Borderline personality disorder traits and affect reactivity to positive affect induction followed by a stressor

BACKGROUND AND OBJECTIVES: Affective hyperreactivity is a core feature of Borderline Personality Disorder (BPD), yet little is known about reactivity of positive affect (PA). Objectives were to explore the relationship between BPD traits and affect reactivity in response to a personalized PA-induction and a subsequent stressor. Patient status (seeking outpatient treatment for personality-related problems; yes/no), depressive symptoms, and age were examined as alternative predictors of affect reactivity. METHODS: One hundred and eight females (35 patients) reported on their BPD and depressive symptoms. They completed the Best Possible Self-exercise and a modified Trier Social Stress Task. Trajectories of high and low arousal PA (HAP and LAP) and negative affect (NA) were analyzed with mixed regression modelling. RESULTS: Patient status (for HAP) and depressive symptoms (for LAP and NA) predicted affect reactivity better than BPD traits. Patients showed a weaker HAP increase after PA-induction, and a similar HAP decrease after the stressor, compared to non-patients. Higher depressive symptoms predicted stronger improvement of LAP and NA after PA-induction, and less pronounced deterioration of LAP and NA after the stressor, relative to baseline. LIMITATIONS: The sample was a convenience sample amplified with outpatients. Future research should (1) use clinical groups, (2) randomize to neutral vs. PA-induction, and (3) continue to differentiate between HAP and LAP. CONCLUSIONS: Our results do not support models postulating BPD-specific affective hyperreactivity. HAP and LAP have different trajectories, depending on the degree of psychopathology. The resilience-enhancing potential of a PA-focus in psychotherapy needs further research

Positive cognitive behavior therapy in the treatment of depression:A randomized order within-subject comparison with traditional cognitive behavior therapy

Previous research suggests that a stronger focus on positive emotions and positive mental health may improve efficacy of Cognitive Behavior Therapy (CBT). Objectives were to compare differential improvement of depressive symptoms (primary outcome), positive affect, and positive mental health indices during positive CBT (P-CBT; CBT in a solution-focused framework, amplified with optional positive psychology exercises) versus traditional, problem-focused CBT (T-CBT). Forty-nine patients with major depressive disorder (recruited in an outpatient mental health care facility specialized in mood disorders) received two treatment blocks of eight sessions each (cross-over design, order randomized). Intention-To-Treat mixed regression modelling indicated that depressive symptoms improved similarly during the first, but significantly more in P-CBT compared to T-CBT during the second treatment block. Rate of improvement on the less-frequently measured secondary outcomes was not significantly different. However, P-CBT was associated with significantly higher rates of clinically significant or reliable change for depression, negative affect, and happiness. Effect sizes for the combined treatment were large (pre-post Cohen's d = 2.71 for participants ending with P-CBT, and 1.85 for participants ending with T-CBT). Positive affect, optimism, subjective happiness and mental health reached normative population averages after treatment. Overall, findings suggest that explicitly focusing on positive emotions efficiently counters depressive symptoms

Positivity pays off:Clients' perspectives on positive compared with traditional cognitive behavioral therapy for depression

In this qualitative study, we explored the experiences of clients receiving cognitive behavioral therapy (CBT) for major depressive disorder. All participants received 8 sessions of traditional CBT (based on Beck, Rush, Shaw, & Emergy, 1979) and 8 sessions of positive CBT (order counterbalanced). The aim of the study was to examine clients' experience of positive CBT and to contrast this with their experience of traditional CBT. Positive CBT structurally and selectively focuses on better moments (exceptions to the problem as opposed to the problem), strengths, and positive emotions and integrates traditional CBT with solution-focused brief therapy and positive psychology. In addition to conducting interviews with 12 individuals, the second author attended all therapy sessions of 4 clients and observed biweekly supervision sessions as further methods of data collection. Qualitative analysis showed that, despite initial skepticism, clients preferred positive CBT and indicated experiencing a steeper learning curve during positive, compared with traditional, CBT for depression. The popularity of positive CBT was attributable to 4 influences: feeling good and empowered, benefitting from upward spiral effects of positive emotions, learning to appreciate baby steps, and (re)discovering optimism as a personal strength. Qualitative analysis showed that, despite better moments and building positivity efficiently counters depressive symptoms and builds well-being. Clients perceived positive CBT's upbeat tone as stimulating and as motivating for change. (PsycINFO Database Record (c) 2020 APA, all rights reserved)

