Brain atrophy and cognitive decline in bipolar disorder: Influence of medication use, symptomatology and illness duration.

Bipolar disorder (BPD) is a chronic condition characterized by recurrent episodes of mania and depression. To date, the association of biological and psychopathological processes in BPD has not been extensively studied on a cognitive and cortical basis at the same time. We investigated whether brain atrophy (in prefrontal, temporal and occipital cortices) was associated with cognitive, biological and clinical processes in patients with BPD and healthy controls (HCs). A total of 104 participants (56 with BPD) completed tasks that measured attention, memory, information processing speed, inhibitory control, visuospatial working memory and cognitive flexibility. In addition, structural brain scans were obtained using high-resolution MRI. Outcomes of the measurements were examined using robust multiple mediation analyses. BPD patients showed greater cortical atrophy across all regions of interest when compared to HCs, linked to cognitive decline. BPD patients had slower reaction times and markedly increased errors of commission on the tasks. The outcomes were significantly influenced by medication use, symptomatology and illness duration. The findings showcase the complexity of brain structures and networks as well as the physiological mechanisms underlying diverse BPD symptomatology and endophenotypes. These differences were pronounced in patients with BPD, motivating further investigations of pathophysiological mechanisms involved in brain atrophy and cognitive decline.

Facial processing in bipolar disorder is mediated by clinical and biological aspects

Objective: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. Methods: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. Results: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. Conclusion: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.

Altered brain connectivity during visual stimulation in schizophrenia.

Schizophrenia (SCZ) can be described as a functional dysconnectivity syndrome that affects brain connectivity and circuitry. However, little is known about how sensory stimulation modulates network parameters in schizophrenia, such as their small-worldness (SW) during visual processing. To address this question, we applied graph theory algorithms to multi-electrode EEG recordings obtained during visual stimulation with a checkerboard pattern-reversal stimulus. Twenty-six volunteers participated in the study, 13 diagnosed with schizophrenia (SCZ; mean age = 38.3 years; SD = 9.61 years) and 13 healthy controls (HC; mean age = 28.92 years; SD = 12.92 years). The visually evoked potential (VEP) showed a global amplitude decrease (p < 0.05) for SCZ patients as opposed to HC but no differences in latency (p > 0.05). As a signature of functional connectivity, graph measures were obtained from the Magnitude-Squared Coherence between signals from pairs of occipital electrodes, separately for the alpha (8-13 Hz) and low-gamma (36-55 Hz) bands. For the alpha band, there was a significant effect of the visual stimulus on all measures (p < 0.05) but no group interaction between SCZ and HZ (p > 0.05). For the low-gamma spectrum, both groups showed a decrease of Characteristic Path Length (L) during visual stimulation (p < 0.05), but, contrary to the HC group, only SCZ significantly lowered their small-world (SW) connectivity index during visual stimulation (SCZ p < 0.05; HC p > 0.05). This indicates dysconnectivity of the functional network in the low-gamma band of SCZ during stimulation, which might indirectly reflect an altered ability to react to new sensory input in patients. These results provide novel evidence about a possible electrophysiological signature of the global deficits revealed by the application of graph theory onto electroencephalography in schizophrenia.

Improvement in visual performance after nicotine gum administration in tobacco use disorder: a case report.

Chronic tobacco consumption, identified as Tobacco Use Disorder (TUD), is a public health problem. We present a case report of a 37-year-old Brazilian male diagnosed with TUD at age 26, with no comorbidities, that presented visual improvements (i.e., lower thresholds and better discrimination) after nicotine gum administration. Here, we assessed contrast sensitivity and chromatic discrimination using the Metropsis and the Cambridge Colour Test, respectively. Results showed lower thresholds for both visual tasks after the use of nicotine gum. Even considering this is a single case report, our intent is to open new avenues for research involving smoking, addiction and the use of nicotine gum as a replacement tool or adjuvant tool for improvement of visual and/or cognitive processing. It is well known that nicotine gum has protective effects for some diseases, and improves some cognitive functions. However, unclear were its effects on visual processing of people with TUD.

Serum levels of olanzapine are associated with acute cognitive effects in bipolar disorder.

