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Pathogenic SRY-box transcription factor 2 (SOX2) variants typically cause severe ocular defects within a SOX2 disorder spectrum that includes hypogonadotropic hypogonadism. We examined exome-sequencing data from a large, well-phenotyped cohort of patients with idiopathic hypogonadotropic hypogonadism (IHH) for pathogenic SOX2 variants to investigate the underlying pathogenic SOX2 spectrum and its associated phenotypes. We identified 8 IHH individuals harboring heterozygous pathogenic SOX2 variants with variable ocular phenotypes. These variant proteins were tested in vitro to determine whether a causal relationship between IHH and SOX2 exists. We found that Sox2 was highly expressed in the hypothalamus of adult mice and colocalized with kisspeptin 1 (KISS1) expression in the anteroventral periventricular nucleus of adult female mice. In vitro, shRNA suppression of mouse SOX2 protein in Kiss-expressing cell lines increased the levels of human kisspeptin luciferase (hKiss-luc) transcription, while SOX2 overexpression repressed hKiss-luc transcription. Further, 4 of the identified SOX2 variants prevented this SOX2-mediated repression of hKiss-luc. Together, these data suggest that pathogenic SOX2 variants contribute to both anosmic and normosmic forms of IHH, attesting to hypothalamic defects in the SOX2 disorder spectrum. Our study describes potentially novel mechanisms contributing to SOX2-related disease and highlights the necessity of SOX2 screening in IHH genetic evaluation irrespective of associated ocular defects.

During mammalian development, gonadotropin-releasing-hormone-1 neurons (GnRH-1ns) migrate from the developing vomeronasal organ (VNO) into the brain asserting control of pubertal onset and fertility. Recent data suggest that correct development of the olfactory ensheathing cells (OEC) is imperative for normal GnRH-1 neuronal migration. However, the full ensemble of molecular pathways that regulate OEC development remains to be fully deciphered. Loss-of-function of the transcription factor Gli3 is known to disrupt olfactory development, however, if Gli3 plays a role in GnRH-1 neuronal development is unclear. By analyzing Gli3 extra-toe mutants (Gli3Xt/Xt), we found that Gli3 loss-of-function compromises the onset of achaete-scute family bHLH transcription factor 1 (Ascl-1)+ vomeronasal progenitors and the formation of OEC in the nasal mucosa. Surprisingly, GnRH-1 neurogenesis was intact in Gli3Xt/Xt mice but they displayed significant defects in GnRH-1 neuronal migration. In contrast, Ascl-1null mutants showed reduced neurogenesis for both vomeronasal and GnRH-1ns but less severe defects in OEC development. These observations suggest that Gli3 is critical for OEC development in the nasal mucosa and subsequent GnRH-1 neuronal migration. However, the nonoverlapping phenotypes between Ascl-1 and Gli3 mutants indicate that Ascl-1, while crucial for GnRH-1 neurogenesis, is not required for normal OEC development. Because Kallmann syndrome (KS) is characterized by abnormal GnRH-1ns migration, we examined whole-exome sequencing data from KS subjects. We identified and validated a GLI3 loss-of-function variant in a KS individual. These findings provide new insights into GnRH-1 and OECs development and demonstrate that human GLI3 mutations contribute to KS etiology. [ABSTRACT FROM AUTHOR]

The article offers tips on how to pick and deal with a jury during a Voir Dire. According to the article, it is vital to learn a lot about one's prospective panel by researching how potential jurors have voted at the County Clerk's office and checking several Web sites like Facebook. Other suggestions on how to connect with prospective jurors include asking open-ended questions, listening well and being fair to them. An overview of conservative juries and preponderance of evidence is offered.

Objective: Patients who have experienced child abuse often have complex clinical presentations; whether a history of child abuse (HCA) affects psychotherapy outcomes is unclear. The authors examined relationships between HCA, clinical baseline variables, and change in these variables after three different psychotherapies for panic disorder (PD)., Methods: Two hundred adults with PD (with or without agoraphobia) were randomly assigned to one of three treatments across two sites: panic-focused psychodynamic psychotherapy (PFPP), cognitive-behavioral therapy (CBT), or applied relaxation training (ART). Differences in demographic and clinical variables between those with and without HCA were compared. The primary analysis addressed odds of meeting clinical response criteria on the Panic Disorder Severity Scale (PDSS) between treatments, as moderated by HCA. This effect was examined via continuous outcomes on the PDSS and psychosocial functioning (Sheehan Disability Scale)., Results: Compared with patients without HCA (N=154), patients with HCA (N=46) experienced significantly more severe symptoms of PD (d=0.60), agoraphobia (d=0.47), and comorbid depression (d=0.46); significantly worse psychosocial impairment (d=0.63) and anxiety sensitivity (d=0.75); greater personality disorder burden (d=0.45)-particularly with cluster C disorders (d=0.47)-and more severe interpersonal problems (d=0.54). HCA significantly moderated the likelihood of clinical response, predicting nonresponse to ART (B=-2.05, 95% CI=-4.17 to -0.30, OR=0.13, z=-2.14, p=0.032) but not CBT or PFPP. HCA did not interact with treatment condition to predict slopes of PDSS change., Conclusions: The results of this study highlight the importance of HCA in formulating treatment recommendations. Increased awareness of HCA's effects on severity of PD and treatment responsiveness among patients with PD may improve outcomes., Competing Interests: Dr. Milrod reports receiving book royalties from the Taylor & Francis Group. Dr. Barber reports receiving book royalties from Guilford Press and Cambridge University Press. The other authors report no financial relationships with commercial interests. Holly A. Swartz, M.D., Editor of the journal, was the decision editor during peer review.

