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Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD., Competing Interests: Declaration of Competing Interest The remaining authors declare that the research was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD., Competing Interests: Declaration of Competing Interest Giovanni Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. Ileana Andriola was speaker at Janssen-sponsored conferences. Bernardo Dell'Osso has received lecture honoraria from Angelini, Lundbeck, Janssen, Pfizer, Neuraxpharm, Arcapharma, and Livanova. Antonio Vita received grant/research support and speaker/consultant fees from Angelini, Boheringer Ingelheim, Innovapharma, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Recordati, Roche, Rovi Pharma, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD., Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch., Methods: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up., Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch., Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

During the first Covid-19 outbreak, the Niguarda Hospital of Milan featured two Psychiatry wards, one for SARS-CoV-2 positive patient and one for patients requiring hospitalization and negative for SARS-CoV-2. The two groups of patients were compared and were similar in distribution of psychiatric diagnosis, duration of illness and previous hospitalizations. SARS-CoV-2 positive participants had a lower severity of symptoms both at admission and discharge, a lower frequency of psychotic symptoms and substance intoxication at admission. These findings suggest that patients admitted to the COVID ward were hospitalized not only for their mental health condition but also because of the infection., Competing Interests: Declaration of Competing Interest The Authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Background: Treatment-resistant Depression (TRD) represents a widespread disorder with significant direct and indirect healthcare costs. esketamine, the S-enantiomer of ketamine, has been recently approved for TRD, but real-world studies are needed to prove its efficacy in naturalistic settings., Objectives: Evaluate the effectiveness and safety of esketamine nasal spray in a clinical sample of patients with TRD from several Italian mental health services., Methods: REAL-ESK study is an observational, retrospective and multicentric study comprising a total of 116 TRD patients treated with esketamine nasal spray. Anamnestic data and psychometric assessment (MADRS, HAMD-21, HAM-A) were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups., Results: A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. A dramatic increase in clinical response (64.2 %) and remission rates (40.6 %) was detected at T2 compared to T1. No unexpected safety concerns were observed, side effects rates were comparable to those reported in RCTs. No differences in efficacy have been found among patients with and without psychiatric comorbidities., Limitations: The open design of the study and the absence of a placebo or active comparator group are limitations. The study lacks an inter-rater reliability evaluation of the assessments among the different centres. Side effects evaluation did not involve any specific scale., Conclusions: Our findings support the safety and tolerability of esketamine in a real-world TRD sample. The later response and the non-inferiority in effectiveness in patients with comorbidities represent novel and interesting findings., Competing Interests: Conflict of interest Giovanni Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier and Recordati. Alessandro Bertolino and Ileana Andriola were both speakers at Jannssen-sponsored conference. Andrea Fagiolini has been a consultant and/or a speaker and/or has received research grants from Allergan, Angelini, Apsen, Boehringer Ingelheim, Doc Generici, FB-Health, Italfarmaco, Janssen, Lundbeck, Mylan, Otsuka, Pfizer, Recordati, Sanofi Aventis, Sunovion, Vifor. Bernardo Dell'Osso has received lecture honoraria from Angelini, Lundbeck, Janssen, Pfizer, Neuraxpharm, Arcapharma, and Livanova. Massimo di Giannantonio has been a consultant and/or a speaker and/or has received research grants from Angelini, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, Recordati. Antonio Vita received grant/research support and speaker/consultant fees for Angelini, Boheringer Ingelheim, Innovapharma, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Recordati, Roche, Rovi Pharma, Takeda. Giuseppe Maina has been a consultant/speaker for Angelini, Boheringer, Fb Health, Innovapharma, Italfarmaco, Janssen, Otsuka, Lundbeck, Sanofi. Gabriele Sani has been a consultant/speaker for Angelini, Fb Health, Italfarmaco, Janssen, Otsuka, Lundbeck, Sanofi. Roger McIntyre has received grant/research support from CIHR/GACD/Chinese National Natural Research Foundation and speaking or consultation fees from AbbVie, Bausch Health, Eisai, Intra-Cellular, Janssen, Kris, Lundbeck, Minerva, Neurocrine, Novo Nordisk, Eli Lilly, Otsuka, Pfizer, Purdue, Sunovion, and Takeda; he is also the CEO of Champignon Brands, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: The aim of this study was to compare the 5-year survival and success rates of 3.3 mm dental implants either made from titanium-zirconium (TiZr) alloy or from Grade IV titanium (Ti Grade IV) in mandibular implant-based removable overdentures., Methods: The core study had a follow-up period of 36 months and was designed as a randomized, controlled, double-blind, split-mouth multicenter clinical trial. Patients with edentulous mandibles received two Straumann Bone Level implants (diameter 3.3 mm, SLActive®), one of TiZr (test) and one of Ti Grade IV (control), in the interforaminal region. This follow-up study recruited patients from the core study and evaluated the plaque and sulcus bleeding indices, radiographic crestal bone level, as well as implant survival and success 60 months after implant placement., Results: Of the 91 patients who initially received implants, 75 completed the 36 month follow-up and 49 were available for the 60 month examination. Two patients were excluded so that a total of 47 patients with an average age of 72 ± 8 years were analysed. The characteristics and 36-month performance of the present study cohort did not differ from the non-included initial participants (p > 0.05). In the period since the 36-month follow-up examination, no implant was lost. The cumulative implant survival rate was 98.9 % for the TiZr group and 97.8 % for the Ti Grade IV group. Crestal bone level changes at 60 months were not different in the test and control group (TiZr -0.60 ± 0.69 mm and Ti Grade IV -0.61 ± 0.83 mm; p = 0.96). The cumulative implant success rate after 60 months was 95.8 and 92.6 % for TiZr and Ti Grade IV, respectively., Conclusions: After 60 months, the positive outcomes of the 36 month results for TiZr and Ti Grade IV implants were confirmed, with no significant differences with regard to crestal bone level change, clinical parameters and survival or success rates. TiZr implants performed equally well compared to conventional Ti Grade IV 3.3 mm diameter-reduced implants for mandibular removable overdentures., Trial Registration: Registered on www.clinicaltrials.gov: NCT01878331.

