Seroprevalence of SARS-CoV-2 antibodies in a prospective cohort of patients admitted to an acute psychiatric ward in Norway during the initial months of the COVID-19 pandemic.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) spread around the world during the first part of 2020. The purpose of the study was to assess the prevalence of SARS-CoV-2 infection among patients acutely admitted to the Psychiatric Clinic, Haukeland University Hospital. METHODS: Serum tests to assess for antibodies to SARS-CoV-2 were administered at admission to the clinic together with a questionnaire on symptoms and demographical information. Further information was obtained from the medical records. RESULTS: The cumulative seroprevalence in the 266 participants was 0.75%, the cumulative reported cases in the Norwegian general population was 0.61% at the end of the inclusion period of the study. Twenty-five percent of participants had risk factors for a serious course of COVID-19. There was a low prevalence of cohabitation and only 20% had their main income derived from ordinary salaries (not welfare). CONCLUSION: The prevalence of SARS-CoV-2 infection in a sample of patients acutely admitted to the Psychiatric Clinic, Haukeland University Hospital, was comparable to reported cases in the general population. A possible link to governmental and municipal restrictions, general low workplace participation and cohabitation is discussed.

Seroprevalence of SARS-CoV-2 antibodies is comparable to the general population.Twenty-five percent of patients had elevated risk for a serious course of COVID-19 because of somatic conditions.Fifty-seven percent lived alone, 17% with one other person in the household.Twenty percent had regular salary as the main income source for the last three months before admission.

Use of Benzodiazepines and Antipsychotic Drugs Are Inversely Associated With Acute Readmission Risk in Schizophrenia.

PURPOSE: Little is known about the impact of different psychotropic drugs on acute readmission risk, when used concomitantly in a real-life setting. We aimed to investigate the association between acute readmission risk and use of antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines in patients with schizophrenia. METHODS: A cohort study included all patients diagnosed with schizophrenia admitted to a psychiatric acute unit at Haukeland University Hospital in Bergen, Norway, during a 10-year period (N = 663). Patients were followed from discharge until first readmission or censoring. Cox multiple regression analyses were conducted using antipsychotic drugs, antidepressants, mood stabilizers, and benzodiazepines as time-dependent variables, and periods of use and nonuse were compared within individual patients. Adjustments were made for sex, age at index admission, and excessive use of alcohol and illicit substances. RESULTS: A total of 410 patients (61.8%) were readmitted during follow-up, and the mean and median times in days to readmission were 709 and 575, respectively. Compared with nonuse, the use of antipsychotic drugs was associated with reduced risk of readmission (adjusted hazards ratio, 0.20; P < 0.01; confidence interval, 0.16-0.24), and the use of benzodiazepines was associated with increased risk of readmission (adjusted hazards ratio, 1.51; P < 0.01; confidence interval, 1.13-2.02). However, no relation to readmission risk was found for the use of antidepressants and mood stabilizers. CONCLUSIONS: We found that use of benzodiazepines and antipsychotic drugs are inversely associated with acute readmission risk in schizophrenia.

The Influence of Substance Use on Side Effects of Olanzapine, Quetiapine, Risperidone, and Ziprasidone in Psychosis.

BACKGROUND: Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration. METHODS: All patients (n = 226, mean age 34, females 33%) diagnosed with schizophrenia spectrum disorders (SSD; F20-F29) or other psychosis (F30-F32; F10-F19), were treated with olanzapine, quetiapine, risperidone or ziprasidone, and were assessed at baseline, 4-weeks, 14-weeks, and 27-weeks. The UKU-Side Effects Self-Rating Scale version was used to evaluate the side effect profiles, and the information on substance use was based on the Clinician Drug Use Scale. RESULTS: At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia. CONCLUSION: Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016.