Objective: Established trauma-focused cognitive-behavioral therapies for posttraumatic stress disorder (PTSD) have remission rates of approximately 30%-40%. Alternatively, interpersonal psychotherapy (IPT) and psychodynamic psychotherapy (PDT) focus on disrupted attachment, mentalization, and social connection in PTSD and may help some patients. The authors conducted a meta-analysis on these interpersonal and affect-oriented approaches to treating PTSD., Methods: Building on a prior meta-analysis, the authors searched for randomized controlled trials (RCTs) comparing IPT or PDT with other established PTSD treatments or control conditions for adults diagnosed as having PTSD. Random-effects meta-analyses were conducted to assess outcome effect sizes and dropout rates. RCTs were rated via the Randomized Controlled Trial Psychotherapy Quality Rating Scale., Results: Ten RCTs (eight of IPT) comparing IPT or PDT with control (k=7) or active treatment (k=4) conditions were identified, nine of which were of adequate quality. IPT (k=5) and PDT (k=2), when analyzed together, were superior to control conditions overall (g=-1.14, p=0.011 [as was IPT alone: g=-0.88, p=0.034]) and to waitlist (g=-1.49) and treatment-as-usual (g=-0.70) groups. Effect sizes, however, may have been inflated by outliers or publication bias. IPT (k=3) and PDT (k=1), when analyzed together, were equally efficacious compared with other active PTSD treatments (primarily exposure-based psychotherapies), as was IPT alone, and had lower dropout rates (relative risk=0.63, p=0.049 for IPT and PDT analyzed together; relative risk = 0.61, p=0.098 for IPT alone)., Conclusions: Affect-focused therapies hold promise in the treatment of PTSD. IPT has demonstrated efficacy in multiple trials, whereas the evidence base for PDT is sparse., Competing Interests: The authors report no financial relationships with commercial interests. Holly A. Swartz, M.D., Editor of the journal, was the decision editor during peer review.

Competing Interests: The author reports no financial relationships with commercial interests.

Current treatments for trauma are ineffective for many patients. For traumas involving violence that targets aspects of patients' identities, treatments that do not address systemic factors involved in the trauma (e.g., past and ongoing experiences of identity-based oppression and marginalization, developmental sequelae of invalidation or policing of identity, and identity-related patterns of transference and countertransference) may be ineffective. Psychodynamic approaches can flexibly address the identity-related dynamics between therapist and patient and incorporate patients' experiences of their various identities, in the context of trauma, into clinical formulation and treatment. The authors present concepts relevant to the dynamics of intersectional identities that may arise between therapist and patient and provide a case study illustrating how a patient's various identities affect their symptom manifestation and treatment course. The authors advocate for cultural humility and self-exploration of biases and assumptions among clinicians, because therapists do not hold expert knowledge of their patients' cultural experiences., Competing Interests: The authors report no financial relationships with commercial interests.

