3 Chapter 1. Separation anxiety disorder ... pag.06 1.1 Separation anxiety disorder... pag.06 1.2 Adult separation anxiety disorder ... pag.06 1.3 Biological Correlates of ASAD... pag.07 1.4 Pharmacological treatment of Anxiety Disorder... pag.08 Chapter 2. Translocator protein: structure, functions and involvement in pathology .. pag.10 2.1 Translocator protein ... pag.10 2.2 Molecular identity of TSPO ... pag.10 2.3 Molecular structure of TSPO ... pag.11 2.4 Biosynthesis of neuroactive steroids... pag.13 2.5 Modulation of γ-aminobutyric acid type A (GABAA) receptors by neuroactive
steroids... pag.15 2.6 TSPO and cholesterol ... pag.15 2.7 TSPO distribution in healthy tissues ... pag.17 2.8 TSPO expression in pathological specimens ... pag.17 2.9 Psichiatric Disorder and steroids... pag.18 2.10 Anxiety Disorder and TSPO ... pag.20 Chapter 3. Ala147Thr substitution in Translocator Protein (TSPO) is associated
with adult separation anxiety in patients with depression ... pag.22 3.1 Aim of the study ... pag.22 3.2 Experimental section ... pag.23 3.2.1 Subject ... pag.23 3.2.2 Psichometric evaluation ... pag.23 3.2.3 DNA Genotyping... pag.24 3.2.4 Statistical analysis ... pag.25 3.3 Results and discussion ... pag.26 Chapter 4. The spontaneous Ala147Thr aminoacid substitution within the
Translocator Protein influences pregnenolone production in lymphomonocytes
of healthy individuals ... pag.29 4.1 Aim of the study ... pag.29 4.2 Experimental section ... pag.30 4.2.1 Subjects ... pag.30 4.2.2 DNA genotyping ... pag.30 4.2.3 Pregnenolone measurement ... pag.30
4 4.2.4 Cholesterol parameters determination ... pag.32 4.2.5 Statistical analysis ... pag.32 4.3 Results and discussion ... pag.34 4.3.1 Genotyping of the TSPO Ala147Thr SNP... pag.34 4.3.2 Characterization of pregnenolone synthetic enzyme expression ... pag.35 4.3.3 Pregnenolone assessment ... pag.37 4.3.4 Comparison of pregnenolone production in genotype groups ... pag.37 4.3.5 Comparison of plasma cholesterol parameters in genotype groups ... pag.39 Chapter 5. Translocator Protein and attachment styles among depressed
patients diagnosed with adult separation anxiety ... pag.41 5.1 Aim of the study ... pag.41 5.2 Experimental section ... pag.43 5.2.1 Subjects and psychometric evaluation ... pag.43 5.2.2 Adulthood separation anxiety evaluation ... pag.43 5.2.3 Attachment style evaluation ... pag.43 5.2.4 DNA genotyping ... pag.45 5.2.5 Statistical analysis ... pag.45 5.3 Results and discussion ... pag.46 5.3.1 TSPO G439A SNP association study... pag.46 5.3.2 Relationship between TSPO expression levels and G439A SNP...pag.47 Chapter 6. Oxytocin: structure, function and involvement in pathology...pag.50 6.1 Oxytocin: gene and peptide structures...pag.50 6.2 Oxytocin receptor ... pag.51 6.3 Oxytocin: mean peripheral functions ... pag.52 6.4 Brain functions of OXT ... pag.54 6.5 Behavioural actions of OXT in humans...pag.55 Chapter 7. Oxytocin receptor polymorphisms and adult attachment style in
patients with depression ... pag.57 7.1 Aim of the study ... pag.57 7.2 Experimental section ... pag.59 7.2.1 Subjects and psychometric evaluation ... pag.59 7.2.2 Attachment style evaluation ... pag.59 7.2.3 Adulthood separation anxiety evaluation ... pag.60
5 7.2.4 DNA genotyping and Haplotype analysis ... pag.60 7.2.5 RNA splicing analysis ... pag.61 7.2.6 Statistical analysis ... pag.61 7.3 Results and discussion ... pag.62 7.3.1 Case-control Associations ... pag.62 7.3.2 Haplotype Frequencies and Linkage Disequilibrium Pattern ... pag.63 7.3.3 Scores on HAM-D, HAM-A, Attachment Style Questionnaire and
Adult Separation Anxiety Checklist in GG individuals and A-Carries ... pag.64 7.3.4 RNA splicing analysis ... pag.66 7.3.5 Conclusion ... pag.67 References. ... pag.68