Camilla Gesi

Oxytocin receptor polymorphisms and adult attachment style in patients with depression

Much evidence of an association between specific attachment styles and depression prompted us to investigate, in depressive disorders, the potential role of polymorphisms within the gene encoding the receptor of the main neurohormone involved in attachment processes, oxytocin. For this purpose, two single nucleotide polymorphisms (SNPs), 6930G>A (rs53576) and 9073G>A (rs2254298), within the oxytocin receptor gene (OXTR), were studied in a cohort of 185 patients with major depression (50.3%) or bipolar I or II disorders (49.7%) and 192 matched healthy controls. A positive association between the GG genotype of OXTR SNPs (6930G>A or 9073G>A) and unipolar depression was demonstrated. In this group, GG individuals showed high scores on Attachment Style Questionnaire factors that have been previously associated with depression. Moreover, the GG genotype was also associated with high levels of adult separation anxiety. These findings support the involvement of the oxytocinergic system in the mechanisms that underlie depression and specific adult attachment styles.

Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders

Pini S, Abelli M, Shear KM, Cardini A, Lari L, Gesi C, Muti M, Calugi S, Galderisi S, Troisi A, Bertolino A, Cassano GB. Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders.

Ala147thr substitution in translocator protein is associated with adult separation anxiety in patients with depression

Departments of Human Morphology and Applied Biology, Psychiatry, Neurobiology, Pharmacology and Biotechnology, Biology, University of Pisa, Pisa and Psychiatry, University of Naples SUN, Naples, Italy Correspondence to Professor Stefano Pini, MD, Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy Tel: + 39 050 993559; fax: + 39 05

Peripheral-type benzodiazepine receptor binding sites in platelets of patients with panic disorder associated to separation anxiety symptoms.

RationaleAlthough it is still a matter of debate whether panic disorder (PD) and separation anxiety (SA) are associated or causally linked disorders, some investigators have suggested that SA may be a specific subtype of panic-agoraphobic spectrum. Several psychiatric disorders, including PD, are associated with lower levels of peripheral-type benzodiazepine receptor (PBR).ObjectivesThe aim of the present study was to evaluate the kinetic binding parameters of the specific PBR ligand, PK 11195, in platelets from patients with PD in relation to the presence and severity of adulthood SA.MethodsUsing the specific radioligand, [3H] PK 11195, the kinetic binding parameters of PBR were determined on platelet membranes of 27 adult outpatients with a DSM-IV diagnosis of PD and 18 healthy controls. Patients were assessed with the SCID-I, the Panic Disorder Severity Scale, the Structured Clinical Interview for Separation Anxiety Symptoms and the Adult Separation Anxiety Checklist.ResultsPD patients had significantly lower PBR density than controls. However, the lower density was only evident in the subgroup of PD patients who also fulfilled the DSM-IV criteria for adult separation anxiety disorder. PBR density was negatively correlated with each of the two SA scales total scores.ConclusionsPatients with SA symptoms had significantly lower densities of PBRs. PBR expression might become a useful biological marker of these two associated conditions.

Platelet 18 kDa Translocator Protein density is reduced in depressed patients with adult separation anxiety.

RATIONALE Recent studies indicate that Adult Separation Anxiety Disorder (ASAD) may represent a discrete diagnostic entity worthy of attention. Adults with separation anxiety report extreme anxiety and fear about separations from major attachment figures (partner, children or parents). These symptoms affect individuals behavior, lead to severe impairment in social relationships and are not better accounted for by the presence of agoraphobia. In a previous study we found platelet expression reduction of the 18 kDa Translocator Protein (TSPO) (the new nomenclature for the peripheral-type benzodiazepine receptor) in patients with panic disorder who also fulfilled the diagnostic criteria for ASAD. OBJECTIVES To explore whether separation anxiety might be a factor differentiating TSPO expression in a sample of patients with major depression. METHODS The equilibrium binding parameters of the specific TSPO ligand [3H]PK 11195 were estimated on platelet membranes from 40 adult outpatients with DSM-IV diagnosis of MDD, with or without separation anxiety symptoms, and 20 healthy controls. Patients were assessed by SCID-I, HAM-D, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-report Checklist (ASA-27). RESULTS A significant reduction of platelet TSPO density mean value was found in depressed patients with associated ASAD symptoms, while no significant differences were found between depressed patients without ASAD and the control group. Individual TSPO density values were significantly and negatively correlated with both SCI-SAS-A and ASA-27 total scores, but not with HAM-D total score or HAM-D anxiety/somatization factor score. CONCLUSIONS The reduction of platelet TSPO density in our sample of patients with depression was specifically related to the presence of ASAD. These data suggest that TSPO expression evaluation is a useful biological marker of ASAD.

