Cigarette Smoking and Schizophrenia: Etiology, Clinical, Pharmacological, and Treatment Implications

Recent data suggests that the prevalence of smoking in schizophrenia remains high. While reports suggest that smoking increases the risk of developing schizophrenia, the potential causative role of smoking in this relationship needs further investigation. Smokers with schizophrenia are more likely to have more intense positive symptoms and lower cognitive function, but diminished intensity of extrapyramidal side effects than nonsmoking patients with schizophrenia. They were also more likely to exhibit aggressive behaviour compared to nonsmokers, which could suggest higher levels of baseline aggression. The significant cost associated with regular tobacco expenditure can detract from investment in key domains. Large-scale trials have shown that pharmacotherapy for smoking cessation is effective and does not worsen the risk of developing neuropsychiatric symptoms compared to placebo. Electronic cigarette use among schizophrenia patients is high, and there is emerging evidence supportive of its efficacy. Future improvements include large-scale trials assessing the utility, efficacy, and safety of electronic cigarettes in schizophrenia patients.

Comparison of Efficacy and Safety between Long-Acting Injectable Antipsychotic Monotherapy and Combination of Long-Acting Injectable and Oral Antipsychotics in Patients with Schizophrenia

Background. Long-acting injectable (LAI) antipsychotics are used as a monotherapy in patients with schizophrenia. However, the combination of LAI and oral antipsychotics is commonly used in clinical practice, despite there being very limited studies investigating the efficacy and safety of this combination compared with LAI antipsychotic monotherapy. Objective. To study the efficacy and safety of LAI antipsychotic monotherapy compared with the combination of LAI and oral antipsychotics in patients with schizophrenia. Methods. This study was a retrospective cohort study, which classified eligible patients into two groups: the LAI antipsychotic monotherapy group and the combination of LAI and oral antipsychotic group. The primary outcome was hospitalization between groups. The duration of the study was 2 years. Results. In total, 86 patients completed the study and were analysed (LAI antipsychotic monotherapy group: n = 25 ; combination of LAI and oral antipsychotic group: n = 61 ). There was no significant difference in hospitalization between the two groups ( P = 1.000 ). For other outcomes, there were also no significant differences in both all-cause discontinuation ( P = 0.667 ) and adverse drug reactions ( P = 0.732 ) between the two groups. Conclusion. The efficacy and safety of LAI antipsychotic monotherapy appeared similar to the combination of LAI and oral antipsychotics in patients with schizophrenia. Therefore, the combination of LAI and oral antipsychotics, which is commonly used in clinical practice, may not be necessary.

Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia—disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects ( p = 0.0041 ), and this may be due to the lower folate level in patients ( p = 0.0072 ). In patients, negative correlation was found between the level of Hcy both with the level of folate ( ρ = − 0.38 , p = 0.0063 ) and with the level of B12 ( ρ = − 0.36 , p = 0.0082 ). At the same time, patients showed higher levels of oxidative modification of serum proteins ( p = 0.00046 ) and lower catalase (CAT) activity ( p = 0.014 ). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 μmol/l, n = 42 ) compared with other patients ( n = 8 ), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019 ), lack of spontaneity and flow in conversation (N6, p = 0.022 ), stereotyped thinking (N7, p = 0.013 ), and motor retardation (G7, p = 0.050 ). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

Suicide Behavior and Its Predictors in Patients with Schizophrenia in Ethiopia

Background. People with schizophrenia (PWS) are at greater risk of suicide. However, suicide behaviors that occur in PWS are often overlooked, inadequately characterized, and not consistently integrated into treatment. Despite this burden and consequences in Ethiopia, there is a dearth of studies concerning suicide behavior in PWS. Therefore, this study is aimed at assessing the magnitude of suicide behavior and its predictors among PWS in Ethiopia. Methods. An institution based cross-sectional study was employed. Data were collected using the structured interviewer-administered questionnaire from a sample of 300 PWS at Amanuel Mental Specialized Hospital (AMSH). The revised version of Suicide Behavior Questionnaire (SBQ-R) was used to assess suicide behavior in PWS. The data was collected from March 1 to 30, 2019. Binary logistic regression was performed to identify independent predictors of suicidal behavior at 95% confidence level. Statistical significance was declared at p value <0.05. Result. A total of 300 patients with schizophrenia participated in the study. More than two-thirds of 203 (67.7%) of the participants were males, and 116 (38.7%) participants were between the ages of 28 and 37 years. We found that the prevalence of suicide behavior among PWS was 30.3%. Being unemployed ( AOR = 3.65 , CI = 1.32 , 10.05), family history of suicide ( AOR = 3.16 , CI = 1.38 , 7.23), substance use ( AOR = 2.51 , CI = 1.13 , 5.59), current positive psychotic symptoms (hallucination ( AOR = 6.39 , CI = 2.86 , 14.29), and delusion ( AOR = 4.15 , CI = 1.95 , 14.29) and presence of comorbid depression ( AOR = 4.81 , CI = 1.98 , 11.68) were independent significant predictors with suicidal behavior in PWS. Conclusion. The prevalence of suicidal behavior among PWS was found to be high. Hence, designing strategies for early screening and intervention is the most critical prevention strategy of suicide in PWS.