Bipolar (BPD) patients have deficits in cognition, but there are still controversies about the effects of some medications on their cognitive performance. Here, we investigated the relationship between cognition in terms of executive functions, memory, and attention in both first-episode medication-naive BPD patients and BPD patients taking olanzapine. Forty-one healthy controls, 40 unmedicated drug-naive BPD patients, and 34 BPD patients who took only olanzapine were recruited for the study. Cognitive performance was assessed using the Flanker test, Stroop test, and Corsi-block test. Bayesian multivariate regression analysis was run considering maximum robustness to avoid bias and to predict the outcomes. Our results revealed that unmedicated medication-naive BPD patients performed worse than healthy controls and the olanzapine group in some tasks. Additionally, BPD patients who took olanzapine had better cognitive performance than healthy controls and unmedicated BPD patients. The acute cognitive effects were predicted by olanzapine dosage and serum levels (i.e., large effects). The potential pro-cognitive effects of olanzapine in BPD patients should be carefully interpreted by considering various other clinical variables. We expect that our findings will contribute to further research in this area, with the goal of helping other researchers, patients, and the population.

Eye movement impairments in children with malnutrition.

Malnutrition is characterised by deficient nutrient ingestion and absorption and is still one of the most important causes of morbidity and mortality in children worldwide. Our main rationale was that protein-energy malnutrition (PEM) may affect eye movement in children with malnutrition. Twenty children without PEM (mean age = 10.8; SD = 1.0 years) and 18 children with PEM (mean age = 10.9; SD = 1.2 years) were included in the present study. We applied three types of tests: one that consisted of a maze and two versions of the Spot the Seven Errors test using boats and elephants. Our results indicated that children with PEM exhibited performance deficits in the maze test (p < .001) and Spot the Seven Errors test for both boats (p < .001) and elephants (p < .001). These data suggest that nutritional impairments during the first year of life (i.e., a critical period) can directly impact eye movement. Eye tracking is a reliable technique to investigate higher-order processes, but our results should be interpreted with caution. Our findings highlight the relevance of cognitive development in malnourished children, which can negatively affect their development. Screening, assessment and rehabilitation strategies are essential in this at-risk population.

Correlates of clinical variables on early-stage visual processing in schizophrenia and bipolar disorder.

The use of noninvasive tools can help understand mental states and changes that are caused by medications, symptom severity, and other clinical variables. We investigated low-level visual processing using the contrast sensitivity function (CSF), a reliable, robust, and widely used approach. Our main purpose was (1) to evaluate visual impairments in schizophrenia (SCZ) and bipolar disorder (BPD) patients and (2) to investigate associations between clinical variables and visual function in both diseases. Fifty-six healthy controls (HCs; mean age = 31.04 years), 42 BPD patients (mean age = 32.84 years) who took only lithium, and 39 SCZ patients who took only olanzapine (mean age = 32.80 years) were recruited for this study. CSF differed between groups. Both groups of patients exhibited lower discrimination at low, mid-, and high spatial frequencies compared with HCs. No differences were observed between patients, with the exception of high spatial frequency. These impairments were also related to clinical variables, revealed by a strong effect in the mediation analyses. These findings may aid investigations of other clinical variables and the role of state- and trait-like effects on visual and cognitive processing in these patient populations. This study underscores the need for visual remediation interventions.

Combined influence of medication and symptom severity on visual processing in bipolar disorder.

Previous studies have reported visual impairments in patients with bipolar disorder (BPD), but unclear were whether clinical variables would be associated with those disturbances. Here, we investigate the relationship between visual functioning, in terms of color discrimination, and the impact of BPD duration, mood state, and the patients' medication. Forty-five participants (25-45 years old) were recruited for this study. Color discrimination was performed using the Cambridge Colour Test. Serial multiple mediations were run to investigate the assumption of association between color discrimination and the clinical variables. Our findings showed that, compared with healthy controls, BPD patients' performance was worse for the Protan, Deutan, and Tritan vectors, revealing deterioration of color discrimination. In addition, the mediation analyses revealed a strong direct (p < .001) and moderate-to-high indirect effects (p < .01) of medication and symptom severity on color discrimination. Overall, both longer the duration of the disease and greater the symptom severity of BPD patients resulted in worse performance. It highlights the importance of examining the wider clinical context of an affective disorder to understand how it affects visual processing in this population.

Heavy and light smokers have slight differences in chromatic discrimination.

Objectives: The effects of smoking on color vision have been scarcely studied. To bridge such gap, this study examined if there were differences in chromatic discrimination between heavy and light smokers. Methods: The psychophysical Trivector test was used to evaluate chromatic discrimination in healthy controls (n = 36), heavy smokers (n = 29), and light smokers (n = 32). The subject's task was to identify the orientation of the Landolt C ring gap - presented and randomized in one of the four positions (e.g., up, down, right, and left). Results: The thresholds for Protan (red), Deutan (green) and Tritan (blue) were higher in heavy smokers compared to nonsmokers but not to light smokers. Conclusions: The results confirm that heavy smoking and chronic exposure to its harmful compounds affect color discrimination when compared to light smoking; and this is more pronounced in heavy smokers than light smokers. This is particularly important to understand the differences among smokers on visual and multisensory processing.

