Cognitive Deficits In Schizophrenia Research Articles

Individual alpha peak frequency is slower in schizophrenia and related to deficits in visual perception and cognition

The brain at rest generates cycles of electrical activity that have been shown to be abnormal in people with schizophrenia. The alpha rhythm (~ 10 Hz) is the dominant resting state electrical cycle and each person has a propensity toward a particular frequency of oscillation for this rhythm. This individual alpha peak frequency (IAPF) is hypothesized to be central to visual perceptual processes and may have downstream influences on cognitive functions such as attention, working memory, or problem solving. In the current study we sought to determine whether IAPF was slower in schizophrenia, and whether lower IAPF predicted deficits in visual perception and cognition that are often observed in schizophrenia. Eyes-closed resting state EEG activity, visual attention, and global cognitive functioning were assessed in individuals with schizophrenia (N = 104) and a group of healthy controls (N = 101). Compared to controls, the schizophrenia group showed slower IAPF and was associated with poorer discrimination of visual targets and nontargets on a computerized attention task, as well as impaired global cognition measured using neuropsychological tests across groups. Notably, disruptions in visual attention fully mediated the relationship between IAPF and global cognition across groups. The current findings demonstrate that slower alpha oscillatory cycling accounts for global cognitive deficits in schizophrenia by way of impairments in perceptual discrimination measured during a visual attention task.

Altered brain activity in the bilateral frontal cortices and neural correlation with cognitive impairment in schizophrenia

Cognitive impairments are core aspects of schizophrenia and are highly related to poor outcomes. However, the effect of therapy on cognitive impairments remains unsatisfactory as its biological mechanisms are not fully understood. The purpose of this study was to investigate the disrupted intrinsic neural activity of the frontal areas and to further examine the functional connectivity of frontal areas related to cognitive impairments in schizophrenia. We collected brain imaging data using a 3T Siemens Prisma MRI system in 32 patients with schizophrenia and 34 age- and sex-matched healthy controls. The mean fractional amplitude of low-frequency fluctuation (mfALFF) in the frontal regions was calculated and analyzed to evaluate regional neural activity alterations in schizophrenia. Seed regions were generated from clusters showing significant changes in mfALFF in schizophrenia, and its resting-state functional connectivity (rs-FC) with other brain regions were estimated to detect possible aberrant rs-FC indicating cognitive impairments in schizophrenia. We found that mfALFF in the bilateral frontal cortices was increased in schizophrenia. mfALFF-based rs-FC revealed that decreased rs-FC between left middle frontal gyrus (MFG) and left medial superior frontal gyrus (MFSG) was associated with poor delayed memory (r = 0.566, Bonferroni-corrected p = 0.012). These findings demonstrate increased neural activity in the frontal cortices in schizophrenia. FC analysis revealed a diminished rs-FC pattern between the left MFG and left MSFG that was associated with cognitive impairments. These findings have provided deeper insight into the alterations in brain function related to specific domains of cognitive impairment and may provide evidence for precise interventions for cognitive deficits in schizophrenia.

Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia.

Decades of research have highlighted the importance of optimal stimulation of cortical dopaminergic receptors, particularly the D1R receptor (D1R), for prefrontal-mediated cognition. This mechanism is particularly relevant to the cognitive deficits in schizophrenia, given the abnormalities in cortical dopamine (DA) neurotransmission and in the expression of D1R. Despite the critical need for D1R-based therapeutics, many factors have complicated their development and prevented this important therapeutic target from being adequately interrogated. Challenges include determination of the optimal level of D1R stimulation needed to improve cognitive performance, especially when D1R expression levels, affinity states, DA levels, and the resulting D1R occupancy by DA, are not clearly known in schizophrenia, and may display great interindividual and intraindividual variability related to cognitive states and other physiological variables. These directly affect the selection of the level of stimulation necessary to correct the underlying neurobiology. The optimal mechanism for stimulation is also unknown and could include partial or full agonism, biased agonism, or positive allosteric modulation. Furthermore, the development of D1R targeting drugs has been complicated by complexities in extrapolating from in vitro affinity determinations to in vivo use. Prior D1R-targeted drugs have been unsuccessful due to poor bioavailability, pharmacokinetics, and insufficient target engagement at tolerable doses. Newer drugs have recently become available, and these must be tested in the context of carefully designed paradigms that address methodological challenges. In this paper, we discuss how a better understanding of these challenges has shaped our proposed experimental design for testing a new D1R/D5R partial agonist, PF-06412562, renamed CVL-562.

