Cognitive Symptoms Of Schizophrenia Research Articles

Gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia.

This study aims to explore the gender differences in cognitive improvements after two months of atypical antipsychotic treatment in first episode schizophrenia (FES). 82 patients with FES, including 50 male patients and 32 female patients, were enrolled in the present study. Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were respectively conducted to evaluate the clinical symptoms and cognitive function of patients with FES at baseline and after treatment. Repeated measure ANOVA was performed to compare gender differences in cognitive domains scores between baseline and 2-month follow-up. Stepwise liner regression model was performed to explore the effect factors of cognitive improvements in patients. There was no significant difference in age of onset, education years, PANSS scores, duration of untreated psychosis and Olanzapine equivalent doses between male and female patients (all p > 0.05). In the comparisons of cognition function, male patients exhibited better performance in social cognition compared with female patients at baseline (t = 3.20, p < 0.05). After treatment, improvements of attention/vigilance and working memory were both found in male patients and female patients (attention/vigilance, F = 11.867, p < 0.05; working memory, F = 18.265, p < 0.05). In addition, improvement of speed of information processing was only found in female patients (F = 11.65, p < 0.01). Significant interaction between time and gender was found in speed information of processing (F = 4.140, p = 0.045). Stepwise liner regression model revealed that improvements of negative symptoms promote improvements of cognitive function in female patients (all p < 0.05). Our findings revealed gender differences of cognitive improvements in patients with FES after 2-month treatment. It provides new evidence for gender differences in cognitive symptoms of schizophrenia, and also provides preliminary clues for further individualized cognitive intervention strategies.

Effect of Sodium Benzoate as an Add-on Therapy on the Clinical and Cognitive Symptoms of Schizophrenia: A Case Series

Effect of Sodium Benzoate as an Add-on Therapy on the Clinical and Cognitive Symptoms of Schizophrenia: A Case Series

A narrative review on the association between smoking and schizophrenia symptoms

Smoking is commonly observed in patients with schizophrenia (SCZ). However, the relationship between smoking and SCZ-related risk factors remains unclear. In addition, whether smoking works as a self-treatment to alleviate SCZ symptoms is unknown. Our study aimed to investigate the complex relationship between smoking behavior and specific SCZ symptoms. We conducted a literature search on PubMed using the keyword &amp;ldquo;smoking self-treatment and SCZ&amp;rdquo; and identified 191 studies. After screening for relevance, 47 studies were included in the study. Most studies confirmed a correlation between smoking status and the severity of negative, positive, and cognitive symptoms in SCZ. In addition, most studies investigated the association between cognitive symptoms and SCZ with inconsistent findings. We confirmed that smoking status is associated with symptom severity, including cognitive, negative, extrapyramidal, and positive symptoms. These findings support the theory of self-treatment and highlight the importance of addressing smoking behavior in SCZ patients.

Gm527 deficiency in dentate gyrus improves memory through upregulating dopamine D1 receptor pathway.

Dopamine D1 receptor (D1R) hypofunction is associated with negative and cognitive symptoms in schizophrenia; therefore, the mechanism of D1R function modulation needs further investigation. Gm527 is the rodent homologous of the schizophrenia-related gene C14orf28, encoding a predicated D1R-interacting protein. However, the role of Gm527-D1R interaction in schizophrenia needs to be clarified. Gm527-floxed mice were generated and crossed with D1-Cre mice (D1:Gm527-/-) to knockout Gm527 in D1R-positive neurons. Then behavioral tests were performed to explore the schizophrenia-related phenotypes. Immunofluorescence, fluorescence in situ hybridization, electrophysiological recording, quantitative real-time PCR, and western blotting were conducted to investigate the mechanisms. Working memory, long-term memories, and adult neurogenesis in the DG were enhanced in D1:Gm527-/- mice. LTP was also increased in the DG in D1:Gm527-/- mice, resulting from the Gm527 knockout-induced D1R expression enhancement on the plasma membrane and subsequently cAMP signaling and NMDA receptor pathways activation. The requirement of Gm527 knockout in the DG was confirmed by reversing Gm527 expression or knockdown Gm527 in the DG D1R-positive neurons through AAV-CAG-FLEX-Gm527-GFP or AAV-CMV-FLEX-EGFP-Gm527-RNAi injection. The DG Gm527 knockout induces D1R hyperfunction in improving schizophrenia cognitive symptoms.

