Keith H Nuechterlein

University of California, Los Angeles | UCLA · Department of Psychiatry and Biobehavioural Sciences

This longitudinal study evaluated the cortical thickness, gray-to-white matter contrast (GWC), and frontal lobe intracortical myelin (ICM) volume in first-episode schizophrenia (FES) patients treated with oral antipsychotics (OAP) versus a long-acting injectable antipsychotic, paliperidone palmitate (PP). 2D proton density and inversion recovery im...

Objective Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for co...

We report primary results of the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial designed to compare the effectiveness of paliperidone palmitate (PP) versus oral antipsychotics (OAP) in delaying time to first treatment failure (TtFTF) in participants with recent-onset schizophrenia or schizo...

Individuals with schizophrenia demonstrate impaired implicit learning on cognitively complex tasks and preserved implicit motor learning. However, little is known about how implicit learning may be related to other linguistic and cognitive variables, including development of complex language including comprehension and syntax. This study explored t...

Schizophrenia is a psychiatric disorder characterized by a disruption in reality testing most often manifest in the form of delusions and hallucinations. Because determining the reality-basis of prior experiences is dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality test...

Objective: Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The...

Schizophrenia (SCZ) is a chronic cognitive and behavioral disorder associated with abnormal cortical activity during information processing. Several brain structures associated with the seven performance domains evaluated using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB)...

Background Patients with schizophrenia spectrum disorders have been increasingly recognised to form cognitive subgroups with differential levels of impairment. Using cluster analytical techniques, this study sought to identify cognitive clusters in a sample of first-episode psychosis (FEP) patients and examine clinical and developmental differences...

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second‐generation antipsychotics usually preferred to first‐generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is eviden...

Visual processing abnormalities in schizophrenia (SZ) are poorly understood, yet predict functional outcomes in the disorder. Bipolar disorder (BD) may involve similar visual processing deficits. Converging evidence suggests that visual processing may be relatively normal at early stages of visual processing such as early visual cortex (EVC) but th...

Background Latency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertak...

Background: Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder. Methods: We completed a 12-month randomized controlled trial of cognitive remediation...

Background Early-stage visual processing deficits are evident in chronic schizophrenia. Consistent with a cascade model of information processing, whereby early perceptual processes have downstream effects on higher-order cognition, impaired visual processing is associated with deficits in social cognition in this clinical population. However, the...

Background Schizophrenia is a psychiatric disorder characterized by a deficit in reality testing, most often manifest in the form of delusions and hallucinations. Because differentiating real from imagined experiences is critically dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impai...

Background Increasing evidence supports the benefits of regular aerobic exercise for cognition and functioning in schizophrenia. The extent to which these gains are dependent on the amount of aerobic exercise completed remains unclear, although variability in adherence to intended exercise regiments is evident. Furthermore, strategies for encouragi...

Background Groups with differential levels of cognitive impairment are increasingly recognized among patients with schizophrenia spectrum disorders. Using cluster analytical techniques, this study sought to explore cognitive clusters in a sample of first-episode psychosis patients and compare levels of symptomatology as well as childhood and adoles...

Recently emerging evidence indicates accelerated age-related changes in the structure and function of the brain in schizophrenia, raising a question about its potential consequences on cognitive function. Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patient...

This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortica...

Aim The peak onset of psychotic disorders occurs during adolescence and early adulthood, yet treatments for youth at clinical high risk (CHR) for psychosis are generally designed for adults. CHR youth, despite poor academic and social engagement, spend hours each day playing complicated videogames. The aim of this study was to test the feasibility...

Background Poor insight (unawareness) about having a mental disorder is considered to be a core feature of the disorder. Further, poor insight has been associated with another core feature of schizophrenia, neurocognitive deficits. However, previous meta-analyses have shown that poor insight is more strongly related to positive symptoms and social...

Aim Individual Placement and Support (IPS) improves vocational outcomes in first‐episode psychosis patients, but policy makers need information on costs (and personnel time required) to conduct effective IPS. Methods Using chart records of 42 clients in a first‐episode psychosis study, we examined service time for specific activities over 18 month...

We aimed to validate the Czech version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB is a test battery designed to assess cognitive treatment effects in clinical trials of patients with schizophrenia. The valid, reliable and replicable measurement of cognition in schizophrenia is of substantial importance for such clinical trial studi...

Introduction: Elevated levels of pro-inflammatory cytokines have been reported in meta-analyses of multi-episode schizophrenia patients when compared to controls. However, little is known about whether these same relationships are present in the early course of schizophrenia. Objective: To assess first episode schizophrenia patients for depressi...