Deficits in access consciousness, integrative function, and consequent autonoetic thinking in schizophrenia

Alterations within consciousness in schizophrenia can be evidenced by impediments in self-awareness and loss of agency. Ned Block’s definition of access consciousness is applied in order to further delineate cognitive deficits involving reflective thought and autonoetic thinking in persons with schizophrenia. Current theories on the nature and functioning of consciousness are discussed, which include Global Workspace Theory and metarepresentational characterizations. These describe a recursive, integrative quality to consciousness, contributed to by the functions of access consciousness, that is relevant in examining cognitive deficits in schizophrenia. The integrative deficit that is described as operating in conscious process involves a failure to incorporate prior outputs from a separate cognitive task and integrate these into a novel working schema. The alterations in access consciousness in persons with schizophrenia appear to be a consequence of disrupted integrative cognitive functions. An anteceding problem with cortical circuits involving integrative functions related to access consciousness is therefore hypothesized to manifest as subsequent cognitive dysfunction that leads to symptoms of schizophrenia. Constitutive failures to integrate information in schizophrenia could lead to an inability to create experiential unity and manage content in autonoetic consciousness. Some of the aberrant reasoning manifested by persons with schizophrenia, including problems with hierarchical relational reasoning, model-based-learning, J-con, ipseity, and source monitoring, could also reflect alterations in access consciousness, and their investigation offers additional approaches for scientific inquiry.

Towards Clinically Relevant Oculomotor Biomarkers in Early Schizophrenia.

In recent years, psychiatric research has focused on the evaluation and implementation of biomarkers in the clinical praxis. Oculomotor function deviances are among the most consistent and replicable cognitive deficits in schizophrenia and have been suggested as viable candidates for biomarkers. In this narrative review, we focus on oculomotor function in first-episode psychosis, recent onset schizophrenia as well as individuals at high risk for developing psychosis. We critically discuss the evidence for the possible utilization of oculomotor function measures as diagnostic, susceptibility, predictive, monitoring, and prognostic biomarkers for these conditions. Based on the current state of research we conclude that there are not sufficient data to unequivocally support the use of oculomotor function measures as biomarkers in schizophrenia.

Haloperidol rescues the schizophrenia-like phenotype in adulthood after rotenone administration in neonatal rats.

Neuropsychiatric disorders are multifactorial disturbances that encompass several hypotheses, including changes in neurodevelopment. It is known that brain development disturbances during early life can predict psychosis in adulthood. As we have previously demonstrated, rotenone, a mitochondrial complex I inhibitor, could induce psychiatric-like behavior in 60-day-old rats after intraperitoneal injections from the 5th to the 11th postnatal day. Because mitochondrial deregulation is related to psychiatric disorders and the establishment of animal models is a high-value preclinical tool, we investigated the responsiveness of the rotenone (Rot)-treated newborn rats to pharmacological agents used in clinical practice, haloperidol (Hal), and methylphenidate (MPD). Taken together, our data show that Rot-treated animals exhibit hyperlocomotion, decreased social interaction, and diminished contextual fear conditioning response at P60, consistent with positive, negative, and cognitive deficits of schizophrenia (SZ), respectively, that were reverted by Hal, but not MPD. Rot-treated rodents also display a prodromal-related phenotype at P35. Overall, our results seem to present a new SZ animal model as a consequence of mitochondrial inhibition during a critical neurodevelopmental period. Therefore, our study is crucial not only to elucidate the relevance of mitochondrial function in the etiology of SZ but also to fulfill the need for new and trustworthy experimentation models and, likewise, provide possibilities to new therapeutic avenues for this burdensome disorder.

