Marta Serati

Neuropsychobiological aspects, comorbidity patterns and dimensional models in borderline personality disorder.

Borderline personality disorder (BPD) is a comorbid and disabling condition with high prevalence in psychiatric settings. The pathogenesis of BPD involves complex interactions among genetic, neurobiological and environmental factors, resulting in multiple core symptom domains such as emotional dysregulation, impulse dyscontrol, aggression, cognitive dysfunctions and dissociative states. Neurobiological studies show that symptoms and behaviors of BPD are partly associated with alterations in glutamatergic, dopaminergic and serotonergic systems. In addition, neuroimaging studies in BPD patients indicate differences in the volume and activity of specific brain regions related to emotion and impulse control, such as the prefrontal and cingulate cortex, amygdala and hippocampus. Neurobiological alterations are related to cognitive disturbances in patients with BPD and neuropsychological tests have shown abnormalities of memory, attention, language, and executive functions. The aim of the present review is to provide an updated overview of the main neuropsychobiological aspects of BPD and their relation to clinical symptoms, comorbidity patterns and dimensional models.

Augmentative quetiapine in partial/nonresponders with generalized anxiety disorder: a randomized, placebo-controlled study.

Generalized anxiety disorder (GAD) is a chronic and disabling condition. The aim of this study was to evaluate the effectiveness of low-dose augmentative quetiapine (mean dose=50 mg/day) in patients with GAD and partial/no response to selective serotonin reuptake inhibitors (SSRIs). Twenty patients with GAD and partial/no response to SSRIs were randomized to quetiapine (n=10) or placebo (n=10) for 8 weeks, continuing their treatment with SSRIs. Analyses of variance with repeated measures on Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression (CGIs; severity of illness) were carried out at baseline and after 8 weeks and the number of responders/remitters was computed and compared between the groups. HAM-A scores at baseline were 15.60 (±4.48) in the placebo group and 18.50 (±6.59) in the quetiapine group, and at the end-point, HAM-A scores in the placebo group were 10.40 (±4.88) and 9.20 (±5.86) in the quetiapine group. A significant time-by-treatment effect was found on the HAM-A (F=5.19, P=0.035) and CGIs scores (F=19.60, P<0.001) in favor of the quetiapine group. The number of responders was numerically superior in the quetiapine group (60 vs. 30%) without reaching statistical significance (&khgr;2=1.82, degree of freedom=1, P=0.37, &phgr;=0.30). Remitters were 40% for the quetiapine group versus 20% for the placebo group (&khgr;2=0.95, degree of freedom=1, P=0.63, &phgr;=0.22). Low-dose augmentative quetiapine may be an useful treatment option for patients with GAD and partial/no response to SSRIs. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results. Larger randomized controlled trials are warranted to confirm these data.

Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia

The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed‐up for 36u2009months.

Duloxetine in Affective Disorders: a Naturalistic Study on Psychiatric and Medical Comorbidity, Use in Association and Tolerability Across Different Age Groups

Objective: Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is currently approved in many countries for the treatment of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD). The present naturalistic study was aimed to investigate tolerability of Duloxetine in a sample of patients with affective disorders and psychiatric/medical comorbidity, comparing tolerability in monotherapy versus polytherapy and across different age groups. Methods: The sample included 165 patients, affected by anxiety and/or mood disorders with or without comorbidity, who had been taken Duloxetine for at least 1 month. Sample variables were collected through a retrospective chart review. Results: Most common primary diagnoses were MDD (49.1 %), Bipolar Disorder (BD) (15.7 %) and GAD (5.5%). The 40 % of the sample had psychiatric comorbidity: in particular, anxiety disorders (15.8 %) (GAD 7.9%, Panic Disorder –PD- 7.3%) and personality disorders (9.1%) as the most frequent ones. With respect to medical comorbidities (68% of the sample), hypertension (12.1%) and diabetes (7.3%) were the most common ones. Mean duration of treatment and dosage of Duloxetine were, respectively, 11 months (± 9.1) and 70 mg/day (± 28.6). The 68 % of the sample received Duloxetine in association with other drugs. Minor side-effects, in particular drowsiness and gastrointestinal problems, were reported by 15 % of the sample. No difference in terms of tolerability across distinct groups, divided on the basis of mono- vs polytherapy as well as of different age, was found. Conclusion: Duloxetine, mostly administered in patients with affective disorders with psychiatric/ medical comorbidity and in association with other drugs, appeared to be well tolerated, showing limited rates of side effects of mild intensity. Further naturalistic studies are warranted to confirm present results.