Background: Scientific data and clinical observations appear to indicate that an adequate width of attached mucosa may facilitate oral hygiene procedures thus preventing peri-implant inflammation and tissue breakdown (eg, biologic complications). Consequently, in order to avoid biologic complications and improve long-term prognosis, soft tissue conditions should be carefully evaluated when implant therapy is planned. At present the necessity and time-point for soft tissue grafting (eg, prior to or during implant placement or after healing) is still controversially discussed while clinical recommendations are vague., Objectives: To provide a review of the literature on the role of attached mucosa to maintain periimplant health, and to propose a decision tree which may help the clinician to select the appropriate surgical technique for increasing the width of attached mucosa., Results: The available data indicate that ideally, soft tissue conditions should be optimized by various grafting procedures either before or during implant placement or as part of stage-two surgery. In cases, where, despite insufficient peri-implant soft tissue condition (ie, lack of attached mucosa or movements caused by buccal frena), implants have been uncovered and/or loaded, or in cases where biologic complications are already present (eg, mucositis, peri-implantitis), the treatment appears to be more difficult and less predictable., Conclusion: Soft tissue grafting may be important to prevent peri-implant tissue breakdown and should be considered when dental implants are placed. The presented decision tree may help the clinician to select the appropriate grafting technique.

Objective: The aim of this report is to describe symptoms that can suggest the presence of a patent nasopalatine duct and to illustrate three cases., Summary: Patent nasopalatine ducts connecting the oral cavity with the nasal cavity are extremely rare. This malformation can be considered a developmental abnormality. Clinically, patent nasopalatine ducts appear as single or double spherical or oval apertures lateral or posterior to the incisive papilla. This type of anatomical malformation can be associated with an unclear pain sensation in the anterior maxillary region, which may be misinterpreted for example as toothache of endodontic origin. However, persisting nasopalatine ducts can also exist as an asymptomatic abnormality with no clinical sign of discomfort. Accordingly, understanding the differential diagnosis of a possible patent nasopalatine duct can prevent a general practitioner from performing unnecessary interventions, such as endodontic treatments, apical surgeries, or tooth extractions.

Owing to its single surgical intervention, immediate implant placement has the advantage of shortening treatment time, and thus positively affects patient morbidity. According to the bone resorption pattern after tooth extraction, bone loss should be anticipated if immediate implant placement is considered. The present case report aims to present a possible treatment option and to demonstrate that a partially edentulous arch may be rehabilitated esthetically by immediate implant placement and by corresponding anticipatory measures.

Objective: This retrospective observational pilot study examined differences in peri-implant bone level changes (ΔIBL) between two similar implant types differing only in the surface texture of the neck. The hypothesis tested was that ΔIBL would be greater with machined-neck implants than with groovedneck implants., Method and Materials: 40 patients were enrolled; n = 20 implants with machined (group 1) and n = 20 implants with a rough, grooved neck (group 2), all placed in the posterior mandible. Radiographs were obtained after loading (at 3 to 9 months) and at 12 to 18 months after implant insertion. Case number calculation with respect to ΔIBL was conducted. Groups were compared using a Brunner-Langer model, the Mann-Whitney test, the Wilcoxon signed rank test, and linear model analysis., Results: After the 12- to 18-month observation period, mean ΔIBL was -1.11 ± 0.92 mm in group 1 and -1.25 ± 1.23 mm in group 2. ΔIBL depended significantly on time (P < .001), but not on group. In both groups, mean marginal ΔIBL was significantly less than -1.5 mm. Only insertion depth had a significant influence on the amount of periimplant bone loss (P = .013). Case number estimate testing for a difference between group 1 and 2 with a power of 90% revealed a sample size per group of 1,032 subjects., Conclusion: ΔIBL values indicated that both implant designs fulfilled implant success criteria, and the modification of implant neck texture had no significant influence on ΔIBL.

