Cognitive Deficits In Schizophrenia Research Articles

Visual Attention Deficits in Schizophrenia Can Arise From Inhibitory Dysfunction in Thalamus or Cortex.

Schizophrenia is associated with diverse cognitive deficits, including disorders of attention-related oculomotor behavior. At the structural level, schizophrenia is associated with abnormal inhibitory control in the circuit linking cortex and thalamus. We developed a spiking neural network model that demonstrates how dysfunctional inhibition can degrade attentive gaze control. Our model revealed that perturbations of two functionally distinct classes of cortical inhibitory neurons, or of the inhibitory thalamic reticular nucleus, disrupted processing vital for sustained attention to a stimulus, leading to distractibility. Because perturbation at each circuit node led to comparable but qualitatively distinct disruptions in attentive tracking or fixation, our findings support the search for new eye movement metrics that may index distinct underlying neural defects. Moreover, because the cortico-thalamic circuit is a common motif across sensory, association, and motor systems, the model and extensions can be broadly applied to study normal function and the neural bases of other cognitive deficits in schizophrenia.

Relationship of common variants in CHRNA5 with early-onset schizophrenia and executive function

Altered cholinergic neural transmission is hypothesized to increase susceptibility to cognitive deficits in psychotic disorders such as schizophrenia (SCZ). The nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) is reported to be associated with cognitive function in nicotine-dependent populations and SCZ in non-smoking SCZ patients. Nevertheless, it is still not clear whether the CHRNA5 gene contributes to susceptibility to the cognitive deficits of SCZ without smoking. To further clarify the role of CHRNA5, we designed a two-stage, case-control study to examine the association between CHRNA5 and SCZ and its clinical features adjusted for smoking status in early-onset SCZ patients. A total of 15 tag single nucleotide polymorphisms (SNPs) on CHRNA5 were genotyped in the discovery stage, which included 485 early-onset SCZ patients and 1018 controls, and then, we replicated this association in a confirmatory population of 674 patients and 1886 controls. The rs16969968 SNP was identified as significantly associated with SCZ in both datasets. In addition, the severity of psychotic symptoms and cognitive deficits was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Wisconsin Card Sorting Test (WCST). The rs16969968 SNP was associated with psychotic symptoms in patients and with cognitive function in patients and controls. Our results show that rs16969968 on CHRNA5 is tightly linked to genetic susceptibility, psychotic symptoms and cognitive deficits in SCZ in an early-onset Chinese population, suggesting that CHRNA5 may play an important role in the etiology of SCZ.

Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and Prefrontal Spatial Encoding

Decreased hippocampal-prefrontal synchrony may mediate cognitive deficits in schizophrenia, but it remains unclear which cells orchestrate this long-rangesynchrony. Parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons show histological abnormalities in individuals with schizophrenia and are hypothesized to regulate oscillatory synchrony within the prefrontal cortex. To examine the relationship between interneuron function, long-range hippocampal-prefrontal synchrony, and cognition, we optogenetically inhibited SOM and PV neurons in the medial prefrontal cortex (mPFC) of mice performing a spatial working memory task while simultaneously recording neural activity in the mPFC and the hippocampus (HPC). We found that inhibiting SOM, but not PV, interneurons during the encoding phase of the task impaired working memory accuracy. This behavioral impairment was associated with decreased hippocampal-prefrontal synchrony and impaired spatial encoding in mPFC neurons. These findings suggest that interneuron dysfunction may contribute to cognitive deficits associated with schizophrenia by disrupting long-range synchrony between the HPC and PFC.

The Time Course of Dorsal and Rostral-Ventral Anterior Cingulate Cortex Activity in the Emotional Stroop Experiment Reveals Valence and Arousal Aberrant Modulation in Patients with Schizophrenia

This paper aims to investigate the temporal dynamics within the dorsal anterior cingulate cortex (dACC) and the rostral-ventral (rv) ACC during the interaction of emotional valence and arousal with cognitive control in patients with Schizophrenia (SZ). Although cognitive deficits in SZ are highly relevant and emotional disturbances are common, the temporal relationship of brain regions involved in the interaction of emotional and cognitive processing in SZ is yet to be determined. To address this issue, the reaction time (RT), event-related potential (ERP) and temporal dynamics of the dACC and rvACC activity were compared between SZ subjects and healthy controls (HC), using a modified emotional Stroop experiment (with factors namely congruence, arousal and valence). EEG was recorded with 64 channels and source localisation was performed using the sLORETA software package. We observed slower initial increase and lower peaks of time course activity within the dACC and rvACC in the SZ group. In this particular group, the dACC activity during late negativity was negatively correlated with a significantly higher RT in the high arousal conflict condition. In contrast to HC subjects, at the N450 window, there was no significant valence (ERP and rvACC ROI) modulation effect in the SZ subjects. Using high density EEG and source localisation, it was possible to distinguish various disturbances within the dACC and rvACC in patients with SZ, during emotion–cognition processing.

Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia.

By examining alpha7 nicotinic receptor biology and recent efforts to target the receptor in clinical trials, it is hoped that investigators will be motivated to explore novel, promising directions focusing on the receptor as a strategy to treat cognitive symptoms in schizophrenia.

Sodium nitroprusside treatment for psychotic symptoms and cognitive deficits of schizophrenia: A randomized, double-blind, placebo-controlled trial

Schizophrenia presents with a broad range of negative, positive, and cognitive symptoms, and comprehensive treatment is still a challenge. Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms and improve cognitive functions in patients with schizophrenia, providing a new possible direction for treatment. In this study, we tested whether SNP can improve psychotic symptoms and cognitive function in schizophrenia patients with longer disease history. This was a randomized, double-blind, placebo-controlled trial conducted between May 2016 and April 2017. Forty-two schizophrenia patients aged 18–45 years were recruited from Henan Province Mental Hospital. Baseline psychiatric symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), and baseline cognitive functions were measured using the Wechsler Adult Intelligence Scale. Patients received two SNP or placebo infusions (0.5 μg/kg per min for 4 h) at a one-week interval. We reassessed psychiatric symptoms and cognitive functions using the same tests shortly after the first and second infusions and 4 weeks after the second infusion. We did not find any significant effect of SNP over placebo on psychotic symptoms or cognitive functions, although SNP was relatively well tolerated with a good safety profile.

Posterior Parietal Cortex Dysfunction Is Central to Working Memory Storage and Broad Cognitive Deficits in Schizophrenia.

PFC dysfunction is widely believed to underlie working memory (WM) deficits in people with schizophrenia (PSZ), but few studies have focused on measures of WM storage devoid of manipulation. Research in neurotypical individuals has shown that storage capacity is more closely related to posterior parietal cortex (PPC) than PFC, suggesting that reductions in WM storage capacity in schizophrenia that are associated with broad cognitive deficits may be related to neural activity in PPC. In the present human neuroimaging study, 37 PSZ and 37 matched healthy control subjects of either sex completed a change detection task with varying set sizes while undergoing fMRI. The task was designed to emphasize WM storage with minimal top-down control demands. Whole-brain analysis identified areas in which BOLD activity covaried with the number of items maintained in WM (K), as derived from task performance at a given set size. Across groups, K values independent of set size predicted BOLD activity in PPC, including superior and inferior parietal lobules and intraparietal sulcus, and middle occipital gyrus. Whole-brain interaction analysis found significantly less K-dependent signal modulation in PSZ than healthy control subjects in left PPC, a phenomenon that could not be explained by a narrower K value range. The slope between K and PPC activation statistically accounted for 43.4% of the between-group differences in broad cognitive function. These results indicate that PPC dysfunction is central to WM storage deficits in PSZ and may play a key role in the broad cognitive deficits associated with schizophrenia.SIGNIFICANCE STATEMENT People with schizophrenia exhibit cognitive deficits across a wide range of tasks. Explaining these impairments in terms of a small number of core deficits with clearly defined neural correlates would advance the understanding of the disorder and promote treatment development. We show that a substantial portion of broad cognitive deficits in schizophrenia can be explained by a failure to flexibly modulate posterior parietal cortex activity as a function of the amount of information currently stored in working memory. Working memory deficits have long been considered central to schizophrenia-related cognitive deficits, but the focus has been on paradigms involving some form of top-down control rather than pure storage of information, which may have unduly narrowed the focus on prefrontal dysfunction.

