• bereavement
• complicated grief
• low magnitude events
• manic/hypomanic symptoms
• Mitochondrial translocatorprotein
• partial
• Peripheral Benzodiazepine Receptor (PBR)
• Post -Traumatic Stress Disorder(PTSD)
• stress
• subthreshold mania
• subthreshold symptoms

Post-Traumatic Stress Disorder (PTSD) is an invaliding psychiatric condition with typical onset following traumatic and stressful situations. Recently, nvestigators have emphasized the importance of a revision of current diagnostic criteria in order to include both a broaden spectrum of events among potential trauma,including the so called “low-magnitude” events, and subthreshold and subsyndromal forms of the disorder that are progressively showing to be as disruptive and invalidating as the full blown.
In line With these studies, researchers from the University of Pisa (Italy), as part of the international collaboration project named “Spectrum Project”, have developed a new instrument to assess the trauma and loss spectrum: the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal manifestations of Post-Traumatic Stress Disorder (PTSD) and prolonged grief disorder. This latest, also sometimes called Complicated Grief (CG), has been recently explored as an independent form of stress response. The items of the interview include, in addition to a subset of the DSM-IV criteria for PTSD, a number of features derived from clinical experience and from a review of the phenomenological descriptions of post-traumatic syndromes including CG. TheSCI-TALS also includes two specific sections that apply the “spectrum” concept to the definition of the trauma including losses and traumatic events, exploring both the exposure to DSM-IV qualifying traumas and less severe experiences.
Primary aim of the present thesis is to describe the SCI-TALS, and to evaluate its acceptability, validity and reliability that was assessed through a national multicenter validation study. Study participants were enrolled at 6I talian Academic Departments of Psychiatry coordinated by the University of Pisa, and included 48 consecutive patients with PTSD (DSM-IV), 44 with CG, and 48 healthy controls, with outcurrent or lifetime psychiatric history. Assessments included: SCID (DSM-IV-TR), IES, ICG.
The SCI-TALS significantly discriminated subjects with PTSD or CG from controls. As expected, the instrument did not discriminate between those with PTSD and CG, except on the domain of grief reactions. Validity and reliability of the instrument were proved to be substantial and acceptability was excellent.
Besides progresses in clinical assessments, recent studies attempting to delineate clear-cut diagnostic criteria for PTSD, have suggested the relevance of biological markers of PTSD. Although the findings have been highly variable, a great number of data have suggested the presence of characteristic alterations in the function of hypothalamic -pituitary-adrenal (HPA) axis and some reported alterations in the mitochondrial translocator protein (Peripheral Benzodiazepine Receptor, PBR), that is a protein complexessential for steroid synthesis. PBR has been found decreased in combat-related PTSD but no data have been reported in non-combat related PTSD.
Secondary aim of the present thesis was to assess mitochondrial PBR density in lymphomonocytes from civilian patients with PTSD (DSM-IV), exposed to non¬ combat related traumas versus controls.
Moreover, in psychiatric literature, the presence of a manic/hypomanic state has been recently hypothesized as the most critical risk factor for PTSD onset after trauma exposure in patients with Bipolar Disorder. Secondary aim of the present thesis was also to explore the correlation between PBR density and the presence of lifetime manic/hypomanic spectrum symptoms.
Assessments for this second phase of the study included the MOOD Spectrum Self Report (MOODS-SR) lifetime version, as harpened instrument assessing mood spectrum symptomatology, that was administered to those patients with PTSD and controls that, enrolled for the multicenter national validation study at the Pisa site, accepted to complete this second phase of thestudy after procedures and possible side effects were explained to them. Blood samples (16 ml) were processed to assess PBR binding parameters in lymphomonocyte mitochondrial membranes.
Results show that PTSD patients presented significant PBR density decrease with respect to controls. No correlation resulted between PBR density and IES scores. Significant correlation was found between PBR density and the number of lifetime MOODS-SR manic/hypomanic symptoms.
In conclusion,data from the present thesis show that the SCI-TALS is a userfriendly instrument to both clinicians and patients that provides information on a broads pectrum of trauma, loss events and related symptoms beyond those covered by existing instruments and maybe used in research settings. Moreover, for the first time, PBR density decrease has been reported in PTSD patients with not war-related traumas, supporting the potential role of this biochemical marker in PTSD diagnosis. A significant correlation between this alteration and the presence of lifetime manic spectrum symptoms was found, corroborating the relevance of an accurate assessment of subthreshold mania as risk factor for PTSD.