Linking childhood trauma and dissociation to psychotic symptoms in major depressive disorder, bipolar disorders, and schizophrenia: A transdiagnostic examination using patient and clinician ratings.

OBJECTIVE: Symptomatic overlap between dissociation and psychosis is well documented; however, the pathogenesis of these two phenomena might be distinct. Few studies have analyzed the relation of dissociative and psychotic symptoms transdiagnostically. The current study examines an emerging trauma-dissociation theoretical model that accounts for psychotic symptoms across affective disorders and schizophrenia (SCZ). METHOD: Psychiatric inpatients with DSM-5 major depressive disorder (MDD), bipolar disorders (BD) currently in a major depressive episode, and SCZ, and healthy controls (HC) were recruited. Potentially traumatizing events in childhood, dissociative symptoms, and psychotic symptoms were assessed. In addition to participant's self-report, dissociative and psychotic symptoms were rated by psychiatrists blind to the hypothesis. Path analysis was conducted. RESULTS: Dissociation was commonly experienced by clinical participants, particularly for those with MDD or BD. For the SCZ group, ratings of dissociation differed between patient and clinician; specifically, patient-reported dissociation scores, but not clinician-rated scores, were higher than that of the HC group. Importantly, the links between childhood trauma, dissociation, and psychotic symptoms were not homogenous across the diagnostic groups. Dissociation mediated the relationship between childhood trauma and psychotic symptoms in the MDD and BD groups, but not the SCZ group. CONCLUSION: Depending on the psychiatric condition, dissociation and psychosis have different clinical implications. Childhood trauma and dissociation provide an account for psychotic symptoms in patients diagnosed with MDD and BD, but not with SCZ. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Do bipolar disorder symptom profiles matter for suicide risk? A latent class approach to investigating differences in suicidal desire and acquired capability.

INTRODUCTION: Depressive and mixed symptoms in bipolar disorder (BD) have been linked to higher suicide risk. Based on Klonsky and May's three-step theory and Joiner's Interpersonal Psychological Theory of Suicide, we hypothesized that patients diagnosed with BD who reported severe levels of depressive symptoms and mixed depressive and manic symptoms would also report higher levels of suicidal desire and acquired capability of suicide, as well as suicidal thoughts and behaviors. METHODS: The sample included 177 outpatients diagnosed with BD. Latent class analysis was conducted to replicate the identified groups of a previously conducted study using a smaller but overlapping dataset. Between-class and pairwise analyses with measures of suicidal desire and acquired capability were conducted. RESULTS: As expected, the classes characterized by severe depressive symptoms and mixed symptoms reported higher levels of suicidal desire. However, the results regarding acquired capability were less consistent. CONCLUSION: Given the overall elevated suicide risk of BD and the consistent relationship between depressive symptoms and other strong correlates of suicide, clinicians who work with patients diagnosed with BD should closely monitor changes in their depressive symptoms.

10 Lessons Learned in Launching a Division-Wide Measurement-Based Care Initiative.

Mental health problems are a major source of morbidity and mortality for children and adolescents, affecting 15% to 20% of those under 18 years of age in the US.1 Half of all mental health conditions start by age 14 years, although most cases remain undetected and untreated.2 Despite knowing much about mental health conditions affecting children, many speculate that the lack of standardized approaches to patient care contribute to poor outcomes, including substantial diagnostic variation, few remissions, risk for relapse or recidivism, and, ultimately, greater mortality due to an inability to accurately predict who will make a suicide attempt.3-5 Studies support this over-reliance on the "art of medicine" (ie, subjective judgment without use of standardized measures), finding that only 17.9% of psychiatrists and 11.1% of psychologists in the US routinely administer symptom rating scales to their patients, despite studies suggesting that when using clinical judgment alone, mental health providers detect deterioration for only 21.4% of patients.4.

Sensation Seeking in Children and Adults with Pediatric-Onset Bipolar Disorder.

Bipolar disorder (BD) is one of the most impairing psychiatric illnesses. Those with pediatric-onset BD tend to have worse outcomes; therefore, accurate conceptualization is important for aspects of care, such as tailored treatment interventions. Sensation seeking behaviors may be a window into the psychopathology of pediatric-onset BD. Participants with BD and healthy controls (HC) ages 7-27 completed self-report assessments, including the Sensation Seeking Scale- V (SSS-V). Among the BD group, there was a significant positive correlation between the Disinhibition subscale and age. Analyses indicated that the BD group scored lower on the Thrill and Adventure Seeking subscale but higher on the Disinhibition scale when compared to the HC group. We found that individuals with pediatric-onset BD are more likely to engage in socially risky behaviors. These results are an important step in understanding sensation seeking characteristics in BD youth and improving treatment, ultimately helping individuals live a more stable life.