Purpose: Extended grafting procedures in atrophic ridges are invasive and time-consuming and increase cost and patient morbidity. Therefore, ridge-splitting techniques have been suggested to enlarge alveolar crests. The aim of this cohort study was to report techniques and radiographic outcomes of implants placed simultaneously with a piezoelectric alveolar ridge-splitting technique (RST). Peri-implant bone-level changes (ΔIBL) of implants placed with (study group, SG) or without RST (control group, CG) were compared., Materials and Methods: Two cohorts (seven patients in each) were matched regarding implant type, position, and number; superstructure type; age; and gender and received 17 implants each. Crestal implant bone level (IBL) was measured at surgery (T0), loading (T1), and 1 year (T2) and 2 years after loading (T3). For all implants, ΔIBL values were determined from radiographs. Differences in ΔIBL between SG and CG were analyzed statistically (Mann-Whitney U test). Bone width was assessed intraoperatively, and vertical bone mapping was performed at T0, T1, and T3., Results: After a mean observation period of 27.4 months after surgery, the implant survival rate was 100%. Mean ΔIBL was -1.68 ± 0.90 mm for SG and -1.04 ± 0.78 mm for CG (P = .022). Increased ΔIBL in SG versus CG occurred mainly until T2. Between T2 and T3, ΔIBL was limited (-0.11 ± 1.20 mm for SG and -0.05 ± 0.16 mm for CG; P = .546). Median bone width increased intraoperatively by 4.7 mm., Conclusions: Within the limitations of this study, it can be suggested that RST is a well-functioning one-stage alternative to extended grafting procedures if the ridge shows adequate height. ΔIBL values indicated that implants with RST may fulfill accepted implant success criteria. However, during healing and the first year of loading, increased IBL alterations must be anticipated.

Objectives: The aim of this observational, cross-sectional study was to analyse the relationship between dental anxiety (DA) and health-related quality of life aspects associated with oral conditions of a population with dental treatment needs in Switzerland., Methods: The measurements of DA were collected by means of two questionnaires, the Dental Anxiety Scale (DAS) and a Visual Analogue Scale (VAS). Oral health-related quality of life (OHRQoL) was assessed with the Oral Health Impact Profile (OHIP). The sample included 223 patients enrolled at a university clinic which specialises in oral prosthetic rehabilitation and temporomandibular disorders. Of them, 78.9% were at or above the age of 50., Results: No gender or age dependencies were observed. A comparison of answers regarding OHRQoL and DA revealed a significant interdependence (p = 0.0118); highly anxious patients were 3.55 times more likely to suffer from poor quality of life compared with less anxious ones., Conclusion: This cross-sectional study of mostly elderly patients seeking dental treatment in Switzerland found that increased DA was associated with an impaired OHRQoL. The average DA was slightly higher than the results of other industrialised countries and the average OHRQoL was reduced., (© 2012 The Gerodontology Society and John Wiley & Sons A/S.)

The goal of the study was to calculate the direct costs of therapy for patients with MAP. This retrospective study included 242 MAP patients treated at the Department of Prosthodontics of the University of Bern between 2003 and 2006. The following parameters were collected from the clinical charts: chief complaint, diagnosis, treatment modalities, total costs, costs of the dental technician, number of appointments, average cost per appointment, length of treatment, and services reimbursed by health insurance agencies. The average age of the patients was 40.4 ± 17.3 years (76.4% women, 23.6% men). The chief complaint was pain in 91.3% of the cases, TMJ noises (61.2%) or limitation of mandibular mobility (53.3%). Tendomyopathy (22.3%), disc displacement (22.4%), or a combination of the two (37.6%) were more often diagnosed than arthropathy alone (7.4%). Furthermore, 10.3% of the MAP patients had another primary diagnosis (tumor, trauma, etc.). Patients were treated with counseling and exercises (36.0%), physiotherapy (23.6%), or occlusal splints (32.6%). The cost of treatment reached 644 Swiss francs for four appointments spread over an average of 21 weeks. In the great majority of cases, patients can be treated with inexpensive modalities. 99.9% of the MAP cases submitted to the insurance agencies were reimbursed by them, in accordance with Article 17d1-3 of the Swiss Health Care Benefits Ordinance (KLV) and Article 25 of the Federal Health Insurance Act (KVG). The costs of treatment performed by dentists remain modest. The more time-consuming services, such as providing information, counseling and instructions, are poorly remunerated. This aspect should be re-evaluated in a future revision of the tariff schedule.

