Major Depression in Comorbidity with Substance use Disorders: Patients' Features and Clinical-Neurobiological Rationale of Antidepressant Treatments.

The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders (SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive function. These symptoms lead to an inability to control cravings, more substance use, increased relapse rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity, mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients are inconclusive and often conflicting because of a number of confounding factors in clinical trials or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential. This approach aims to address unmet needs and optimize the outcomes in a clinical population often underrepresented in treatment paradigms.

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.

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.

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.

Suicidal risks with psoriasis and atopic dermatitis: Systematic review and meta-analysis.

OBJECTIVE: Evidence of increased suicidal risk in association with psoriasis is growing, but findings concerning atopic dermatitis are inconsistent. METHODS: We systematically reviewed reports of suicidal ideation, attempts, or suicides among subjects diagnosed with psoriasis or atopic dermatitis compared to healthy controls or persons with other illnesses. Reported rates of suicidal ideation and behavior were compared among the groups, using meta-analyses to compare suicidal rates with dermatologic patients versus controls, as well as between dermatological diagnoses. RESULTS: Mean rates of suicidal ideation with psoriasis were 1.60-fold (13.9%/8.67%) above controls, and with atopic dermatitis, 1.84-fold higher (16.8%/9.12%); meta-analyses found similar differences: psoriasis (OR = 1.97 [CI: 1.26-3.08]; p = 0.003) and atopic dermatitis (OR = 2.62 [1.32-5.19]; p = 0.006). For suicidal acts, with psoriasis, mean rates versus controls were 2.51-fold higher (3.34%/1.33%), and 2.81-fold higher (5.03%/1.79%) with atopic dermatitis; meta-analyses found significantly more suicidal acts with psoriasis (OR = 1.42 [1.05-1.92]; p = 0.02) and a similar tendency with atopic dermatitis (OR = 1.53 [0.96-2.45]; p = 0.08). CONCLUSIONS: The study findings support emerging evidence of increased risk of suicidal ideation and behavior with psoriasis and extend it to increased risk of suicidal ideation and a trend toward increased suicidal acts with atopic dermatitis.

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

BACKGROUND: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. OBJECTIVE: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. METHOD: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. RESULTS: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R2  = 0.337). CONCLUSION: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.

Lurasidone: efficacy and safety in the treatment of psychotic and mood disorders.

INTRODUCTION: Lurasidone ([3aR,4S,7R,7aS]-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1yl-methyl] cyclohexylmethyl]-hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; Latuda®) is a novel benzisothiazole, second-generation antipsychotic drug developed by Dainippon Sumitomo Pharma Corporation in Japan. Similar to other atypical antipsychotics it has a distinctive pharmacodynamic profile, Areas covered: This review updates reported research findings on the efficacy, safety and tolerability of LRSD for treatment of psychotic and major affective disorders, with meta-analyses. Short-term efficacy of LRSD in schizophrenia is supported by several randomized, controlled trials with daily doses of 40-160 mg, yielding relatively modest symptomatic improvements. Lurasidone has regulatory approval for treatment of undefined duration in schizophrenia. Long-term benefits and effects in schizophrenia, and both short- and long-term use for other psychotic disorders and mania have not been tested. LRSD shows unusual efficacy in acute bipolar depression even without psychotic features. However, trials of adding LRSD to lithium or valproate for bipolar disorder have yielded inconsistent findings. Expert opinion: Available research findings indicate that LRSD is effective and well-tolerated for short-term treatment of schizophrenia, and for acute bipolar depression. It has low risk of inducing weight-gain, metabolic, or cardiac abnormalities, but its risk of akathisia may exceed that of other modern antipsychotics. Needed is adequate long-term testing in schizophrenia and bipolar disorder and testing for other indications, including against alternative treatments.

Neurocognition in schizophrenia: from prodrome to multi-episode illness.

