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Additional file 1. Supplementary material: methods, results, tables and figures.

Background Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive–compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal–thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms. Case presentation We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient’s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine. Conclusion This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

Desire is characterized by fluctuations in quality and quantity in most people, but sometimes these changes may result in a psychiatric condition. The spectrum of possible alterations is wide, and it may be characterized by very different clinical pictures. The main role of the neurobiological mechanisms that underlie desire is played by dopamine, a neurotransmitter whose concentration can be modified by use or abuse of several compounds, which may have a therapeutic role, in the case of medicines, or may lead to dysfunctional situations, in the case of substances or alcohol. Neuroimaging studies have allowed a better knowledge of brain areas involved in mental illnesses, recording functional changes during the execution of specific tasks. The improvement of these techniques in the near future will improve the choice of the most appropriate treatment for each disease, leading to patient tailored therapies. Different approaches to the treatment of disorders associated with an alteration of desire are currently available; often their combination, such as the one between psychophamacological drugs and psychotherapy, can lead to a better therapeutic result and to a reduction, or mitigation, of episodes’ of severity and recurrences., Lebenswelt. Aesthetics and philosophy of experience., No 4 (2014)

Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies.

The aim of the present study was to investigate psychopharmacological prescribing patterns in a large sample (n = 1815) of patients suffering from obsessive–compulsive disorder (OCD) recruited in 4 Italian centers specialized in OCD, in comparison to available national and international guidelines. The centers were asked to complete a specific data sheet questionnaire on patients' therapeutic status. Statistical analyses were carried out by SPSS. The results showed that almost all patients referred to the centers of Milan, Pisa and Rome received psychotropic medications, whereas only 59.9% (313) did so in Turin. Selective serotonin reuptake inhibitors were the most used drugs ranging between 49.0% and 71.5%. Clomipramine was prescribed more often in Rome and Pisa than in Milan and Turin. The same was true for other tricyclic antidepressants. Second-generation antipsychotics were more often prescribed in Pisa and in Milan. Mood stabilizers were almost exclusively used in Pisa. Taken together, the overall findings would suggest that, although the main Italian centers specialized in OCD follow available guidelines, a certain degree of variability does exist. This may depend on the different educational background, availability of other specific therapeutic strategies, as well as varying levels of severity and comorbidity of the patients.

In the DSM-5 a new “tic-related” specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder (“OCTD”). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) – mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.