Risk factors for suicide attempts among rural youth with a history of suicidal ideation.

Youths in rural areas have approximately double the risk for suicide than do urban youth. This study analyzed data from 580 youth aged 10 to 17-years-old who endorsed lifetime suicidal ideation on intake at three large rural behavioral health centers. Results indicated that a five-factor model including older age, number of inpatient hospitalizations, gender (female), impaired legal functioning, and higher impulsivity accounted for the most variance in differentiation between ideators and attempters. These results advance our assessment of rural youth who may be at increased risk for a suicide attempt.

A Randomized Controlled Trial of the Collaborative Assessment and Management of Suicidality (CAMS) Versus Treatment as Usual (TAU) for Suicidal College Students.

This randomized controlled trial compared the Collaborative Assessment and Management of Suicidality (CAMS) and Treatment as Usual (TAU) for suicidal college students within a feasibility trial. Sixty-two suicidal college students were randomized to CAMS (n = 33) or TAU (n = 29). We hypothesized that those receiving CAMS would show more improvement in suicide-related measures, and effects would be moderated by borderline personality disorder (BPD), prior suicide attempts, and age. Both treatment groups showed improvements in all outcome variables; CAMS had a significantly higher impact on depression and suicidal ideation when measured weekly during care and was more likely than TAU to decrease hopelessness among students with fewer BPD features, no suicide attempt history, and older age. Conversely, TAU did better for students with BPD features and history of multiple suicide attempts.

Latent class analysis of bipolar disorder symptoms and suicidal ideation and behaviors.

Individuals with bipolar disorder are at increased risk of dying by suicide compared to healthy controls and those with unipolar depression. Previous studies show that depressive symptoms and mixed episodes of mania and depression are related to suicide. However, most of these studies adopt a variable-centered approach to understanding how specific symptoms relate to suicidal ideation, without addressing how these symptoms and symptom profiles relate to suicidal behaviors. OBJECTIVES: Using latent class analysis, this study adopts a person-centered approach to examine whether subtypes of patients with bipolar disorder differ in their levels of suicidal ideation and behaviors. METHODS: A total of 150 patients from a behavioral health outpatient clinic were recruited. Latent classes were generated based on self reports of their depressive and manic symptoms. RESULTS: Five classes of patients with bipolar disorder were identified, namely, a minimal symptom, mania, moderately depressed, severely depressed, and mixed depression-mania subtypes. Those in the severely depressed and mixed depression-mania groups reported significantly higher levels of suicidal ideation and behaviors compared to the other groups. CONCLUSIONS: Our findings provide further support for the strong relationship between depressive symptoms and suicidality. These findings are significant as they shed light on the different suicide risk profiles among a heterogenous group of patients with bipolar disorder. Name of clinical trial: Suicidal Behavior in Patients Diagnosed with Bipolar Disorder: The Roles of Biological and Childhood and Adult Environmental Risk Factors. ClinicalTrials.gov Identifier: NCT02604277.

Developing Adaptive Treatment Strategies to Address Suicidal Risk in College Students: A Pilot Sequential, Multiple Assignment, Randomized Trial (SMART).

This pilot study investigated the potential to utilize adaptive treatment strategies for treating moderate to severe suicidal risk among college students. This article will describe the unique study design and report on feasibility and acceptability findings. A 2-stage Sequential Multiple Assignment Randomized Trial (SMART) was conducted: In Stage 1, 62 suicidal college students were randomized to either a suicide-focused or a treatment-as-usual condition (4-8 weeks). Those deemed insufficient responders were re-randomized to one of two Stage 2 interventions-both suicide-focused but one comprehensive and multimodal and the other flexible and theoretically agnostic (4-16 additional weeks). Recruitment rates were high, treatment dropout levels were lower than expected for the setting, study dropouts were rare, and counselors were able to deliver suicide-focused approaches with fidelity. Treatment satisfaction was high among clients and moderately high among counselors. Findings from this pilot show that a SMART is highly feasible and acceptable to suicidal college students, counselors, and campuses.

Suicide on railroad rights-of-way: a psychological autopsy study.

Findings from 55 psychological autopsies of decedents who perished on U.S. railroad rights-of-way between October 1, 2007, and September 30, 2010 are reported. Described are distal, proximal, and contextual factors of risk; understandings of why these suicides occurred on railroad rights-of-way; and opportunities for prevention of similar suicides. International comparisons of suicides on railroad rights-of-way are made to highlight distinct findings regarding U.S. cases. Decedents studied exhibited considerable predisposing risk for suicide, with a high prevalence of severe mental disorders and substance abuse. In addition, a number of acute risk factors were commonly observed, notably suicide ideation, hopelessness, anxiety, and anger. In the context of that acute risk, associated situational variables and a relative absence of protective factors are described.