Impact of Negative Symptom Domains and Other Clinical Characteristics on Functional Outcomes in Patients with Schizophrenia

Negative symptoms of schizophrenia have generally been defined using five factors; however, few studies have examined the relationship between these five factors and functional outcomes. In addition, there is no definitive conclusion regarding the association between negative symptoms and various aspects of functional outcomes (daily living, social, and vocational). This study is aimed at examining the relationship between these five domains of negative symptoms and different functional outcomes. Patients diagnosed with chronic schizophrenia ( n = 100 ) were selected for the evaluation. We used the Brief Negative Symptom Scale to assess negative symptoms, the Brief Psychiatric Rating Scale to assess positive symptoms, the Schizophrenia Cognition Rating Scale to assess cognition, and the Evaluative Beliefs Scale (negative self-assessment) to assess psychological factors. We analyzed their relative impact on Social Functioning Scale domains using hierarchical multiple regression analysis. Concerning the relationship between daily living and negative symptoms, cognitive function showed the highest association with residential outcomes, such as self-care and shopping, while avolition appeared to show an additional contribution; however, for recreational outcomes, avolition showed the main association, whereas cognitive function showed no additional contribution. For social outcomes, asociality and negative self-assessment showed the main associations, while vocational outcomes were determined by both cognitive function and multiple negative symptoms, such as avolition, anhedonia, asociality, and alogia. Since negative symptom domains appear to differentially impact each outcome, specifically daily living outcome, it is important to evaluate the residential outcomes and recreational outcomes separately. Overall, the present study points to the importance of formulating psychosocial treatment strategies specific for each type of preferred outcome in patients with schizophrenia.

Polygenic Risk Scores for Subtyping of Schizophrenia

Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p=0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE, p=0.0099; PROCESSING SPEED, p=0.0006; WORKING MEMORY, p=0.0023; and REASONING, p=0.0015). Class II had modest reduction of positive symptoms (p=0.0492) and better PROCESSING SPEED (p=0.0071). Class IV had a specific reduction of negative symptoms (p=0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction.

Two Thalamic Regions Screened Using Laser Capture Microdissection with Whole Human Genome Microarray in Schizophrenia Postmortem Samples

We used whole human genome microarray screening of highly enriched neuronal populations from two thalamic regions in postmortem samples from subjects with schizophrenia and controls to identify brain region-specific gene expression changes and possible transcriptional targets. The thalamic anterior nucleus is reciprocally connected to anterior cingulate, a schizophrenia-affected cortical region, and is also thought to be schizophrenia affected; the other thalamic region is not. Using two regions in the same subject to identify disease-relevant gene expression differences was novel and reduced intersubject heterogeneity of findings. We found gene expression differences related to miRNA-137 and other SZ-associated microRNAs, ELAVL1, BDNF, DISC-1, MECP2 and YWHAG associated findings, synapses, and receptors. Manual curation of our data may support transcription repression.

The Prevalence and Correlates of Social Anxiety Symptoms among People with Schizophrenia in Ethiopia: An Institution-Based Cross-Sectional Study

