Carlotta Palazzo

The C9ORF72 hexanucleotide repeat expansion is a rare cause of schizophrenia

A hexanucleotide repeat expansions in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. The same mutation has been described in a patient with bipolar disorder, but up to now, not in patients suffering from schizophrenia. We determined the frequency of the C9ORF72 hexanucleotide repeat expansions in a population of 298 patients with schizophrenia or schizoaffective disorder. The pathogenic repeat expansion was detected in 2 patients (0.67%). Both of them presented with auditory hallucinations and had comorbid alcohol abuse. In addition, a positive family history for psychiatric and/or neurodegenerative diseases was present. The repeat expansion in the C9ORF72 gene is a rare, but possible, cause of schizophrenic spectrum disorders. We cannot rule out however whether the number of repeats influence the phenotype.

Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia

Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n = 271) or BPD (n = 237) as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls. A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49–0.80), rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55–0.89) and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56–0.91). Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001) and were not correlated with age. In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

OBJECTIVE Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. METHODS In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. RESULTS The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. CONCLUSIONS Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD.

Childhood, adolescent and adult age at onset and related clinical correlates in obsessive–compulsive disorder: a report from the International College of Obsessive–Compulsive Spectrum Disorders (ICOCS)

Abstract Objective: Many studies suggest that age at onset (AAO) is an important factor for clinically differentiating patients with juvenile and adult onset of obsessive–compulsive disorder (OCD). The present international study aimed to assess the prevalence of different AAO groups and compare related socio-demographic and clinical features in a large sample of OCD patients. Methods: A total of 431 OCD outpatients, participating in the ICOCS network, were first categorised in groups with childhood (≤12 years), adolescent (13–17 years) and adult-onset (≥18 years), then in pre-adult and adult onset (≥18 years) and their socio-demographic and clinical features compared. Results: Twenty-one percent (n = 92) of the sample reported childhood onset, 36% (n = 155) adolescent onset, and 43% (n = 184) adult onset. Patients with adult onset showed a significantly higher proportion of females compared with the other subgroups (χ2 = 10.9, p< 0.05). Childhood- and adolescent-onset patients had been more frequently treated with cognitive behavioural therapy (CBT), compared to adult-onset patients (χ2 = 11.5; p < 0.05). The pre-adult- versus adult-onset analysis did not show any additional significant difference. Conclusions: The present international multicentre study confirms that OCD onset occurs more frequently before adult age, with approximately one out of five patients showing childhood onset. Pre-adult onset was associated with higher rate of CBT, while adult onset was more prevalent in females.

Factors characterizing access and latency to first pharmacological treatment in Italian patients with schizophrenia, mood, and anxiety spectrum disorders

Latency to first pharmacological treatment [duration of untreated illness (DUI)] in psychiatric disorders can be measured in years, with differences across diagnostic areas and relevant consequences in terms of socio-occupational functioning and outcome. Within the psychopathological onset of a specific disorder, many factors influence access and latency to first pharmacotherapy and the present study aimed to investigate such factors, through an ad-hoc developed questionnaire, in a sample of 538 patients with diagnoses of schizophrenia-spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients with SZs showed earlier ages at onset, first diagnosis and treatment, as well as shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently onset-related stressful events, benzodiazepines as first treatment, and autonomous help seeking compared with patients with SZs. In terms of first therapist, psychiatrist referral accounted for 43.6% of the cases, progressively decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas psychologist referrals remained constant. The present findings confirm the presence of a relevant DUI in a large sample of Italian patients with different psychiatric disorders (5 years, on average), pointing out specific differences, in terms of treatment access and latency, between psychotic and affective patients. Such aspects are relevant for detection of at-risk patients and implement early intervention programs.

Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

OBJECTIVE Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. METHODS A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearsons chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. RESULTS 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. CONCLUSIONS Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.

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.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS)

INTRODUCTION Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age<vs≥65years, and then divided on the basis of the median age of the sample (age<vs≥42years). Socio-demographic and clinical variables were compared between groups (Pearson Chi-squared and t tests). RESULTS G-OCD compared with younger patients represented a significant minority of the sample (6% vs 94%, P<.001), showing a significantly later age at onset (29.4±15.1 vs 18.7±9.2years, P<.001), a more frequent adult onset (75% vs 41.1%, P<.001) and a less frequent use of cognitive-behavioural therapy (CBT) (20.8% vs 41.8%, P<.05). Female gender was more represented in G-OCD patients, though not at a statistically significant level (75% vs 56.4%, P=.07). When the whole sample was divided on the basis of the median age, previous results were confirmed for older patients, including a significantly higher presence of women (52.1% vs 63.1%, P<.05). CONCLUSIONS G-OCD compared with younger patients represented a small minority of the sample and showed later age at onset, more frequent adult onset and lower CBT use. Age at onset may influence course and overall management of OCD, with additional investigation needed.

Which factors influence onset and latency to treatment in generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder?

Anxiety disorders are common, comorbid, and disabling conditions, often underdiagnosed and under-treated, typically with an early onset, chronic course, and prolonged duration of untreated illness. The present study aimed to explore the influence of sociodemographic and clinical factors in relation to onset and latency to treatment in patients with generalized anxiety disorder (GAD), panic disorder (PD), and obsessive–compulsive disorder (OCD). A total of 157 patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM-IV-TR) diagnosis of PD (n=49), GAD (n=68), and OCD (n=40) were recruited, and epidemiological and clinical variables were collected through a specific questionnaire. Statistical analyses were carried out to compare variables across diagnostic groups. PD, GAD, and OCD patients showed a duration of untreated illness of 53.9±81.5, 77.47±95.76, and 90.6±112.1 months, respectively. Significant differences between groups were found with respect to age, age of first diagnosis, age of first treatment, family history of psychiatric illness, onset-related stressful events, benzodiazepine prescription as first treatment, antidepressant prescription as first treatment, and help-seeking (self-initiated vs. initiated by others). Patients with GAD, PD, and OCD showed significant differences in factors influencing onset and latency to treatment, which may, in turn, affect condition-related outcome and overall prognosis. Further studies with larger samples are warranted in the field.

EXPLORING SOCIODEMOGRAPHIC AND CLINICAL CORRELATES OF OLDER ADULTS WITH OBSESSIVE-COMPULSIVE DISORDER: A REPORT FROM THE INTERNATIONAL COLLEGE OF OBSESSIVE-COMPULSIVE DISORDERS (ICOCS)

. Introduction Obsessive compulsive disorder (OCD) is a chronic and disabling condition, often showing an early onset (1). OCD has been extensively studied in adults, adolescents, and children, but a critial gap remains in the clinical characterization of older patients (2). The present study was aimed to assess prevalence of geriatric OCD (G-OCD ≥ 65 years) and associated sociodemographic and clinical correlates of geriatric OCD in a large international sample of OCD patients. Methods Data of 416 outpatients recruited by different OCD Clinics worldwide, participating in the International College of Obsessive-compulsive Spectrum Disorders (ICOCS) network (3), were assessed and first categorized into 2 groups, age Results Patients with G-OCD represented a significant minority of the overall sample (n=24, 6% of the total sample vs age When the whole sample was divided on the basis of the median age (age Conclusions The present international multicenter study revealed a significantly lower rate of patients with age ≥ 65 years compared to patients younger than 65 years. Patients with G-OCD showed a significantly higher age at onset and rate of adult onset compared to non-geriatric patients. Moreover, in G-OCD patients CBT was less frequently utilized. Subgroups divided on the basis of the median age of the sample showed that the age ≥ 42 years group had a significantly later onset of illness and higher rate of adult onset and female gender.