AIMS: The aim of this study was to investigate time trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia. METHODS: We retrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups (young, adults and elderly). RESULTS: Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1000 inhabitants between 2006 and 2016 (+2.4%, annual change: 0.07 users/1000 inhabitants/year, 95% CI: 0.02-0.20, P = 0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall 1-year prevalence of 4.05-9.97 users/1000 inhabitants (annual change: 0.57 users/1000 inhabitants/year, 95% CI: 0.54-0.60, P < 0.001). Quetiapine showed a marked decrease in mean doses during the 11-year study period (0.46-0.28 defined daily doses (DDD)/user/day: 39.1%, -0.02 DDD/user/day/year, 95% CI: -0.020 to -0.015, P < 0.001). In 2016, the highest mean doses were seen for clozapine (0.90-1.07 DDD/user/day) and olanzapine (0.66-0.88 DDD/user/day). CONCLUSIONS: There is an increased prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study.

The influence of substance use on the effectiveness of antipsychotic medication: a prospective, pragmatic study.

Background: Psychosis is associated with a high prevalence of substance use, leading to worsened prognosis. Less is known about how comorbid substance abuse may influence the effectiveness of antipsychotic medications. The aim of this study was to compare the effectiveness of second generation antipsychotics in patients with psychosis with and without substance use. Methods: All patients (n = 226) were aged >18 years old had symptom level scores of ≥4 on selected psychosis items on the Positive and Negative Syndrome Scale and met ICD-10 diagnostic criteria for psychosis. Information on substance use was collected based on the Clinician Drug Use Scale. Patients were grouped at baseline according to the presence of substance use, medication history and diagnosis group. Clinical symptoms at baseline and changes at follow-up were assessed with the PANSS. Results: At baseline about 30% of the patients used substances, most frequently cannabis followed by methamphetamine. About half (47%) of the patients had no prior exposure to antipsychotic medication at inclusion. Patients who had consumed substances showed no substantial differences in the PANSS score reduction as a result of antipsychotic medication compared to patients without substance. There were, however, some group differences in relation to pattern of change that were influenced by medication history. Substance use was found to be related to stronger reduction of positive symptoms from week 4 to week 27. Conclusion: Substance use alone did not influence antipsychotic effectiveness in this sample of patients with psychosis.

Predictors of treatment satisfaction in antipsychotic-naïve and previously medicated patients with acute-phase psychosis.

Background: Treatment satisfaction predicts treatment adherence and long-term outcome for patients with psychosis. It is therefore important to understand the underpinnings of patient satisfaction in psychosis treatment for optimal treatment delivery. Aims: To examine the associations between satisfaction and level and change in positive symptoms, insight, depression and side effects of antipsychotics in previously medicated and antipsychotic-naïve patients. Method: Data derive from a randomised trial, with 226 respondents at baseline and 104 at follow-up. The measures were the positive subscale and insight item from the Positive and Negative Syndrome Scale, Calgary Depression Scale, the UKU Consumer Satisfaction Rating Scale, and the UKU side effects scale. Structural equation modelling was used to test the model. The full information maximum likelihood estimator used all available data. Results: In the sample of 226 patients, 67.3% were male and 44.2% were antipsychotic-naïve. The mean age was 34.1 years. For previously medicated patients, satisfaction was predicted by level of insight (b = -2.21, ß = -0.42) and reduction in positive symptoms (b = -0.56, ß = -0.39). For antipsychotic-naïve patients, satisfaction was predicted by level and change of insight (b = -2.21, ß = -0.46), change in depression (b = -0.37, ß = -0.26) and side effects (b = -0.15, ß = -0.30). All predictors were significant at the 0.05 level. Conclusion: Reducing positive symptoms and side effects are important to enhance patient satisfaction. However, improving insight and reducing depression are more important in antipsychotic-naïve patients.

Associations between C-reactive protein levels and cognition during the first 6 months after acute psychosis.