Anhedonia is a salient transdiagnostic psychiatric symptom associated with increased illness severity and chronicity. Anhedonia is also present to varying degrees in non-clinical cohorts. Here, we sought to examine factors influencing expression of anhedonia. Participants (N = 335) were recruited through the Nathan Kline Institute-Rockland Sample, an initiative to deeply phenotype a large community sample across the lifespan. Utilizing a data-driven approach, we evaluated associations between anhedonia severity, indexed by Snaith-Hamilton Pleasure Scale (SHAPS), and 20 physical, developmental, and clinical measures, including Structured Clinical Interview for DSM-IV, Beck Depression Inventory, State-Trait Anxiety Inventory, NEO Five-Factor Inventory-3 (NEO-FFI-3), BMI, Hemoglobin A1C, and demography. Using a bootstrapped AIC-based backward selection algorithm, seven variables were retained in the final model: NEO-FFI-3 agreeableness, extraversion, and openness to experience; BMI; sex; ethnicity; and race. Though median SHAPS scores were greater in participants with psychiatric diagnoses (18.5) than those without (17.0) (U = 12238.5, z = 2.473, p = 0.013), diagnosis and symptom measures were not retained as significant predictors in the final robust linear model. Participants scoring higher on agreeableness, extraversion, and openness to experience reported significantly lower anhedonia. These results demonstrate personality as a mild-to-moderate but significant driver of differences in experiencing pleasure in a community sample., Competing Interests: Declaration of competing interest R.H.T. has received grant support from Axial Therapeutics Inc., F. Hoffmann-La Roche Ltd, Janssen, and MapLight Therapeutics Inc. and has attended advisory boards for F. Hoffmann-La Roche Ltd. In the last ten years, D.V.I. has received consulting honoraria from Alkermes, Allergan, Angelini, Axsome, Biogen, Boehringer Ingelheim, Centers for Psychiatric Excellence, Clexio, Global Medical Education, Jazz, Lundbeck, Neumora, Otsuka, Precision Neuroscience, Relmada, Sage, and Sunovion and research support (through his academic institutions) from Alkermes, AstraZeneca, Brainsway, LiteCure, NeoSync, Otsuka, Roche, and Shire. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals report higher rates of exposure to traumatic events and posttraumatic stress disorder (PTSD) compared with heterosexual and cisgender individuals. No treatment outcomes research has focused on PTSD in the LGBTQ population. Trauma-focused psychodynamic psychotherapy (TFPP) is a brief, manualized, attachment- and affect-focused psychotherapy for PTSD. TFPP explicitly incorporates broad identity-related and societal factors into its conceptualization of trauma and its consequences, which may be especially helpful for LGBTQ patients with minority stress who seek affirmative care., Methods: Fourteen LGBTQ patients with PTSD, assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), received 24 sessions of twice-weekly (12 weeks) TFPP via teletherapy provided by supervised early-career therapists inexperienced in the modality. Sessions were videotaped to monitor therapists' treatment adherence. Patients were assessed at baseline, week 5, termination (week 12), and 3 months posttreatment for PTSD symptoms (assessed with the CAPS-5) and secondary outcomes., Results: TFPP was well tolerated by patients, with 12 (86%) completing the intervention. CAPS-5-measured PTSD symptoms, including dissociation, significantly improved during treatment (mean decrease=-21.8, d=-1.98), and treatment gains were maintained at follow-up. Most patients experienced PTSD clinical response (N=10, 71%) or diagnostic remission (N=7, 50%). Patients generally experienced significant, concomitant improvements in complex PTSD symptoms, general anxiety, depression, and psychosocial functioning. Adherence to the intervention among therapists was high, with 93% of rated sessions meeting adherence standards., Conclusions: TFPP shows promise in the treatment of PTSD among sexual and gender minority patients seeking LGBTQ-affirmative PTSD care., Competing Interests: Dr. Milrod is a coauthor of Trauma-Focused Psychodynamic Psychotherapy: A Step-by-Step Treatment Manual and receives royalties from Oxford University Press. The other authors report no financial relationships with commercial interests.

Interpretations are a hallmark of psychodynamic treatment and a method used in other theoretical orientations as well. Therapists use interpretations to increase patients' insight concerning unconscious and preconscious elements in their lives, with the ultimate aim to reduce mental pain and suffering and improve mental health. This systematic review focuses on the association between the therapists' use and accuracy of interpretation and immediate (within-session), intermediate (between-session), and distal (end-of-treatment) outcomes. This synthesis of the research literature is based on 18 independent samples of 1,011 total patients in individual psychotherapy. The results suggest that the use and accuracy of interpretations were associated, in half the studies, with patient disclosure of emotions and increased insight at the immediate, moment-to-moment enfolding of the session. At the intermediate postsession outcome, the use of interpretations was associated with a stronger alliance and greater depth, in half the studies. At the end of treatment, however, while there is some evidence for a positive effect of the use of interpretations on treatment success, there are also neutral effects and even evidence that interpretations have the potential to be harmful in some particular situations. The article concludes with training implications and therapeutic practices based on the integration of clinical experience and research evidence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