Myosin VI is required for targeted membrane transport during cytokinesis.

Myosin VI plays important roles in endocytic and exocytic membrane-trafficking pathways in cells. Because recent work has highlighted the importance of targeted membrane transport during cytokinesis, we investigated whether myosin VI plays a role in this process during cell division. In dividing cells, myosin VI undergoes dramatic changes in localization: in prophase, myosin VI is recruited to the spindle poles; and in cytokinesis, myosin VI is targeted to the walls of the ingressing cleavage furrow, with a dramatic concentration in the midbody region. Furthermore, myosin VI is present on vesicles moving into and out of the cytoplasmic bridge connecting the two daughter cells. Inhibition of myosin VI activity by small interfering RNA (siRNA)-mediated knockdown or by overexpression of dominant-negative myosin VI tail leads to a delay in metaphase progression and a defect in cytokinesis. GAIP-interacting protein COOH terminus (GIPC), a myosin VI binding partner, is associated with the function(s) of myosin VI in dividing cells. Loss of GIPC in siRNA knockdown cells results in a more than fourfold increase in the number of multinucleated cells. Our results suggest that myosin VI has novel functions in mitosis and that it plays an essential role in targeted membrane transport during cytokinesis.

Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells.

In polarized epithelial cells, newly synthesized membrane proteins are delivered on specific pathways to either the apical or basolateral domains, depending on the sorting motifs present in these proteins. Because myosin VI has been shown to facilitate secretory traffic in nonpolarized cells, we investigated its role in biosynthetic trafficking pathways in polarized MDCK cells. We observed that a specific splice isoform of myosin VI with no insert in the tail domain is required for the polarized transport of tyrosine motif containing basolateral membrane proteins. Sorting of other basolateral or apical cargo, however, does not involve myosin VI. Site-directed mutagenesis indicates that a functional complex consisting of myosin VI, optineurin, and probably the GTPase Rab8 plays a role in the basolateral delivery of membrane proteins, whose sorting is mediated by the clathrin adaptor protein complex (AP) AP-1B. Our results suggest that myosin VI is a crucial component in the AP-1B-dependent biosynthetic sorting pathway to the basolateral surface in polarized epithelial cells.

Myosin VI targeting to clathrin-coated structures and dimerization is mediated by binding to Disabled-2 and PtdIns(4,5)P2.

Vesicle transport is essential for the movement of proteins, lipids and other molecules between membrane compartments within the cell. The role of the class VI myosins in vesicular transport is particularly intriguing because they are the only class that has been shown to move 'backwards' towards the minus end of actin filaments. Myosin VI is found in distinct intracellular locations and implicated in processes such as endocytosis, exocytosis, maintenance of Golgi morphology and cell movement. We have shown that the carboxy-terminal tail is the key targeting region and have identified three binding sites: a WWY motif for Disabled-2 (Dab2) binding, a RRL motif for glucose-transporter binding protein (GIPC) and optineurin binding and a site that binds specifically and with high affinity (Kd = 0.3 microM) to PtdIns(4,5)P2-containing liposomes. This is the first demonstration that myosin VI binds lipid membranes. Lipid binding induces a large structural change in the myosin VI tail (31% increase in helicity) and when associated with lipid vesicles, it can dimerize. In vivo targeting and recruitment of myosin VI to clathrin-coated structures (CCSs) at the plasma membrane is mediated by Dab2 and PtdIns(4,5)P2 binding.

A tissue-specific exon of myosin Va is responsible for selective cargo binding in melanocytes.

Class V myosins are molecular motors used for intracellular transportation and organelle tethering. The mouse Myosin Va (MyoVa) is encoded by the dilute locus, which is alternatively spliced to generate several tissue specific isoforms. The tail of MyoVa is the putative cargo-binding domain. To determine the functions of different isoforms of MyoVa and the minimal cargo-binding region, we tagged various isoforms and different portions of the mouse MyoVa tail with a green fluorescent protein and examined their intracellular localizations in the mouse melan-a cells. We found that the amino acid sequence encoded by an alternatively spliced exon, exon F, is necessary for the selective binding of MyoVa to melanosome. The MyoVa isoforms lacking this amino acid sequence are not targeted to the melanosomes, but localized to the perinuclear region instead. These findings suggested that MyoVa is able to bind to more than one types of cargos, with the selectivities determined by alternative spliced sequences.