Anomalous self-experiences in cognition are negatively associated with neurocognitive functioning in schizophrenia

ABSTRACT Introduction: Anomalous self-experiences (ASEs) are disturbances in the subjective experience of the self and are common in people with schizophrenia. Theorists have suggested that ASEs may underlie the neurocognitive deficits that are also common in people with schizophrenia; however, few studies have empirically investigated the relationship between these variables. Thus, the current study aimed to determine whether self-reported ASEs, particularly disturbances in cognitive or mental experiences, are meaningfully related to neurocognitive performance in individuals with schizophrenia. Methods: 48 individuals with schizophrenia and 34 healthy comparison participants completed the Inventory of Psychotic-Like Anomalous Experiences (IPASE), which is composed of five subscales including disturbances in cognition, and the MATRICS Consensus Cognitive Battery (MCCB). Results: Participants with schizophrenia performed worse than controls on each MCCB domain and had higher ASE scores on the total IPASE and all five subscales. Only the IPASE-Cognition subscale was associated with cognitive performance. Specifically, IPASE-Cognition was negatively correlated with scores in attention, visual learning, reasoning, and working memory. Conclusions: These results suggest that self-reported subjective disturbances in cognition may be meaningfully associated with several objectively-measured domains of neurocognition. Severity of ASEs may therefore be an important consideration when analysing the extent of cognitive deficits in schizophrenia.

Schizophrenia-associated LRRTM1 regulates cognitive behavior through controlling synaptic function in the mediodorsal thalamus.

Reduced activity of the mediodorsal thalamus (MD) and abnormal functional connectivity of the MD with the prefrontal cortex (PFC) cause cognitive deficits in schizophrenia. However, the molecular basis of MD hypofunction in schizophrenia is not known. Here, we identified leucine-rich-repeat transmembrane neuronal protein 1 (LRRTM1), a postsynaptic cell-adhesion molecule, as a key regulator of excitatory synaptic function and excitation-inhibition balance in the MD. LRRTM1 is strongly associated with schizophrenia and is highly expressed in the thalamus. Conditional deletion of Lrrtm1 in the MD in adult mice reduced excitatory synaptic function and caused a parallel reduction in the afferent synaptic activity of the PFC, which was reversed by the reintroduction of LRRTM1 in the MD. Our results indicate that chronic reduction of synaptic strength in the MD by targeted deletion of Lrrtm1 functionally disengages the MD from the PFC and may account for cognitive, social, and sensorimotor gating deficits, reminiscent of schizophrenia.

Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder

Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the “motivation and pleasure” dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.

Hyperactivity of Ventral Hippocampal Mossy Cells Degrades Dorsal Hippocampal Mnemonic Function via Longitudinal Projections

The anterior hippocampus in early psychosis or schizophrenia is hyperactive compared to controls. In rodent models, the ventral hippocampus (vHPC), analogous to the human anterior HPC, is also hyperactive. How anterior HPC hyperactivity influences intrahippocampal function across the structure’s longitudinal axis is unknown, an important question to understand why cognitive deficits in schizophrenia involve both anterior and posterior HPC function. We hypothesized that hyperactivity of ventral HPC mossy cells (MCs), which send longitudinal projections within the HPC, disrupts spatial memory encoding, a dorsal HPC (dHPC)-dependent function.

Computational methods for integrative evaluation of confidence, accuracy, and reaction time in facial affect recognition in schizophrenia

People with schizophrenia (SZ) process emotions less accurately than do healthy comparators (HC), and emotion recognition have expanded beyond accuracy to performance variables like reaction time (RT) and confidence. These domains are typically evaluated independently, but complex inter-relationships can be evaluated through machine learning at an item-by-item level. Using a mix of ranking and machine learning tools, we investigated item-by-item discrimination of facial affect with two emotion recognition tests (BLERT and ER-40) between SZ and HC. The best performing multi-domain model for ER40 had a large effect size in differentiating SZ and HC (d = 1.24) compared to a standard comparison of accuracy alone (d = 0.48); smaller increments in effect sizes were evident for the BLERT (d = 0.87 vs. d = 0.58). Almost half of the selected items were confidence ratings. Within SZ, machine learning models with ER40 (generally accuracy and reaction time) items predicted severity of depression and overconfidence in social cognitive ability, but not psychotic symptoms. Pending independent replication, the results support machine learning, and the inclusion of confidence ratings, in characterizing the social cognitive deficits in SZ. This moderate-sized study (n = 372) included subjects with schizophrenia (SZ, n = 218) and healthy controls (HC, n = 154).