OBJECTIVE: Inverse relationships between the C-reactive protein (CRP) levels and cognitive performance in acute psychosis have been demonstrated. We aimed to investigate how the serum level and initial change of CRP in acutely admitted patients with psychosis was correlated with cognitive performance during a 6-months follow-up period. METHODS: The study is part of a pragmatic, randomised trial comparing four different second-generation antipsychotic drugs, and consists of 208 acute phase patients recruited at admittance for psychosis. This study reports data for all groups collectively, and does not compare treatment groups. Measurements of CRP and cognitive performance were conducted at baseline (T1) and after 4 weeks on average after inclusion (T2). Cognition was also assessed after 3 months (T3) and 6 months (T4) of follow-up. RESULTS: Global cognition improved during the follow-up period of 6 months, especially in the T1-T2 interval. The different cognitive subdomains showed different time-dependent profiles of improvement, with memory and attention improving significantly also in the later phases. Reduction of the CRP level during the initial follow-up interval (T1-T2) was associated with increased overall cognitive performance in the T2-T4 interval, but not in the T1-T2 interval. For the cognitive subdomains, we found an inverse association between change in CRP level and verbal abilities (T2-T4 interval), and attention (T2-T3 interval). CONCLUSION: These findings indicate that initial changes in the serum level of CRP in the acute phase of psychosis may predict cognitive function in later phases of the disease.

The serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis.

BACKGROUND: Inflammatory processes have been implicated in the etiology of schizophrenia and related psychoses, in which cognitive deficits represent core symptoms. The aim of the present study was to investigate possible associations between the level of the inflammation marker C-reactive protein (CRP) and cognitive performance in patients through the acute phase of psychosis. METHODS: A total of 124 patients were assessed at admittance to hospital and 62 patients were retested at discharge or after 6 weeks at the latest, with measurements of the CRP levels and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: There was an inverse relationship between overall cognitive performance and CRP level at admittance. The association increased in sub-analyses including only patients with schizophrenia. In cognitive subdomain analyses statistically significant inverse associations were found between the CRP level and Delayed memory and Attention, respectively. No associations were found between CRP level and other measures of psychopathology including psychosis symptoms, depression, or functioning. At follow-up the association between CRP level and cognition was no longer present. There was a significant increase in cognitive performance between baseline and follow-up. There was a stronger increase in overall cognition scores in patients with higher baseline CRP levels. CONCLUSIONS: The findings indicate that signs of inflammation may serve as a state-dependent marker of cognitive dysfunctions in acute psychosis. TRIAL REGISTRATION: ClinicalTrials.gov ID; NCT00932529 , registration date: 02.07.2009.

Patient satisfaction after acute admission for psychosis.

Background Measuring patient satisfaction in mental health care potentially provides valuable information, but studies in acutely admitted psychosis patients are scarce. Aims The aims were to assess satisfaction among patients acutely admitted with psychosis, to compare satisfaction in voluntarily versus involuntarily admitted patients, and to assess the influence of symptom load and insight. Methods The UKU Consumer Satisfaction Rating Scale (UKU-ConSat) was used. A total of 104 patients completed the UKU-ConSat at discharge/follow-up (between 6-11 weeks after admittance if not discharged earlier) (mean duration of stay 4 weeks), thus corresponding to the end of the acute treatment phase. Results A total of 88.4% had total scores above zero (satisfied). Only three of the eight single items were statistically significantly different among patients admitted voluntarily versus involuntarily, and only the information item score remained significantly different in adjusted analyses. Insight level at admittance, and an increasing level of insight during the acute phase were positively associated with patient satisfaction, whereas levels and changes in positive and negative psychosis symptoms were indirectly related to satisfaction via this process of insight. Conclusions The vast majority of the acutely admitted patients were satisfied with treatment. There were few differences between the involuntarily and voluntarily admitted patient groups, except that the involuntary care group was clearly less satisfied with the information provided. Poor insight had a major negative impact on treatment satisfaction in psychosis. The provision of sufficient and adequate information is an important target for mental health care service improvement.

Borderline Personality Disorder and Posttraumatic Stress Disorder at Psychiatric Discharge Predict General Hospital Admission for Self-Harm.

