Novel coronavirus disease 2019 (COVID-19) vaccine hesitancy is a barrier to achieving herd immunity, and thus, a prominent public health concern. This study aimed to identify the determinants of ...COVID-19 vaccine hesitancy based on the World Health Organization's '3Cs' model (i.e., confidence, complacency, and convenience) in the United States (U.S.) and Canada. Data from 7678 adults ages 18 or older were collected from the four most populous U.S. States, specifically New York, California, Florida, and Texas, and from English-speaking Canada at three timepoints, in May and July 2020, and March 2021 using a web-based survey (www.covid19-database.com). Sociodemographic information was collected, and comprehensive psychological assessments were administered. Univariate analyses were performed to identify the individual determinants of vaccine hesitancy, which were categorized as: 1) vaccine confidence, 2) vaccine complacency, 3) sociodemographic, and 4) other psychological factors. A series of models were computed using these categorizations. Mistrust of vaccine benefit (beta(SE) = 0.67(0.01), p<0.001, partial eta.sup.2 = 0.26) and lower perceived seriousness of COVID-19 (beta(SE) = 0.68(0.02), p<0.001, partial eta.sup.2 = 0.12) were the principal determinants of vaccine hesitancy. Right-wing political affiliation (beta(SE) = 0.32(0.02), p<0.001, partial eta.sup.2 = 0.03), higher risk propensity (beta(SE) = 0.24(0.02), p<0.001, partial eta.sup.2 = 0.03), and less negative mental health effects of the COVID-19 pandemic (beta(SE) = 0.20(0.01), p<0.001, partial eta.sup.2 = 0.03) were the main sociodemographic and psychological determinants. Other sociodemographic determinants included younger age, women, race, and employment status. Lack of vaccine confidence and complacency explained 38% and 21% of the variance in vaccine hesitancy, respectively; whereas, sociodemographic and psychological determinants explained 13% and 11% of the variance in vaccine hesitancy, respectively. Targeted and tailored public health interventions that enhance the public's confidence in vaccines and emphasize the risk and seriousness of COVID-19 may address COVID-19 vaccine hesitancy. Efforts directed toward specific marginalized and underserved groups may be required to promote vaccine confidence.
Adherence to antipsychotic medication is critical for the treatment of patients with schizophrenia. Impaired insight into illness is one of the principal drivers of medication nonadherence, which ...contributes to negative clinical outcomes. The aims of this study were to examine the relationships between impaired insight and (1) rates of antipsychotic medication nonadherence, and (2) time to medication nonadherence using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Insight was assessed using the Positive and Negative Syndrome Scale (PANSS) item G12 (lack of judgment and insight). Patients were divided into 3 groups based on their degree of insight impairment, i.e. no impairment (PANSS G12 = 1), minimal impairment (PANSS G12 = 2–3), and moderate-to-severe insight impairment (PANSS G12 ≥ 4). Medication nonadherence was defined as taking less than 80% of monthly pill counts. Kaplan-Meier survival and Cox regression analyses were performed to examine differences in time to medication nonadherence between insight groups. There were significant differences between insight groups in the percentage of nonadherent patients at 6 months (χ2(2) = 8.80, p = 0.012) and 18 months (χ2(2) = 10.04, p = 0.007) after study initiation. Moderate-to-severe insight impairment was associated with earlier nonadherence compared to minimal (χ2 = 4.70, p = 0.030) or no impairment (χ2 = 11.92, p = 0.001). The association remained significant after adjustment for illness severity, substance use, attitudes toward medication, cognition, level of hostility, and depression. The results of this study indicate a strong link between impaired insight and antipsychotic medication nonadherence. Interventions to enhance insight early during treatment may help improve medication adherence, and in turn, long-term clinical and functional outcomes in patients with schizophrenia.
This article is part of the issue entitled ‘Special Issue on Antipsychotics’.
•Impaired insight predicts earlier antipsychotic medication nonadherence.•The association between impaired insight and nonadherence remained significant after adjustment for related factors.•Interventions to enhance insight are needed to improve medication adherence in schizophrenia.
Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan ...degradation. Evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia. However, this has never been assessed through a meta-analysis. A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: December 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies measuring KYNA levels using any method in patients with schizophrenia and healthy controls (HCs) were identified. Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups. Subgroup analyses were separately performed for nonoverlapping participant samples, KYNA measurement techniques, and KYNA sample source. The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression. Thirteen studies were deemed eligible for inclusion in the meta-analysis. In the main analysis, KYNA levels were elevated in the patient group. Subgroup analyses demonstrated that KYNA levels were increased in nonoverlapping participant samples, and centrally (cerebrospinal fluid and brain tissue) but not peripherally. Patients' age, %medicated, and %male were each positively associated with study SMDs. Overall, KYNA levels are increased in patients with schizophrenia, specifically within the central nervous system. An improved understanding of KYNA in patients with schizophrenia may contribute to the development of novel diagnostic approaches and therapeutic strategies.
Brain imaging is a non-invasive and in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain. The main objective of this ...review was to analyze functional and structural neuroimaging studies of individuals at risk for suicide. We reviewed articles published between 2005 and 2018, indexed in PubMed and Medline, assessing structural and functional alterations of the brain of individuals at high risk for suicide and at low risk for suicide. We reviewed functional and structural neuroimaging studies which included individuals with a history of suicidal ideation or attempt in major depressive disorder (MDD), bipolar disorder (BD), psychosis, and borderline personality disorder (BPD). We selected 45 papers that focused on suicidality in MDD, 17 papers on BD, 11 papers on psychosis, and 5 papers on BPD. The suicidal brain across psychiatric diagnoses seems to heavily involve dysfunction of the fronto-temporal network, primarily involving reductions of gray and white matter volumes in the pre-frontal cortex (PFC), anterior cingulate, and superior temporal gyrus. Nonetheless, there are several ways to define suicidal behaviour and ideation. Therefore, it still remains difficult to combine the evidence from imaging studies that used different definitions of suicidality.
Abstract Findings from neuroimaging studies in patients with schizophrenia suggest widespread structural changes although the mechanisms through which these changes occur are currently unknown. ...Glutamatergic activity appears to be increased in the early phases of schizophrenia and may contribute to these structural alterations through an excitotoxic effect. The primary aim of this review was to describe the possible role of glutamate-mediated excitotoxicity in explaining the presence of neuroanatomical changes within schizophrenia. A Medline® literature search was conducted, identifying English language studies on the topic of glutamate-mediated excitotoxicity in schizophrenia, using the terms “schizophreni⁎ ” and “glutam⁎ ” and ((“MRS” or “MRI” or “magnetic resonance”) or (“computed tomography” or “CT”)). Studies concomitantly investigating glutamatergic activity and brain structure in patients with schizophrenia were included. Results are discussed in the context of findings from preclinical studies. Seven studies were identified that met the inclusion criteria. These studies provide inconclusive support for the role of glutamate-mediated excitotoxicity in the occurrence of structural changes within schizophrenia, with the caveat that there is a paucity of human studies investigating this topic. Preclinical data suggest that an excitotoxic effect may occur as a result of a paradoxical increase in glutamatergic activity following N-methyl- d -aspartate receptor hypofunction. Based on animal literature, glutamate-mediated excitotoxicity may account for certain structural changes present in schizophrenia, but additional human studies are required to substantiate these findings. Future studies should adopt a longitudinal design and employ magnetic resonance imaging techniques to investigate whether an association between glutamatergic activity and structural changes exists in patients with schizophrenia.
Abstract Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of ...this work is to review the literature on the role of dopamine D3 receptors in cognition, and propose dopamine D3 receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D3 receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included “dopamine D3 receptor” and “cognition”. The literature search identified 164 articles. The results revealed: (1) D3 receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D3 receptor blockade appears to enhance while D3 receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D3 receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D3 receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects.