Facial processing in bipolar disorder is mediated by clinical and biological aspects.

OBJECTIVE: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. METHODS: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. RESULTS: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. CONCLUSION: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.

Relation between smoking and visual processing in bipolar disorder.

Background: Although some studies have shown impairments in patients with bipolar disorder (BPD) and in smokers, it is unclear how these two factors work together. Our premise was that chronic smoking affects color discrimination and this is more pronounced in BPD. Objective: Our main purpose was to investigate the influence of smoking and BPD on color discrimination. Methods: Twenty-three smokers and 23 BPD smokers patients, aged 25-45 years old, participated in this study. Color vision testing was performed using the Trivector subtest of the Cambridge Colour Test. Participants' task was to indicate the pseudoisochromatic stimulus in four directions (up, down, right, and left). Results: It was shown that the smokers had better color vision than BPD smokers for the Protan (p < .001), Deutan (p < .001), and Tritan (p < .001) (red, green, and blue, respectively) axes. Thus, the BPD smokers' group had greater difficulty distinguishing the chromaticity variations (i.e., presented diffuse color vision impairments and not specific to any axis). Conclusions: The present study highlights a possible relationship between smoking and BPD in color discrimination. This highlights the importance of understanding the diffuse effects of this relationship.

Interventions with Serious Games and Entertainment Games in Autism Spectrum Disorder: A Systematic Review.

The use of serious games and entertainment games was compared as adjuvant tools for intervention in Autism Spectrum Disorder (ASD). A comprehensive search was performed in the MEDLINE, PsycINFO, Scopus, and Web of Science databases. From 295 studies, 53 studies were selected and included in this review. Overall, studies showed improvement after intervention, regardless of the type of video games, mostly for social skills and behavior. However, these changes should be regarded with caution, as they are limited to the tests applied. Furthermore, neither the entertainment nor the serious approach had a therapeutic impact on emotional resilience, representing the current gap in the field. Thus, even considering the limitations, our study is important because it shows that both categories have strengths.

Visual processing and BDNF levels in first-episode schizophrenia.

Previous studies have shown that patients diagnosed with schizophrenia (SCZ) have deficits in early visual processing, namely contrast processing. The brain-derived neurotropic factor (BDNF) is an important measure to investigate neuroplasticity in some visual functions like visual perception. In this study, we investigated the relationship between visual processing and BDNF levels in first-episode SCZ patients. Thirty-nine healthy controls and 43 first-episode SCZ patients were enrolled. Contrast sensitivity measurements were conducted using low, mid- and high spatial frequencies. First-episode SCZ patients had higher contrast sensitivity than healthy controls for all frequencies, except for the middle spatial frequency. Negative correlations were found between BDNF, contrast sensitivity and clinical variables, mostly for middle and high spatial frequencies among females. Our results provide support for (i) the association of SCZ with alterations of magno- and parvocellular pathway functioning and (ii) decreased BDNF levels in first-episode SCZ patients. This study highlights the importance of using biomarkers along with other measures to investigate visual processing in SCZ and other disorders.

Nicotine gum enhances visual processing in healthy nonsmokers.

OBJECTIVE: The main purpose of this study was to investigate the isolated effects of nicotine on visual processing, namely contrast processing. METHODS: Thirteen participants, aged 18-40 years, were enrolled in this double blind, randomized and pilot controlled trial involving nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants' instruction was to detect the location of vertical gratings (0.2; 1.0; 3.3; 5.7; 8.8; 13.2 and 15.9 cycles per degree) when it was presented either left or right on the monitor screen. A repeated multivariate analysis of variance was conducted to analyse the results for the visual processing tasks. Bayesian analyses were also carried out considering maximum robustness to avoid bias. RESULTS: The findings that nicotine gum administration resulted in better contrast discrimination when compared to placebo gum (p < .001). More specifically, the 4-mg resulted in better visual sensitivity when compared to the 2-mg (p < .01) and the placebo (p < .001) gum. Demographic data were not related to the outcomes. CONCLUSIONS: These data bring the need for support the findings. If proved, it is possible that nicotine, in small doses, can have a potential therapeutic use for those populations with low vision. TRIAL REGISTRATION NUMBER: RBR-46tjy3.

Short-term effects of nicotine gum on facial detection in healthy nonsmokers: a pilot randomized controlled trial.