The use of zonisamide for the treatment of psychiatric disorders: A systematic review

Objective Traditional pharmacotherapy has undoubtedly improved the outcome of patients with psychiatric disorders, but partial efficacy or poor tolerability persists in a number of these subjects. Among different compounds, zonisamide has been used to address unmet needs of standard pharmacotherapy. The purpose of the present article is to provide a review about the use of zonisamide for the treatment of psychiatric conditions. Methods A research in the main database sources has been conducted to obtain an overview of the use of zonisamide in psychiatric disorders or associated conditions (obesity and smoking cessation). Results Most available data indicate the possible effectiveness of zonisamide for the treatment of acute phases of bipolar disorder, binge-eating disorder (BED), alcohol misuse, and obesity. A further assessment of the safety and tolerability of zonisamide is made necessary by the fact that, with the exception of BED, for all other disorders at least some data come from studies with combined pharmacological therapies. Conclusions Zonisamide may have some utility, especially as an adjunctive therapy, for the management of acute phases and weight gain in bipolar disorder and for prevention of alcohol misuse. Preliminary evidence indicates zonisamide as a candidate compound for the treatment of BED and obesity. However, open-label design and small sample sizes of most available studies prevent from drawing sound conclusions about the utility of this compound in psychiatry.

Psychiatric Symptoms in Patients with Stroke: A Six-Month Follow-Up Study.

We read with interest the paper by Al-Busaidi and Alamri,1 wherein the authors found that 18.4% and 23.7% of poststroke patients, respectively, showed clinically significant anxiety and depression. We conducted a similar study with a sample of poststroke patients, but considering as predictors of future psychiatric illness also the clinical features associated with stroke. Psychiatric symptoms, social functioning, and quality of life of 36 patients (25 male and 11 female) with a diagnosis of stroke and with a mean age of 67 ± 13 years were evaluated during a 6-month follow-up period using the following rating scales: the Hamilton Depression Rating Scale (HAM-D) for depressive symptoms, the Hamilton Anxiety Rating Scale (HAM-A) and the State-Trait Anxiety Inventory (STAI-Y) for anxiety symptoms, the Brief Psychiatric Rating Scale (BPRS) for general psychopathology, the Mania Rating Scale (MRS) for manic symptoms, the Global Assessment of Functioning (GAF) and the Disability Scale (DISS) for the global functioning, and the European Quality of Life (EQ-5D) and the Short Form Health Survey 36 (SF-36) for the quality of life. We performed multivariate analyses of variance (MANOVAs) to compare the scores of rating scales in relation to the following: the presence of aphasia in the first hours after stroke, lesion site (cortical or subcortical one, right or left hemisphere, anterior or posterior circulation), and subtype of stroke (ischemic or hemorrhagic). During the follow-up period, only 1 patient developed a major depressive episode (HAM-D > 17) and 2 patients developed a hypomanic episode (MRS > 10). All these 3 patients had a psychiatric history or a family history of psychiatric disorders. Twelve patients (33%) developed subsyndromal depression (HAM-D score: 8-17)2 and 10 patients (28%) developed subsyndromal anxiety (HAM-A score: 10-17).3,4 The mean scores of rating scales resulted to be worse in patients with aphasia than in patients without aphasia: HAM-A at few days after stroke (8.75 ± 4.11 versus 2.90 ± 2.81, F = 9.065, P < .01), HAM-D at 3 months after stroke (9 ± 7.35 versus 2.10 ± 2.85, F = 6.95, P = .02) (Fig 1), GAF at 3 months after stroke (69.75 ± 12.69 versus 90.50 ± 8.96, F = 12.25, P < .01). Furthermore, the left-hemisphere strokes were associated with a worse psychopathological state and a worse perception of social functioning and quality of life during the follow-up period than the right-hemisphere ones: BPRS at 1 month after stoke (25.00 ± 4.07 versus 20.17 ± 2.48, F = 6.55, P = .03), global function of DISS at 1 month after stroke (10 ± 7.27 versus .83 ± 1.60, F = 9.03, P = .01). Finally, strokes of anterior circulation were associated with worse well-being perception than strokes of posterior circulation: general health of SF-36 at 3 months after stroke (52.30 ± 18.63 versus 77 ± 11.61, F = 5.93, P = .03). No statistically significant differences in rating scale scores were found in relation to subtype of stroke and cortical or subcortical lesion site. Similar to what was reported by Al-Busaidi and Alamri, we found that stroke survivors frequently develop subsequent subthreshold depressive symptoms and that history of psychiatric disorders might increase the vulnerability for mood disorders after a stroke. In our sample, a stroke did not result to be associated with major mood episodes during the 6-month follow-up period, but it might unmask a vulnerability for affective disorders. Aphasia was found to be a predictor of psychiatric symptoms, particularly anxiety, and of worse perception of social functioning and quality of life. The worse scores in patients with left-hemisphere and anterior circulation strokes may be due to the fact that aphasia is more common in this type of stroke.

Sex Steroids and Major Psychoses: Which Role for DHEA-S and Progesterone?

Objective: Endocrine pathways seem to play a role in the etiology of major psychoses. The identification of biomarkers associated with psychotic symptoms in schizophrenia (SKZ) and mood disorders would allow the identification of high-risk subjects for delusions and hallucinations. The aim of this study was to evaluate dehydroepiandrosterone sulfate (DHEA-S) and progesterone plasma levels in drug-free patients with major psychoses and their relation with the diagnosis and history of psychotic symptoms. Methods: Eighty-nine consecutive drug-free male inpatients with SKZ or mood disorders were recruited, and DHEA-S and progesterone plasma levels were measured. The groups, divided according to pathological/normal-range hormone levels, were compared in terms of clinical variables using χ2 tests with Bonferronis corrections or multivariate analyses of variance. The same analyses were performed for groups divided according to the presence/absence of lifetime psychotic symptoms. Binary logistic regression analysis was performed using hormone levels as independent variables and history of lifetime psychotic symptoms as a dependent one. Results: A higher number of patients with abnormal DHEA-S levels was found to have a family history of major depressive disorder (p < 0.05). Higher DHEA-S levels (F = 8.31; p = 0.005) were found in patients with a history of psychotic symptoms. In addition, binary logistic regression confirmed that DHEA-S levels were associated with a higher probability of lifetime psychotic symptoms (p = 0.037). Conclusions: Our results confirm previous data about the role of endocrine factors in the etiology of major psychoses. A high DHEA-S level might be a risk factor for psychotic symptoms. Studies with larger samples are needed to confirm these data.

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.

Post-partum obsessive-compulsive disorder associated with 9q33.1 deletion

According to the Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5 [American Psychiatric Association, 2013]) obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts, impulses, images (obsessions) or repetitive behaviour or mental acts in response to a mental obsession (compulsions), interfering with everyday living. Pregnancy and puerperium can precipitate pre-existing OCD or trigger OCD onset, negatively affecting the new-born care and mother–child relationship (Williams and Koran, 1997). The prevalence of OCD is reported to be approximately 2–3% in the general population, although some studies have found higher rates among women in the post-partum period. A 40-year-old woman showing aggressive obsessions, fear of harming her child and related compulsions (avoidance of being alone with her child) was sent to our post-partum psychiatric service. She had never presented psychiatric symptoms before. According to DSM-5 criteria, she received an OCD diagnosis, and treatment with fluvoxamine (titrated till 150 mg/day) was prescribed. Due to a partial response, after 4 weeks, risperidone 0.5 mg/day was added. Due to the new-born clinical presentation (bilateral twisted feet, minor facial alterations, muscle hypertonia, pylore stenosis) a genetic evaluation by array-based Comparative Genomic Hybridization (CGH) was performed, in order to detect DNA copy number variations as a consequence of amplifications/duplications or deletions. The analysis reported a deletion of 229 Kb copies of DNA in 9q33.1, involving pregnancy-associated plasma protein A (PAPPA) gene and 3′ portion of astrotactin 2 (ASTN2) gene (Table 1). Our patient presented the same genetic alterations of her son. When asked, she agreed in publishing this report. A 9q33.1 deletion was incidentally found after a post-partum OCD onset, and authors’ opinion is that hormonal and immunological changes could have unmasked an OCD genetic predisposition. Actually, no associations are reported between PAPPA gene and psychiatric disorders; however, increased levels of PAPPA have been found in patients with high risk for cardiovascular diseases, causing systemic inflammation and immunological abnormalities, Letter

P01-409 - Cognitive impairments in patients with bipolar disorder during different phases of illness

Introduction Several studies have reported that Bipolar Disorder (BD) is characterized by neuropsychological deficits both during affective episodes and euthymic phases; in particular, bipolar patients (BPs) show psychomotor slowing and impairment of memory during Major Depressive Episodes and frontal-executive deficits in Hypomania. Aims The aim of the present study is to compare possible differences in cognitive performances of BPs during euthymia or during an affective episode. Methods 22 BPs with an affective episode (depressivexa0=xa07, mixedxa0=xa07, manicxa0=xa08) and 5 euthymic patients underwent neuropsychological tests, after assessing the diagnosis by SCID-I. The cognitive abilities tested by raters included attention, verbal abilities, memory, abstract reasoning, executive functioning and semantic knowledge. One-way ANOVAs were performed on mean total scores of neuropsychological tests comparing euthymics versus BPs in the different phases of illness. Results The 20% of euthymic patients showed attentive, verbal and memory deficits; the 40% showed perceptual and executive functioning deficits. Depressed (pxa0=xa00.03) and manic (pxa0=xa00.01) patients showed worse scores at Trail Making Test A (TMT-A) than euthymics. Manic patients presented the most severe deficits in memory as showed by the scores of Corsis test (Fxa0=xa04.96, pxa0=xa00.01), Recall of Prose (Fxa0=xa04.06, pxa0=xa00.02) and California Verbal Learning Test (Fxa0=xa03.67, pxa0=xa00.03). Conclusions Euthymic patients showed deficits in several cognitive domains. Manic patients had more severe deficits in attention and memory in comparison with depressed, mixed and euthymic patients. Controlled studies with larger samples are needed to confirm these data.