Although clozapine is the main antipsychotic medication for treatment-resistant schizophrenia, 40–70% of patients on clozapine have persistent psychotic symptoms (i.e. ultra-treatment-resistant ...schizophrenia, UTRS). We aimed to examine clozapine response/non-response patterns in patients with treatment-resistant schizophrenia, as well as determine patient clinico-demographic factors associated with long-term clozapine non-response. Clinico-demographic characteristics of 241 patients on clozapine were collected through a retrospective chart review. The median (interquartile range, IQR) follow-up from illness onset was 25.0 (IQR = 24.0) years. Clozapine response was assessed at median 10.8 (IQR = 14.0) months (Time 1, T1) and 7.2 (IQR = 13.5) years (Time 2, T2) after its initiation. It was evaluated by chart reviewers based on the information provided in clinical notes. Binomial logistic regression was used to determine clinico-demographic factors associated with clozapine non-response at both T1 and T2 (i.e. stable UTRS, S-UTRS) compared to clozapine response at both times (i.e. stable clozapine responders, S-ClozResp). Among clozapine responders (
n
= 122) at T1, 83.6% remained clozapine responsive and 16.4% became non-responsive at T2. In the UTRS group (
n
= 119) at T1, 87.4% remained clozapine non-responsive and 12.6% became responsive at T2. Duration of delay in clozapine initiation (OR = 0.94, Wald
χ
2
= 5.33,
p
= 0.021) and number of pre-clozapine hospitalizations (OR = 0.95, Wald
χ
2
= 5.20,
p
= 0.023) were associated with S-UTRS. Most UTRS patients were non-responsive to clozapine from the start of treatment. Preventing delay in initiating clozapine and relapses could help promote long-term clozapine response in patients with treatment-resistant schizophrenia. Future longitudinal studies are required to explore the neuropathological correlates of relapses and delay in clozapine initiation.
Transcranial direct current stimulation (tDCS) has generated interest in recent years as a potential adjunctive treatment for patients with schizophrenia. The primary objective of this meta-analysis ...was to evaluate the efficacy of tDCS on positive symptoms, particularly auditory hallucinations, and negative symptoms. A literature search of randomized sham-controlled trials was conducted using the OVID database on October 9, 2018. The standardized mean differences (SMDs) were calculated to examine changes in symptom severity between active and sham groups for the following symptom domains: auditory hallucinations, positive symptoms (including auditory hallucinations), and negative symptoms. Moderator analyses were performed to examine the effects of study design and participant demographics. We identified 10 eligible studies. Main-analyses showed no effects of tDCS on auditory hallucinations (7 studies, n = 242), positive symptoms (9 studies, n = 313), or negative symptoms (9 studies, n = 313). Subgroup analyses of studies that applied twice-daily stimulation showed a significant reduction in the severity of auditory hallucinations (4 studies, n = 138, SMD = 1.04, p = 0.02). Studies that applied ≥10 stimulation sessions showed a reduction in both auditory hallucination (5 studies, n = 186, SMD = 0.86, p = 0.009) and negative symptom severity (7 studies, n = 257, SMD = 0.41, p = 0.04). Meta-regression analyses revealed a negative association between mean age and the SMDs for auditory hallucinations and negative symptoms, and a positive association between baseline negative symptom severity and the SMDs for negative symptoms. Our findings highlight the need to optimize tDCS parameters and suggest twice-daily or 10 or more stimulation sessions may be needed to improve clinical outcomes in patients with schizophrenia.
•Our primary analyses showed no effects of tDCS on positive or negative symptoms.•Twice-daily tDCS was associated with reduced severity of auditory hallucinations.•More than 10 tDCS sessions was associated with reduced auditory hallucination and negative symptom severity.•Effects of tDCS on symptom severity were negatively associated with age.
Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence ...suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics-particularly the second generation, or "atypical" antipsychotics-can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health.
Aberrant brain insulin signaling has been posited to lie at the crossroads of several metabolic and cognitive disorders. Intranasal insulin (INI) is a non-invasive approach that allows investigation ...and modulation of insulin signaling in the brain while limiting peripheral side effects.
The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals.
MEDLINE, EMBASE, PsycINFO, and Cochrane CENTRAL were systematically searched from 2000 to July 2021. Eligible studies were randomized controlled trials that studied the effects of INI on cognition. Two independent reviewers determined study eligibility and extracted relevant descriptive and outcome data.
Twenty-nine studies (pooled N = 1,726) in healthy individuals as well as those with Alzheimer's disease (AD)/mild cognitive impairment (MCI), mental health disorders, metabolic disorders, among others, were included in the quantitative meta-analysis. Patients with AD/MCI treated with INI were more likely to show an improvement in global cognition (SMD = 0.22, 95% CI: 0.05-0.38 p = <0.00001, N = 12 studies). Among studies with healthy individuals and other patient populations, no significant effects of INI were found for global cognition.
This review demonstrates that INI may be associated with pro-cognitive benefits for global cognition, specifically for individuals with AD/MCI. Further studies are required to better understand the neurobiological mechanisms and differences in etiology to dissect the intrinsic and extrinsic factors contributing to the treatment response of INI.
PDF