Objective: The main purpose of this study was to investigate short-term effects of nicotine gum on facial detection. Methods: Fourteen participants (mean age = 26.8 years, SD = 2.5 years; eight males) were enrolled in this pilot randomized controlled trial of nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants were instructed to detect the location of a face when it was presented in a face/nonface pair on the screen. A repeated multivariate analysis of variance was conducted to analyze the results for reaction time and discrimination index. Demographics were used to explore significant association on facial detection. Bayesian analyses were also carried out considering maximum robustness to avoid bias. Results: The results indicated that the 2-mg dose resulted in faster reaction time and better discrimination than the 4-mg dose (p < 0.001). The 4-mg dose resulted in slower reaction time and lower discrimination index compared to both placebo (p < 0.01) and 2-mg doses (p < 0.001). Demographic data were not related to the outcomes. Conclusions: The results indicate that nicotine improved facial detection, but only at low doses (i.e., 2-mg), following a U-shaped curve. We trust future studies will continue to advance this research field, and if further work supports these preliminary findings, nicotine can act as therapeutic target in populations such as those with low vision.

Impairments of facial detection in tobacco use disorder: baseline data and impact of smoking duration.

OBJECTIVE: Chronic tobacco consumption, classified as tobacco use disorder (TUD), has been associated with a variety of health problems. Investigations of face processing in TUD are hampered by lack of evidence. Here, we evaluated facial detection in TUD and assessed test-retest reliability for a facial detection task. METHODS: Participants were instructed to detect the orientation (either left or right) of a face when it was presented with a face/non-face pair on the monitor screen, using Bayesian entropy estimation. Bland-Altman analysis and intraclass correlation coefficients were used to test the reliability of the task. The general linear model and Bayesian statistics were then used to evaluate differences between TUD (n=48) and healthy controls (n=34). RESULTS: The reliability of the task was high for the 96 stimuli presentations. Slower reaction times (p < 0.001) and lower discrimination index (p < 0.001) were observed in the TUD group than for healthy controls. Mediation analysis indicated direct effects of smoking duration on reaction time (p < 0.001) and discrimination index (p < 0.001). CONCLUSIONS: Overall, we observed high reliability of this task and reduction of facial detection in tobacco use disorder. We conclude our findings are significant for public health initiatives and call for follow-up studies.

Effects of Nicotine Gum Administration on Vision (ENIGMA-Vis): Study Protocol of a Double-Blind, Randomized, and Controlled Clinical Trial.

Studies reported that tobacco addiction was related to visual impairments, but one unresolved issue is whether the impairments are related to the many compounds existing in the cigarettes or to the effects of nicotine. On the other hand, nicotine gum can be used as replacement therapy or as a neuroprotective agent for some diseases. The main purpose of this controlled trial is to investigate the effects of nicotine gum on vision. The ENIGMA-Vis trial aims to compare two dosages of nicotine gum (2 and 4 mg) and a placebo gum in a randomized, double-blind, placebo-controlled trial of 100 participants to be allocated into a single group assignment of repeated measures (two studies; N = 50 for each one). Eligibility criteria are healthy non-smokers not diagnosed with substance abuse and without an acute or chronic medical condition. Intervention will last three sessions for each participant with a window frame of 1 week per session. Study outcomes are (1) short-term effects of nicotine gum on contrast sensitivity; (2) short-term effects of nicotine gum on chromatic contrast discrimination; and (3) whether demographics, body mass index, or serum cotinine predicts response of visual processing. This study addresses an important gap in the effects of nicotine on vision. One of the main takeaways of this study is to understand the effects of nicotine on contrast sensitivity and chromatic contrast discrimination. This information will provide a further understanding of how nicotine interacts with early visual processes and help determine how the different components present during smoking can affect vision. Clinical Trial Registration Number: RBR-46tjy3.

Opposite effects of smoking and nicotine intake on cognition.

Our main purpose was to investigate how smoking and nicotine interacted with specific aspects of cognitive functioning. The research was conducted in two parts: (i) an investigation of cognition in heavy smokers and healthy nonsmokers, and (ii) an investigation of cognition in healthy nonsmokers enrolled in a clinical trial involving administration of nicotine gum. Results indicated that the relationship between smoking and nicotine was characterized by an inverted U-shaped effect. On the one hand, cognitive test performance of the heavy smokers group was reduced on all of the cognitive tasks used here. On the other hand, healthy nonsmokers who used 2-mg of nicotine gum performed better, whilst the 4-mg group performed worse than the 2-mg and the placebo group. Demographic data were not related to the cognitive tasks. These data suggest that small doses of nicotine can have an activating function that leads to improved cognition, while heavy smoking on a chronic (and possibly acute) basis leads to cognitive impairment.

Combined influence of illness duration and medication type on visual sensitivity in schizophrenia

Objective: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. Methods: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. Results: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. Conclusion: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.