miR-124-3p target genes identify globus pallidus role in suicide ideation recovery in borderline personality disorder.

Borderline personality disorder (BPD) is characterized by patterns of unstable affect, unstable interpersonal relationships, and chronic suicidal tendencies. Research on the genetics, epigenetics, and brain function of BPD is lacking. MicroRNA-124-3p (miR-124-3p) was recently identified in a Genome-Wide Association Study as likely associated with BPD. Here, we identified the anatomical brain expression of genes likely modulated by miR-124-3p and compared morphometry in those brain regions in BPD inpatients vs. controls matched for psychiatric comorbidities. We isolated lists of targets likely modulated by miR-124-3p from TargetScan (v 8.0) by their preferentially conserved targeting (Aggregate PCT > 0.99, see Supplementary Table 1). We applied Process Genes List (PGL) to identify regions of interest associated with the co-expression of miR-124-3p target genes. We compared the gray matter volume of the top region of interest co-expressing those genes between BPD inpatients (n = 111, 46% female) and psychiatric controls (n = 111, 54% female) at The Menninger Clinic in Houston, Texas. We then correlated personality measures, suicidal ideation intensity, and recovery from suicidal ideation with volumetrics. Gene targets of miR-124-3p were significantly co-expressed in the left Globus Pallidus (GP), which was smaller in BPD than in psychiatric controls. Smaller GP volume was negatively correlated with agreeableness and with recovery from suicidal ideation post-treatment. In BPD, GP volume may be reduced through miR-124-3p regulation and suppression of its target genes. Importantly, we identified that a reduction of the GP in BPD could serve as a potential biomarker for recovery from suicidal ideation.

Reward Processing in Psychiatric Inpatients With Depression.

BACKGROUND: Previous neuroimaging studies have investigated reward-processing dysfunction in major depressive disorder and have led to the common finding that major depressive disorder is associated with reduced reward responses within the reward circuit. Yet it is unclear whether such reward-processing dysfunction is specifically associated with the severity of depressive symptoms in major depressive disorder or is associated with common comorbidities. METHODS: We investigated reward-processing differences using a classic juice-delivery functional magnetic resonance imaging experiment to compare psychiatric patients with severe depressive symptoms (DEPs) to both psychiatric control subjects (PCs) and healthy control subjects. In this study, the DEPs (n = 108) were matched to healthy control subjects (n = 62) for demographic characteristics and to the PCs (n = 108) for demographics and comorbid psychiatric diagnoses. An a priori region of interest, the left putamen, was selected using previous studies. An exploratory whole-brain analysis was performed to explore for nonhypothesized regions. RESULTS: Relative to the PCs and healthy control subjects, the DEP group showed smaller responses to reward stimulus in the left putamen. Whole-brain exploratory analysis revealed that DEPs had significantly lower responses to reward stimulus in the bilateral dorsal striatum (putamen and caudate), middle frontal gyrus, left precentral gyrus, and middle cingulate cortex than PCs. CONCLUSIONS: Our findings suggest that DEPs may have a lesser ability to modulate behavior as a function of reward, especially in those individuals who experience the most severe depressive symptoms. In both DEPs and PCs, the severity of depressive symptoms was related to reduced reward responses in the left putamen.

Nighttime Sleep Quality and Daytime Sleepiness Predicts Suicide Risk in Adults Admitted to an Inpatient Psychiatric Hospital.

As sleep problems have been identified as an important, yet understudied, predictor of suicide risk, the present study analyzed the relationship between daytime sleepiness and nighttime sleep disturbance in a high-risk population of adults admitted to an inpatient psychiatric hospital. Objectives were to (1) examine the time course of subjective daytime sleepiness, nighttime sleep disturbance, and suicide risk throughout inpatient psychiatric treatment, (2) examine pre- to post-treatment changes in sleep disturbance with treatment as usual in an inpatient psychiatric setting, and (3) investigate whether daytime sleepiness and nighttime sleep disturbance predicted suicide risk above and beyond anxiety and depression. Participants were 500 consecutively admitted adults admitted to an intermediate length of stay (4-6 weeks) inpatient psychiatric hospital (47% female; 18-87 years of age). Measures of sleep, suicide risk, depression, and anxiety were completed at admission, weeks 1 through 4, and at discharge. Latent growth curve modeling (LGM) and hierarchal linear modeling (HLM) were conducted. The LGM analysis demonstrated that daytime sleepiness, nighttime sleep disturbance, and suicide risk all improved throughout inpatient treatment. Further, HLM showed that daytime sleepiness predicted suicide risk above and beyond symptoms of anxiety, depression, major sleep medications, and prior suicidal ideation and attempts, while nighttime sleep disturbance predicted suicide risk above and beyond symptoms of anxiety, major sleep medications, and prior suicidal ideation and attempts. Findings indicate the need to reevaluate safety protocols that may impact sleep, particularly that may increase daytime sleepiness, and to develop evidence-based sleep interventions for individuals admitted to inpatient psychiatric hospitals.

Impact of personality dysfunction on interdisciplinary treatment team working alliance in an inpatient psychiatric population.

Cluster B personality disorders (PDs) share specific traits that can result in interpersonal conflict. As therapeutic working alliance has a strong relationship with improved outcomes, there is interest in understanding the relationship between PDs, working alliance, and clinical outcomes. This is especially compelling in inpatient populations, where symptoms are severe, and patients are working with a treatment team. The aims of this study were to (a) assess whether higher team working alliance is associated with lower depressive symptoms, (b) assess whether patients with Cluster B PD traits have worse working alliance with their team than patients without those Cluster B PD traits, and (c) assess whether higher team working alliance is associated with lower depressive symptoms when Cluster B PD traits are present. Team working alliance was measured at baseline and at discharge for 3,406 inpatients at a psychiatric hospital. Improved team working alliance was associated with lower depression scores at discharge. Patients with borderline personality disorder traits had worse team working alliance, whereas patients with narcissistic personality disorder and antisocial personality disorder traits had similar working alliance scores as other patients. Borderline personality disorder and antisocial personality disorder traits moderated the association between team working alliance and depressive symptoms differently. Findings suggest that team working alliance works similarly to therapist working alliance. Of clinical importance is the finding that team working alliance and its relationship with depression symptoms differ based on Cluster B PD traits, and the importance of strong working alliance regardless of interpersonal challenges due to personality pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Nature and Assessment of Personality Pathology and Diagnosis.

This article demonstrates the contribution of Otto Kernberg's object relations theory of personality pathology to the current understanding of the nature and assessment of personality pathology and diagnosis. The article introduces recent advances in psychiatric nosology and presents differing views on the meaning of the general severity criterion common to all personality pathology (i.e., level of personality functioning as described in criterion A of the Alternative DSM-5 Model for Personality Disorders). Next, the significance of Kernberg's theory to recent nosological advances is discussed, with a focus on two important features: first, a definition of personality that goes beyond signs and symptoms to include structural motivational components, in the domains of self- and interpersonal functioning, that are common to all personality manifestations and that fulfill an intrapsychic, organizing function; second, identity formation and consolidation as the ultimate end point of healthy personality functioning. That these cornerstone features of Kernberg's theory, articulated more than 50 years ago, align with the most up-to-date conceptualization of personality pathology confirms that Kernberg's theory represents an idea whose time has finally come.

Leading improvement at scale in healthcare: Sir John Oldham.

BACKGROUND: When I became senior partner at my general practice I undertook a part time MBA at Manchester Business School in the late 90s to learn the things medical school hadn't taught me; organizational design and behaviour, finance, strategic management and human resources (as it was then called). My dissertation was on quality methods in other industries that could be applied in healthcare. JOURNEY: We tried out total quality management methods in my practice and began to demonstrably improve care, services and the use of resources. I titled this in presentations in the early noughties the Quality Trinity, which morphed into the now widely adopted triple aim. The practice won awards and I became a sessional advisor to the Dept of Health. I was invited to Boston by Don Berwick and saw the collaborative method of improvement. When a new Government came to power pledging to improve quality I designed a means of using the collaborative for large scale change. This opened a parallel career in quality improvement for the next 20 years, though I continued to be a practicing GP for the majority of that. REFLECTIONS: When I started there was literature on total quality management in other industries but very little in healthcare, and nothing on large scale change. The methods challenged orthodoxy about how you changed healthcare delivery and met resistance, even hostility. Much that was suspect is now embraced, techniques that were unheard of are now common and the literature is expanding. This article gives experiential insight into large scale change gathered in my career that I hope may help others now charged with these tasks.