Individuals with schizophrenia present a neuropsychological deficit throughout the course of the disorder. Few studies have addressed the progression of the deficit since the prodromal phase of the disorder. This investigation explored neurocognition in accordance with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus recommendations. The aim of the study was to explore the presence of neurocognitive impairment in ultra-high-risk individuals and the stage of this impairment in samples at different phases of illness. Thirty-six individuals with a prodromal syndrome, 53 first-episode and 44 multi-episode schizophrenia patients were assessed to examine neuropsychological performance. ANCOVA analysis adjusted for possible confounder factors and planned contrasts with healthy controls were undertaken. The results revealed deficits in speed-of-processing, visual-learning and social-cognition in prodromal individuals, and of all other neuropsychological domains in both first-episode and multi-episode patients. Furthermore impairment was found in the first-episode and in the multi-episode group, respectively on working-memory and attention. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of neuropsychological impairment before the onset of full-blown psychosis. Moreover, the deficits are larger in the more chronic groups, according to the theory of an ongoing neurodevelopmental alteration.

Basic symptoms and psychotic symptoms: their relationships in the at risk mental states, first episode and multi-episode schizophrenia.

In the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.

Symptom correlates of facial emotion recognition impairment in schizophrenia.

BACKGROUND: The ability to facial emotion recognition (FER), a key component of socioemotional competence, is often impaired in schizophrenic disorders. The purpose of the present study was to examine the relationship between emotion recognition performance and symptoms in a group of patients with schizophrenia spectrum disorders. SAMPLING AND METHODS: Seventy-nine patients meeting DSM-IV-TR criteria for schizophrenia, schizophreniform disorder and schizoaffective disorder were assessed by the Positive and Negative Syndrome Scale and a FER task. In schizophrenia patients and healthy control subjects, FER performance was compared. In order to avoid a possible confounding role of cognitive impairment, we carried out partial correlations corrected for an index of global cognition. RESULTS: Patients performed worse than a healthy control group on all negative emotions. Partial correlations showed that cognitive/disorganized symptoms correlated with a worse performance in the FER task, whereas no correlations were found with positive, negative, excitement and depressive symptoms. CONCLUSIONS: Our findings support that in schizophrenia FER impairment is specific for negative emotions and that there is a relationship between this deficit and cognitive/disorganized symptoms, regardless of the general cognitive level.

Facial emotion recognition impairment is related to disorganisation in multi-episode schizophrenia.

The present investigation explores the relationship between facial emotion recognition (FER) and symptom domains in three groups of schizophrenia spectrum patients (43 ultra-high-risk, 50 first episode and 44 multi-episode patients) in which the existence of FER impairment has already been demonstrated. Regression analysis showed that symptoms and FER impairment are related in multi-episode patients, regardless of the illness duration. We suggest that the link between symptoms and FER impairment is involved in the progression of the disease.

Emotion recognition impairment is present early and is stable throughout the course of schizophrenia.

Individuals with schizophrenia experience problems in the perception of emotion throughout the course of the disorder. Few studies have addressed the progression of the deficit over time. The present investigation explores face emotion recognition (FER) performance throughout the course of schizophrenia. The aim of the study was to test the hypotheses that: 1) FER impairment was present in ultra high-risk (putatively prodromal) individuals, and that 2) impairment was stable across the course of the illness. Forty-three individuals with a putative prodromal syndrome, 50 patients with first episode of schizophrenia, 44 patients with multi-episode schizophrenia and 86 unaffected healthy control subjects were assessed to examine emotion recognition ability. ANCOVA analysis adjusted for possible confounder factors and subsequent planned contrasts with healthy controls was undertaken. The results revealed deficits in recognition of sadness and disgust in prodromal individuals, and of all negative emotions in both first-episode and multi-episode patients. Furthermore, there were no significant differences between clinical groups. Within the framework of the neurodevelopmental model of schizophrenia, our results suggest the presence of emotional recognition impairment before the onset of full-blown psychosis. Moreover, the deficit remains stable over the course of illness, fitting the pattern of a vulnerability indicator in contrast to an indicator of chronicity or severity.