A Measure to Assess Illness Awareness in Problem Gambling: Gambling Awareness and Insight Scale (GAS).

Impaired subjective awareness of problem gambling may act as a barrier to help-seeking and treatment adherence. However, the impact of impaired problem gambling awareness on clinical and social outcomes has received little empirical study. The aim of this study was to develop and investigate the psychometric properties of a novel scale that measures impaired illness awareness in individuals with problem gambling. We developed the Gambling Awareness and Insight Scale (GAS), a self-report measure that assesses the core theoretical constructs of illness awareness in problem gambling, namely General Disorder or Problem Awareness, Accurate Symptom Attribution, Awareness of Need for Treatment and the Negative Consequences attributable to problem gambling ( www.illnessawarenessscales.com ). Data were acquired from an online survey platform, Dynata, to evaluate the psychometric properties of the GAS. A total of 100 participants aged 18 years or older with problem gambling defined by a score of 4 or more on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Pathological Gambling Diagnostic Form were included. The GAS demonstrated good convergent (r = 0.57, p < 0.001) and discriminant validity (r = - 0.18, p = 0.080). It also demonstrated good internal consistency (Cronbach's α = 0.80) and one-month test-retest reliability (intra-class correlation = 0.86). An exploratory factor analysis suggested retention of two components. The GAS is a novel psychometric tool designed to evaluate impaired subjective illness awareness in problem gambling. Initial evidence suggests that the GAS can be used in research and clinical settings to evaluate the impact of impaired problem gambling awareness on adherence to treatment programs, clinical and psychosocial outcomes. Replication in applied settings is needed.

The effect of second-generation antipsychotics on anxiety/depression in patients with schizophrenia: A systematic review and meta-analysis.

OBJECTIVE: Despite the high prevalence of anxiety in schizophrenia, no established guideline exists for the management of these symptoms. We aimed to synthesize evidence on the effect of second-generation antipsychotics (SGAs) on anxiety in patients with schizophrenia. METHODS: We systematically searched Medline, Embase, PsycInfo, Web of Science, PubMed, and Cochrane library to identify randomized controlled trials of SGAs that reporting anxiety measures in schizophrenia. The search was limited to English-language articles published before February 2024. Data were pooled using a random-effects model. RESULTS: Among 48 eligible studies, 29 (n = 7712) were included in the meta-analyses comparing SGAs to placebo, haloperidol, or another SGAs for their effect on anxiety/depression. SGAs had a small effect on anxiety/depression versus placebo (SMD = -0.28 (95 % CI [-0.34, -0.21], p < .00001, I2 = 47 %, n = 5576)) associated with efficacy for positive (z = 5.679, p < .001) and negative symptoms (z = 4.490, p < .001). Furthermore, SGAs were superior to haloperidol (SMD = -0.44, 95 % CI [-0.75, -0.13], p = .005, n = 1068) with substantial study-level heterogeneity (I2 = 85 %). Excluding one study of quetiapine in first-episode patients (SMD = -3.05, n = 73), SGAs showed a small effect on anxiety/depression versus haloperidol without heterogeneity (SMD = -0.23, 95 % CI [-0.35, -0.12], p = 01; I2 = %0). Risperidone's effect on anxiety/depression was comparable to olanzapine (SMD = -0.02, 95 % CI [-0.24,0.20], p = .87, I2 = 45 %, n = 753) and amisulpride (SMD = 0.27, 95 % CI [-1.08,0.61], p = .13, I2 = 50 %, n = 315). CONCLUSION: While SGAs showed a small effect on anxiety/depression, the findings are inconclusive due to scarcity of research on comorbid anxiety in schizophrenia, heterogeneity of anxiety symptoms, and the scales used to measure anxiety. Further studies employing specific anxiety scales are required to explore antipsychotics, considering their receptor affinity and augmentation with serotonin/norepinephrine reuptake inhibitors or benzodiazepines for managing anxiety in schizophrenia.

Clozapine treatment and astrocyte activity in treatment resistant schizophrenia: A proton magnetic resonance spectroscopy study.

Clozapine is the only antipsychotic approved for treating treatment-resistant schizophrenia (TRS), characterized by persistent positive symptoms despite adequate antipsychotic treatment. Unfortunately, clozapine demonstrates clinical efficacy in only ~30-60 % of patients with TRS (clozapine-responders; ClzR+), while the remaining ~40-70 % are left with no pharmacological recourse for improvement (clozapine-resistant; ClzR-). Mechanism(s) underlying clozapine's superior efficacy remain unclear. However, in vitro evidence suggests clozapine may mitigate glutamatergic dysregulations observed in TRS, by modulating astrocyte activity in ClzR+, but not ClzR-. A factor that if proven correct, may help the assessment of treatment response and development of more effective antipsychotics. To explore the presence of clozapine-astrocyte interaction and clinical improvement, we used 3 T proton-magnetic resonance spectroscopy to quantify levels of myo-Inositol, surrogate biomarker of astrocyte activity, in regions related to schizophrenia neurobiology: Dorsal-anterior-cingulate-cortex (dACC), left-dorsolateral-prefrontal-cortex (left-DLPFC), and left-striatum (left-striatum) of 157 participants (ClzR- = 30; ClzR+ = 37; responders = 38; controls = 52). Clozapine treatment was assessed using clozapine to norclozapine plasma levels, 11-12 h after last clozapine dose. Measures for symptom severity (i.e., Positive and Negative Symptoms Scale) and cognition (i.e., Mini-Mental State Examination) were also recorded. Higher levels of myo-Inositol were observed in TRS groups versus responders and controls (dACC (p < 0.001); left-striatum (p = 0.036); left-DLPFC (p = 0.023)). In ClzR+, but not ClzR-, clozapine to norclozapine ratios were positively associated with myo-Inositol levels (dACC (p = 0.004); left-DLPFC (p < 0.001)), and lower positive symptom severity (p < 0.001). Our results support growing in vitro evidence of clozapine-astrocyte interaction in clozapine-responders. Further research may determine the viability of clozapine-astrocyte interactions as an early marker of clozapine response.

Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.

BACKGROUND AND HYPOTHESIS: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index. STUDY DESIGN: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity. STUDY RESULTS: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01). CONCLUSIONS: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.