Disorganization domain as a putative predictor of Treatment Resistant Schizophrenia (TRS) diagnosis: A machine learning approach.

BACKGROUND: Treatment Resistant Schizophrenia (TRS) is the persistence of significant symptoms despite adequate antipsychotic treatment. Although consensus guidelines are available, this condition remains often unrecognized and an average delay of 4-9 years in the initiation of clozapine, the gold standard for the pharmacological treatment of TRS, has been reported. We aimed to determine through a machine learning approach which domain of the Positive and Negative Syndrome Scale (PANSS) 5-factor model was most associated with TRS. METHODS: In a cross-sectional design, 128 schizophrenia patients were classified as TRS (n = 58) or non-TRS (n = 60) after a structured retrospective-prospective analysis of treatment response. The random forest algorithm (RF) was trained to analyze the relationship between the presence/absence of TRS and PANSS-based psychopathological factor scores (positive, negative, disorganization, excitement, and emotional distress). As a complementary strategy to identify the variables most associated with the diagnosis of TRS, we included the variables selected by the RF algorithm in a multivariate logistic regression model. RESULTS: according to the RF model, patients with higher disorganization, positive, and excitement symptom scores were more likely to be classified as TRS. The model showed an accuracy of 67.19%, a sensitivity of 62.07%, and a specificity of 71.43%, with an area under the curve (AUC) of 76.56%. The multivariate model including disorganization, positive, and excitement factors showed that disorganization was the only factor significantly associated with TRS. Therefore, the disorganization factor was the variable most consistently associated with the diagnosis of TRS in our sample.

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.

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.

Efficacy and clinical determinants of antipsychotic polypharmacy in psychotic patients experiencing an acute relapse and admitted to hospital stay: results from a cross-sectional and a subsequent longitudinal pilot study.

Background. Antipsychotic polypharmacy is used in several psychiatric disorders, despite poor evidence existing to support this practice. Aim. We evaluated whether psychotic patients in acute relapse exposed to antipsychotic polypharmacy (AP + AP) showed different demographic, clinical, or psychopathological features compared to those exposed to one antipsychotic (AP) and whether AP + AP patients showed significantly higher improvement compared to AP patients after a 4-week treatment. Methods. Inpatients were subdivided into AP + AP and AP ones. In the cross-sectional step, patients were compared according to demographics, clinical variables, and scores on rating scales. In the longitudinal step, patients remained for 4 weeks under admission medications and were compared for clinical improvement. Results. AP + AP patients were more frequently diagnosed with schizophrenia and mental retardation as a comorbid illness. AP + AP patients were more frequently under first-generation antipsychotics and had worse clinical presentation. After 4 weeks of treatment, both AP + AP and AP patients improved compared to the baseline. However, AP patients scored significantly less than AP + AP patients at the Clinical Global Impression Scale at the 4-week time point but not at the baseline, indicating a treatment-specific improvement. Conclusions. Antipsychotic polypharmacy may be offered to specific types of psychotic patients. However, efficacy of this strategy is limited at best.

Tobacco smoking in treatment-resistant schizophrenia patients is associated with impaired cognitive functioning, more severe negative symptoms, and poorer social adjustment.

Tobacco smoking is common in schizophrenia patients. It has been reported that schizophrenia patients who are tobacco smokers have better cognitive performances compared to those who are nonsmokers. However, little is known on the effects of tobacco smoking in treatment-resistant schizophrenia (TRS) patients. The aim of this study was to compare cognitive performances, psychotic symptoms, and social adjustment in tobacco smoker TRS patients compared to nonsmoker TRS patients. Smoker and nonsmoker TRS patients did not differ in demographics and in mean daily antipsychotic dose. Smoker TRS patients had significantly higher scores than nonsmoker patients on the positive and negative syndrome scale (PANSS) and on the negative symptoms subscale. These patients also performed worse than nonsmoker patients on problem-solving cognitive domain. Social adjustment was not significantly different between the two groups. In both groups of patients, worse cognitive performances were mostly predicted by higher severity of negative symptoms. Worse performances on the verbal memory and problem-solving cognitive domains were correlated with social-functioning impairment in tobacco smoker TRS patients but not in nonsmoker ones. The results showed that tobacco smoking was not significantly associated with better cognitive performances in TRS patients, while it was significantly associated with higher negative symptoms. Even if a direct causative mechanism cannot be inferred and despite the fact that these patients may use tobacco to self-medicate, it could be speculated that these associations may, at least partially, be related to a tobacco-smoking-induced worsening of abnormal dopamine dysfunction, which has been suggested to occur in TRS patients.

Differential cognitive performances between schizophrenic responders and non-responders to antipsychotics: correlation with course of the illness, psychopathology, attitude to the treatment and antipsychotics doses.

Multiple lines of evidence demonstrate that schizophrenia patients may perform worse than normal controls in several cognitive tasks. However, little is known on putative differences in cognitive functioning between schizophrenia patients responding to antipsychotics and those resistant to the treatment. In this cross-sectional study, 63 subjects (41 schizophrenia and schizoaffective patients and 22 age and sex-matched controls) were enrolled. Patients were divided in resistant (TRS, n=19) and non-resistant to pharmacological treatment (non-TRS, n=22) according to the American Psychiatric Association (APA) criteria for treatment resistance. The Brief Assessment of Cognition in Schizophrenia (BACS) was administered to patients and controls. The following rating scales were administered to schizophrenia patients: the Positive and Negative Syndrome Scale (PANSS), the Drug Attitude Inventory (DAI) and the Subjective Well-being under Neuroleptics (SWN). Statistically significant differences among non-TRS patients, TRS ones, and controls were detected at the BACS. TRS patients performed significantly worse than non-TRS ones on Verbal Memory task, exhibited higher PANSS total and subscales scores and were prescribed higher antipsychotic doses. Poorer performances at the BACS significantly correlated with more severe negative symptoms in TRS but not in non-TRS patients. These results may suggest that TRS patients suffer from a form of the disease with prominent cognitive impairment possibly related to negative symptoms.