The burden of depressive disorders in musculoskeletal diseases: is there an association between mood and inflammation?

IMPORTANCE: Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management. OBJECTIVE: The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered. FINDINGS: Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood-brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches. CONCLUSIONS: The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued.

Motivation as a Measurable Outcome in Stroke Rehabilitation: A Systematic Review of the Literature.

Motivated behaviours are thought to lead to enhanced performances. In the neurorehabilitation field, motivation has been demonstrated to be a link between cognition and motor performance, therefore playing an important role upon rehabilitation outcome determining factors. While motivation-enhancing interventions have been frequently investigated, a common and reliable motivation assessment strategy has not been established yet. This review aims to systematically explore and provide a comparison among the existing motivation assessment tools concerning stroke rehabilitation. For this purpose, a literature search (PubMed and Google Scholar) was performed, using the following Medical Subject Headings terms: "assessment" OR "scale" AND "motivation" AND "stroke" AND "rehabilitation". In all, 31 randomized clinical trials and 15 clinical trials were examined. The existing assessment tools can be grouped into two categories: the first mirroring the trade-off between patients and rehabilitation, the latter reflecting the link between patients and interventions. Furthermore, we presented assessment tools which reflect participation level or apathy, as an indirect index of motivation. In conclusion, we are left to put forth a possible common motivation assessment strategy, which might provide valuable incentive to investigate in future research.

A comprehensive evaluation of adverse childhood experiences, social-emotional impairments, and neurodevelopmental disorders in cannabis-use disorder: Implications for clinical practice.

BACKGROUND: Adverse childhood experiences (ACEs), social-emotional impairments (SEIs), and neurodevelopmental disorders (NDs) are frequent in psychiatric disorders, including substance-use disorders. We aimed to determine the prevalence of ACE, SEI, or ND in individuals with cannabis-use disorder (CUD). We compared individuals with preCUD-onset ACE, SEI, or ND to those without. METHODS: We crosssectionally studied 323 inpatients or outpatients with a history of past or current CUD, aged 12-35 years (mean age 22.94 ± 4.79), 64.5% of whom were male. The sample was divided into two groups: the non-premorbid (N = 52) and the premorbid ACE/SEI/ND group (N = 271). Within the premorbid group, further subgroups were based on ACEs, SEI, and NDs. We also analyzed other substance use and psychiatric symptoms/diagnoses based on the non-premorbid-premorbid dichotomy in the CUD sample. RESULTS: Pre-CUD ACE-SEI-ND had higher prevalence of bipolar, schizoaffective, borderline personality, and attention-deficit/hyperactivity disorders, and a history of agitation, hallucinations, and self-injury. The ACE group had higher rates of agitation, depression, delusions, hallucinations, eating disorders, and use of cocaine, amphetamines, and hallucinogens than the SEI or ND. Patients in the premorbid group initiated cannabis use at an earlier age, experienced the first comorbid psychiatric episode earlier, and were hospitalized earlier than those in the non- premorbid ACE-SEI-ND group. CONCLUSIONS: PreCUD-onset ACE, SEI, or ND conditions in individuals with CUDare linked to earlier onset of comorbid mental illness. Furthermore, ACEs contribute to significant and potentially severe clinical symptoms, as well as the use of substances other than cannabis.

Brexpiprazole in patients with schizophrenia with or without substance use disorder: an observational study.

Background: Partial dopamine D2 receptor agonists are used for psychotic symptoms in adults with schizophrenia spectrum disorders. Recently, interest surged for partial dopamine D2 receptor agonists in substance use disorders (SUDs). Since it is believed that SUDs decrease the efficacy of pharmacotherapy of underlying psychiatric disorders, we tested the efficacy of the partial D2 agonist brexpiprazole in patients with schizophrenia who were either comorbid with a SUD (SUD group) or not comorbid (non-SUD) to assess treatment response and the effect of brexpiprazole on substance craving in SUD. Methods: We included patients with DSM-5/DSM-5-TR schizophrenia (using SCID-5-CV) aged 18-66 years with either comorbid SUD or non-SUD to treat with brexpiprazole 4 mg/day for 6 months during February-October 2022. Patients were assessed with the Clinical Global Impressions-Severity (CGI-S) scale, the 24-item Brief Psychiatric Rating Scale (BPRS), and the Positive And Negative Syndrome Scale (PANSS) at baseline, weekly for the first 2 months and monthly for the next four. Furthermore, we assessed substance craving in SUD with a visual analog scale for craving (VAScrav) at the same timepoints. Results: The total sample was 86 (85 analysable) 18- to 64-year-old (mean 39.32 ± 14.09) patients with schizophrenia [51 men (59.3%) and 35 women (40.7%)], of whom 48 SUD (55.8%) (37 men and 11 women) and 38 non-SUD (44.2%) (14 men and 24 women). No serious or persistent adverse events developed over the study period, but one patient dropped out for subjective akathisia. Results indicated the main effects of time with improvements over the course of the study for CGI-S, BPRS, and PANSS in both SUD and non-SUD groups and the entire sample, and for VAScrav in SUD. Brexpiprazole was associated with similar significant improvements in both groups at the 6 month endpoint compared to baseline. Conclusion: Treatment with brexpiprazole for 6 months improved psychotic symptoms in patients with schizophrenia, independently from whether they belonged to the SUD or the non-SUD group; hence, SUD comorbidity did not confer treatment resistance to brexpiprazole. Furthermore, in the SUD group, we observed reduced substance craving.

