Cognitive Impairment in Schizophrenia Is the Core of the Disorder

“in a Neurodevelopmental Schizophrenia Model”

“GABAAR as a therapeutic target for schizophrenia Given that cognitive deficits are considered to be core features of schizophrenia (Elvevag and Goldberg, 2000), and given the strong evidence implicating disturbances in GABA signaling as contributing to these deficits, it is not surprising that the…”

“Schizophrenia patients demonstrate impairments on a variety of working memory tests (Elvevåg and Goldberg, 2000).”

“For example, cognitive deficits are increasingly seen as part of the core pathology of schizophrenia (Elvevag and Goldberg 2000).”

“Cognitive dysfunctions, including impaired attention, decreased working memory and decreased long term memory retention, are described as core symptoms of schizophrenia [45].”

“Exploratory plots of the AUC(Pr) vs load response in each of these regions considered separately (Figure 5) confirmed that (1) schizophrenic patients generally performed poorly and had a reduced positive or negative load response compared with healthy volunteers; (2) the effect of lorazepam markedly reduced the load r…”

“Altered regulation of actin dynamics and cortical dendritic spine deficits in schizophrenia In schizophrenia, deficits in cognitive functions are core and clinically critical features of the illness (Elvevåg and Goldberg, 2000).”

“The KO mice exhibit a comprehensive array of behavioral impairments characteristic of schizophrenia patients (Elvevag and Goldberg, 2000; Goldman-Rakic, 1994), including impairments in latent inhibition, pre-pulse inhibition and social interaction (Miyakawa et al., 2003), as well as a severe…”

“…et al., 2004), particularly as they relate to the cerebellum, are well-defined (reviewed in Bernard andMittal, 2014, 2015), and cognitive dysfunction represents a core deficit of the disease (Elvevag and Goldberg, 2000) making these networks particularly interesting targets of investigation.”

“Schizophrenia is associated with substantial cognitive impairments (Nuechterlein and Dawson 1984; Goldberg et al. 1988; Morice 1990; Nelson et al. 1990; Tamlyn et al. 1992; Paulus et al. 1996; Kuperberg and Heckers 2000) that constitute core aspects of the disorder (Elvevag and Goldberg 2000).”

“Impaired cognitive function is a key characteristic of schizophrenia (see Sullivan, et al., 1994; Elvevag and Goldberg, 2000; Kuperberg and Heckers, 2000 for reviews) and is becoming increasingly important as impaired cognition has been implicated in social and vocational outcome (Marder and…”

“…functions have been shown to be selectively impaired in schizophrenia patients (Silver, Feldman, Bilker, & Gur, 2003; Weickert et al., 2000), and have been proposed as the ‘core’ neuropsychological deficit in schizophrenia (Elvevag & Goldberg, 2000; Goldman-Rakic, 1994; Palmer & Heaton, 2000).”

“…featuring both positive and negative symptoms (Andreasen and Olsen, 1982), in addition to cognitive dysfunction (eg., Barch and Smith, 2008; Elvevag and Goldberg, 2000; Heinrichs and Zakzanis, 1998; Ranganath et al., 2008) and motor abnormalities (eg., Bernard and Mittal, 2014; Bernard et…”

“working memory is one of the prominent features of schizophrenia symptomatology (39-41).”

“Cognitive impairments, such as deficits in working memory, are among the most disabling and difficult to treat features of schizophrenia (1;2) and appear to be linked to impairments in the circuitry of the prefrontal cortex (PFC) (3).”

“62 pISSN 1738-1088 / eISSN 2093-4327 Clinical Psychopharmacology and Neuroscience 2015;13(1):62-67 Copyrightc 2015, Korean College of Neuropsychopharmacology”

“A core and disabling feature of schizophrenia involves disturbances in cognitive functioning, including impairments in attention, memory, and executive functions, such as the ability to plan, initiate, and regulate goal-directed behavior (Elvevag and Goldberg 2000).”

“Schizophrenia is characterised by positive symptoms (e.g. hallucinations and delusions), negative symptoms (e.g. avolition and anhedonia) and cognitive symptoms (e.g. impaired working memory, sen- sorimotor gating and attentional set-shifting) (Andreasen 1995; Elvevag and Goldberg 2000).”

“It is proposed that they may in fact be considered to be the “endophenotype” for schizophrenia.(8,20) An endophenotype is an intermediate expression of the genetic predisposition for a disease that”

“DISC1 is expressed in limbic regions of the brain including the hippocampus [4,5,30], a region of the brain involved in learning and memory processes, which are known to be impaired in schizophrenia and bipolar disorder [2,11, 19 ,20,25].”

“Adults with schizophrenia tend to perform more poorly on one or several measures of working memory, verbal memory, executive functioning, language and verbal fluency, oculomotor scanning, psychomotor speed, and general intelligence ( Elvevag & Goldberg, 2000 ; Goldberg et al, 1998 ).”