Diminished modulation of motor cortical reactivity during context-based action observation in schizophrenia

BackgroundDeficient mirror neuron system (MNS)-activity is associated with social cognition deficits in schizophrenia. However, it is not known how socio-emotional contexts modulate the MNS-response. In a Transcranial Magnetic Stimulation (TMS)-experiment, we aimed to compare putative MNS-responses to action observation stimuli with and without a context, in patients with schizophrenia and healthy subjects. MethodTMS-evoked motor cortical reactivity was measured by single and paired [short interval intracortical inhibition (SICI) and facilitation (ICF)] pulse-paradigms in schizophrenia patients (n = 39) and healthy subjects (n = 28) while they observed three experimental-blocks: a static image, a neutral hand action (NA) and a context-based hand action (CA). The degree of cortical reactivity facilitation with the two action observation blocks, relative to the static block provided indirect measures of premotor MNS-activity. A subset of patients (n = 31) also underwent comprehensive social cognition assessments. ResultsRMANOVA demonstrated significantly higher cortical reactivity during the CA-block in both groups (all TMS-paradigms); albeit significantly less pronounced in patients (SICI and ICF paradigms). MNS-activity during the CA-block was significantly higher compared to that during the NA-block in both groups (all TMS-paradigms), but significantly less pronounced in patients (SICI and single-pulse paradigms). MNS-activity during the CA-block measured by the ICF paradigm was positively correlated with social cognition performance. ConclusionProviding a context to the action modulates MNS-activity. This modulation is diminished in schizophrenia patients, suggestive of a diminished sensorimotor associative learning process. This novel, ecologically valid paradigm to tap into the MNS may serve as a neuro-marker of social cognition performance in schizophrenia.

TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal learning deficits via GABAA receptor agonist mechanism: possible therapeutic target for cognitive deficit in schizophrenia

GABAergic drugs are of interest for the treatment of anxiety, depression, bipolar disorder, pain, cognitive impairment associated with schizophrenia (CIAS), and other neuropsychiatric disorders. Some evidence suggests that TPA-023, (7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b] pyridazine), a GABAA α2,3 subtype-selective GABAA partial agonist and α1/5 antagonist, and the neurosteroid, pregnenolone sulfate, a GABAA antagonist, may improve CIAS in pilot clinical trials. The goal of this study was to investigate the effect of TPA-023 in mice after acute or subchronic (sc) treatment with the N-methyl-d-aspartate receptor (NMDAR) antagonist, phencyclidine (PCP), on novel object recognition (NOR), reversal learning (RL), and locomotor activity (LMA) in rodents. Acute TPA-023 significantly reversed scPCP-induced NOR and RL deficits. Co-administration of sub-effective dose (SED) TPA-023 with SEDs of the atypical antipsychotic drug, lurasidone, significantly potentiated the effect of TPA-023 in reversing the scPCP-induced NOR deficit. Further, scTPA-023 co-administration significantly prevented scPCP-induced NOR deficit for 5 weeks. Also, administration of TPA-023 for 7 days following scPCP reversed the NOR deficit for 1 week. However, TPA-023 did not blunt acute PCP-induced hyperactivity, suggesting lack of efficacy as a treatment for psychosis. Systemic TPA-023 significantly blocked lurasidone-induced increases in cortical acetylcholine, dopamine, and glutamate without affecting increases in norepinephrine and with minimal effect on basal release of these neurotransmitters. TPA-023 significantly inhibited PCP-induced cortical and striatal dopamine, serotonin, norepinephrine, and glutamate efflux. These results suggest that TPA-023 and other GABAA agonists may be of benefit to treat CIAS.

Rapid instruction-based task learning (RITL) in schizophrenia.

Individuals with schizophrenia demonstrate broad impairments in neurocognitive functioning as measured through laboratory-based tasks. Neuropsychological measures depend on rapid instruction-based task learning (RITL), the ability to rapidly translate task instruction into goal-directed behavior. Here, the authors present the first known investigation of RITL in schizophrenia and aim to test whether RITL deficits exist in schizophrenia, are associated with abnormal brain activation, and contribute to the generalized cognitive deficit. Twenty-nine schizophrenia participants and 31 healthy controls completed a previously established RITL task while in a functional magnetic resonance imaging (fMRI) scanner and completed a brief assessment of general cognition outside the scanner. Patients were significantly impaired in RITL accuracy and reaction time (RT). Compared to controls, patients had reduced activation of the caudate and left inferior frontal junction (LIFJ) while viewing task instructions, and across all subjects, lower activation in these regions was associated with worse RITL performance. During practice trials, activation in the anterior insula, LIFJ, and middle frontal gyrus also related to performance. RITL ability was robustly associated with general cognitive ability, explained a significant proportion of the variance in the generalized cognitive deficit, and was associated with LIFJ activity during RITL instructions. These results indicate that the ability to rapidly learn task instructions is impaired in schizophrenia and associated with abnormal activation of the caudate and LIFJ. Abnormalities in RITL represent a critical cognitive facet for understanding the broad profile of cognitive deficits in schizophrenia. (PsycINFO Database Record