NMDAR Neurotransmission Needed for Persistent Neuronal Firing: Potential Roles in Mental Disorders.

The dorsolateral prefrontal cortex (dlPFC) generates the mental representations that are the foundation of abstract thought, and provides top-down regulation of emotion through projections to the medial PFC and cingulate cortices. Physiological recordings from dlPFC Delay cells have shown that the generation of mental representations during working memory relies on NMDAR neurotransmission, with surprisingly little contribution from AMPAR. Systemic administration of low “antidepressant” doses of the NMDAR antagonist, ketamine, erodes these representations and reduces dlPFC Delay cell firing. In contrast to the dlPFC, V1 neuronal firing to visual stimuli depends on AMPAR, with much less contribution from NMDAR. Similarly, neurons in the dlPFC that respond to sensory events (cue cells, response feedback cells) rely on AMPAR, and systemic ketamine increases their firing. Insults to NMDAR transmission, and the impaired ability for dlPFC to generate mental representations, may contribute to cognitive deficits in schizophrenia, e.g., from genetic insults that weaken NMDAR transmission, or from blockade of NMDAR by kynurenic acid. Elevated levels of kynurenic acid in dlPFC may also contribute to cognitive deficits in other disorders with pronounced neuroinflammation (e.g., Alzheimer's disease), or peripheral infections where kynurenine can enter brain (e.g., delirium from sepsis, “brain fog” in COVID19). Much less is known about NMDAR actions in the primate cingulate cortices. However, NMDAR neurotransmission appears to process the affective and visceral responses to pain and other aversive experiences mediated by the cingulate cortices, which may contribute to sustained alterations in mood state. We hypothesize that the very rapid, antidepressant effects of intranasal ketamine may involve the disruption of NMDAR-generated aversive mood states by the anterior and subgenual cingulate cortices, providing a “foot in the door” to allow the subsequent return of top-down regulation by higher PFC areas. Thus, the detrimental vs. therapeutic effects of NMDAR blockade may be circuit dependent.

Factors affecting cognitive remediation outcome in schizophrenia: The role of treatment resistance

IntroductionTreatment-resistant schizophrenia (TRS) represents a major clinical issue, characterized by worse psychopathological outcome, a more disrupted neurobiological substrate and higher healthcare costs. Cognitive impairment is a core feature of schizophrenia, strongly associated with patients’ functional outcome. Different studies showed that TRS patients exhibit poorer neurocognitive performance, particularly on verbal domains. To date Cognitive Remediation Therapy (CRT) represents the best available tool for treating cognitive deficits in schizophrenia. However, CRT outcomes are highly heterogeneous and significant treatment predictors are still lacking.ObjectivesTo investigate possible differences of CRT outcome among patients with schizophrenia, stratified according to antipsychotic response (TRSs vs. first-line responders - FLRs).Methods150 patients with schizophrenia, (95 FLRs, 55 TRSs) were assessed for neurocognition with BACS and WCST at baseline and after CRT. General Linear Models (GLMs) were performed to investigate possible differences between groups on basal cognition and CRT outcome (Cohen’s d Effect Size).ResultsAt baseline, GLMs showed significant differences in Verbal Memory (F=4,66; p=0,03) and WCST–executive functions (F=5,59; p=0,02), both worse in TRS group. Effecr Sizes of CRT outcome resulted significantly different in domains of Verbal Memory (F=4,68; p=0,03) and WCST–executive functions (F=4,62; p=0,03), with greater improvements among TRS patients.ConclusionsThis is the first study to indicate treatment-resistance as a possible predictor of CRT outcome in schizophrenia. Moreover, we observed that CRT resulted able to fill the cognitive gap between treatment groups. Thus, these results further highlight the importance of early cognitive interventions in order to reduce the neuropsychological and functional burden associated with the disease, especially for TRS patients.DisclosureNo significant relationships.

Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.

A polydiagnostic approach to cognitive deficits in schizophrenia

IntroductionCognitive deficits are common, clinically relevant and closely linked to poor functional outcomes in everyday functioning in patients with schizophrenia and other psychoses.ObjectivesTo ascertain to which extent a polydiagnostic assessment of schizophrenia is associated with clinically-derived criteria of cognitive impairment and gold-standard neuropsychological assessment.MethodsWe assessed 98 patients with a psychotic disorder. We tested if patients met criteria for schizophrenia according to five diagnostic classifications: Krapelin, Bleuler, Schneider, ICD-10 and DSM-IV. Also, we applied a set of clinically-derived criteria to assess cognitive impairment associated with psychosis (CIAPs). Gold-standard neuropsychological assessment was administered, covering the cognitive domains included in the MATRICS Cognitive Battery: attention, processing speed, verbal memory, visual memory, working memory, executive function and social cognition. MANOVAs were performed to test the association between polydiagnostic and clinically-derived criteria and neuropsychological assessment.ResultsMANOVA profile analyses revealed that patients who met CIAPs criteria showed cognitive impairment in all the cognitive domains except for social cognition. Patients diagnosed with Kraepelin’s criteria showed significant differences in processing speed, visual memory, working memory and GCI. Patients fulfilling Bleuler and DSM-IV criteria showed significant deficits in processing speed and verbal memory, respectively. Schneider and ICD-10 diagnostic criteria did not reveal differences in cognition between patients who fulfilled these criteria.ConclusionsCIAPs criteria were the most accurate classifying patients with cognitive impairment, followed by Kraepelin’s criteria, which were the ones among diagnostic criteria which better differentiated patients regarding cognitive impairment. These criteria take into consideration the outcome in addition to symptoms.DisclosureThis work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148). Both had no further role in the study des

Sociodemographic, lifestyle and clinical factors associated with good performance in paired associates learning (PAL) test in patients with schizophrenia

IntroductionMemory and learning deficits are central among cognitive deficits in schizophrenia. However, to a varying proportion ca. 20-25% of patients could not be considered deficit.ObjectivesDescription of sociodemographic, lifestyle and clinical factors related to good performance in PAL-test in schizophrenia patients.MethodsParticipants (N=4500) were members of the Finnish SUPER study on the genetic mechanisms of psychotic disorders (SUPER). The database of the Northern Finland Birth Cohort 1966 (NFBC 1966) was utilized as a reference data. Visual memory and new learning were assessed using Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) test. The 50th percentile scores (10 error score or less) for outcome measure total errors adjusted (TEA) of NFBC 1966 was used as a cut-off for good performance in PAL test.ResultsThe sociodemographic and lifestyle factors related good performance for both sexes were: younger age (p&lt;.001), higher basic education (p &lt;.001), independent form of dwelling (p&lt;.001), hazardous drinking (p &lt;.001), cannabis use (p &lt;.001) and being married (females p = 0.009, males p = 0.049). The clinical factors related to good performance for both sexes were not using antipsychotic medication regularly (p &lt;.001), not using all psychotropic medication (females p=0.05, males p &lt;.001), less hospitalization times due to psychosis (p &lt;.001), younger age at first hospitalization due to psychosis (p &lt;.001), lower number of hospitalization days (p &lt;.001) and lower percentage of time in hospital after first psychosis episode (p &lt;.001).ConclusionsSeveral factors related to good performance in the PAL–test in the crude analysis without any confounders.

