Background: The objective of this study was to investigate the DRD2 rs1800497, rs1799732, rs1801028, DRD3 rs6280, and HTR2A rs6314, rs7997012, and rs6311 single-nucleotide polymorphism (SNP) correlations with resistance to second-generation antipsychotics (SGAs) in a real-world sample of patients with treatment-resistant mental disorders. Methods: We divided 129 participants into a high treatment resistance (HTR) group (current treatment with two SGAs, or clozapine, or classic neuroleptics for a failure of previous SGAs trials) and a low treatment resistance (LTR) group (current treatment with one atypical antipsychotic). We used Next-Generation Sequencing on DNA isolated from peripheral blood samples to analyze the polymorphisms. We performed logistic regression to search for predictors of HTR membership. Results: A diagnosis of schizophrenia significantly predicted the HTR membership compared to other diagnoses. Other predictors were the DRD3 rs6280 C|T (OR = 22.195) and T|T (OR = 18.47) vs. C|C, HTR2A rs7997012 A|G vs. A|A (OR = 6.859) and vs. G|G (OR = 2.879), and DRD2 rs1799732 I|I vs. D|I (OR = 12.079) genotypes. Conclusions: A diagnosis of schizophrenia and the DRD2 rs1799732, DRD3 rs6280, and HTR2A rs7997012 genotypes can predict high treatment resistance to SGAs.

Schizophrenia spectrum disorders represent a varied class of mental illnesses characterised by psychosis. In addition to negative and positive symptoms, a significant lack of insight often hinders the therapeutic process. We performed an overview of the existing literature concerning these disorders to summarise the state of knowledge in the psychotherapies applied to treating psychotic symptoms. We searched the PubMed database, including randomised controlled and clinical trials, including 17 studies conducted on 1203 subjects. Psychotherapy of schizophrenia spectrum disorders can improve social functioning and positive symptoms, as well as many other symptomatic areas, and could therefore be considered a helpful adjunctive treatment of schizophrenia spectrum disorders. Among cognitive-behavioural therapies and the newest derived approaches, there is evidence that they can improve different psychotic symptoms. On the other hand, psychodynamic psychotherapies can have a positive influence on psychotic symptoms as well. Further studies are needed to identify better-tailored treatment protocols for schizophrenia spectrum disorders.