Neurobiology of cognitive remediation in schizophrenia: Effects of EAAT2 polymorphism

Cognitive deficits represent core features of schizophrenia, affecting quality of life and functioning. The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate reuptake and its activity is crucial for glutamatergic neurotransmission, prevention of excitotoxic damage and cerebral metabolism. Different studies reported that EAAT2 rs4354668 (−181 T/G) influences cognitive functions and brain structures in patients with schizophrenia. Specifically, the G allele, linked to lower EAAT2 expression, was associated with impaired prefrontal cognitive performance and reduced grey matter volumes. Cognitive remediation therapy (CRT) is one of the best available tool to treat cognitive deficits in schizophrenia, able to induce a neuroplastic modulation of cognitive functions. The present study aims to investigate the effects of rs4354668 on CRT outcome, also considering possible genotype interaction with antipsychotic (AP) treatment, since EAAT2 expression is negatively influenced by clozapine.We examined rs4354668 in 88 clinically stabilized patients with schizophrenia, treated with CRT and assessed at enrolment, at the end of CRT and after 3 months. We observed greater working memory improvements among patients carrying the T/T genotype, regardless of AP treatment. Moreover, we reported a significant interaction between pharmacological treatment and rs4354668 on executive functions, with greater improvements among T/T patients treated with APs other than clozapine.These observations suggest that impaired EAAT2 expression may attenuate CRT outcome. Moreover, our results indicate the possibility that rs4354668 could also differentially influence the response to CRT depending on the AP treatment.

Improving working memory in schizophrenia: Effects of 1 mA and 2 mA transcranial direct current stimulation to the left DLPFC

Deficits in various cognitive processes, such as working memory, are characteristic for schizophrenia, lowering patients' functioning and quality of life. Recent research suggests that transcranial direct stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) may be a potential therapeutic intervention for cognitive deficits in schizophrenia. Here, we examined the effects of online tDCS to the DLPFC on working memory (WM) performance in 40 schizophrenia patients in two separate experiments with a double blind, sham-controlled, cross-over design. Patients underwent single sessions of active and sham tDCS in a randomized order. Stimulation parameters were anode F3, cathode right deltoid muscle, 21 min tDCS duration, 1 mA tDCS in Experiment 1 (N = 20) and 2 mA tDCS in Experiment 2 (N = 20). Primary outcome was the change in WM performance as measured by a verbal n-back paradigm (1- to 3-back). Irrespective of the stimulation intensity, data analysis showed a significant higher WM accuracy during active tDCS than during sham tDCS (p = 0.019), but no main effect of stimulation intensity (p = 0.392). Subsequent separate analyses revealed a significantly improved WM performance only during 1 mA (p = 0.048). TDCS facilitated WM functioning in schizophrenia, with an advantage of 1 mA over 2 mA. Our results support the notion that tDCS may be a potential treatment for cognitive deficits in schizophrenia and emphasize the need for future research on the specific stimulation parameters.

Neural correlates of global and specific cognitive deficits in schizophrenia

Cognitive deficits are a core feature of schizophrenia, but the neural mechanisms that contribute to these characteristics are not fully understood. This study investigated whether volume of the dorsal lateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG), hippocampus, and white matter were associated with impairment in specific cognitive domains, including executive functioning, working memory, verbal memory, verbal fluency, processing speed, versus global functioning. The multi-site data used in this study was collected from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP), and consisted of 206 healthy controls and 247 individuals with either schizophrenia or schizoaffective disorder. The neuroimaging data was segmented based on the Destrieux atlas in FreeSurfer. Linear regression analyses revealed that global cognition, executive functioning, working memory, and processing speed were associated with all brain structures, except the DLPFC was only associated with executive fucntion. When controlling for the global cognitive deficit, executive function was trending significance with white matter, but continued to be associated with the DLPFC and IFG, as did the association between processing speed and the hippocampus. These findings suggest that volumes of the DLPFC, IFG, hippocampus, and white matter are associated with the global cognitive impairment seen in schizophrenia, but some brain structures may also be specifically related to domain-specific deficits (primarily executive function) over-and-beyond the global cognitive deficit.