The aim of this naturalistic study was to evaluate the potential influence of the duration of untreated illness (DUI)--defined as the time elapsed between the occurrence of the first mood episode and the first adequate pharmacological treatment with mood stabilizers--on the clinical course of bipolar disorder (BD). Three hundred and twenty outpatients (n = 320) with a DSM-IV diagnosis of BD--either Type I or Type II--were interviewed; their clinical features were collected and they were naturalistically followed-up for 5 years. At the end of the follow-up observation, the sample was subdivided into two groups: one group with a DUI < or =2 years (n = 65) and another group with a DUI >2 years (n = 255). The main demographic and clinical variables were analyzed and compared between the two subgroups of patients using chi-square tests for dichotomous variables or Mann-Whitney U tests for continuous variables. Patients with a longer DUI showed a higher frequency of suicide attempts (Z = -2.11, P = 0.035), a higher number of suicide attempters (chi(2) = 4.13, df = 1, P = 0.04), and a longer duration of illness (Z = -6.79, P < 0.0001) when compared to patients with a shorter DUI. Moreover, patients with a longer DUI had a depressive first episode more frequently than patients with a shorter DUI (chi(2) = 11.28, df = 2, P = 0.004). A further analysis performed dividing the total sample into two subgroups on the basis of a DUI of 6 years (corresponding to the median value of the DUI in the study sample) confirmed prior findings. Results indicate a potential association between a longer DUI and a worse outcome in BD, particularly in terms of suicidality, and confirm the clinical relevance of early diagnosis and pharmacological intervention with mood stabilizers in BD.

Introduction: Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset., Methods: The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset 30-45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features., Results: The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032)., Conclusions: Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset.

In this study, the authors investigated if CNS degenerative abnormalities could correlate with depressive symptoms in elderly patients, if the presence of mild/moderate cognitive impairment could be related to the response to treatment and the role of peculiar clinical features in influencing the response to treatment. Fifty-three patients (60-75 years) diagnosed as affected by late onset (after 60 years) Major Depressive Episodes according to DSM-IV criteria were studied. Brain vascular and degenerative markers were assessed by computed tomography (CT) through measurements of a lateralized version of the bifrontal index and a rating scale addressing subcortical disease. The presence of mild/moderate cognitive impairment [(24-28 total score at the Mini-Mental State Examination (MMSE)], and of specific symptoms were assessed at baseline and evaluated with respect to the antidepressant response. Patients with CT abnormalities showed higher baseline scores on Hamilton Rating Scale for Depression (HAM-D) items "late insomnia" (t=-2.674, P=.002), "somatic symptoms" (t=-3.355 P=.002), and Brief Psychiatric Rating Scale (BPRS) item "emotional withdrawal" (t=-3.355, P=.002). No significant correlation was found between the vascular index and baseline clinical symptoms, while the HAM-D "depressed mood" item was negatively correlated to the right frontal index (R=-0.692, P=.006). Patients with CT abnormalities showed a lower reduction of HAM-D total scores than patients with normal CT (time effect: F=29.277, P<.0001; group effect: F=5.154, P<.03), while a significant reduction of symptoms in time (time effect: F=33.33, P<.0001) but no differences between groups were found on Hamilton Rating Scale for Anxiety (HAM-A). Both patients with and without mild cognitive impairment improved on the HAM-D (time effect: F=19.668, P<.0001), BPRS (time effect: F=18.345, P<.0001), and HAM-A (time effect: F=17.959, P<.0001) total scores. Patients with emotional withdrawal showed lower improvement on BPRS total scores (time effect: F=26.946, P<.0001; group effect: F=5.121, P<.03). The results from this study showed that patients with baseline emotional withdrawal and CT abnormalities have poorer outcome. Further investigations on larger samples are needed to confirm these findings.

Infective agents (e.g., viruses) together with functional alterations of the immune system have been hypothesized to be implicated in the multifactorial pathogenesis of schizophrenia. The viral hypothesis of schizophrenia has been supported by the observation of birth peaks in winter seasons, prenatal exposure to virus epidemics and specific geographic patterns. On the other hand, not all the data published have shown consistent results supporting the immune hypothesis. Thus, it is likely that immune response factors may play a role in the pathogenesis of the disease only in specific subgroups of patients. The aim of the study was to investigate for the presence of differences of IL-6, IL-6R, gp130 and CC16 among four groups of chronic schizophrenic patients categorized according to the season of birth. We hypothesized that patients born in winter and spring would have had increased values of these cytokines. No significant differences were found among the four groups in any of the measures considered. These preliminary results appear to exclude a major role of the season of birth in determining reported interleukins system alterations in chronic schizophrenia.