Matteo Muti

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.

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.

Serum uric acid levels and different phases of illness in bipolar I patients treated with lithium

Recent findings support the role of purinergic system dysfunction in the pathophysiology of bipolar disorder (BD). The present study aimed to evaluate the pattern of serum uric acid levels in a sample of 98 BD I patients followed-up prospectively in a naturalistic study and treated with lithium monotherapy or in association with other mood stabilizers (valproate or carbamazepine), in relation to different phases of illness and to pharmacological treatment. The results showed that uric acid levels were significantly higher in patients suffering from a manic/mixed episode, than in those euthymic or during a depressive phase. Further, these levels were related to the Clinical Global Impression-Bipolar Version (CGI-BP) scale score for the severity of manic symptoms. A positive correlation was found also with male sex and with serum lithium levels. These findings suggest that a dysregulation of the purinergic system may occur during manic/mixed episodes, and they support a possible role of serum uric acid levels as a state-dependent marker of BD manic phases.

Prescribing patterns of lithium or lithium+valproate in manic or mixed episodes: a naturalistic study.

The present study aimed to identify the prescribing patterns of lithium or of lithium+valproate in 75 bipolar I outpatients in a manic or a mixed phase within a naturalistic setting. The differences between the two treatments and the correlation between serum lithium levels and response were also examined. The results showed that patients with lithium levels of 0.60 mEq/l or more had higher remission rates and greater symptom reduction than the other patients. Patients on lithium and valproate showed greater improvement in mixed, anxiety, and psychotic symptoms than those on lithium only, as assessed by the Clinical Global Impression-Bipolar version scale scores. Finally, our findings suggest that a range of lithium levels between 0.40 and 0.60 mEq/l, albeit below the therapeutic range, seems sufficient to maintain a good effect when lithium is coadministered with valproate.