Background. The comorbidity of social anxiety disorder is very common in schizophrenia patients and affects almost all age groups. This social anxiety disorder negatively impacts the quality of life, medication adherence, and treatment outcomes of people with schizophrenia. It is not well recognized in clinical settings. Therefore, assessing social anxiety symptoms and its associated factors was significant to early intervention and management of schizophrenia patients in Ethiopia. Methods. An institution-based cross-sectional study was conducted at Amanuel Mental Specialized Hospital in Addis Ababa, Ethiopia. Data collectors randomly recruited 423 schizophrenic patients by using the systematic sampling technique. A face-to-face interviewer-administered questionnaire was used to collect data. The standardized Liebowitz Social Anxiety Scale (LSAS) was employed to assess individual social anxiety symptoms. We computed bivariate and multivariate binary logistic regressions to identify factors associated with social anxiety symptoms. Statistical significance was declared at p<0.05. Results. The prevalence of social anxiety symptoms was 36.2% (95% CI: 31.50, 40.80). Male sex (AOR=2.03, 95% CI: 1.20, 3.44), age of onset of schizophrenia (AOR=1.91, 95% CI:1.17, 3.12), positive symptoms (AOR=0.75, 95% CI:0.67, 0.83), depression/anxiety symptoms (AOR=1.29, 95% CI: 1.18, 1.41), number of hospitalizations (AOR=2.80, 95% CI:1.32, 5.80), and suicidal ideation (AOR=0.44, 95% CI: 0.26, 0.74) were factors significantly associated with social anxiety symptoms at p<0.001, whereas poor social support (AOR=5.23, 95% CI:2.03, 14.70) and suicide attempts (AOR=1.93, 95% CI: 1.14, 3.26) were statistically associated with social anxiety symptoms at p<0.01. Conclusion. The prevalence of social anxiety symptoms among schizophrenia patients was found to be high. Timely treatment of positive and depression/anxiety symptoms and suicide risk assessments and interventions need to be done to manage the problems.

Lack of Association between the IL6R Gene Asp358Ala Variant (rs2228145), IL-6 Plasma Levels, and Treatment Resistance in Chilean Schizophrenic Patients Treated with Clozapine

Alterations in neuroinflammatory processes have been suggested to contribute to the development of Schizophrenia (SZ); one component of the inflammatory system that has been linked to this disorder is interleukin-6 (IL-6). The minor allele of rs2228145, a functional polymorphism in the IL-6 receptor gene, has been associated to elevated IL-6 plasma levels and increased inflammatory activity, making it an interesting candidate to study as a possible factor underlying clinical heterogeneity in SZ. We studied a sample of 100 patients undergoing treatment with clozapine. Their symptoms were quantified by Brief Psychotic Rating Scale; those with the lowest scores (“remitted”) were compared with the highest (“clozapine treatment resistant”). We determined allelic frequencies for rs2228145 and IL-6 plasma levels. Our results do not support a role of IL-6 in response to treatment with clozapine. Further studies accounting for potential confounding factors are necessary.

Attitude towards Antipsychotic Medications in Patients Diagnosed with Schizophrenia: A Cross-Sectional Study at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia

Background. Poor attitude towards antipsychotic drugs is high, and it is a factor for non-adherence to treatment. This increases the risk of relapse, associated healthcare utilization, and costs. This study aimed to assess attitude towards antipsychotic medication among patients with schizophrenia. Objectives. The aim of this institution based cross-sectional study was to assess attitude towards antipsychotic medications and associated factors among patients with schizophrenia who attend the outpatient clinics at Amanuel Mental Specialized Hospital, 2018. Methods. In a cross-sectional study, 393 schizophrenic patients from Amanuel Mental Specialized Hospital were recruited by a systematic random sampling technique. Drug Attitude Inventory (DAI-10) was used to assess attitude, experience, and belief about antipsychotics. Glasgow antipsychotic side effect scale modified version, positive and negative syndrome scale, and Birch wood’s insight scale for psychosis were the instruments used to assess the associated factors. Simple and multiple linear regression analysis models were fitted, and the adjusted unstandardized beta (β) coefficient at 95% confidence interval was used. Results. The mean score of attitude towards antipsychotic medications was 6.51 with standard deviation (SD) of 2.22. In multiple linear regression, positive symptoms (β= -0.07, 95% CI: (-0.09, -0.05)), negative symptoms (β= -0.04, 95% CI: (-0.06,-0.02)), shorter (≤5 years) duration of illness (β= -0.39, 95% CI: (-0.63, -0.15)), first generation antipsychotics (β = -0.35, 95% CI: (-0.55,-0.14)), having sedation (β= -0.28, 95% CI: (-0.52, -0.02)), and extra-pyramidal side effects (β= -0.34, 95% CI: (-0.59,-0.09)) were factors negatively associated with attitude towards antipsychotic medication treatment. Insight to illness (β= 0.24, 95% CI: (0.20, 0.27) was a factor positively associated with attitude towards antipsychotic medications. Conclusion. The result suggests that the mean score of participants’ attitude towards antipsychotic medications was good. Prevention of side effects particularly due to first generation antipsychotics is necessary.