Interrelation of visual and olfactory impairments in schizophrenia

IntroductionIn schizophrenia, there are disorders in all sensory modalities, but the regularities of their occurrence, their pathogenesis and attitude towards cognitive functions are not sufficiently studied.ObjectivesExamine the interrelation between the dysfunctions in different analysers (olfactory and visual) and their dependence on the duration of the disease and the severity of psychotic symptoms and cognitive deficit in schizophrenic patients (F20 according to ICD 10 criteria).MethodsAll subjects were determined the threshold of olfactory sensitivity to n-butanol, the ability to discriminate against odors and the amount of error in comparing the same sections. Cognitive functions were evaluated using the BACS scale.ResultsThe inverse correlation between the value of the visual assessment error and the reduction of the threshold of olfactory sensitivity (r=- 0.56; p &lt; 0.05) and the inverse correlation between the value of the visual assessment error and the ability to discriminate smells (0.64; p &lt; 0.05) were revealed. There are no significant correlations between the duration of the disease and sensory disturbances. Olfactory and visual disturbances in schizophrenic patients were connected with cognitive functions ((r=-0,62; p&lt; 0,05 and r=-0,84, p&lt; 0,001 accordingly).ConclusionsThe data confirm that sensory impairments have a common pathogenesis and are closely related to cognitive deficits. Sensory and cognitive deficits in schizophrenia may be the result of top-down regulation failure.DisclosureNo significant relationships.

Associations between cognition and white matter microstructure in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls: A multivariate pattern analysis

BackgroundCognitive functions have been associated with white matter (WM) microstructure in schizophrenia, but most studies are limited by examining only select cognitive measures and single WM tracts in chronic, medicated patients. It is unclear if the cognition-WM relationship differs between antipsychotic-naïve patients with schizophrenia and healthy controls, as differential associations have not been directly examined. Here we examine if there are differential patterns of associations between cognition and WM microstructure in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls, and we characterize reliable contributors to the pattern of associations across multiple cognitive domains and WM regions, in order to elucidate white matter contribution to the neural underpinnings of cognitive deficits. MethodsThirty-six first-episode antipsychotic-naïve patients with schizophrenia and 52 matched healthy controls underwent cognitive tests and diffusion-weighted imaging on a 3T Magnetic Resonance Imaging scanner. Using a multivariate partial least squares correlation analysis, we included 14 cognitive variables and mean fractional anisotropy values of 48 WM regions. ResultsInitial analyses showed significant group differences in both measures of WM and cognition. There was no group interaction effect in the pattern of associations between cognition and WM microstructure. The combined analysis of patients and controls lead to a significant pattern of associations (omnibus test p = .015). Thirty-four regions and seven cognitive functions contributed reliably to the associations. ConclusionsThe lack of an interaction effect suggests similar associations in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls. This, together with the differences in both WM and cognitive measurements, supports the involvement of WM in cognitive deficits in schizophrenia. Our findings add to the field by showing a coherent picture of the overall pattern of association between cognition and WM. These findings increase our understanding of the impact of WM on cognition, contributing to the search for neuromarkers of cognitive deficits in schizophrenia.

Anxiety and executive functions relationships in schizophrenia: A meta-analysis

Poor executive functions (EF) in schizophrenia are prevalent and most frequently explained as neuropathological conditionality. However, a growing number of studies argue that the contribution of psychological factors (e.g. anxiety) to cognitive deficits in schizophrenia is underestimated. The aim of this study was therefore to meta-analytically investigate the correlations between anxiety and EF performance among patients with a schizophrenia diagnosis. The meta-analysis included 10 studies conducted on a group of 518 patients with schizophrenia; the grand effect was not statistically significant. However, the exclusion of outlier results led to a small significant correlation (r = −0.11) between anxiety and EF in schizophrenia. Moreover, extant relations between state anxiety and EF (r = −0.12), anxiety and EF measures based on reaction time (r = −0.17), and anxiety and EF tests operating on verbal material (r = −0.12) were observed. The results interpreted in light of Attentional Control Theory indicate that the heightened level of anxiety observed among persons diagnosed with schizophrenia might be one of the sources of EF deficits.

The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure

Cognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = −0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002–0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy.