and they have never been directly compared. We sought to determine if shared and disorder-specific fronto-limbic connectivity patterns charact...

Background Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We pres...

Objective This study aims to document rates of sexual activity among youth with bipolar spectrum disorder (BD) and to examine demographic and clinical factors associated with first sexual activity and sexual risk behavior during follow-up. Method The sample was drawn from the Course and Outcome of Bipolar Youth (COBY) study of 413 youth 7 to 17 ye...

Objective There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables. Method Cognitive functioning was measured in 135 participant...

Objectives: To identify mood symptoms that distinguishes bipolar disorder (BP) depression versus unipolar depression in youth during an acute depressive episode. Methods: Youth with BP (N = 30) were compared with youth with unipolar depression (N = 59) during an acute depressive episode using the depression and mania items derived from the Sched...

Objective: To provide the first longitudinal characterization of mood and psychosocial functioning in youth with comorbid bipolar (BD) and autism spectrum (ASD) disorders. Method: The Course and Outcome of Bipolar Youth study followed 368 youth (aged 7-17 years) with DSM-IV bipolar I (BP-I), BP-II, or Not Otherwise Specified (NOS) for, on averag...

Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or "not otherwise...

Inspired by an article on 50 terms that, in the interest of clarity in scientific reasoning and communication in psychology, psychiatry, and allied fields, “should be avoided or at most be used sparingly and only with explicit caveats,”1 we propose a list of terms to avoid or think twice about before using when writing for the International Journal...

To determine the longitudinal impact of borderline personality disorder (BPD) on the course and outcome of bipolar disorder (BP) in a pediatric BP sample. Participants (N = 271) and parents from the Course and Outcome of Bipolar Youth (COBY) study were administered structured clinical interviews and self-reports on average every 8.7 months over a m...

This study examined the longitudinal association between mood episode severity and relationships in youth with bipolar (BP) disorder. Participants were 413 Course and Outcome of Bipolar Youth study youth, aged 12.6 ± 3.3 years. Monthly ratings of relationships (parents, siblings, and friends) and mood episode severity were assessed by the Adolescen...

Anorexia Nervosa (AN) is a chronic psychiatric disease characterized by a refusal to maintain body weight at or above 85% of that which is normal for height, body dysmorphia, and fear of gaining weight. Genetic studies have had limited success identifying risk loci and a recent genome-wide association study (GWAS) of 1033 AN cases and 3733 controls...

Objective: The authors sought to identify and evaluate longitudinal mood trajectories and associated baseline predictors in youths with bipolar disorder. Method: A total of 367 outpatient youths (mean age, 12.6 years) with bipolar disorder with at least 4 years of follow-up were included. After intake, participants were interviewed on average 10...

Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to sma...

Animal studies indicate that gonadal hormones at puberty have an effect on the development of masculine and feminine traits. However, it is unknown whether similar processes occur in humans. We examined whether women with anorexia nervosa (AN), who often experience primary amenorrhea, exhibit attenuated feminization in their psychological character...

Objectives: There is concern that treatment of serious mental illness in the United States declines precipitously following legal emancipation at age 18 years and transition from specialty youth clinical settings. We examined age transition effects on treatment utilization in a sample of youth with bipolar disorder. Methods: Youth with bipolar d...

Substance use disorders (SUD) are common and problematic in bipolar disorder (BP). We prospectively examined predictors of first-onset SUD among adolescents with BP. Adolescents (12-17 years old; N = 167) in the Course and Outcome of Bipolar Youth (COBY) study fulfilling criteria for BP-I, BP-II, or operationalized BP not otherwise specified, witho...

Previous studies of prognostic factors of anorexia nervosa (AN) course and recovery have followed clinical populations after treatment discharge. This retrospective study examined the association between prognostic factors-eating disorder features, personality traits, and psychiatric comorbidity-and likelihood of recovery in a large sample of women...

To assess whether relative severity of irritability symptoms versus elation symptoms in mania is stable and predicts subsequent illness course in youth with DSM-IV bipolar I or II disorder or operationally defined bipolar disorder not otherwise specified. Investigators used the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Ag...

Objective: To assess whether relative severity of irritability symptoms versus elation symptoms in mania is stable and predicts subsequent illness course in youth with DSM-IV bipolar I or II disorder or operationally defined bipolar disorder not otherwise specified. Method: Investigators used the Kiddie Schedule for Affective Disorders and Schizoph...

Women with eating disorders have a significantly higher prevalence of substance use disorders than the general population. The goal of the current study was to assess the temporal pattern of comorbid anorexia nervosa (AN) and alcohol use disorder (AUD) and the impact this ordering has on symptomatology and associated features. Women were placed int...

Background: Factor analysis has been used to identify potential clinical subtypes of mania in pediatric bipolar disorder. Results vary in the number of factors retained. The present study used a formal diagnostic instrument to examine how symptoms of mania in young people are expressed, depending on age of symptom onset and current age. Methods:...

To examine childhood perfectionism in anorexia nervosa (AN) restricting (RAN), purging (PAN), and binge eating with or without purging (BAN) subtypes. The EATATE, a retrospective assessment of childhood perfectionism, and the eating disorder inventory (EDI-2) were administered to 728 AN participants. EATATE responses revealed general childhood perf...

Context Individuals with early onset of bipolar disorder are at high risk for suicide. Yet, no study to date has examined factors associated with prospective risk for suicide attempts among youth with bipolar disorder. Objective To examine past, intake, and follow-up predictors of prospectively observed suicide attempts among youth with bipolar dis...

To further refine our understanding of impulsivity, obsessions, and compulsions in anorexia nervosa (AN) by isolating which behaviours--binge eating, purging, or both--are associated with these features. We conducted regression analyses with binge eating, purging, and the interaction of binge eating with purging as individual predictors of scores f...

Anorexia nervosa remains an enigma and its clinical challenge is intimidating. But the potential for new insights has been advancing, largely as a result of elegant research in the neurosciences that has modeled behavioral processes resembling key features of the illness. Unfortunately, many in the eating disorder field seem to know little of this...

This exploratory study assessed whether maternal recall of childhood feeding and eating practices differed across anorexia nervosa (AN) subtypes. Participants were 325 women from the Genetics of Anorexia Nervosa study whose mothers completed a childhood feeding and eating questionnaire. Multinomial logistic regression analyses were used to predict...

Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder, but, to our knowledge, no studies examined the course of anxiety disorders in youth and adults with bipolar disorder. As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for Diagnostic and Statistical...

This analysis is a follow-up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case-control results revealed no statistically significant differences in single nucleotide polymorphisms, herein, we investigate alternative phenotypes associated...

To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. Subjects were 140 children and adolescents recruited from clinical r...

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a...

Comorbidity among eating disorders, traumatic events, and posttraumatic stress disorder (PTSD) has been reported in several studies. The main objectives of this study were to describe the nature of traumatic events experienced and to explore the relationship between PTSD and anorexia nervosa (AN) in a sample of women. Eight hundred twenty-four part...

Background / Purpose: To examine the association between obesity and the course of pediatric bipolar disorder (BP).Subjects (N=323), 7-17 years old, were in the Course and Outcome of Bipolar Illness among Youth (COBY) study. Illness characteristics during 4 years of follow-up were examined as they relate to obesity at intake. Main conclusion:...

Extensive population-based genome-wide association studies have identified an association between the FTO gene and BMI; however, the mechanism of action is still unknown. To determine whether FTO may influence weight regulation through psychological and behavioral factors, seven single-nucleotide polymorphisms (SNPs) of the FTO gene were genotyped...

We investigated the sociodemographic characteristics in women with and without lifetime eating disorders. Participants were from a multisite international study of eating disorders (N = 2,096). Education level, relationship status, and reproductive status were examined across eating disorder subtypes and compared with a healthy control group. Overa...

We studied the relation between intrusive and repetitive hair pulling, the defining feature of trichotillomania, and compulsive and impulsive features in 1,453 individuals with anorexia nervosa and bulimia nervosa. We conducted a series of regression models examining the relative influence of compulsive features associated with obsessive-compulsive...

Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective. To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different...

This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another...

We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 week...

One of the primary facets of borderline personality disorder (BPD) is behavioral dysregulation, a wide array of behaviors that are difficult to control and harmful to the individual. The purpose of this study was to explore the association between BPD and a variety of dysregulated behaviors, some of which have received little empirical attention. U...

Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n...

The purpose of this study is to examine the prevalence and correlates of non-suicidal self-injury (NSSI) among children and adolescents diagnosed with bipolar disorder (BP). Four hundred-thirty two youth with a diagnosis of BP and their parents, including 193 children and 239 adolescents, completed a diagnostic interview and instruments to assess y...

Anorexia nervosa (AN) is perhaps the most lethal mental disorder, in part due to starvation-related health problems, but especially because of high suicide rates. One potential reason for high suicide rates in AN may be that those affected face pain and provocation on many fronts, which may in turn reduce their fear of pain and thereby increase ris...

We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case...

The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome. Adolescents (ages 12-18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression w...