To assess the current status of psychodynamic therapy (PDT) as an empirically supported treatment (EST), we carried out a pre-registered systematic umbrella review addressing the evidence for PDT in common mental disorders in adults, based on an updated model for ESTs. Following this model, we focused on meta-analyses of randomized controlled trials (RCTs) published in the past two years to assess efficacy. In addition, we reviewed the evidence on effectiveness, cost-effectiveness and mechanisms of change. Meta-analyses were evaluated by at least two raters using the proposed updated criteria, i.e. effect sizes, risk of bias, inconsistency, indirectness, imprecision, publication bias, treatment fidelity, and their quality as well as that of primary studies. To assess the quality of evidence we applied the GRADE system. A systematic search identified recent meta-analyses on the efficacy of PDT in depressive, anxiety, personality and somatic symptom disorders. High quality evidence in depressive and somatic symptom disorders and moderate quality evidence in anxiety and personality disorders showed that PDT is superior to (inactive and active) control conditions in reducing target symptoms with clinically meaningful effect sizes. Moderate quality evidence suggests that PDT is as efficacious as other active therapies in these disorders. The benefits of PDT outweigh its costs and harms. Furthermore, evidence was found for long-term effects, improving functioning, effectiveness, cost-effectiveness and mechanisms of change in the aforementioned disorders. Some limitations in specific research areas exist, such as risk of bias and imprecision, which are, however, comparable to those of other evidence-based psychotherapies. Thus, according to the updated EST model, PDT proved to be an empirically-supported treatment for common mental disorders. Of the three options for recommendation provided by the updated model (i.e., "very strong", "strong" or "weak"), the new EST criteria suggest that a strong recommendation for treating the aforementioned mental disorders with PDT is the most appropriate option. In conclusion, PDT represents an evidence-based psychotherapy. This is clinically important since no single therapeutic approach fits all psychiatric patients, as shown by the limited success rates across all evidence-based treatments., (© 2023 World Psychiatric Association.)

Objective: The aim of this article was to construct an empirical bridge between object relations theory and attachment theory by investigating how researchers in both traditions have contributed to understanding and assessing identity diffusion (a keystone of personality pathology) and object relations in patients with borderline personality disorder during 1 year of transference-focused psychotherapy (TFP)., Methods: The Adult Attachment Interview (AAI) and the Structured Interview of Personality Organization (STIPO) were administered to patients (N=104, all women) before and after 1 year of treatment. This study was part of a randomized controlled trial in which 104 patients with borderline personality disorder were randomly assigned to receive either TFP (a manualized, structured psychodynamic treatment approach) or treatment by experienced community psychotherapists. Changes on the AAI in attachment representations, narrative coherence, and reflective function were examined for their associations with changes on the STIPO in identity, object relations, and aggression., Results: Patients who shifted from disorganized (unresolved) to organized attachment on the AAI after 1 year of TFP (but not treatment by experienced community psychotherapists) showed hypothesized improvements in domains of personality organization on the STIPO, including identity, object relations, and aggression. Those who did not change from disorganized (unresolved) to organized attachment improved only in the domain of aggression., Conclusions: These findings highlight the centrality of identity diffusion to borderline personality disorder pathology and the importance of targeting it in treatment. Furthermore, the results suggest that identity may be indexed by measures of attachment security, narrative coherence, and personality organization.

