Core Symptoms Of Schizophrenia Research Articles

Oral administration of a specific kynurenic acid synthesis (KAT II) inhibitor attenuates evoked glutamate release in rat prefrontal cortex

Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy. We determined, in adult Wistar rats, if the orally available KAT II inhibitor BFF816 a) prevents KYNA elevations in prefrontal cortex (PFC) after a systemic kynurenine injection and b) reverses the kynurenine-induced attenuation of evoked prefrontal glutamate release caused by stimulation of the nucleus accumbens shell (NAcSh). Systemic injection of kynurenine (25 or 100 mg/kg, i.p.) increased KYNA levels in PFC (532% and 1104% of baseline, respectively). NMDA infusions (0.15 μg/0.5 μL) into NAcSh raised prefrontal glutamate levels more than 30-fold above baseline. The two doses of kynurenine reduced evoked glutamate release in PFC (by 43% and 94%, respectively, compared to NMDA alone). Co-administration of BFF816 (30 or 100 mg/kg, p.o.) with kynurenine (25 mg/kg, i.p.) attenuated the neosynthesis of KYNA and dose-dependently restored NMDA-stimulated glutamate release in the PFC (16% and 69%, respectively). The ability to prevent KYNA neosynthesis and to normalize evoked glutamate release in PFC justifies further development of KAT II inhibitors for the treatment of cognitive deficits in SZ.

17. Effects of Cariprazine on Negative Symptoms, Cognitive Impairment, and Prosocial Functioning in Patients With Predominant Negative Symptoms: Post Hoc Analysis of a Phase III, Placebo-, and Active-Controlled Study

Abstract Background: Negative symptoms and cognitive deficits are core symptoms of schizophrenia that have proven to be difficult to treat and are associated with poor social/vocational functioning. Cariprazine (CAR), a D3/D2 receptor partial agonist, is approved in the United States for the treatment of schizophrenia in adults. This post hoc analysis of a Phase 3, randomized, double-blind, placebo- and active-controlled CAR study in adults with acute exacerbation of schizophrenia evaluated the effects of CAR on positive, negative, cognitive, and prosocial functioning domains in a subset of patients with predominant negative symptoms (PNS). Methods: Randomized patients received 6 weeks of double-blind treatment with CAR 3 mg/d, CAR 6 mg/d, aripiprazole 10 mg/d (ARI), or placebo (PBO). For post hoc analyses, patients with PNS were identified using baseline Positive and Negative Syndrome Scale factor scores (PANSS-FS) for positive symptoms (score ≤19; mild to moderate), negative symptoms (score ≥24; moderate to severe), and cognitive impairment (score ≥27; severe). Efficacy parameters included change from baseline to Week 6 in PANSS total score and PANSS-FS for negative, cognitive, and prosocial domains. Results: In all, 131 of 604 randomized patients met criteria for PNS (placebo = 35; CAR 3 mg/d = 27; CAR 6 mg/d = 34; ARI = 35). For CAR 6 mg/d, least squares mean differences (LSMDs) of change from baseline to Week 6 versus placebo were statistically significant on the PANSS total score (-13.9, P = .0132), and negative (-3.3, P = .0112), cognitive (-1.6, P = .0092), and prosocial (-2.9, P = .0035) factor scores. For CAR 3 mg/d, LSMDs versus placebo at Week 6 were statistically significant on the PANSS total score (-14.0; P = .0156), and cognitive (-1.5, P = .0164) and prosocial (-2.5, P = .0187) factor scores. For the negative symptoms factor score, numerical improvement was seen for CAR 3 mg/d over placebo, but the LSMD was not statistically significant at Week 6 (-2.6, P = .0515). In contrast, LSMDs for aripiprazole versus placebo were not statistically significant on PANSS total score (-9.6, P = .0800), negative (-0.6, P = .6449), cognitive (-0.6, P = .3108), or prosocial factor scores (-1.1, P = .2482). In addition, on PANSS-FS for negative symptoms, the LSMD between CAR 6 mg/d and ARI met statistical significance (-2.8, P = .0315). Conclusion: Cariprazine significantly improved overall schizophrenia symptoms, as well as negative, cognitive, and prosocial function versus placebo, in a subset of patients with PNS. These results suggest that cariprazine may be an effective treatment option for the negative symptoms of schizophrenia and its associated domains. Limitations of this analysis include the short duration (6 weeks) for evaluation of negative symptom improvement and the potential that improvements in at least some of the negative symptoms may have been secondary to improvements in positive symptoms.

