G. Camuri

Epigenetic modulation of BDNF gene: Differences in DNA methylation between unipolar and bipolar patients

BACKGROUNDnThe brain derived neurotrophic factor (BDNF) gene and its epigenetic regulation have been repeatedly implicated in the pathophysiology of mood disorders. Following previous investigation in the field, we further investigated differences in BDNF promoter gene methylation in patients with mood disorders, comparing unipolar and bipolar subjects, on the basis of illness phase, gender, age and psychotropic prescription.nnnMETHODSn154 patients (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, and 44 age-matched, healthy controls were recruited. BDNF methylation levels from peripheral blood mononuclear cells (PBMCs) were compared by analysis of variance followed by Bonferroni׳s post-hoc test.nnnRESULTSnSimilar, higher levels of BDNF gene promoter methylation were found in BD II and MDD patients, compared to BD I subjects (P<0.01). When stratified on the basis of mood status, methylation levels of depressed patients were significantly higher, compared to the levels of manic/mixed patients (P<0.01). While gender and age did not seem to influence methylation levels of BDNF gene promoter, patients on lithium and valproate showed overall lower levels.nnnLIMITATIONSnCross-sectional analysis using PBMCs with further investigation with larger samples, including drug-naïve patients, needed to replicate findings in neuronal cells.nnnCONCLUSIONSnPresent data confirm our previous results of higher methylation levels in BD II (compared to BD I) and MDD patients (compared to controls). A closer relationship between BD II and MDD, compared to BD I patients as well an association of lower methylation levels with the presence of mania/mixed state, compared to the depressive phase, was observed.

Patterns of Axis I comorbidity in relation to age in patients with Bipolar Disorder: A cross-sectional analysis

BACKGROUNDnSeveral data indicate that the clinical course and treatment response of Bipolar Disorder (BD) is influenced by comorbidity. However, whether differences in comorbidity patterns exist in relation to classes of age remains debated. The present study was aimed to evaluate differences in terms of cross-sectional Axis I comorbidity among young (≤30 years), adult (>30 and ≤45 years) and older adult patients with BD (>45 years).nnnMETHODSnStudy sample included 508 patients with BD, subdivided into 3 groups of age: ≤30 years (n=52), >30 and ≤45 years (n=186) and >45 years (n=270). Demographic and clinical variables, with specific emphasis on Axis I comorbidity, were compared across the different groups using chi-square tests. Furthermore, a binary logistic regression was performed.nnnRESULTSnTwo-hundred eleven patients (41.5%) showed at least another concomitant Axis I disorder. The 3 groups were homogenous in terms of type of diagnosis (type 1 or 2 BD) and gender. However, they were different in terms of cross-sectional Axis I comorbidity (p=0.001) with a higher frequency of substance abuse (p=0.04) and Anorexia (p=0.014) in young patients, and of Obsessive Compulsive Disorder in adult patients (p=0.001). In addition, young patients showed more frequently the presence of a second comorbid Axis I condition compared to the other sub-groups (p=0.05). With regard to the type of abuse, young subjects were more frequently cannabis (p<0.001) and cocaine abusers (p<0.001) compared to the other subgroups.nnnLIMITATIONSnLifetime Axis I and Axis II and cross-sectional Axis II comorbidity patterns were not analyzed.nnnCONCLUSIONSnPreliminary results from the present exploratory study seem to suggest different profiles of cross-sectional Axis I comorbidity and abuse in bipolar patients in relation to age. This aspect should be taken into account for the choice of pharmacological treatments and global management in clinical practice.

Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessive–compulsive disorder

The latency to first pharmacological treatment (duration of untreated illness or ‘DUI’) is supposed to play a major role in terms of outcome in psychotic conditions. Interest in the field of affective disorders and, in particular, of duration of untreated anxiety, has been recently registered as well. However, a preliminary epidemiologic investigation of the phenomenon is necessary. The present study was aimed to investigate and compare age at onset, age at first pharmacological treatment and DUI in a sample of patients affected by different anxiety disorders. DUI was defined as the interval between the onset of the specific anxiety disorder and the administration of the first adequate pharmacological treatment in compliant subjects.

Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features

BACKGROUNDnThe presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the with psychotic features specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area.nnnMETHODSnThe present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N=360), with (BDPs, N=207) and without a lifetime history of psychosis (BDNPs, N=153).nnnRESULTSnAn overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7±10.5 vs 30.1±12.3years; p=0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p<0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p<0.001) and most recent episode (69.8% vs 35.6%; p<0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p=0.002), more lifetime hospitalizations (3.8±6.1 vs 2±3; p=0.002) and involuntary commitments (1±1.9 vs 0.1±0.4; p<0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p=0.001), more current antipsychotic use (90.1% vs 70.9%; p<0.001), and lower GAF (62.3±14.2 vs 69.3±12.5; p<0.001), but shorter duration of most recent episode (34.1±45.4 vs 50.3±65.7days; p=0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p=0.005), and antidepressant use (19.4% vs 56.6%; p<0.001).nnnCONCLUSIONSnThe present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.

Structural and metabolic differentiation between bipolar disorder with psychosis and substance-induced psychosis: An integrated MRI/PET study

BACKGROUNDnBipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET).nnnMETHODSnTwenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired.nnnRESULTSnGray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients.nnnCONCLUSIONSnThese findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.

Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders.

Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori‐defined epochs.

Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.

The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness‐intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs.

Prevalence and disability of comorbid social phobia and obsessive–compulsive disorder in patients with panic disorder and generalized anxiety disorder

Abstract Objective. Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive–compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58). Methods. Patients were classified as having threshold, subthreshold, or no comorbidity, and related prevalence rates, as well as disability (Sheehan Disability Scale, SDS), were compared across diagnostic subgroups. Results. SP and OCD comorbidities were present in 30.4% of the sample, with subthreshold comorbidities present at twice the rate of threshold ones (22.6% vs. 11.3%). Compared with GAD patients, PD patients showed significantly higher subthreshold and threshold comorbidity rates (27.6% and 13.8% vs. 17.5% and 8.8%, respectively). Comorbid PD patients had higher SDS scores than the comorbid and non-comorbid GAD subjects. The presence of threshold SP comorbidity was associated with the highest SDS scores. Conclusions. SP and OCD comorbidities were found to be prevalent and disabling among GAD and PD patients, with higher subthreshold than threshold rates, and a negative impact on quality of life. Present findings stress the importance of a dimensional approach to anxiety disorders, the presence of threshold and subthreshold comorbidity being the rule rather than the exception.

Italian patients with more recent onset of Major Depressive Disorder have a shorter duration of untreated illness

Previous investigation on the duration of untreated illness (DUI) in patients with Major Depressive Disorder (MDD) revealed a different latency to first antidepressant treatment, with adverse consequences in terms of outcome for individuals with a longer DUI. Recent reports, moreover, documented a reduced DUI, as observed with the passage of time, in patients with different psychiatric disorders. Hence, the present study was aimed to assess DUI and related variables in a sample of Italian patients with MDD as well as to investigate potential differences in subjects with onset before and after 2000.

P-597 - Determination of psychopatological onset and latency to treatment in psychiatric disorders through the “psychopatological onset and latency to treatment questionnaire”

Introduction Few questionnaires on the psychopathological onset and latency to treatment in psychiatric patients are currently available. Objectives In this perspective we developed a brief questionnaire: the Psychopathological Onset Latency and Treatment Questionnaire (POLQ). Methods The questionnaire was administered to 265 patients with any psychiatric diagnosis. Statistical analyses were performed using SPSS. Results The sample showed the following demographic variables in terms of age (48xa0±xa015 years), occupation (17% unemployed) and familiarity (54%). Clinical variables included: age at onset (30.66xa0±xa015 years), age at first diagnosis (36xa0±xa019 years) and age at first drug treatment (35xa0±xa014 years). The most common symptoms at onset were related to the anxiety spectrum (41.2%), mood spectrum (24.5%) or both (25.3%). Stressful life-events in relation to onset occurred in 63% of patients (12.1% familiar issues, 11.3% work problems, bereavement or end of a relationship in 16.6%). Most frequent first diagnoses were major depressive episode (26.8%), manic/hypomanic/mixed episode (13.6%) and anxiety disorders (11.7%). Average latency to the first visit was 34 months. In the 76.2% of the sample, the first contact was with a psychiatrist, a psychologist in 15.8%; 78.1% were treated with drugs as a first treatment, 11.7% with psychotherapy, 7.2% with both. The average duration of first treatment was 23 months (4 weeks - 360 months) and reasons for discontinuation were: lack of efficacy (23.8%) or complete remission (21.9%). Conclusions POLQ resulted to be a useful and reliable instrument in the collection of information on the psychopatological onset and latency to treatment.