Biomarkers of Change in BPD After Metacognitive Interpersonal Therapy-standard Approach (CLIMAMITHE)

Neuroimaging and Clinical Markers of Change in Borderline Personality Disorder After Metacognitive Interpersonal Therapy - Standard Approach

The present randomised clinical trial aims to assess the clinical and neurobiological changes following Metacognitive Interpersonal Therapy -standard approach (MIT-SA) compared with Clinical Structured Treatment (CST) derived from specific recommendations in APA guidelines for borderline personality disorder (BPD). The investigators will assess clinical changes in metacognitive abilities and in emotion regulation and changes in brain activation patterns at the resting state and while they view emotional pictures. A multidimensional assessment will be performed at the baseline, at 6, 12, 18 months. The investigators will take structural and functional Magnetic Resonance Images (MRIs) in MIT-Treated BPD (N=30) and CST-treated BPD (N=30) at baseline and after treatment, as well as a group of 30 healthy and unrelated volunteers that will be scanned once for comparison. Furthermore, blood analyses will be done in order to assess level of BDNF and some hormone levels (oxytocin and vasopressin) before and after treatments.

Patients will be randomly allocate to two kind of interventions: MIT-SA and CST. Patients will be enrolled in 3 centres: Unit of Psychiatry, IRCCS San Giovanni di Dio-FBF, Brescia; Terzo Centro di Psicoterapia Cognitiva-School of Cognitive Psychotherapy, Rome; Mental Health Department ASL Roma G, Rome, Italy. A multidimensional evaluation with standardized tools will assess: level of psychopathology, depression, anger, impulsiveness, level of functioning. In particular, the assessment will include: the Structured Clinical Interview for DSM disorder; the Difficulties in Emotion Regulation Scale (DERS) (primary outcome); Metacognition Assessment Interview to assess metacognitive functions. Neuropsychological assessment will assess different cognitive domains, empathy and emotional recognition with standardized tools . Additionally, the emotional priming paradigm to evaluate emotion processing will be included. Data on demographics, traumatic exposure, suicide attempts, self-injury and aggression episodes, hospitalizations, and pharmacotherapy will be collected. Structural and functional MRI will be collected in MIT-Treated BPD (N=30) and CST-treated BPD (N=30) at baseline and after treatment. Healthy volunteers (N=30) will be scanned once for comparison. Specific MRI analyses:1) Whole brain (cortical thickness) analyses will be conducted to explore the correlates of psychotherapy and treatment response. Functional connectivity studies will consider A) activity at rest, both before and after treatment; B) functional activation in response to standardized emotional material from the International Affective Pictures System (IAPS). 2) Region of interest analyses: regions of particular elevance (hippocampus, amygdale, insula) will be studied using advanced neuroimaging tools. Blood samples will be collected in order to assess variations in levels of BDNF and some hormones (oxytocin and vasopressin) pre- and post treatment.

Metacognitive Interpersonal Therapy -standard approach (MIT-SA) is a cognitive behavior-based psychotherapeutic approach that works to increase metacognitive abilities and to improve interpersonal relationships

Clinical changes in metacognitive abilities and in emotion regulation assessed with the Difficulties in Emotion Regulation Scale (DERS)

Change from Baseline in activation in the amygdala at 12 months in response to standardized emotional material from the International Affective Pictures System

Inclusion Criteria: Meet DSM 5 criteria for BPD Able to provide informed consent Exclusion Criteria: lifetime diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, organic mental syndromes; active substance abuse or dependence in the 6 months before the enrolment; concurrent psychotherapy; cognitive impairment or dementia; relevant neurological signs; pregnancy/lactating.

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Magni LR, Carcione A, Ferrari C, Semerari A, Riccardi I, Nicolo' G, Lanfredi M, Pedrini L, Cotelli M, Bocchio L, Pievani M, Gasparotti R, Rossi R; CLIMAMITHE Study group. Neurobiological and clinical effect of metacognitive interpersonal therapy vs structured clinical model: study protocol for a randomized controlled trial. BMC Psychiatry. 2019 Jun 24;19(1):195. doi: 10.1186/s12888-019-2127-2.