Activating the dorsomedial and ventral midbrain projections to the striatum differentially impairs goal-directed action in male mice

The cognitive symptoms of schizophrenia are wide ranging and include impaired goal-directed action. This could be driven by an increase in dopamine transmission in the dorsomedial striatum, a pathophysiological hallmark of schizophrenia. Although commonly associated with psychotic symptoms, dopamine signalling in this region also modulates associative learning that aids in the execution of actions. To gain a better understanding of the role of subcortical dopamine in learning and decision-making, we assessed goal-directed action in male mice using the cross-species outcome-specific devaluation task (ODT). First, we administered systemic amphetamine during training to determine the impact of altered dopaminergic signaling on associative learning. Second, we used pathway-specific chemogenetic approaches to activate the dorsomedial and ventral striatal pathways (that originate in the midbrain) to separately assess learning and performance. Amphetamine treatment during learning led to a dose-dependent impairment in goal-directed action. Activation of both striatal pathways during learning also impaired performance. However, when these pathways were activated during choice, only activation of the ventral pathway impaired goal-directed action. This suggests that elevated transmission in the dorsomedial striatal pathway impairs associative learning processes that guide the goal-directed execution of actions. By contrast, elevated transmission of the ventral striatal pathway disrupts the encoding of outcome values that are important for both associative learning and choice performance. These findings highlight the differential roles of the dorsomedial and ventral inputs into the striatum in goal-directed action and provides insight into how striatal dopamine signaling may contribute to the cognitive problems in those with schizophrenia.

Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.

Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia.

Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration.

The cognitive symptoms of schizophrenia (SZ) present a significant clinical burden. They are treatment resistant and are the primary predictor of functional outcomes. Although the neural mechanisms underlying these deficits remain unclear, pathological GABAergic signaling likely plays an essential role. Perturbations with parvalbumin (PV)-expressing fast-spiking (FS) interneurons in the prefrontal cortex (PFC) are consistently found in post-mortem studies of patients with SZ, as well as in animal models. Our studies have shown decreased prefrontal synaptic inhibition and PV immunostaining, along with working memory and cognitive flexibility deficits in the MK801 model. To test the hypothesized association between PV cell perturbations and impaired cognition in SZ, we activated prefrontal PV cells by using an excitatory DREADD viral vector with a PV promoter to rescue the cognitive deficits induced by adolescent MK801 administration in female rats. We found that targeted pharmacogenetic upregulation of prefrontal PV interneuron activity can restore E/I balance and improve cognition in the MK801 model. Our findings support the hypothesis that the reduced PV cell activity levels disrupt GABA transmission, resulting in the disinhibition of excitatory pyramidal cells. This disinhibition leads to an elevated prefrontal excitation/inhibition (E/I) balance that could be causal for cognitive impairments. Our study provides novel insights into the causal role of PV cells in cognitive function and has clinical implications for understanding the pathophysiology and management of SZ.

Abnormal Structural Network Communication Reflects Cognitive Deficits in Schizophrenia.

Schizophrenia has long been thought to be a disconnection syndrome and several previous studies have reported widespread abnormalities in white matter tracts in individuals with schizophrenia. Furthermore, reductions in structural connectivity may also impair communication between anatomically unconnected pairs of brain regions, potentially impacting global signal traffic in the brain. Therefore, we used different communication models to examine direct and indirect structural connections (polysynaptic) communication in large-scale brain networks in schizophrenia. Diffusion-weighted magnetic resonance imaging scans were acquired from 62 patients diagnosed with schizophrenia and 35 controls. In this study, we used five network communication models including, shortest paths, navigation, diffusion, search information and communicability to examine polysynaptic communication in large-scale brain networks in schizophrenia. We showed less efficient communication between spatially widespread brain regions particulary encompassing cortico-subcortical basal ganglia network in schizophrenia group relative to controls. Then, we also examined whether reduced communication efficiency was related to clinical symptoms in schizophrenia group. Among different measures of communication efficiency, only navigation efficiency was associated with global cognitive impairment across multiple cognitive domains including verbal learning, processing speed, executive functions and working memory, in individuals with schizophrenia. We did not find any association between communication efficiency measures and positive or negative symptoms within the schizophrenia group. Our findings are important for improving our mechanistic understanding of neurobiologicalprocess underlying cognitive symptoms in schizophrenia.

Investigation of the Relationship Between Cognitive Functions and Retinal Findings From Spectral Optical Coherence Tomography in Patients With Schizophrenia and Their Healthy Siblings.

Retinal structural changes which were investigated by optical coherence tomography (OCT) have been reported in schizophrenia. Since cognitive dysfunction is a core feature of schizophrenia, the correlations between retinal findings and cognitive functions of patients and their healthy siblings may provide insight into the pathophysiological processes of the disorder. We aimed to investigate the relationship between neuropsychiatric tests and retinal changes in schizophrenia patients and their healthy siblings. We measured OCT parameters and cognitive performance (via Trail Making Tests, verbal fluency tests, and The Digit Span Tests) of 72 participants (36 patients with schizophrenia and 36 healthy siblings) and disease severity (with Positive and Negative Syndrome Scale, Global Assessment of Functioning, and Clinical Global Impression scales) in patients with schizophrenia and evaluated the relationship between retinal findings and clinical parameters, especially neurocognitive tests. We found decreased ganglion cell layer-inner plexiform layer thickness and macular volume in the patient group. There were strong correlations between neurocognitive tests and OCT findings in both groups. On the other hand, there was not any correlation between retinal findings and disease parameters. The cognitive symptoms of schizophrenia may be more closely related to structural changes in the retina.

Antipsychotic drugs and their effects on cognitive function: protocol for a systematic review, pairwise, and network meta-analysis

BackgroundThere is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning.MethodsIn our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings.DiscussionThis systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients’ and physicians’ decision-making processes based on the latest available evidence.Systematic review registrationPROSPERO CRD42022312483

EPA guidance on treatment of cognitive impairment in schizophrenia

AbstractAlthough cognitive impairment is a core symptom of schizophrenia related to poore outcome in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented.The aim of the European Psychiatric Association (EPA) guidance paper was to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia, structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments.Based on the reviewed evidence, the EPA guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive symptoms in schizophrenia. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. As for cognitive remediation, some variables have been confirmed as core elements for treatment effectiveness.The dissemination of the EPA guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve clinical recovery in this population.Disclosure of InterestNone Declared

Vortioxetine improved negative and cognitive symptoms of schizophrenia in subchronic MK-801 model in rats

Schizophrenia is a devastating psychiatric disorder with complex symptoms and neurobiology. Serotonergic dysregulation is known to contribute to the pathogenesis of schizophrenia although dopaminergic and glutamatergic systems are thought to have central roles in neurobiology. No significant success can be achieved in the treatment of negative and cognitive symptoms while positive symptoms can be significantly reduced with current pharmacotherapy. Vortioxetine is a new multimodal antidepressant with 5-HT1A agonism, 5-HT1B partial agonism, 5-HT3, 5-HT7, and 5-HT1D antagonism, and serotonin reuptake inhibition. A limited number of studies suggest its therapeutic effect on the negative and cognitive symptoms of schizophrenia. Therefore, we investigated the potential beneficial effects of vortioxetine on behavioral and molecular deficits in the MK-801 model of schizophrenia in rats. Female Wistar albino rats (10–12 weeks) were grouped as saline, MK-801 (0.2 mg/kg), MK-801 + vortioxetine (2.5 mg/kg), MK-801 + vortioxetine (5 mg/kg), MK-801 + vortioxetine (10 mg/kg), MK-801 + risperidone (0.3 mg/kg), MK-801 + haloperidol (1 mg/kg) (n = 8 in each group). MK-801 has been daily administered (i.p.) for 14 days. Vortioxetine and antipsychotic treatments were injected for 21 days after a washout period of MK-801 and locomotor activity (LA), social interaction (SI), novel object recognition (NOR), Y-maze and prepulse inhibition (PPI) tests were performed at the 16–20th days of treatments, respectively. ELISA test was conducted to evaluate molecular analyses. MK-801 decreased PPI (%), social behaviors, and discrimination index in NOR and alternation (%) in the Y-maze test. In NOR and Y-maze tests, especially vortioxetine 5 and 10 mg/kg increased discrimination index and alternation (%) compared to MK-801. In addition, vortioxetine administration increased social behaviors. Moreover, MK-801 decreased GAD67 and parvalbumin levels while vortioxetine increased these protein levels compared to MK-801. Herein, we first suggested a potential therapeutic effect of vortioxetine, a new multimodal antidepressant, on negative and cognitive symptoms and neurobiological deficits including GAD67 and parvalbumin low expression in the MK-801 model in rats. It would be beneficial to confirm our results in different rodent models and to shed light on the possible mechanisms underlying these effects.

Behavioral effect of Cassia singueana Del. (Fabaceae) extract against isolation rearing-induced cognitive impairment in albino rats

Early life stress negatively alters brain development and couldlead to the development of psychiatricdisorder. Exposing animals to early-life adverse events, including maternal separation or social isolation, greatly affects brain development and adult behaviour and may contribute to the occurrence of psychiatric manifestations, such as positive, negative and cognitive symptoms of schizophrenia. These symptoms can be depicted in different animal models. Aim: This study is aimed at evaluating the effect of Cassia singueana on isolation rearing-induced cognitive impairment in rats. Materials and Methods: Pharmacological intervention (Risperidone 1mg/kg/day, graded doses of Cassia singueana extract or Distilled water 10ml/kg) was introduced 4 weeks(adolescence) and one group 8 weeks(young adulthood) after IR (i.e., rats were 7- or 11-week-old). The intervention lasted for 8 weeks, after which the rats in all the various groups were subjected toopen field test, forced swim test, novel object recognition test, y-maze and post isolation grooming test. Rats’ hippocampus immediately after sacrifice was removed to measure the level of MDA, SOD and GSH. Results: Cassia singueana extract significantly decrease the hyper locomotion in open field, it also significantly decrease the duration of immobility in forced swim test. CSE also increase the exploration time of novel object and improved the recognition index. The extract also significantly increases the number of actual alternation and spontaneous alternation in y-maze. However the extract did not improve the duration of grooming in isolation reared rats. CSE also significantly improved the level of antioxidant enzymes. Conclusion: The study results revalidate the utility of the isolation rearing paradigm in exploring mental disorders with neurodevelopmental origin, especially schizophrenia and Cassia singueana extract contained phytochemicals with tendency to ameliorate all the three symptoms of schizophrenia possibly through their antioxidant properties.

Ulotaront: a TAAR1/5-HT1A agonist in clinical development for the treatment of schizophrenia

ABSTRACT Introduction Current antipsychotics are postsynaptic dopamine-2(D2) receptor blockers, which often, but not always, effectively improve acute psychotic symptoms and prevent relapse in schizophrenia and other severe mental disorders, but are associated with various side effects, including parkinsonism, akathisia, sedation/somnolence, and cardiometabolic alterations. Furthermore, the efficacy of current antipsychotics for negative and cognitive symptoms in schizophrenia is limited. Ulotaront is a novel trace-amine-associated receptor-1(TAAR1) agonist with serotonin-1A receptor agonist activity, and without postsynaptic D2-receptor antagonism. Phase 2 clinical data for ulotaront in patients with acutely exacerbated schizophrenia are promising regarding the potential improvement in positive, negative, and depressive symptoms. Areas covered An overview of the pharmacokinetic and pharmacodynamic properties of ulotaront is given. Summary of clinical efficacy and safety/tolerability from Phase 1/2-trials, and of ongoing Phase 3-trials, is also given. Expert opinion Ulotaront is a promising agent for the treatment of schizophrenia with an apparent benign safety profile, which might provide a much-needed new and different treatment option for various domains of schizophrenia. Data from larger Phase 3-trials, including for relapse prevention, schizophrenia subdomains, and in adolescents, are awaited. If ongoing Phase 3-trials in adults are successful, further research on combination regimens with existing antipsychotics, and in treatment-resistant schizophrenia as well as in mood disorders would be desirable.