Efficacy of mindfulness-based cognitive therapy in relation to prior history of depression: randomised controlled trial

Background: There appears to be consensus that patients with only one or two prior depressive episodes do not benefit from treatment with mindfulness-based cognitive therapy (MBCT). Aims: To investigate whether the effect of MBCT on residual depressive symptoms is contingent on the number of previous depressive episodes (trial number NTR1084). Method: Currently non-depressed adults with residual depressive symptoms and a history of depression (≤2 prior episodes: n = 71; ≥3 episodes: n = 59) were randomised to MBCT (n = 64) or a waiting list (control: n = 66) in an open-label, randomised controlled trial. The main outcome measured was the reduction in residual depressive symptoms (Hamilton Rating Scale for Depression, HRSD-17). Results: Mindfulness-based cognitive therapy was superior to the control condition across subgroups (β = -0.56, P<0.001). The interaction between treatment and subgroup was not significant (β = 0.45, P = 0.16). Conclusions: Mindfulness-based cognitive therapy reduces residual depressive symptoms irrespective of the number of previous episodes of major depression

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Preliminary clinical and cost effectiveness of augmented depression therapy versus cognitive behavioural therapy for the treatment of anhedonic depression (ADepT): a single-centre, open-label, parallel-group, pilot, randomised, controlled trial

Background Anhedonia (reduced interest/pleasure) symptoms and wellbeing deficits are core to depression and predict a poor prognosis. Current depression psychotherapies fail to target these features adequately, contributing to sub-optimal outcomes. Augmented Depression Therapy (ADepT) has been developed to target anhedonia and wellbeing. We aimed to establish clinical and economic proof of concept for ADepT and to examine feasibility of a future definitive trial comparing ADepT to Cognitive Behavioural Therapy (CBT). Methods In this single-centre, open-label, parallel-group, pilot randomised controlled trial, adults meeting diagnostic criteria for a current major depressive episode, scoring ≥10 on the Patient Health Questionnaire (PHQ-9) and exhibiting anhedonic features (PHQ-9 item 1 ≥ 2) were recruited primarily from high intensity Improving Access to Psychological Therapy (IAPT) service waiting lists in Devon, UK. Participants were randomised to receive 20 sessions of CBT or ADepT, using a mimimisation algorithm to balance depression severity and antidepressant use between groups. Treatment was delivered in an out-patient university-based specialist mood disorder clinic. Researcher-blinded assessments were completed at intake and six, 12, and 18 months. Co-primary outcomes were depression (PHQ-9) and wellbeing (Warwick Edinburgh Mental Wellbeing Scale) at 6 months. Primary clinical proof-of-concept analyses were intention to treat. Feasibility (including safety) and health economic analyses used complete case data. This trial is registered at the ISRCTN registry, ISRCTN85278228. Findings Between 3/29/2017 and 7/31/2018, 82 individuals were recruited (102% of target sample) and 41 individuals were allocated to each arm. A minimum adequate treatment dose was completed by 36/41 (88%) of CBT and 35/41 (85%) of ADepT participants. There were two serious adverse events in each arm (primarily suicide attempts; none of which were judged to be trial- or treatment-related), with no other evidence of harms. Intake and six-month primary outcome data was available for 37/41 (90%) CBT participants and 32/41 (78%) ADepT participants. Between-group effects favoured ADepT over CBT for depression (meanΔ = −1.35, 95% CI = −3.70, 1.00, d = 0.23) and wellbeing (meanΔ = 2.64, 95% CI = −1.71, 6.99, d = 0.27). At 18 months, the advantage of ADepT over CBT was preserved and ADepT had a >80% probability of cost-effectiveness. Interpretation These findings provide proof of concept for ADepT and warrant continuation to definitive trial

Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes

The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11–q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3×10−5). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3×10−4). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3×10−39), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts