Treatment resistant schizophrenia and neurological soft signs may converge on the same pathology: Evidence from explanatory analysis on clinical, psychopathological, and cognitive variables.

Here, we investigated neurological soft signs (NSSs) in treatment resistant schizophrenia (TRS) vs treatment responder schizophrenia (SZ) patients. TRS is a severe condition, affecting approximately one-third of schizophrenia patients and representing a relevant clinical challenge. NSSs are neurological abnormalities reportedly described in schizophrenia patients and linked to dysregulated network connections. We explored the possibility that NSSs may be: i) more severe in TRS patients; ii) differentially associated to clinical/cognitive variables in TRS vs SZ; iii) predictive of having TRS. In addition, we evaluated whether diagnosis may mediate NSSs associations with the above-mentioned variables. Consecutive patients with schizophrenia diagnosis underwent stringent assessment for TRS diagnosis. Demographics and clinical variables were recorded. Psychopathology (by Positive and Negative Syndrome Scale, PANSS), cognitive performances, and NSSs (by Neurological Evaluation Scale, NES) were tested. TRS had higher scores than SZ patients in total NES score and in almost all NES subscales, even after correction for duration of illness and antipsychotic dose (ANCOVA, p<0.05). NSSs significantly correlated with multiple clinical, psychopathological, and cognitive variables (above all: duration of disease and negative symptoms) in TRS but not in SZ patients. Two-way ANOVA showed NSS-x-diagnosis interaction in determining outcomes on multiple cognitive performances, but not in other clinical variables. However, simple main effect analysis detected a significant relationship between high severity NSSs and TRS diagnosis on multiple clinical and cognitive outcomes. Hierarchical regression analysis showed that diagnosis was among a discrete number of predictors yielding significant increases in variance explained on NES total, Sensory Integration and Other Signs subscales' scores. NSSs, together with antipsychotic dose and disease severity, were found to be significantly predictive of TRS diagnosis in a binary logistic regression model. These results suggest a stringent association between NSSs and TRS diagnosis, and may imply that NSSs association with clinical, psychopathological, and cognitive variables may be in part mediated by TRS diagnosis.

Assessing patient-rated vs. clinician-rated adherence to the therapy in treatment resistant schizophrenia, schizophrenia responders, and non-schizophrenia patients.

The present study evaluated consistency, reliability, and determinants of two real-world measures of adherence to prescription in 57 schizophrenia and 61 non-schizophrenia patients. Treatment resistant schizophrenia (TRS) was additionally diagnosed in 28 of the schizophrenia patients. Patients were screened for clinical severity, cognitive functioning, and adherence by 10-item Drug Attitude Inventory (DAI-10) or Adherence-to-Therapy (AtT), a clinician-rated tool developed by our group. DAI-10 and AtT scores showed a significant correlation (p=0.039; ρ=0.21; df=103). Compared to the DAI-10 scale, a higher number of variables were associated with AtT. In schizophrenia and TRS patients, substance abuse was the only significant predictor of lower DAI-10 score (p=0.027, F=5.2, R2=0.07, and p=0.06, F=8.9, R2=0.23, respectively). Lower AtT score was significantly associated with first-generation antipsychotic use (p=0.001, RR: 2.00 [1.40-2.87]), positive symptoms (p=0.02, RR: 1.63 [1.05-2.53]), impaired verbal fluency (p=0.01, RR: 1.88 [0.81-4.32]) or problem solving (p=0.01, RR: 2.14 [0.92-4.98]). AtT, but not DAI-10, score correlated with the score on the Personal and Social Performance scale (p=0.02, F=5.86, R2=0.08). Overall, AtT score was predicted by pharmacological, psychopathological, and cognitive factors, and predictive of psychosocial functioning. Therefore, AtT measure may represent a convenient and practical tool to evaluate schizophrenia patients' adherence.

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.

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.

Premorbid circadian profile of patients with major depression and panic disorder.

AIMS: This study aims to compare some behavioural characteristics related to circadian functions in healthy subjects, in patients with major depressive disorder (MDD) and panic disorder (PD) during adulthood (disease period) and during the premorbid age (between 12 and 20 years old). METHODS: 132 adult patients with MDD, 144 with PD and 151 adult healthy controls were enrolled in the study. All subjects completed a retrospective questionnaire. RESULTS: Several behaviours (such as falling asleep, awakening, having, appetite, perceiving energy and cognitive functioning) showed a phase delay or a phase advance in MDD and PD patients compared to healthy controls. Behavioural differences where found in patients even before the clinical onset of the disease. CONCLUSIONS: Circadian profiles of MDD and PD patients diverge from those of healthy controls not only during the disorder but also in the ages preceding its clinical onset. The analysis of these circadian patterns may aid physicians to early identify subjects with specific psychiatric vulnerabilities.