The Glutamate Model of Schizophrenia: It's All About Signal Muscarinic Connections.

Sensorimotor gating is an endophenotype of schizophrenia that is used extensively in animal models of the disease. Memory impairments are also associated with core symptoms of schizophrenia, but defining their exact relation to explicit or implicit deficits has been more elusive ([Vakalopoulos, 2011

The brief negative symptom scale: validation of the German translation and convergent validity with self-rated anhedonia and observer-rated apathy

BackgroundNegative symptoms are considered core symptoms of schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to measure this symptomatic dimension according to a current consensus definition. The present study examined the psychometric properties of the German version of the BNSS. To expand former findings on convergent validity, we employed the Temporal Experience Pleasure Scale (TEPS), a hedonic self-report that distinguishes between consummatory and anticipatory pleasure. Additionally, we addressed convergent validity with observer-rated assessment of apathy with the Apathy Evaluation Scale (AES), which was completed by the patient’s primary nurse.MethodsData were collected from 75 in- and outpatients from the Psychiatric Hospital, University Zurich diagnosed with either schizophrenia or schizoaffective disorder. We assessed convergent and discriminant validity, internal consistency and inter-rater reliability.ResultsWe largely replicated the findings of the original version showing good psychometric properties of the BNSS. In addition, the primary nurses evaluation correlated moderately with interview-based clinician rating. BNSS anhedonia items showed good convergent validity with the TEPS.ConclusionsOverall, the German BNSS shows good psychometric properties comparable to the original English version. Convergent validity extends beyond interview-based assessments of negative symptoms to self-rated anhedonia and observer-rated apathy.

Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation.

Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects.

GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments.

Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia.

Background:Dysfunction of dopaminergic, GABAergic, and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP), and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterize alterations in hippocampal neurotransmitter-related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model.Methods:Fifty-four male Lister-hooded rat pups either received phencyclidine (PCP, 10mg/kg, s.c.) on post-natal days (PND) 7, 9, and 11 before being weaned on PND 23 into separate cages (isolation; PCP-SI; n = 31) or received vehicle injection and group-housing (2–4 per cage; V-GH; n = 23) from weaning. The effect of lamotrigine on locomotor activity, novel object recognition, and prepulse inhibition of acoustic startle was examined (PND 60–75) and drug-free hippocampal gene expression on PND 70.Results:Acute lamotrigine (10–15mg/kg i.p.) reversed the hyperactivity and novel object recognition impairment induced by PCP-SI but had no effect on the prepulse inhibition deficit. Microarray revealed small but significant down-regulation of hippocampal genes involved in glutamate metabolism, dopamine neurotransmission, and GABA receptor signaling and in specific schizophrenia-linked genes, including parvalbumin (PVALB) and GAD67, in PCP-SI rats, which resemble changes reported in schizophrenia.Conclusions:Findings indicate that alterations in dopamine neurotransmission, glutamate metabolism, and GABA signaling may contribute to some of the behavioral deficits observed following PCP-SI, and that lamotrigine may have some utility as an adjunctive therapy to improve certain cognitive deficits symptoms in schizophrenia.

Special Supplement Introduction: The Fourth Kraepelin Symposium-Cognitive Dysfunction in Schizophrenia: Origins and Innovative Treatment.

This Special Supplement presents reports from working groups meeting at the Fourth Kraepelin Symposium in Munich, Germany, in September 2014. It covers the origins and therapy of cognitive dysfunction in schizophrenia. Cognitive deficits are core symptoms of schizophrenia being decisive for the long-term prognosis only improved moderately by antipsychotic treatment, however, showing more evidence for cognitive remediation. The authors refer to neurobiological and psychological underpinnings of cognitive deficits and to innovative treatment interventions aimed at improving cognitive dysfunction in order to improve outcome and to support coping with the illness. Therapeutic approaches include aerobic exercise, cognitive training, psychoeducation, cognitive therapy, noninvasive brain stimulation and pharmacotherapy in acute to post-acute patients. The supplement also presents novel diagnostic tools for early recognition, such as biomarkers, as well as cognitive training to prevent worsening of symptoms in individuals at clinical high risk for psychosis. In recent years there has been progress in basic science and outcomes research as well as psychopharmacological and psychological treatment options. Despite of this, treatment of cognitive deficits needs significant improvement and further research is needed.

Effect of antidepressants on spatial memory deficit induced by dizocilpine.

Cognitive deficits are a core symptom of schizophrenia. It is controversial whether antidepressants could improve cognitive symptoms in schizophrenia patients. The present study was designed to identify the therapeutic effect of antidepressants on cognitive deficits in schizophrenia. In the present study, adolescent rats were repeatedly exposed to dizocilpine, which can induce cognitive deficits associated with schizophrenia. Then these rats were treated by six antidepressants (fluvoxamine, sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine) or vehicle. The rats in the control group were exposed to vehicle during the study. Lastly, all rats' spatial memory (a major part of cognition) was assessed using the Morris water maze (MWM) test, and the density of hippocampal parvalbumin (PV) interneurons was evaluated to explore possible mechanisms underlying spatial memory change in schizophrenia. The results of the present study supported the hypothesis of a therapeutic effect of fluvoxamine and escitalopram on spatial memory deficit induced by dizocilpine. Additionally, the data of the present study suggested that fluvoxamine and escitalopram remitted hippocampal PV interneuron reduction induced by dizocilpine. The neuroprotective effect of fluvoxamine and escitalopram may partly explain the therapeutic effect of antidepressants on spatial memory deficit in schizophrenia patients.

Beyond Psychopharmacology: Emerging Psychosocial Interventions for Core Symptoms of Schizophrenia

Psychiatrists who work with patients with severe mental illness often are more focused on diagnosis, medical management, and psychopharmacology than on psychosocial treatments. Furthermore, many psychosocial interventions that show great promise may not be available locally, making it harder for psychiatrists to recognize emerging trends. Finally, there has not been an update in the American Psychiatric Association's Practice Guideline for the Treatment of Schizophrenia for many years, and the most recent Patient Outcomes Research Team (PORT) review of evidence-based psychosocial treatments for schizophrenia was published eight years ago. This article reviews a selection of psychosocial interventions that have shown success in treating some of the more vexing and persistent core schizophrenia symptoms that often continue despite optimal pharmacologic treatment; formerly these had been considered too risky or out of reach for psychosocial intervention. The interventions reviewed include cognitive-behavioral therapy for psychosis (CBTp), which aims to reduce distress and disability from psychotic symptoms; CBT and other behavioral interventions focused for comorbid posttraumatic stress syndrome; cognitive training (remediation) interventions that use computerized training programs to reduce the severity and consequence of cognitive impairment associated with schizophrenia; clubhouse and peer support models that address the social alienation and social defeat endemic to persons with severe mental illness; and supported employment interventions that are effective in helping patients get back to work in a competitive job environment. The interventions are reviewed with the needs of the prescribing mental health clinician in mind. Each intervention's strengths and weaknesses are described, as well as their role in recovery-oriented treatment services.

A Review of Anticipatory Pleasure in Schizophrenia.

Anhedonia, traditionally defined as a diminished capacity to experience pleasure, has long been considered a core symptom of schizophrenia. However, recent research calls into question whether individuals with schizophrenia are truly anhedonic, suggesting intact subjective and neurophysiological response to rewarding stimuli in-the-moment. Despite a presumably intact capacity to experience pleasure, people with schizophrenia still engage in fewer reward-seeking behaviors. This discrepancy has been explained as a dissociation between "liking" and "wanting", with dopaminergic and prefrontal influences on incentive salience leading hedonic responses to not effectively translate into motivated behavior. In the current review, the literature on a key aspect of the wanting deficit is reviewed, anticipatory pleasure. Results provide consistent evidence for impairment in some aspects of anticipatory pleasure (e.g., prospection, associative learning between reward predictive cues and outcomes), and inconsistent evidence for others (e.g., anticipatory affect and affective forecasting). Mechanisms underlying anticipatory pleasure abnormalities in schizophrenia are discussed and a new model of anticipatory pleasure deficits is proposed. Findings suggest that anticipatory pleasure may be a critical component of impairments in wanting that impact motivated behavior in schizophrenia.

Self-continuity across time in schizophrenia: An exploration of phenomenological and narrative continuity in the past and future

BackgroundDisorders of the self, such as a reduced sense of personal continuity in time, are a core symptom of schizophrenia, but one that is still poorly understood. In the present study, we investigated two complementary aspects of self-continuity, namely phenomenological and narrative continuity, in 27 patients with schizophrenia, and compared them with 27 control participants. MethodsParticipants were asked to identify important past events and to narrate a story from their life that included these events. They were also asked to imagine important events that might happen in their personal future and to build a narrative of their future life. The vividness of these important life events and the proportion of self-event connections in the narratives were used as a measure of phenomenological and narrative continuity, respectively. ResultsOur study showed patients with schizophrenia experienced less vivid representations of personally significant events (p = .02) for both temporal directions (past and future) (p < .001). In addition, their ability to make explicit connections between personal events and self-attributes in life narratives was also impaired (p = .03), but only in the case of past narratives (p < .001). ConclusionsThese results shed new light on the cognitive mechanisms underlying self-disorders in schizophrenia. The clinical and therapeutic implications of these findings are discussed.

Increased superior frontal gyrus activation during working memory processing in psychosis: Significant relation to cumulative antipsychotic medication and to negative symptoms

ObjectivesImpairment in working memory (WM) is a core symptom in schizophrenia. However, little is known about how clinical features influence functional brain activity specific to WM processing during the development of first-episode psychosis (FEP) to schizophrenia (SZ). We compared functional WM-specific brain activity in FEP and SZ patients, including the effects of the duration of illness, psychopathological factors and antipsychotic medication. MethodsCross-sectional study of male FEP (n=22) and SZ (n=20) patients performing an n-back task when undergoing functional magnetic resonance imaging (fMRI). Clinical features were collected by semi-structured interviews and medical records. ResultsThe SZ group performed significantly worse than the FEP group in the 2-back condition. The SZ group also showed significantly higher activation in the left superior frontal gyrus in the 2-back versus 0-back condition (2-back>0-back). This frontal activation correlated positively with negative symptoms and with cumulative antipsychotic medication during the year before the fMRI examination. There were no significant correlations between activation and duration of illness. ConclusionThere was greater frontal neural activation in SZ than in FEP. This indicated differences in WM processing, and was significantly related to cumulative antipsychotic exposure and negative symptoms, but not to the duration of illness.

Phenomenology and neural correlates of formal thought disorder

Speech and language disorders, such as concretism and formal thought disorder (FTD) are core symptoms of Schizophrenia, but do occur to a similar extent in other diagnoses such as bipolar disorder and major depression. We will review clinical rating scales of FTD and introduce a new, validated scale, the TALD. Further, structural and functional brain imaging data will be reviewed and own novel findings presented, relating speech and language dysfunctions to neural networks, within schizophrenia and across the “functional psychoses”. The impact of genetic variance and NNDA receptor blockage on brain function will be addressed with a particular focus on speech and language (dys-) function. We demonstrate, from the genetic to the brain structural and functional level, that particular aspects of the neural language system are disrupted in patients with FTD across traditional diagnoses.Disclosure of interestThe author has not supplied his declaration of competing interest.

Self-continuity across time in schizophrenia: An exploration of phenomenological and narrative continuity in the past and future

Disorders of the self, such as the “loss of continuity” of the self in time, are a core symptom of schizophrenia, but one, which is still poorly understood. In the present study, we investigated two complementary aspects of self-continuity, namely phenomenological and narrative continuity, in 27 patients with schizophrenia, and compared them with 27 control participants. Participants were asked to identify 7 important past events and to narrate a story taken from their life that included these events. They were then asked to imagine 3 important events that might happen in their personal future and to build a narrative of their future life. The memory vividness of these important life-events and the proportion of self-event connections in the narratives were used as a measure of phenomenological and narrative continuity, respectively. Our results showed that the difficulty for patients to construct vivid representations of personally significant events was observed in both temporal directions, past and future. Patients’ ability to establish explicit connections between personal events and attributes of self in life narratives was also impaired, but only in the case of past narratives. Our results yield a fresh understanding of the cognitive mechanisms of self-disorders in schizophrenia. The clinical and therapeutic implications of these findings are discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A Cognitive Neuroscience View of Voice-Processing Abnormalities in Schizophrenia: A Window into Auditory Verbal Hallucinations?

Auditory verbal hallucinations (AVH) are a core symptom of schizophrenia. Like "real" voices, AVH carry a rich amount of linguistic and paralinguistic cues that convey not only speech, but also affect and identity, information. Disturbed processing of voice identity, affective, and speech information has been reported in patients with schizophrenia. More recent evidence has suggested a link between voice-processing abnormalities and specific clinical symptoms of schizophrenia, especially AVH. It is still not well understood, however, to what extent these dimensions are impaired and how abnormalities in these processes might contribute to AVH. In this review, we consider behavioral, neuroimaging, and electrophysiological data to investigate the speech, identity, and affective dimensions of voice processing in schizophrenia, and we discuss how abnormalities in these processes might help to elucidate the mechanisms underlying specific phenomenological features of AVH. Schizophrenia patients exhibit behavioral and neural disturbances in the three dimensions of voice processing. Evidence suggesting a role of dysfunctional voice processing in AVH seems to be stronger for the identity and speech dimensions than for the affective domain.

Decreased interhemispheric resting state functional connection in schizophrenic patients with auditory hallucinations

IntroductionAuditory hallucination (AH) has been always concerned as a main core symptom of schizophrenia. However, the mechanisms of AH are still unclear.ObjectivesThe aim of this study is to further explore the complicated neuroimaging mechanism of AHs from a new insight by using voxel-mirrored homotopic connectivity (VMHC).MethodsForty-two patients with AH (APG), 26 without AHs (NPG) and 82 normal controls (NC) participated in resting state fMRI scan. Correlation analyses were used to assess the relationships between VMHC and Hoffman scores. Additionally, ROI analysis was used to further know about the functional connectivity between the brain areas with changed interhemispheric FC and the whole brain.ResultsAPG showed reduced VMHC in the parahippocapus, fusiform gyrus, rolandic operculum, insula, heschl's gyrus and superior temporal gyrus (STG). Hoffman score of APG group had negative correlation with VMHC in these regions. Besides, ROI analysis supported decreased interhemispheric FC in schizophrenia with AH and verified functional connectivity abnormalities in schizophrenia.ConclusionsThese findings suggest impairment of interhemispheric coordination and whole brain FC in schizophrenia with AH, which may be implicated to the neuroimaging mechanism of auditory hallucination. Furthermore, this research highly support dysconnectivity hypothesis that schizophrenia related to abnormalities in neuronal connectivity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

From “What” to “How”: The Effort to Fill the Gaps in Understanding Cognitive Processes Underpinning Remission in Schizophrenia

Introduction: The accumulation of robust evidence culminated in the establishment of the cognitive deficits as a core symptom of Schizophrenia (SCZ). To date, there has been reliable evidence that cognitive deficits are associated with poor symptomatic outcomes in SCZ. Nevertheless, they have not been incorporated in definitions of remission and a systematic understanding of how cognition contributes to remission is still lacking. Although the standardized remission in SCZ criteria proposed in 2005 has encouraged studies to understand the role of cognitive function in symptomatic remission from SCZ, most investigations were cross-sectional and have studied samples of chronically ill patients. The purpose of the present study was to bring together the efforts of recent follow-up studies in early in earlier stages of the disease to fill the gap in the literature on understanding how cognitive impairment is related to remission. Methods: A comprehensive search of the PsycINFO and MEDLINE/PUBMED databases was conducted. Results: One study evaluated executive functioning in Early-Onset Schizophrenia (EOS) across stages of illness and suggested that executive impairment is present at the onset of SCZ and persists in attenuated but stable form after the resolution of psychotic symptoms. Studies in first-episode schizophrenia (FES) patients highlighted that despite verbal memory performance is strongly related to clinical remission in FES spectrum, it appears to have not a meaningful contribution to functional recovery. Longitudinal studies in SCZ patients suggested that executive function and higher premorbid Intelligence Quotient (IQ) were the best predictors of remission. Conclusion: Since were emphasized the need to conduct longitudinal follow-up studies to assess the relation of cognitive performance to the proposed remission criteria, some efforts have been made to fill the gaps in understanding cognitive processes underpinning remission in schizophrenia. Notwithstanding the question regarding how aspects of symptomatic remission affect, and are affected by, aspects of cognitive function, remain not yet clarified, these long-term prospective studies addressing different domains of neurocognition in schizophrenia patients undergoing remission, mainly in early stages of illness, are being very enlightening to guide and encourage new researches.

Brexpiprazole: so far so good.

This article describes the role of a newly approved antipsychotic agent brexpiprazole in the treatment of schizophrenia and major depressive disorder. This drug has high affinity for 5-HT1A, 5-HT2A, D2 and α1B,2C receptors. It displays partial agonism at 5-HT1A and D2 receptors and potent antagonism at 5-HT2A and α1B,2C adrenergic receptors. It also has some affinity (antagonism) for D3, 5-HT2B, 5-HT7 and α1A,1D receptors, and moderate affinity for H1 and low affinity for M1 receptors. These all lead to a favorable antipsychotic profile in terms of improvement of cognitive performance and sleep patterns, as well as effects on affective states and potential to treat core symptoms in schizophrenia and major depressive disorder, including cognitive deficits with a low risk of adverse effects (extrapyramidal symptoms, metabolic complications, weight gain, akathisia potential) that are commonly encountered with other typical and second-generation antipsychotic drugs. In our review, we have made an attempt to decipher the pharmacological profile of brexpiprazole from two major trials (VECTOR and BEACON). We have also tried to give a concise but detailed overview of brexpiprazole by head to head comparison of the pharmacological profile of brexpiprazole and its earlier congeners aripiprazole and prototype antipsychotic drug chlorpromazine by accessing individual summaries of product characteristics from the US Food and Drug Administration database, 2015. Relevant preclinical and clinical studies associated with this drug have been discussed with emphasis on efficacy and safety concerns. From the studies done so far, it can be concluded that brexpiprazole can be an effective monotherapy for schizophrenia and as an adjunct to other antidepressant medications in major depressive disorder.

Early-Onset Schizophrenia: Exploring the Contribution of the Thought Disorder Index to Clinical Assessment

Abstract Background: Differentiating diagnostically between schizophrenia and emotional and personality disorders with psychotic or psychotic-like symptoms is a challenging task. It is especially difficult when working with adolescent patients, because their symptoms tend to manifest at lower levels as compared with adult patients. Thought disorder is a core symptom of schizophrenia, and the Rorschach Inkblot Method is widely used for the assessment of formal thought disorder. Objective: In this study, which is situated within ongoing clinical practice, we investigated whether the Rorschach test is helpful for assessing early-onset schizophrenia due to its ability to detect thought disorder. We also wanted to examine whether the Thought Disorder Index (TDI) is superior to the Comprehensive System (CS) for differentiating between patients with early-onset schizophrenia and non-psychotic patients experiencing auditory and visual hallucinations. An additional aim was to examine whether the TDI correlated with the Positive and Negative Syndrome Scale (PANSS). Methods: Twenty-three subjects between the ages of 12 and 18 years were examined with the use of the Rorschach test, and the protocols were scored according to both the TDI and the CS. All subjects were also assessed with the Positive and Negative Syndrome Scale. The sample included 14 subjects who fulfilled the criteria for schizophrenia and 9 subjects who were experiencing hallucinations that emanated from severe emotional and relational problems but who had different non-psychotic disorders. Results: Although the two groups could not be distinguished with regard to their total scores for thought disorder, the identification of specific thought disorder types proved useful for differential diagnosis. Verbalizations that were categorized by the TDI as “absurd responses,” “fluidity,” “contamination,” “autistic logic,” and “word-finding difficulty” were only given by patients who had been diagnosed with schizophrenia. When patients’ responses were scored with the use of the CS, the “contamination” score was the only one found to be specific to schizophrenia. Conclusions: Although the sample size limits the conclusions that can be drawn, the results indicate that the TDI may be superior to the CS for the identification of thought disorder specific to—but not always present in—adolescents with schizophrenia. In other words, the absence of severe thought disorder is not synonymous with the absence of severe psychopathology, but the presence of the most severe thought disorder types (i.e., “absurd responses,” “fluidity,” “incoherence,” “contamination,” and “autistic logic”) seems to be a strong indicator of schizophrenic psychopathology.