Objective: Lesbian, gay, bisexual, and queer (LGBQ)-affirmative cognitive behavioral therapy (CBT) focused on minority stress processes can address gay and bisexual men's transdiagnostic mental and behavioral health concerns. Identifying moderators of treatment outcomes may inform the mechanisms of LGBQ-affirmative CBT and subpopulations who may derive particular benefit., Method: Data were from a clinical trial in which gay and bisexual men with mental and behavioral health concerns were randomized to receive Effective Skills to Empower Effective Men (ESTEEM; an LGBQ-affirmative transdiagnostic CBT; n = 100) or one of two control conditions ( n = 154): LGBQ-affirmative community mental health treatment (CMHT) or HIV counseling and testing (HCT). The preregistered outcome was a comorbidity index of depression, anxiety, alcohol/drug problems, and human immunodeficiency virus (HIV) transmission risk behavior at 8-month follow-up (i.e., 4 months postintervention). A two-step exploratory machine learning process was employed for 20 theoretically informed baseline variables identified by study therapists as potential moderators of ESTEEM efficacy. Potential moderators included demographic factors, pretreatment comorbidities, clinical facilitators, and minority stress factors., Results: Racial/ethnic minority identification, namely as Black or Latino, was the only statistically significant moderator of treatment efficacy ( B = -3.23, 95% CI [-5.03, -1.64]), t (197) = -3.88, p < .001. Racially/ethnically minoritized recipients ( d = -0.71, p < .001), but not White/non-Latino recipients ( d = 0.22, p = .391), had greater reductions in comorbidity index scores in ESTEEM compared to the control conditions. This moderation was driven by improvements in anxiety and alcohol/drug use problems., Discussion: Black and Latino gay and bisexual men experiencing comorbid mental and behavioral health risks might particularly benefit from a minority stress-focused LGBQ-affirmative CBT. Future research should identify mechanisms for this moderation to inform targeted treatment delivery and dissemination. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Impaired reflective functioning (RF) is common among patients with borderline personality disorder (BPD). Transference-focused psychotherapy (TFP) has been demonstrated to improve RF compared to other common BPD treatments. If RF reflects a treatment mechanism for TFP, differences in pretreatment RF may also serve as a prescriptive factor for TFP's effects., Method: A total of 194 patients with BPD were randomized across two clinical trials to receive TFP ( n = 83), dialectical behavior therapy (DBT; n = 31), supportive psychodynamic therapy (SPT; n = 28), or an enhanced treatment as usual (eTAU; n = 52). A mixed-effects model was used to examine whether baseline RF interacted with treatment condition to predict slopes of change in the Brief Symptom Inventory, the shared symptom outcome between trials. Moderation of changes in RF was also examined., Results: Treatment interacted with baseline RF to predict BSI slopes ( p = .011). In TFP/SPT, RF did not predict outcomes, β = -0.00, p = .973, while higher RF was associated with relatively better outcomes in DBT/eTAU, β = -0.54, p < .001. Patients with poor RF (scores of 0/1) benefitted more from TFP/SPT, while patients with relatively ordinary RF (score of 4) had better outcomes in DBT/eTAU. Treatment effects on RF change were also moderated by baseline RF ( p = .014), such that TFP improved RF most strongly among poor RF patients, SPT only among very poor RF patients, and DBT/eTAU not at all., Discussion: Low RF may reflect a deficit that may be targeted by TFP and other manualized psychodynamic treatments for BPD, which may be especially helpful among patients presenting with low RF. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Patients with posttraumatic stress disorder (PTSD) tend to overgeneralize threat to safe stimuli, potentially reflecting aberrant stimuli discrimination. Yet, it is not clear whether threat overgeneralization reflects general discrimination deficits, or rather a specific bias related to aversive stimuli. Here we tested this question and characterized the neural correlates of threat discrimination., Methods: One-hundred and eight participants (33 PTSD; 43 trauma-exposed controls; 32 healthy controls) completed an emotionally neutral complex shape discrimination task involving identifying in 42 similar pairs the previously observed shape; and an emotionally aversive discrimination task, involving providing risk ratings for an aversive conditioned stimulus (CS+), and for several stimuli gradually differing in size from the original CS+. Resting state functional connectivity (rsFC) was collected before completing the tasks., Results: No group differences emerged on the emotionally neutral task. Conversely, on the emotionally aversive task, individuals with PTSD had steeper linear risk rating slopes as the stimuli more resembled the conditioned stimulus. Finally, lower rsFC of amygdala-default mode network (DMN) and DMN-salience network (SN) were associated with steeper risk slopes, while for hippocampus-SN, lower rsFC was found only among participants with PTSD., Conclusions: Individuals with PTSD show deficits in discrimination only when presented with aversive stimuli. Dysregulated discrimination pattern may relate to a lack of input from regulatory brain areas (e.g., DMN/hippocampus) to threat-related brain areas (e.g., SN/amygdala)., (© 2022 Wiley Periodicals LLC.)

The approach of evidence-based medicine has been extended to psychotherapy. More than 20 years ago, criteria for empirically supported psychotherapeutic treatments (ESTs) were defined. Meanwhile a new model for empirically supported psychotherapeutic treatments has been proposed. While the empirical status of psychodynamic therapy (PDT) was assessed in several reviews using the previous criteria, the proposed new model has not yet been applied to PDT. For this reason, we will carry out a systematic review on studies of PDT in common mental disorders applying the revised criteria of ESTs. As suggested by the new model we will focus on recent systematic quantitative reviews. A systematic search for meta-analyses on the efficacy of PDT in common mental disorders will be carried out. Meta-analyses will be selected and evaluated by at least two raters along the criteria of the new proposed model. In addition, systematic reviews and individual studies addressing mechanisms of change in PDT, effectiveness under real-world conditions, cost-effectiveness and adverse events will be systematically searched for and evaluated. Finally, quality of evidence, the extent to which benefits exceed harms and strength of recommendations will be assessed per disorder using GRADE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leichsenring, Abbass, Heim, Keefe, Luyten, Rabung and Steinert.)

Cognitive Processing Therapy (CPT) is efficacious in treating PTSD, but there remains a need to improve outcomes for individuals who do not fully respond to treatment. Differences between patient-therapist dyads in the fidelity (i.e., adherence and competence) of CPT delivery and the quality of the therapeutic relationship may partly explain differential levels of symptom improvement. Sessions were sampled from a randomized trial comparing different consultation conditions in training therapists new to CPT. Among 69 patients, one session from Sessions 1-3 and one session from Sessions 4-7 were reliably rated for adherence and competence using the CPT Therapist Adherence and Competence Scale, and for therapeutic alliance using the Working Alliance Inventory-Observer scale. Mixed models, including detrending using a fixed effect of session, predicted self-reported Posttraumatic Stress Disorder Checklist (PCL-IV) scores in one session using process scores from the previous session. The statistical interaction between fidelity and alliance scores to predict outcome was also examined. Alliance had significant, positive correlations (rs = 0.18-0.21) with same-session adherence and competence. Higher competence scores and higher therapeutic alliance scores in one session were independently associated with lower PCL-IV scores in the subsequent session. Adherence scores, which tended to be very high with relatively less variability, did not significantly relate to subsequent-session PCL-IV scores. Competence significantly interacted with alliance, such that sessions high in both competence and alliance predicted especially lower subsequent-session PCL-IV scores. A strong therapeutic alliance may have a synergistic, salutary effect with the competent delivery of CPT., (Copyright © 2022. Published by Elsevier Ltd.)

Background: No evidence-based therapy for borderline personality disorder (BPD) exhibits a clear superiority. However, BPD is highly heterogeneous, and different patients may specifically benefit from the interventions of a particular treatment., Methods: From a randomized trial comparing a year of dialectical behavior therapy (DBT) to general psychiatric management (GPM) for BPD, long-term (2-year-post) outcome data and patient baseline variables (n = 156) were used to examine individual and combined patient-level moderators of differential treatment response. A two-step bootstrapped and partially cross-validated moderator identification process was employed for 20 baseline variables. For identified moderators, 10-fold bootstrapped cross-validated models estimated response to each therapy, and long-term outcomes were compared for patients randomized to their model-predicted optimal v. non-optimal treatment., Results: Significant moderators surviving the two-step process included psychiatric symptom severity, BPD impulsivity symptoms (both GPM > DBT), dependent personality traits, childhood emotional abuse, and social adjustment (all DBT > GPM). Patients randomized to their model-predicted optimal treatment had significantly better long-term outcomes (d = 0.36, p = 0.028), especially if the model had a relatively stronger (top 60%) prediction for that patient (d = 0.61, p = 0.004). Among patients with a stronger prediction, this advantage held even when applying a conservative statistical check (d = 0.46, p = 0.043)., Conclusions: Patient characteristics influence the degree to which they respond to two treatments for BPD. Combining information from multiple moderators may help inform providers and patients as to which treatment is the most likely to lead to long-term symptom relief. Further research on personalized medicine in BPD is needed.

In this article, we provide an overview of transference-focused psychotherapy for patients with pathological narcissism and narcissistic personality disorder (TFP-N). In TFP-N we have modified and refined the tactics and techniques of TFP, an evidence-based treatment for borderline personality disorder, to meet the specific challenges of working with patients with narcissistic personality pathology whose retreat from reality into an illusory grandiosity makes them particularly difficult to engage in treatment. We first describe a model of narcissistic pathology based on considerations of psychological structure stemming from object relations theory. This model provides a unifying understanding of the core structure of narcissistic pathology, the pathological grandiose self, that underlies the impairments in self and interpersonal functioning of those with narcissistic pathology across the levels of personality organization (from high functioning to borderline to malignant). We then delineate the clinical process of working with patients with pathological narcissism and narcissistic personality disorder. Starting with the assessment process, using a detailed clinical example, we guide the reader through the progression of TFP-N as it helps the patient move from the distorted, unintegrated sense of self underlying the narcissistic presentation to the more integrated, realistic sense of self that characterizes healthier personality functioning. In TFP-N the focus on the disturbed interpersonal patterns of relating in the here and now of the therapeutic interaction is the vehicle to diminish grandiosity and improve relatedness, thereby effecting enduring changes in mental representation and real-world functioning.

Introduction: Panic disorder patients who drop out of treatment typically do not remit from their disorder. How patient-level moderators influence dropping out of one panic-focused treatment over another has never been examined, nor in non-CBT treatments. Method: 200 patients with panic disorder with or without agoraphobia were randomized to receive cognitive-behavioral therapy (CBT), panic-focused psychodynamic psychotherapy (PFPP), or applied relaxation training (ART) across two sites. Therapy was twice a week for 12 weeks. A two-step variable search method was applied to identify potential prognostic predictors and moderators of patient dropout. Survival models predicting hazard of session-by-session dropout tested the resulting variables. Results: Across treatments, unemployment and higher psychosocial disability on the Sheehan Disability Scale predicted increased risk of dropout, while patients with higher anxiety sensitivity were more likely to complete treatment. Patients who reported experiencing childhood abuse had heightened dropout in ART, but not CBT or PFPP. Men were especially likely to complete PFPP. Session 2 expectancies and patient-rated alliance predicted lower dropout only in CBT. Conclusions: Patient-level factors may influence both whether patients will complete any treatment, and whether they continue in a particular panic-focused therapy. Moderators of dropout (e.g., abuse history) may inform treatment decisions for specific patients. Trial registration: ClinicalTrials.gov identifier: NCT00353470.