Differential Response to Three Antidepressants in Patients with Major Depressive Episode Who Suffered Covid-19-Related Trauma.

BACKGROUND: The Covid 19 pandemic might have impacted response to drug treatment in major depressive episode (MDE). We compared responses to three different antidepressant drugs, i.e., vortioxetine, sertraline, and trazodone, in outpatients with MDE during Major Depressive Disorder (MDD), Bipolar Disorder (BD), or schizophrenia and related psychoses (SSOPDs) during two time periods, i.e., before and after suffering Covid-19-related trauma. METHODS: We conducted an observational study on clinically stabilised for at least 6 months outpatients with MDE during the course of MDD (N=58), BD (N=33), or SSOPDs (N=51). Patients, whose baseline assessments of Montgomery-Åsberg Rating Scale (MADRS), Hamilton Anxiety Rating Scale (Ham-A), Brief Psychiatric Rating Scale (BPRS), Visual Analogue Scale for Craving (VAS-crav) and World Health Organization Quality of Life, Brief version (WHOQOL-BREF) were available, were recruited at the time they suffered Covid-19-related traumas. Fifty patients, prior to the pandemic, when they were clinically stable, were treated with 15 mg/die vortioxetine, 44 with 450 mg/die trazodone, and 48 with 150 mg/die sertraline. After experiencing a major Covid-19-related personal trauma, patients showed clinical worsening which required dosage adjustment (20 mg/day vortioxetine; 600 mg/day trazodone, and 200 mg/day sertraline) and, for some of them, hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and genderwise with Student's t test for continuous variables and Χ2 for categorical variables. RESULTS: The sample consisted of 142 outpatients (age, mean 39.63 ± 16.84; 70 men and 72 women); women were older than men (mean age 43.18 ± 17.61 vs. 35.98 ± 15.30; p=0.01). The two genders did not differ on other variables. For all treatments, worsening symptoms were observed at the time of trauma, followed by slow recovery with treatment readjustment. Trauma-related worsening in patients on vortioxetine was less intense than patients on the other two antidepressants and recovery was faster. All drugs were associated with an improvement in QoL. The vortioxetine group showed a lower hospitalisation rate (24%) than sertraline (35.4%) and trazodone (38.6%), but this was not significant (p=0.27). CONCLUSION: All drugs improved symptoms of Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerning the need for hospitalisation.

Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients.

BACKGROUND: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS. METHODS: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity. RESULTS: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus). CONCLUSIONS: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.

Vortioxetine vs. Other Antidepressants in Patients with Major Depressive Episode With or Without Substance Use Disorder.

BACKGROUND: Major Depressive Episodes (MDEs) may characterise many psychiatric disorders. Its pharmacotherapy is laid with unmet needs, rendering the testing of new drugs necessary. OBJECTIVE: To compare the effects of vortioxetine with those of other antidepressants (OADs) in a 1-year naturalistic setting. METHODS: We included 126 adult patients with anMDE in the course of major depressive (MDD), bipolar (BD), or schizophrenia spectrum disorders (SSOPDs), with or without substance use disorder (SUD), who received 5-20 mg/day oral vortioxetine, and compared them with 100 patients receiving OADs at baseline and after 1, 3, 8, and 12 months on their scores on the MADRS, the CGIS, the 24-item BPRS, the YMRS, the Hamilton Anxiety Rating Scale, a Visual Analogue Scale for craving, the Columbia-Suicide Severity Rating Scale, and the WHOQOL-BREF. RESULTS: Patients on vortioxetine improved similarly to those on OADs on all measures, independently from having or not a comorbid SUD. However, they improved with time better than their OADcounterparts if affected by BD or SSOPDs, but not MDD, on the CGI-S, BPRS depression, anxiety, and manic symptoms. SUD hampered the response of anxiety to treatment. Men improved on depression with time better than women. CONCLUSION: MDEs responded to vortioxetine similarly to OADs by improving in depression, general psychopathology, anxiety, suicidal thinking, and quality-of-life, independently from SUD comorbidity. MDEs of patients with BD or SSOPDs on vortioxetine responded better than that of patients on OADs. Clinical Trial Registration No. 17354N.

Developmental trajectories in psychiatric disorders: does substance/alcohol use moderate the effects of affective temperaments as moderators of age at onset? A study in post-acute, hospitalized patients with psychotic or DSM-5 bipolar or major depressive disorders.

BACKGROUND: Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years ± 11.82 men, 43.21 years ± 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 ± 10.09 vs. 27.73 ± 10.35, respectively, p = 0.001, η2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 ± 4.08, p < 0.001, η2 = 0.069) and irritable (8.26 ± 4.69, p < 0.01, η2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (ß = -0.55, p < 0.005) and hyperthymic (ß = -0.95, p < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations. Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.