Emiliano Prinzivalli

Treatment resistant schizophrenia is associated with the worst community functioning among severely-ill highly-disabling psychiatric conditions and is the most relevant predictor of poorer achievements in functional milestones

The aim of this work was to compare achievements in milestones of community functioning in highly disabling psychiatric conditions, including treatment resistant schizophrenia (TRS), schizophrenia (responsive to antipsychotics), bipolar disorder, and anxiety/depressive diseases. Also, we investigated the predictors of community functioning outcomes across several domains. Among consecutive patients screened, 188 met inclusion criteria and 118 ultimately entered the study. Diagnosis of TRS was made by stringent criteria, including historic and perspective evaluations and excluding potential confounding factors. Achievements in functional milestones of everyday living were recorded. Performances in discrete cognitive tasks were assessed. The Positive and Negative Syndrome Scale, the Personal and Social Performance Scale, the Drug Attitude Inventory-10, and the Quality of Life Enjoyment and Satisfaction Questionnaire were administered. TRS patients showed the highest impairment in community functioning among diagnostic groups. TRS was found to have more severe psychopathology, more impaired cognitive functioning, and poorer psychosocial adjustment compared to all the other groups. In the whole sample, the main predictors of community functioning were the diagnostic group (with TRS diagnosis associated with worst functioning) and achievements in the other functional milestones. In psychotic patients, however, the main predictors of community functioning were clinical and psychopathological variables. These results may support the hypothesis that TRS represents a separate schizophrenia subtype, with its own neurobiology, psychopathology and clinical course. Our results identify a group of modifiable predictors to be addressed to prevent community disability.

The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

Chronobiology of Mood Disorders

The strong intimate relationship between mood disorders and life rhythms has been nowadays clearly recognized and analyzed, becoming one of the cornerstones for pathophysiological theorizations and therapeutic interventions in these diseases. Several body functions undergo biological rhythm, e.g., daily variations in hormone secretion or in body temperature or the sleep-wake cycle. Endogenous rhythms are primarily regulated by the circadian clock, a cluster of nerve cells that have their main localization in the hypothalamic suprachiasmatic nucleus. Endogenous rhythms may in turn be modulated by multiple exogenous clues, first of all the dark/light daily variations. Endogenous and exogenous rhythms intermingle in very complex associations, whose effects on human behavior, as well as their molecular determinants, are becoming to be elucidated. The term chronobiology refers both to the characterization of the biological underpinnings of life rhythms and to the clarification of their effects on several biological functions, including behavioral disease. The scope of this chapter is to provide an appraisal of the newest reports on the chronobiology of mood disorders. We will first describe the structural and functional anatomy, as well as the genetic, of the circadian clock, i.e., the suprachiasmatic nucleus. Then, we will review recent findings on the neurobiology and neuroimaging of the sleep-wake cycle. In the third part of the chapter, we will deal with the neurobiology of stress and its relationship with circadian rhythms. In the last section of the chapter, the biological effects of circadian rhythms and stress on affective states and mood disorders will be summarized and discussed.

EPA-1118 - Knowledge of the illness and its relations with quality of life, social functioning, cognitive performances, and adherence in psychotic patients: Toward effectiveness-focused interventions

Introduction Psychosocial factors are often underestimated in psychotic patients, although they may profoundly influence (and be influenced by) clinical presentation and effectiveness of therapeutic interventions in these people. Objectives To investigate relevance, relationship with clinical presentation and overall quality of life of multiple psychosocial factors in psychotic patients. Aims To evaluate whether knowledge about the illness and utilization of health services are defective in psychotic vs. non-psychotic patients and whether these correlates with the type of psychotic symptoms, cognitive performances, global social functioning, quality of life, and acceptance of pharmacotherapy. Methods Approximately 110 patients were enrolled after written informed consent. Patients were administered the Positive and Negative Syndrome Scale (PANSS), the Personal and Social Performance scale (PSP), the Drug Attitude Inventory (DAI), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). All patients were also screened for cognitive performances. Patients and relatives completed a questionnaire on knowledge about the illness and on the level of utilization of mental health services. Patients were subdivided in psychotic (cases) and non-psychotic (controls) based on their score on the PANSS. Results Psychotic patients and their relatives showed lower levels of knowledge about the illness. These features were associated with the other variables assessed in a very complex and multidimensional model of reciprocal influences. Conclusions Lack of response to pharmacological treatments and to overall therapeutic interventions in psychotic patients may also depend on multiple psychosocial factors, which may be carefully investigated and become the target of adjunctive, effectiveness-focused interventions.

EPA-0168 – Can depression affect empathy?

Introduction Empathy is the human ability to understand and share other peoples feelings through knowledge, observation and memory. Lower levels of empathy lead to poor social functioning, like in Major Depressive Disorder (MDD), Schizophrenia and Autism. Until today, very few studies have focused on empathic deficits in depressed patients. Aims Our aim was to evaluate whether MDD causes variations in empathy levels. Objectives We wanted to assess cognitive and affective components of Empathy in a sample of women with MDD, and relate them to clinical issues. We compared these results to a control sample. Methods Our sample included 20 female patients with MDD and a control group, homogeneous for age and gender. We used the Hamilton scale for depression (HAM- D) to evaluate depression severity, the Interpersonal Reactivity Index (IRI) to evaluate cognitive and affective empathy, the Faux pas test to assess cognitive empathy; Pearson and Mann tests for statistic analysis. Results In general, patients showed mild depression levels (HAM- D: 14, 41± 6, 07). Severity of symptoms and empathy levels were inversely related with Faux Pas and IRI results (R: −0, 5805; R: −0, 5145), with patients being worse than the control group. Patients showed deficits in personal distress and perspective taking IRI subscales. Conclusions Our study shows that in depressed patients both components of Empathy are modified; in particular, personal distress increases, while perspective taking decreases. Additional studies and higher numbers of patients will be necessary to further investigate whether empathic deficits are trait- or state-depending MDD characteristics.