We investigated whether posttraumatic stress disorder (PTSD) was predictor of suicidal behavior even when adjusting for comorbid borderline personality disorder (BPD) and other salient risk factors. To study this, we randomly selected 308 patients admitted to a psychiatric hospital because of suicide risk. Baseline interviews were performed within the first days of the stay. Information concerning the number of self-harm admissions to general hospitals over the subsequent 6 months was retrieved through linkage with the regional hospital registers. A censored regression analysis of hospital admissions for self-harm indicated significant associations with both PTSD (ß = .21, p < .001) and BPD (ß = .27, p < .001). A structural model comprising two latent BPD factors, dysregulation and relationship problems, as well as PTSD and several other variables, demonstrated that PTSD was an important predictor of the number of self-harm admissions to general hospitals(B = 1.52, p < .01). Dysregulation predicted self-harm directly (B = 0.28, p < .05), and also through PTSD [corrected]. These results suggested that PTSD and related dysregulation problems could be important treatment targets for a reduction in the risk of severe self-harm in high-risk psychiatric patients.

Auditory verbal hallucinations reflect stable auditory attention deficits: a prospective study.

INTRODUCTION: Previous studies have shown that auditory verbal hallucinations (AVHs) in psychosis are associated with reduced verbal auditory attention. Whether this is an effect of ongoing AVH or reflects a more stable cognitive vulnerability also present after treating the AVH is unknown. The aim of this study was to follow patients with acute psychosis with and without AVH, and to test their auditory attention in a more stabilised clinical phase. METHODS: Fifty patients (35 males and 15 females) were examined when admitted to an acute psychiatry ward and tested three months later with a dichotic listening test with attention instructions. The patients were divided into a frequent (n = 33) and non-frequent (n = 17) AVH group based on their score on the Positive and Negative Syndrome Scale item hallucinatory behaviour (≥4 and ≤3, respectively) at baseline. RESULTS: A significant interaction emerged between AVH group and attention instruction condition; the frequent AVH group failed to control their auditory attention as opposed to the non-frequent AVH group. CONCLUSIONS: Patients with frequent AVH in an acute psychotic state showed impaired auditory attention three months after their AVH had been treated, indicating a stable cognitive vulnerability factor for experiencing AVH.

Association between cytokines and suicidality in patients with psychosis: A multicentre longitudinal analysis.

Suicide is a common cause of death in all phases of schizophrenia spectrum disorder, particularly in the youngest patients. Clinical measures have demonstrated limited value in suicide prediction, spurring the search for potential biomarkers. The causes of suicidal behaviour are complex, but the immune system seems to be involved as it reflects or even causes mental suffering. We aimed to identify cytokines with associations to suicidality in a sample of patients with symptoms of active psychosis. Patients with schizophrenia spectrum disorder (N = 144) participating in a semi-randomized antipsychotic drug trial (the BeSt InTro study) were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) at eight visits across 12 months. The Clinical Global Impression for Severity of Suicidality scale (CGI-SS) was used for assessing suicidality. Serum concentrations of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and IL-10 were measured using immunoassays. A logistic regression model was used to investigate the association between cytokine levels and suicidality. To enhance clinical significance, the CGI-SS scores were dichotomized into two groups before analyses: low (=1) and high (≥2) risk for suicidality. Both uni- and multi-variate analyses revealed an inverse correlation between IL-2 and IL-10 serum levels and suicidality, where lower cytokine concentrations of IL-2 and IL-10 were associated with higher suicidality scores. The results were consistent when adjusted for depression and substance use. These results indicate that inflammatory processes are linked to the risk of suicidality in patients with schizophrenia spectrum disorders.

Hallucinations in acutely admitted patients with psychosis, and effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone: a pragmatic, randomized study.

BACKGROUND: Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up. METHODS: Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS). RESULTS: A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group. CONCLUSIONS: Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category. TRIAL REGISTRATION: ClinicalTrials.gov ID; NCT00932529.

Prospective and concurrent correlates of emotion perception in psychotic disorders: a naturalistic, longitudinal study of neurocognition, affective blunting and avolition.