Associations between P3a and P3b amplitudes and cognition in antipsychotic-naïve first-episode schizophrenia patients.

Cognitive deficits are already present in early stages of schizophrenia. P3a and P3b event-related potentials (ERPs) are believed to underlie the processes of attention and working memory (WM), yet limited research has been performed on the associations between these parameters. Therefore, we explored possible associations between P3a/b amplitudes and cognition in a large cohort of antipsychotic-naïve, first-episode schizophrenia (AN-FES) patients and healthy controls (HC). Seventy-three AN-FES patients and 93 age- and gender-matched HC were assessed for their P3a/b amplitude with an auditory oddball paradigm. In addition, subjects performed several subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). AN-FES patients had significantly reduced P3a/b amplitudes, as well as significantly lower scores on all cognitive tests compared with HC. Total group correlations revealed positive associations between P3b amplitude and WM and sustained attention and negative associations with all reaction time measures. These associations appeared mainly driven by AN-FES patients, where we found a similar pattern. No significant associations were found between P3b amplitude and cognitive measures in our HC. P3a amplitude did not correlate significantly with any cognitive measures in either group, nor when combined. Our results provide further evidence for P3a/b amplitude deficits and cognitive deficits in AN-FES patients, which are neither due to antipsychotics nor to disease progress. Furthermore, our data showed significant, yet weak associations between P3b and cognition. Therefore, our data do not supply evidence for deficient P3a/b amplitudes as direct underlying factors for cognitive deficits in schizophrenia.

Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia.

Impaired Prefrontal Cortical Dopamine Release in Schizophrenia During a Cognitive Task: A [11C]FLB 457 Positron Emission Tomography Study.

Evidence from several lines of research suggests decreased dopamine release in the prefrontal cortex as the neurochemical correlates of cognitive deficits in schizophrenia (SCZ). However, in vivo examination of cortical hypodopaminergia using positron emission tomography (PET) during cognitive task performance in SCZ remains to be investigated. We examined dopamine release in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), using PET while participants were performing a cognitive task. Thirteen drug-free patients with SCZ and 13 healthy volunteers (HV) matched for age and sex participated in the study. Data were acquired between 2011 and 2015. Two PET scans with [11C]FLB 457 were acquired while the participants were performing the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task (SMCT). A magnetic resonance image was acquired for anatomical delineation. Differences in cortical dopamine release between SCZ and HV, indexed as percentage change in binding potential between WCST and SMCT (ΔBPND), were calculated in ACC and DLPFC. We observed significant differences in the ΔBPND in ACC (HV = 4.40 ± 6.00; SCZ = -11.48 ± 15.08; t = 3.52; P = .003) and a trend-level difference in ΔBPND in DLPFC (HV = -0.58 ± 8.45; SCZ = -7.79 ± 11.28; t = 1.84; P = .079), suggesting dopamine depletion in cortical brain regions in patients with SCZ while performing a cognitive task. These results provide the first in vivo evidence for reduced dopamine release or even dopamine depletion while performing cognitive task in ACC and DLPFC in patients with SCZ. The present results provide support for the frontal hypodopaminergia hypothesis of cognitive symptoms in SCZ.

Top-Down Disconnectivity in Schizophrenia During P300 Tasks.

Cognitive deficits in schizophrenia are correlated with the dysfunctions of distinct brain regions including anterior cingulate cortex (ACC) and prefrontal cortex (PFC). Apart from the dysfunctions of the intrinsic connectivity of related areas, how the coupled neural populations work is also crucial in related processes. Twenty-four patients with schizophrenia (SZs) and 24 matched healthy controls (HCs) were recruited in our study. Based on the electroencephalogram (EEG) datasets recorded, the Dynamic Causal Modeling (DCM) was then adopted to estimate how the brain architecture adapts among related areas in SZs and to investigate the mechanism that accounts for their cognitive deficits. The distinct winning models in SZs and HCs consistently emphasized the importance of ACC in regulating the elicitations of P300s. Specifically, comparing to that in HCs, the winning model in SZs uncovered a compensatory pathway from dorsolateral PFC to intraparietal sulcus that promised the SZs' accomplishing P300 tasks. The findings demonstrated that the “disconnectivity hypothesis” is helpful and useful in explaining the cognitive deficits in SZs, while the brain architecture adapted with related compensatory pathway promises the limited brain cognitions in SZs. This study provides a new viewpoint that deepens our understanding of the cognitive deficits in schizophrenia.