Background: Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy., Methods: Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions., Results: One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit., Conclusions: If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.

Personality disorders (PD) carry high psychosocial dysfunction and are associated with treatment resistance in nonspecialized care. Psychodynamic therapies (PDT) are often used to treat PDs, but there has never been a systematic meta-analysis of PDT trials for PD. To evaluate the evidence base for PDTs for PDs across multiple outcome domain, a systematic search for PDT for PD trials was conducted through PubMed and PsycINFO. Sixteen trials were identified, comprising 19 dynamic, 8 active, and 9 control groups predominantly reflecting treatment of borderline and mixed Cluster C PDs, and a random effects meta-analysis was undertaken. PDTs were superior to controls in improving core PD symptoms ( g = -0.63; 95% confidence interval [CI; -0.87, -0.41]), suicidality ( g = -0.79, p = .02; 95% CI [-1.38, -0.20]), general psychiatric symptoms ( g = -0.47; 95% CI [-0.69, -0.25]), and functioning ( g = -0.66; 95% CI [-1.01, -0.32]), but not for interpersonal problems due to heterogeneity ( g = -1.25; 95% CI [-3.22, 0.71]). Outcomes for PDTs were not different from other active treatments in core PD ( g = 0.05; 95% CI [-0.25, 0.35]) or other symptoms. This pattern continued into posttreatment follow-up (average 14 months). Study quality was generally rated as adequate and was unrelated to outcomes. Compared with other treatments, PDTs do not have different acute effects and are superior to controls, although only trials treating BPD employed active controls and non-BPD trials were of lower quality. Underresearched areas include narcissistic PD, specific Cluster C disorders, and personality pathology as a continuous construct. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Introduction: Separation anxiety disorder (SAD) comprises one aspect of attachment dysregulation or insecurity. Although SAD aggravates posttraumatic stress disorder (PTSD) risk, no clinical research has tracked how many patients with PTSD have SAD, its clinical associations, or its response to PTSD treatment. Our open trial of interpersonal psychotherapy (IPT) for veterans with PTSD assessed these SAD domains., Methods: Twenty-nine veterans diagnosed with chronic PTSD on the Clinician-Administered PTSD Scale were assessed for SAD using the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), and for Symptom-Specific Reflective Function (SSRF), another dysregulated-attachment marker capturing patients' emotional understanding of their symptoms. Patients received 14 IPT sessions for PTSD with assessments at baseline, Week 4 (SCI-SAS and SSRF), and termination for SAD, PTSD, and depression., Results: At baseline, 69% of patients met SAD criteria. Separation anxiety did not correlate with baseline PTSD severity, depressive severity, or age when traumatized; patients with and without SAD had comparable PTSD and depression severity. Patients with baseline comorbid SAD who completed IPT (N = 17) reported significantly improved adult separation anxiety (p = .009). Adult SAD improvements predicted depressive improvement (p = .049). Patients with SAD showed a stronger relationship between early SSRF gains and subsequent adult SAD improvement (p = .021) compared with patients without SAD., Discussion: This first exploration of dysregulated/insecure attachment features among patients with PTSD found high SAD comorbidity and adult SAD improvement among patients with SAD following IPT. Highly impaired attachment patients normalized attachment posttreatment: 14-session IPT improved attachment dysregulation. This small study requires replication but begins to broaden clinical understanding of separation anxiety, attachment dysregulation, and PTSD., (© 2020 Wiley Periodicals, Inc.)