This naturalistic study investigated longitudinal and cross-sectional symptomatic and neurocognitive correlates of social cognition indexed by emotion perception. Participants were 31 persons admitted to a psychiatric emergency ward due to acute psychosis. Positive and negative (i.e., affective blunting and avolition) symptoms were assessed at baseline and 12-month follow-up using the Positive and Negative Syndrome Scale. Participants completed neuropsychological assessments with alternative versions of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and at 12-month follow-up. Emotion perception was measured using the Face/Voice Emotion Test at 12-month follow-up. Correlational analyses (Spearman's rho) revealed strong and statistically significant associations between neurocognition and emotion perception (baseline r = 0.58, follow-up r = 0.43). Associations between positive symptoms and emotion perception were weak or non-existent (baseline r = 0.13, follow-up r  =  -0.01). Emotion perception was moderately, but not significantly, associated with affective blunting at follow-up (r = 0.33), but not at baseline (r = 0.21). The association with avolition was non-existent (baseline r  =  -0.05, follow-up r = 0.01). This study supports the notion that emotion perception has neurocognitive correlates. The cross-sectional trend level association with affective blunting suggests that the ability to perceive emotions might be related to, but dissociable from the ability to express emotions.

Dichotic listening, executive functions and grey matter cortical volume in patients with schizophrenia and healthy controls.

Schizophrenia is characterized by cognitive impairment, especially in relation to executive functions. Brain structural abnormalities are also often seen in schizophrenia although little is known of the relationship between cognitive impairment and structural brain changes. Our aim was therefore to investigate this relationship further using MRI and a dichotic listening (DL) task with simple speech sounds and with instructions to focus attention and report only from the left or right ear stimulus. When instructed to focus attention on the left ear syllable a cognitive conflict is induced requiring the allocation of executive resources to be resolved. Grey matter (GM) volume was measured with MRI from four volumes of interests (VOIs), left and right frontal and temporal cortex, respectively, and correlated with DL performance. The results showed significant differences between the groups in their ability to focus attention on and report the left ear stimulus, which was accompanied by reduced GM volume in the left frontal and right temporal lobe VOIs. There was also a significant positive correlation between left frontal GM volume and performance on the DL task, for the groups combined. The results did not support a conclusion that an impairment in cognitive function in schizophrenia was driven by an corresponding impairment in brain structure, since there were no significant correlations when the groups were analyzed separately. It is however concluded that patients with schizophrenia are impaired in executive functions and that they also show reduced GM volumes in left frontal and right temporal lobe areas, compared to healthy controls.

Neural Activation in the Ventromedial Prefrontal Cortex Precedes Conscious Experience of Being in or out of a Transient Hallucinatory State.

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. STUDY DESIGN: We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. STUDY RESULTS: We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. CONCLUSIONS: The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.

Depression trajectories and cytokines in schizophrenia spectrum disorders - A longitudinal observational study.

Depression occurs frequently in all phases of schizophrenia spectrum disorders. Altered activity in the immune system is seen in both depression and schizophrenia. We aimed to uncover depressive trajectories in a sample of 144 adult individuals with schizophrenia spectrum disorders followed for one year, in order to identify possible cytokine profile differences. Patients were assessed longitudinally with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), where a score above 6 predicts depression. The serum cytokine concentrations for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p70 and IL-17A were measured using immunoassays. Latent growth curve models, multilevel models and latent class growth analysis (LCGA) were applied. The LCGA model supported three latent classes (trajectories) with differing CDSS profiles during the one-year follow-up: a high CDSS group (40.8 % of participants), a moderate CDSS group (43.9 %) and a low CDSS group (15.3 %). Five single PANSS items predicted affiliation to depressive trajectory: hallucinations, difficulty in abstract thinking, anxiety, guilt feelings and tension. In the high CDSS group, despite diminishing psychotic symptoms, depressive symptoms persisted throughout one year. The pro-inflammatory cytokines IFN-γ, IL-1ß and TNF-α were differentially distributed between the depressive trajectories, although levels remained remarkably stable throughout 12 months. Significant changes were found for the anti-inflammatory cytokine IL-10 at baseline with an accompanying difference in change over time. More research is required to optimize future treatment stratification and investigate the contribution of inflammation in depressed patients with schizophrenia spectrum disorders.

Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.

OBJECTIVES: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. METHODS: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. RESULTS: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. CONCLUSION: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.

Elevated Systemic Levels of Markers Reflecting Intestinal Barrier Dysfunction and Inflammasome Activation Are Correlated in Severe Mental Illness.

BACKGROUND AND HYPOTHESIS: Gut microbiota alterations have been reported in severe mental illness (SMI) but fewer studies have probed for signs of gut barrier disruption and inflammation. We hypothesized that gut leakage of microbial products due to intestinal inflammation could contribute to systemic inflammasome activation in SMI. STUDY DESIGN: We measured plasma levels of the chemokine CCL25 and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) as markers of T cell homing, adhesion and inflammation in the gut, lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) as markers of bacterial translocation and gut barrier dysfunction, in a large SMI cohort (n = 567) including schizophrenia (SCZ, n = 389) and affective disorder (AFF, n = 178), relative to healthy controls (HC, n = 418). We assessed associations with plasma IL-18 and IL-18BPa and leukocyte mRNA expression of NLRP3 and NLRC4 as markers of inflammasome activation. STUDY RESULTS: Our main findings were: (1) higher levels of sMAdCAM-1 (P = .002), I-FABP (P = 7.6E-11), CCL25 (P = 9.6E-05) and LBP (P = 2.6E-04) in SMI compared to HC in age, sex, BMI, CRP and freezer storage time adjusted analysis; (2) the highest levels of sMAdCAM-1 and CCL25 (both P = 2.6E-04) were observed in SCZ and I-FABP (P = 2.5E-10) and LBP (3) in AFF; and (3), I-FABP correlated with IL-18BPa levels and LBP correlated with NLRC4. CONCLUSIONS: Our findings support that intestinal barrier inflammation and dysfunction in SMI could contribute to systemic inflammation through inflammasome activation.

Systemic Cell Adhesion Molecules in Severe Mental Illness: Potential Role of Intercellular CAM-1 in Linking Peripheral and Neuroinflammation.

BACKGROUND: Cell adhesion molecules (CAMs) orchestrate leukocyte trafficking and could link peripheral and neuroinflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune-mediated responses and mediating signals across blood-brain barrier. We hypothesized that CAMs would be dysregulated in SMI and evaluated plasma levels of different vascular and neural CAMs. Dysregulated CAMs in plasma were further evaluated in vivo in leukocytes and brain tissue and in vitro in induced pluripotent stem cells. METHODS: We compared plasma soluble levels of different vascular (VCAM-1, ICAM-1, P-SEL) and neural (JAM-A, NCAD) CAMs in circulating leukocytes in a large SMI sample of schizophrenia (SCZ) spectrum disorder (n = 895) and affective disorder (n = 737) and healthy control participants (n = 1070) controlling for age, sex, body mass index, C-reactive protein, and freezer storage time. We also evaluated messenger RNA expression of ICAM1 and related genes encoding ICAM-1 receptors in leukocytes using microarray (n = 842) and in available RNA sequencing data from the CommonMind Consortium (CMC) in postmortem samples from the dorsolateral prefrontal cortex (n = 474). The regulation of soluble ICAM-1 in induced pluripotent stem cell-derived neurons and astrocytes was assessed in patients with SCZ and healthy control participants (n = 8 of each). RESULTS: Our major findings were 1) increased soluble ICAM-1 in patients with SMI compared with healthy control participants; 2) increased ITGB2 messenger RNA, encoding the beta chain of the ICAM-1 receptor, in circulating leukocytes from patients with SMI and increased prefrontal cortex messenger RNA expression of ICAM1 in SCZ; and 3) enhanced soluble ICAM-1 release in induced pluripotent stem cell-derived neurons from patients with SCZ. CONCLUSIONS: Our results support a systemic and cerebral dysregulation of soluble ICAM-1 expression in SMI and especially in patients with SCZ.