Decreased plasma levels of gasotransmitter hydrogen sulfide in patients with schizophrenia: correlation with psychopathology and cognition.

Aberrant N-methyl-D-aspartate receptor (NMDAR) function has been implicated in the pathophysiology of schizophrenia. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that regulates NMDAR function. The current study investigated the relationship between plasma H2S levels and both psychopathological and cognitive symptoms in schizophrenia. Forty-one patients with schizophrenia and 40 healthy control subjects were recruited in present study. Schizophrenic symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was evaluated with a neuropsychological battery including seven neurocognitive tests. Plasma H2S levels were measured by reversed-phase high-performance liquid chromatography (RP-HPLC). Patients with schizophrenia performed worse in all of the cognitive tests than the healthy controls except for the visual memory. Plasma H2S levels were significantly lower in patients with schizophrenia relative to healthy control subjects (F= 3.821, p= 0.007). Correlation analysis revealed a significant negative correlation between the H2S levels and the PANSS general scores (r= - 0.413, p= 0.007). Additionally, a positive association was observed between plasma H2S levels and working memory (r= 0.416, p= 0.007), visual memory (r= 0.363, p= 0.020), or executive function (r= 0.344, p= 0.028) in patients. Partial correlation analysis showed that the correlations between the H2S levels and the PANSS general scores, working memory, visual memory, or executive function were still significant when controlling for age, gender, years of education, BMI, duration of illness, and age of onset. The significant relations observed in the current study between H2S and the general psychopathological as well as cognitive symptoms suggest that decreased H2S is involved in the psychopathology and cognitive deficits of schizophrenia, and it might be a promising peripheral biomarker of schizophrenia.

Spared and impaired sleep-dependent memory consolidation in schizophrenia

ObjectiveCognitive deficits in schizophrenia are the strongest predictor of disability and effective treatment is lacking. This reflects our limited mechanistic understanding and consequent lack of treatment targets. In schizophrenia, impaired sleep-dependent memory consolidation correlates with reduced sleep spindle activity, suggesting sleep spindles as a potentially treatable mechanism. In the present study we investigated whether sleep-dependent memory consolidation deficits in schizophrenia are selective. MethodsSchizophrenia patients and healthy individuals performed three tasks that have been shown to undergo sleep-dependent consolidation: the Word Pair Task (verbal declarative memory), the Visual Discrimination Task (visuoperceptual procedural memory), and the Tone Task (statistical learning). Memory consolidation was tested 24 h later, after a night of sleep. ResultsCompared with controls, schizophrenia patients showed reduced overnight consolidation of word pair learning. In contrast, both groups showed similar significant overnight consolidation of visuoperceptual procedural memory. Neither group showed overnight consolidation of statistical learning. ConclusionThe present findings extend the known deficits in sleep-dependent memory consolidation in schizophrenia to verbal declarative memory, a core, disabling cognitive deficit. In contrast, visuoperceptual procedural memory was spared. These findings support the hypothesis that sleep-dependent memory consolidation deficits in schizophrenia are selective, possibly limited to tasks that rely on spindles. These findings reinforce the importance of deficient sleep-dependent memory consolidation among the cognitive deficits of schizophrenia and suggest sleep physiology as a potentially treatable mechanism.

Dysregulation of auditory neuroplasticity in schizophrenia

Schizophrenia is a complex brain syndrome characterized by an array of positive symptoms (delusions, hallucinations, disorganized speech), negative symptoms (alogia, apathy, avolition) and cognitive impairments (memory, executive functions). Although investigations of the cognitive deficits in schizophrenia have primarily concentrated on disturbances affecting higher-order cognitive processes, there is an increasing realization that schizophrenia also affects early sensory processing, which might, in fact, play a significant role in the development of higher-order cognitive impairments. Recent evidence suggests that many of these early sensory processing impairments possibly arise from a dysregulation of plasticity regulators in schizophrenia, resulting in either reduced plasticity or excessive unregulated plasticity. The purpose of the present manuscript is to provide a concise overview of how the dysregulation of cortical plasticity mechanisms contributes to schizophrenia symptoms with an emphasis on auditory dysplasticity and to discuss its relevance for treatment outcomes. The idea that plasticity mechanisms are not constrained only within sensitive periods suggests that many functional properties of sensory neurons can be altered throughout the lifetime.