“Neuropsychological deficits are considered to be core symptoms of schizophrenia (SZ) (Elvevag and Goldberg, 2000; Gold, 2004; Green et al., 2004; Lencz et al., 2006).”

“The majority of chronic individuals, to a variable degree, also experienced a range of cognitive impairments, such as deficits in attention, problem solving, learning, and memory (Elvevag and Goldberg, 2000).”

“This test reflects the function of the orbitofrontal cortex (Fellows and Farah, 2005; Nakamura et al., 2008).”

“Cerebral Cortex July 2009;19:1678--1686 doi:10.1093/cercor/bhn204 Advance Access publication November 21, 2008 Pyramidal Neurons in Rat Prefrontal Cortex Projecting to Ventral Tegmental Area and Dorsal Raphe Nucleus Express 5-HT2A Receptors Pablo Vázquez-Borsetti1, Roser Cortés1,2 and Francesc Artigas1,3 1Department…”

“Given that cogni- tive deficits are one of the core clinical features of schizophrenia (Bora & Pantelis, 2015; Elvevåg & Goldberg, 2000), and cognition is thought to emerge from the dynamic interactions among distributed brain regions (Bressler & Menon, 2010; Cabral et al., 2017;…”

“…schizophrenia, bipolar disorder, neurocognition, sex, moderator Neurocognitive dysfunction is present in both schizophrenia and bipolar disorder and is considered central to the disorders (Bearden, Hoffman, & Cannon, 2001; Elvevåg & Goldberg, 2000; Seidman et al., 2002; Quraishi & Frangou, 2002).”

“Alterations in these neurons might contribute to DLPFCmediated cognitive impairments in schizophrenia, such as working memory dysfunction, through the following mechanism (Elvevag and Goldberg, 2000; Weinberger et al, 2001; Lewis et al, 2005).”

“LC3 was selected as it is the broadest liability class in which all the patients have a schizophrenia spectrum disorder, and thus virtually all have a history of psychosis, which is known to correlate with poorer cognitive function”

“001 (SB-269970, Figure 1) and F[12,156] = 6.”

“In the current study we focus on working memory dysfunction which is considered a core cognitive deficit in schizophrenia (e.g. Park and Holzman, 1992; Goldman-Rakic, 1999; Elvevag and Goldberg, 2000).”

“Cognitive deficits are a core feature of schizophrenia (Elvevag & Goldberg, 2000; MacCabe, 2008; Kahn & Keefe, 2013).”

“Moreover, very little is known about the effects of reelin haploinsufficiency on prefrontal-dependent cognitive control, the disruption of which is one of the hallmark features of schizophrenia (Elvevag and Goldberg 2000; Volk and Lewis 2002).”

“Indeed, cognitive impairments can reach two standard deviations below the normal mean [10].”

“It is well recognized that subjects with schizophrenia exhibit a large spectrum of neuropsychological impairments (Elvevag and Goldberg 2000).”

“Moreover, cognitive deficits, which are central to the illness (Elvevag and Goldberg 2000), are poorly treated, and there is an urgent need for improved treatments.”

“Working memory and attention have been consistently shown to be impaired in schizophrenia (47, 48) and in healthy volunteers administered ketamine (43).”

“Cognitive impairments are considered to be the core feature of the illness and develop upon genetic predisposition and/or environmental challenges (132).”

“N IH -PA Author M anuscript N IH -PA Author M anuscript deficits that are core features of the disorder (Elvevag and Goldberg, 2000).”

“Introduction The cognitive deficits associated with schizophrenia are stable and enduring; they adversely affect everyday functioning and predict functional outcome (Heinrichs and Zakzanis, 1998; Elvevag and Goldberg, 2000; Green et al., 2000; Heaton et al., 2001; Reichenberg and Harvey, 2007).”

“The cognitive impairments of schizophrenia are numerous and disabling (Elvevag and Goldberg, 2000; Green et al., 2004; Heaton et al., 2001; Twamley et al., 2002).”

“Impairments in executive function have long been considered a core feature of schizophrenia [17, 43, 54] as highlighted by the MATRICS initiative [44].”

“A social adjustment composite score was derived from 2 measures: (1) clinician ratings (major role adjustment inventory) of employment, relationships, role performance, and overall functioning and ( 2 ) Social Security employability criteria (includes daily living activities, social functioning, and work readiness) d…”

“Cognitive impairment, including attention disorders, deficits in working memory and executive functions, is a central feature of schizophrenia lacking adequate treatment (Braff, 1993; Elvevag & Goldberg, 2000 ; Green et al. 2000).”

“…deficit with attention and memory being particularly impaired; a pattern consistent with what might be expected from other studies of older individuals with affective and/or psychotic disorders (Castaneda et al., 2008; Elvevag & Goldberg, 2000; Taylor Tavares, Drevets, & Sahakian, 2003).”

“…information-processing deficits, and enhanced responsiveness to psychostimulants (Paylor et al., 2001; Stark et al., 2008; Earls et al., 2011; Kimoto et al., 2012), which are recognized as major deficits of schizophrenia (Elvevag and Goldberg, 2000; Green et al., 2000; Swerdlow et al., 2001).”

“…1998: Riutort, Cuervo, Danion, Peretti, & Salamie, 2003) but have not established whether this is a specific deficit, is attributable to comorbid depression, or is part of the general long-term memory impairment seen in people with schizophrenia (Elvevag & Goldberg, 2000; McKay et al., 1996).”

“The mental disorder, schizophrenia, is characterized by severe cognitive impairment, as well as positive and negative symptoms such as hallucination, delusion, thought disorders, apathy, and social withdrawal [108, 109].”

“The purpose of this study was to verify: (1) whether or not schizophrenia patients had gender differences in cognitive deficits for reasoning and problem solving, and social cognition; (2) if the gender differences identified in our previous study9 using RBANS can be confirm using MCCB; and (3) whether the gender diff…”

“…treatment on neuropsychological functioning include improved attention (Bilder et al., 2002) and reduced motor and psychomotor processing (for review, see Elvevag and Goldberg, 2000), possibly because neuroleptic exposure directly affects striatal functioning (e.g., Buchsbaum et al., 1992).”

“Cognitive impairment has been regarded as a hallmark feature of schizophrenia (Elvevåg and Goldberg, 2000) and 22q11DS (Eliez et al., 2000; Swillen et al., 2000; Bearden et al., 2001).”

“Patients with schizophrenia present with a wide range of cognitive deficits, especially in the domain of memory (for reviews, see [5–7]).”

“…importance of cognitive symptoms has been emphasized in schizophrenia because the symptoms are severe, particularly enduring, and strongly correlated with long-term patient outcomes (Elvevag and Goldberg, 2000; Floresco et al., 2005; Keefe and Fenton, 2007; Lewis and Gonzalez-Burgos, 2006, 2008).”

“…memory in schizophrenia was among the first cognitive functions to be studied in detail, probably because the pathogenesis of the disorder and working memory appear to share a common cortical substrate (the prefrontal lobes) at least macroscopically (Deiber et al. 2007; Elvevag and Goldberg 2000).”

“The precentral gyrus may contribute to the processing of multiple motor-related cognitive functioning, which has been found to be abnormal in schizophrenia [42,43].”

“Cognitive impairment is the core symptom in schizophrenia [1], and is often more damaging to the function outcome of patients with schizophrenia [2].”

“These impairments are thought to be the core features of the illness (Elvevåg and Goldberg, 2000) for the following reasons.”

“In addition to recent demonstrations of neurocognitive mpairments in schizophrenia, involving both behavioural [1] nd brain mapping data [2], studies of brain morphology ave consistently shown grey matter (GM) abnormalities in chizophrenia [3–11], in individuals at high risk for developing chizophrenia [12,13] and in…”

“Other cognitive domains proposed as the ‘‘core’’ deficit in schizophrenia are attention (Barr, 2001; Elvevag and Goldberg, 2000; Hilti et al., 2010), episodic memory (Aleman et al.”

“Since cognitive deficits form a core feature of that disorder [75,77–79], the isoform-specific dysbindin-1 reductions we have found in schizophrenia may contribute to the clinical expression of schizophrenia.”

“Deficits in these cognitive rocesses are found in psychiatric disorders such as depression nd schizophrenia [4–8].”

“Over recent decades, various studies have reached the conclusion that alterations in neuropsychological functioning are a basic characteristic of schizophrenia and not a consequence of other symptoms, medication side-effects or other aspects of the course of the illness (Kremen et al., 2000; Elvevag and Goldberg, 2000…”

“Schizophrenia is also characterized by disturbances in information processing, working memory and executive functions (Elvevag and Goldberg, 2000; GoldmanRakic, 1994).”

“Working memory is frequently impaired in patients with schizophrenia (often prior to or at the onset of the illness), as well as in a portion of their nonschizophrenic, first-degree relatives [49,50].”

“Cognitive deficits may represent a core pathophysiological feature of schizophrenia because these deficits are clearly present at the first episode of illness (Elvevag and Goldberg, 2000).”

“A critical role of prefrontal cortex (PFC) in schizophrenia has also been suggested by a number of neuropsychological studies demonstrating deficits in cognitive domains such as executive functions and working memory (for a review see Elvevag and Goldberg, 2000).”

“Cognitive impairment is a core feature of schizophrenia (Elvevag & Goldberg, 2000).”

“The delayed alternation tasks such as DNMTS T-maze have been widely used to assess working memory function in rats and mice, and impaired working memory is considered a core cognitive deficit in schizophrenia (Elvevag & Goldberg 2000).”

“Compatible with recent evidence, our results revealed that most patients demonstrated at least mild cognitive impairment and multiple cognitive domains were affected (Heinrichs and Zakzanis, 1998; Elvevag and Goldberg, 2000; O'Carroll, 2000).”

“Particularly impairment in working memory, which involves the short-term storage and manipulation of information, has been proposed as a core deficit in schizophrenia 178 .”