The relationship between adult separation anxiety disorder and complicated grief in a cohort of 454 outpatients with mood and anxiety disorders.

BACKGROUND Recent epidemiological studies indicate that separation anxiety disorder occurs more frequently in adults than children. Data from literature suggest that Adult Separation Anxiety Disorder (ASAD) may develop after a bereavement or threat of loss. Research has demonstrated that bereaved persons may present a clinically significant grief reaction, defined as Complicated Grief (CG) that causes a severe impairment in the quality of life. The aim of this study was to evaluate the relationship between ASAD and CG in a large cohort of outpatients with mood and anxiety disorders. METHODS Study participants comprised 454 adult psychiatric outpatients with DSM-IV mood or anxiety disorders diagnoses. Diagnostic assessments were performed using the SCID-I; ASAD was assessed using an adapted version of the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-adult). Complicated grief symptoms were assessed by the Inventory of Complicated Grief (ICG). Social and work impairments were evaluated using the Sheehan Disability Scale (SDS). Adult attachment styles were assessed by the Relationship Questionnaire (RQ). RESULTS The overall frequency of ASAD in our sample was 43% and that of CG was 23%. Individuals with CG had a greater frequency of ASAD (56%) with respect to those without CG (40%). Subjects with CG plus ASAD reported higher scores on ICG and greater impairment on quality of life, as measured with SDS, than CG patients without ASAD. CONCLUSIONS Adult separation anxiety disorder occurs in a high proportion of adult psychiatric outpatients with complicated grief. The association between these two conditions should be further investigated in light of their clinical implications.

A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts.

Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules. Furthermore, positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic–ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be antimanic. The aim of this review is to briefly summarize the potential benefits of lithium salts on neuroprotection and neuroregeneration, emphasizing preclinical and clinical evidence suggesting new therapeutic potentials of this drug beyond its mood stabilizing properties.

Reductions in Platelet 18-kDa Translocator Protein Density Are Associated with Adult Separation Anxiety in Patients with Bipolar Disorder

Background: Recent studies indicate that adult separation anxiety disorder is a discrete diagnostic entity and worthy of attention. Previously, we found a significant association between platelet expression of the 18-kDa translocator protein (TSPO) and adult separation anxiety in patients with panic disorder or major depression. The aim of this study was to explore whether adult separation anxiety might be a factor differentiating TSPO expression in a sample of patients with bipolar disorder. Methods: The equilibrium binding parameters of the specific TSPO ligand [3H]PK 11195 were estimated on the platelet membranes of 24 adult outpatients with a DSM-IV diagnosis of bipolar disorder (with or without separation anxiety disorder) and 14 healthy controls. Patients were assessed by SCID-I, HAM-D, YMRS, the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS-A) and the Adult Separation Anxiety Self-Report Checklist (ASA-27). Results: A significant reduction in mean platelet TSPO density was found in bipolar patients with respect to controls. However, the lower density was only evident in the subgroup of bipolar patients who also fulfilled DSM-IV criteria for adult separation anxiety disorder. Individual TSPO density values correlated significantly and negatively with both SCI-SAS-A and ASA-27 total scores. Conclusions: TSPO expression may be a useful biological marker of adult separation anxiety co-occurring with other anxiety and mood disorders, including bipolar disorder.

Impact of depression on circulating endothelial progenitor cells in patients with acute coronary syndromes: a pilot study.

Aims Depression has been identified as a risk factor for an adverse prognosis and reduced survival in patients with acute coronary syndrome (ACS). The number of endothelial progenitor cells (EPCs) is an independent predictor of clinical outcomes in patients with ACS. The aim of this study was to evaluate the impact of depression on EPC levels in patients with ACS. Methods Out of 74 ACS patients [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a diagnosis of major depressive episode (MDE) according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time of the inclusion in the study. Control groups were as follows: 15 healthy individuals and 18 patients with current MDE without a history of cardiovascular diseases. EPCs were defined as CD34+CD133+KDR+ and evaluated by flow cytometry. All patients underwent standardized cardiological and psychopathological evaluations. Parametric and nonparametric statistical tests were performed wherever appropriate. Results ACS patients with MDE showed a significant decrease in circulating EPC number compared with ACS patients without MDE (P < 0.001). The ACS study population was then subdivided into STEMI and NSTEMI groups, and within each group patients with MDE again showed a significant decrease in circulating CD34+CD133+KDR+ EPCs compared with others (P <0.001). Conclusion We showed that ACS patients with MDE have a reduced number of circulating CD34+CD133+KDR+ cells compared with ACS patients without MDE, suggesting that the presence of MDE reduces the response of bone marrow to acute ischemic events. Considering the reparative role of EPCs in ACS patients, we propose that patients with MDE might be protected less than patients without MDE.

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.