Balanced time perspective and its relationship with clinical and cognitive symptoms in schizophrenia

The adaptive function of balanced time perspective is widely acknowledged within positive psychology, yet little is known regarding the expression of time perspective in clinical populations and its relation to clinical features. The current study aimed to examine the nature of time perspective in schizophrenia and to determine whether alterations in balanced time perspective is associated with maladaptive outcomes in terms of clinical and cognitive symptoms. A total of 104 patients with schizophrenia and 93 matched healthy controls participated in this study. Time perspective, negative symptoms, working memory and response inhibition was measured. Results showed that patients with schizophrenia manifested lower balanced time perspective with marginal significance in the context of impaired working memory but intact response inhibition. Correlation analyses revealed that deviation from balanced time perspective in schizophrenia was negatively associated with working memory capacity, as well as positively associated with negative symptoms such as affective blunting and anhedonia. Our findings point to working memory impairments as a candidate cognitive mechanism underpinning the deviation from balanced time perspective in schizophrenia. We further demonstrate a link between deviation from balanced time perspective and clinical symptomatology in schizophrenia, offering potential avenues for remediation strategies.

The effect of selective nigrostriatal dopamine excess on behaviors linked to the cognitive and negative symptoms of schizophrenia.

Excess dopamine release in the dorsal striatum (DS) is linked to psychosis. Antipsychotics are thought to work by blocking striatal D2 dopamine receptors, but they lack efficacy for the negative and cognitive symptoms of schizophrenia. These observations and the fact that increasing brain-wide dopamine improves cognition have fueled the dogma that excess dopamine is not involved in negative and cognitive symptoms. However, this idea has never been explicitly tested with DS-pathway specificity. To determine if excess DS dopamine is involved in cognitive and negative symptoms, we selectively re-expressed excitatory TRPV1 receptors in DS-projecting dopamine neurons of Trpv1 knockout mice. We treated these mice with capsaicin (TRPV1 agonist) to selectively activate these neurons, validated this approach with fiber photometry, and assessed its effects on social interaction and working memory, behavioral constructs related to negative and cognitive symptoms. We combined this manipulation with antipsychotic treatment (haloperidol) and compared it to brain-wide dopamine release via amphetamine treatment. We found that selectively activating DS-projecting dopamine neurons increased DS (but not cortical) dopamine release and increased locomotor activity. Surprisingly, this manipulation also impaired social interaction and working memory. Haloperidol normalized locomotion, but only partially rescued working memory and had no effect on social interaction. By contrast, amphetamine increased locomotion but did not impair social interaction or working memory. These results suggest that excess dopamine release, when restricted to the DS, causes behavioral deficits linked to negative and cognitive symptoms. Future therapies should address this disregarded role for excess striatal dopamine in thetreatment-resistant symptoms of psychosis.

A comparison of efficacy, mechanism, and side effects of clozapine and risperidone in patients with schizophrenia

Schizophrenia is a chronic psychotic disorder characterized by the presence of psychotic symptoms (hallucinations, delusions), negative symptoms (decreased expressiveness), and cognitive symptoms (lack of executive function). The exact etiology of schizophrenia is unknown, although it is thought to be linked to increased dopaminergic activity in the mesolimbic neuronal pathway and decreased dopaminergic activity in the prefrontal cortical pathway. Treatment of schizophrenia includes both pharmacological and psychosocial intervention. Nonpharmacological treatments are effective in treating the negative and cognitive symptoms of schizophrenia and increasing patient adherence to medications. The first-generation “conventional” antipsychotic drugs are high-affinity antagonists of dopamine D2 receptors that are most effective against psychotic symptoms and atypical agents differ pharmacologically from previous antipsychotic agents in their lower affinity for dopamine D2 receptors Clozapine and risperidone both are atypical antipsychotics. Clozapine has weak D2 blocking action. It mainly acts by blocking 5-HT2, alpha-adrenergic, and D4 receptors. Risperidone acts by blocking 5-HT, alpha-adrenergic and D2 receptors. It is a more potent D2 blocker than clozapine and can cause extrapyramidal symptoms at a high dose. Aggravation of seizures more with olanzapine and fewer chances with risperidone. Clozapine is a high potential atypical antipsychotic to cause metabolic side effects, while risperidone is a low potential antipsychotic to cause metabolic side effects. Clozapine is used in the treatment of resistant schizophrenia and risperidone is the most potent atypical antipsychotic agent available in long-acting injectable form.

Mechanisms underpinning Carpolobia lutea G. Don ethanol extract's neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia

Ethnopharmacological relevancePersistent ketamine insults to the central nervous system block NMDA receptors and disrupt putative neurotransmission, oxido–nitrosative, and inflammatory pathways, resulting in schizophrenia-like symptoms in animals. Previously, the ethnomedicinal benefits of Carpolobia lutea against insomnia, migraine headache, and insanity has been documented, but the mechanisms of action remain incomplete. Aim of the studyPresently, we explored the neuro-therapeutic role of Carpolobia lutea ethanol extract (C. lutea) in ketamine-induced schizophrenia-like symptoms in mice. Materials and methodsSixty-four male Swiss (22 ± 2 g) mice were randomly assigned into eight groups (n = 8/group) and exposed to a reversal ketamine model of schizophrenia. For 14 days, either distilled water (10 mL/kg; p.o.) or ketamine (20 mg/kg; i.p.) was administered, following possible reversal treatments with C. lutea (100, 200, 400, and 800 mg/kg; p.o.), haloperidol (1 mg/kg, p.o.), or clozapine (5 mg/kg; p.o.) beginning on days 8–14. During the experiment, a battery of behavioral characterizations defining schizophrenia-like symptoms were obtained using ANY-maze software, followed by neurochemical, oxido-inflammatory and histological assessments in the mice brains. ResultsA 7-day reversal treatment with C. lutea reversed predictors of positive, negative and cognitive symptoms of schizophrenia. C. lutea also mitigated ketamine-induced neurochemical derangements as evidenced by modulations of dopamine, glutamate, norepinephrine and serotonin neurotransmission. Also, the increased acetylcholinesterase activity, malondialdehyde nitrite, interleukin-6 and tumor necrosis-factor-α concentrations were reversed by C. lutea accompanied with elevated levels of catalase, superoxide dismutase and reduced glutathione. Furthermore, C. lutea reversed ketamine-induced neuronal alterations in the prefrontal cortex, hippocampus and cerebellum sections of the brain. ConclusionThese findings suggest that C. lutea reverses the cardinal symptoms of ketamine-induced schizophrenia in a dose-dependent fashion by modulating the oxido-inflammatory and neurotransmitter-related mechanisms.

PO085 / #1079 TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) FOR SEVERELY ILL SCHIZOPHRENIA PATIENTS: E-POSTER VIEWING

Current pharmacological treatments are effective for treating positive symptoms but have little or no effect to treat negative or cognitive symptoms in schizophrenia. Transcranial direct current stimulation (tDCS) has generated interest in recent years as a potential adjunctive treatment for patients with schizophrenia (1,2,3,4). The aim of this study was to examine the efficacy of frontal cortex tDCS for negative and neurocognitive symptoms in severely ill treatment resistant schizophrenia patients in Niuvanniemi hospital.

New Atypical Antipsychotics in the Treatment of Schizophrenia and Depression.

Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many psychotropic drugs are available but achieving optimal therapeutic effect can be challenging. The evidence correlates well with clinical observations, suggesting that new atypical antipsychotic drugs are effective against negative and cognitive symptoms of schizophrenia, as well as against affective symptoms observed in depression. The purpose of this review presents the background and evidence for the use of the new second/third-generation antipsychotics (aripiprazole, cariprazine, lurasidone, asenapine, brexpiprazole, lumateperone, pimavanserin) in treatment of schizophrenia and depression. We have first provided a brief overview of the major neurobiological underpinnings of schizophrenia and depression. We then shortly discuss efficacy, safety and limitations of ongoing pharmacotherapy used in depression and schizophrenia. Mainly, we have focused this review on the therapeutic potential of new atypical antipsychotic drugs—currently existing—to be effective in psychotic, as well as in affective disorders.