In panic-focused psychodynamic psychotherapy (PFPP), exploration and interpretation of avoided and conflicted emotions and fantasies surrounding anxiety are thought to promote panic-specific reflective functioning (PSRF), which drives panic disorder improvements. Patient emotional expression within a session may be a marker of engaged processing and experiencing of affectively charged material. Degree of in-session expressed emotion, indicating both verbal and nonverbal emotions, was examined across three early therapy sessions for prediction of subsequent outcomes. We further investigated whether personality disorder traits, theorized to relate to constricted (obsessive-compulsive) or heightened (borderline) emotions, moderated this relationship. Emotional expression in Sessions 2, 5, and 10 of a 24-session PFPP protocol was assessed by blinded observers in 44 patients randomized to PFPP in a two-site randomized controlled trial of psychotherapies for panic disorder. Robust regressions were conducted to examine the relationship between average emotional expression across the measured sessions and symptom and PSRF changes subsequent to the sampled sessions, as well as moderation by personality disorder criteria, controlling for early outcomes. Higher levels of emotional expression across the early sessions predicted greater subsequent symptom and PSRF improvement. Elevations in expression of grief/sadness drove the symptomatic finding. Patients meeting more borderline criteria experienced a smaller and potentially negative relationship between emotional expression and symptom improvement. Emotional expression in PFPP may be an indicator of positive therapy process for patients without comorbid borderline personality traits, predicting prospective improvements in both a key mediator (PSRF) and symptoms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective: This study examines whether, in panic-focused psychodynamic psychotherapy (PFPP), interpretations of conflicts that underlie anxiety (panic-focused or PF-interpretations) are specifically associated with subsequent panic disorder (PD) symptom improvement, over and above the provision of non-symptom-focused interpretations. Method: Technique use in Sessions 2 and 10 of a 24-session PFPP protocol was assessed for the 65 patients with complete outcome data randomized to PFPP in a two-site trial of psychotherapies for PD. Sessions were rated in 15-min segments for therapists' use of PF-interpretations, non-PF-interpretations, and PF-clarifications. Robust regressions were conducted to examine the relationship between these interventions and symptom change subsequent to the sampled session. Interpersonal problems were examined as a moderator of the relationship of PF-interpretations to symptom change. Results: At Session 10, but not at Session 2, patients who received a higher degree of PF-interpretations experienced greater subsequent improvement in panic symptoms. Non-PF-interpretations were not predictive. Patients with more interpersonal distress benefitted particularly from the use of PF-interpretations at Session 10. Conclusions: By the middle phase of PFPP, panic-focused interpretations may drive subsequent improvements in panic symptoms, especially among patients with higher interpersonal distress. Interpretations of conflict absent a panic focus may not be especially helpful.

Objective: Personality disorder (PD) is a negative prognostic indicator for treatment, and absolute improvements in functioning among these patients are often modest. This may be because personality features that give rise to dysfunction in PD are not targeted optimally during most treatments. Method: Attachment, mentalization, core beliefs, and personality organization/defense use were identified as personality constructs that have been pursued in treatment studies and that are proposed to underlie PD. Results: All constructs correlate with psychiatric symptoms, PD diagnosis, and functioning. Defense mechanisms and core beliefs further distinguish specific PDs, whereas personality organization separates more versus less severe PDs. Evidence from treatment and naturalistic studies indicate that maturation of defense mechanisms temporally precedes improvements in symptoms and functioning. Changes in attachment and mentalization correlate with some outcomes, but mediation of improvement has not been established. In psychodynamic therapy, transference interpretations may promote amelioration of personality dysfunction. With the exception of attachment, the experimental literature is lacking that could explicate the mechanisms by which these personality constructs maintain psychosocial dysfunction. Conclusions: Future research should aim to identify changes in these mechanisms that mediate positive outcomes in PD, as well as the specific therapeutic procedures that best promote positive change in PD.

Background: It is not known whether common anxiety/mood comorbidities of panic disorder (PD) improve with panic-focused psychological treatment, nor whether there is differential efficacy between therapies in treating comorbidities., Methods: In a randomized controlled trial for PD with and without agoraphobia comparing Cognitive-Behavioral Therapy (CBT) and Panic-Focused Psychodynamic Psychotherapy (PFPP), symptomatic comorbidities of agoraphobia, MDD, GAD, and social anxiety disorder (SAD) were assessed pre-to-post treatment with the Anxiety Disorders Interview Schedule (ADIS). Comparative efficacy of CBT versus PFPP for treating comorbid disorders was tested at termination and 1 year's follow-up. Covariance between panic and comorbidity improvements was also analyzed., Results: Most treatment completers (n = 120) evidenced diagnostic remission of their comorbidity (range = 54-69%), which typically reflected a subclinical score on the ADIS (mean range = 1.3 to 1.8). These improvements were generally retained at follow-up. However, patients with MDD dropped out significantly more often (HR = 2.79). No significant symptom change or remission differences emerged between CBT and PFPP for any comorbidity at termination or at follow-up. Panic change was strongly related to improvements in agoraphobia (r = 0.70) and MDD (r = 0.53), moderately related for GAD (r = 0.31), and not significantly related for SAD (r = 0.20)., Discussion: Patients completing panic-focused psychotherapies often experience meaningful remission for diagnoses of agoraphobia, MDD, GAD, and SAD, with no detectable differences between treatments, although sample sizes for the MDD and SAD comparisons were small. In addition, additional efforts may be needed to keep MDD-comorbid patients in treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)