Schizophrenia (SZ) is associated with impaired adaptive functioning, including difficulties managing the demands of independent living, work, school, and interpersonal relationships. Prior studies have linked the physiological stress response with less effective coping in daily life. Differences in stress-response tendencies may also support hetero...

Importance The Consortium on the Genetics of Schizophrenia (COGS) uses quantitative neurophysiological and neurocognitive endophenotypes with demonstrated deficits in schizophrenia as a platform from which to explore the underlying neural circuitry and genetic architecture. Many of these endophenotypes are associated with poor functional outcome in...

Despite effective pharmacological treatments for psychotic symptoms (eg, hallucinations, delusions), functional outcomes for people with psychotic disorders are often disappointing. Although it is not included in the diagnostic criteria for psychotic disorders, cognitive impairment is one of the strongest determinants of community functioning in th...

Background The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormali...

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRI...

Aim: Computer-based virtual reality assessments of functional capacity have shown promise as a reliable and valid way to assess individuals with multi-episode schizophrenia. However, there has been little research utilizing this innovative approach with young patients who are in the early phase of schizophrenia. Methods: Outpatients in the early...

Objective: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. Meth...

Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related t...

Background Strong empirical evidence has indicated that the severity of cognitive deficits predicts functional outcome in the early course of schizophrenia, while equally strong evidence has shown that supported employment and supported education can substantially increase the proportion of first-episode psychosis patients who return to school or w...

Background Leptin is derived in adipose tissue and circulates in the body to play a key role in metabolism and energy regulation. In non-psychiatric populations, there is evidence that leptin levels are associated with neurocognitive performance. The production of its circulating soluble binding receptor increases during exercise, which has been as...

Background This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling. Methods Individual Placement and Support (IPS) was adapted to meet the goals of in...

Functional magnetic resonance imaging (fMRI) adaptation (also known as fMRI repetition suppression) has been widely used to characterize stimulus selectivity in vivo, a fundamental feature of neuronal processing in the brain. We investigated whether SZ patients and BD patients show aberrant fMRI adaptation for object perception. About 52 SZ patient...

Background: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and...

Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential a...

The goal of this study was to determine if family burden experienced by the families of individuals with a recent-onset of schizophrenia is associated with whether the patient is able to work or attend school during the first year of treatment. Forty-one patients with a recent first episode of schizophrenia and their families enrolled in two NIMH-f...

Recently aerobic exercise training has begun to be systematically examined in randomized controlled trials (RCTs) in schizophrenia. This symposium will report and discuss the results of RCTs that examined the impact of aerobic exercise on physical health, cognition, and everyday functioning across first-episode and established illness phases of sch...

Background Research using virtual reality assessment of functional capacity has shown promise as a reliable and valid way to assess treatment response in patients with established schizophrenia. There has been little work on virtual reality based assessments of functional capacity for patients in the early phase of schizophrenia. We examined whethe...

Background The search for treatments to remediate cognitive deficits and their functional outcome consequences remains a critical frontier in schizophrenia. Cognitive training and aerobic exercise both show promising moderate impact on cognition and everyday functioning. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor...

MRtrix3 Fiber Density Results in MNI space.

FSL FA Results in MNI space.

MRtrix3 FA Results in MNI space.

Reduced fractional anisotropy (FA) is a well-established correlate of schizophrenia, but it remains unclear whether these tensor-based differences are the result of axon damage and/or organizational changes and whether the changes are progressive in the adult course of illness. Diffusion MRI data were collected in 81 schizophrenia patients (54 firs...

Cortical thinning in frontal and temporal regions has been reported in individuals diagnosed with schizophrenia and, less consistently, among their unaffected first-degree relatives. Likewise, first-degree relatives demonstrate attenuated differences in neurocognitive performance relative to healthy controls, indicating that neurocognitive performa...

Objective: Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical sy...

Background: Meta-analyses have reported that the effects of cognitive remediation might go beyond improvement in cognition to include unexpected benefits for schizophrenia patients such as negative symptom reduction and improvements in functioning. In addition, some evidence indicated that these potentially beneficial effects are also present in t...

Background The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls,...

Introduction Deficits in visual perception are well-established in schizophrenia and are linked to abnormal activity in the lateral occipital complex (LOC). Related deficits may exist in bipolar disorder. LOC contains neurons tuned to object features. It is unknown whether neural tuning in LOC or other visual areas is abnormal in patients, contribu...

Although a number of studies examined recollection and familiarity memory in schizophrenia, most of studies have focused on nonsocial episodic memory. Little is known about how schizophrenia patients remember social information in everyday life and whether social episodic memory changes over the course of illness. This study aims to examine episodi...

Background: The Consortium on the Genetics of Schizophrenia (COGS) collected case-control endophenotype and genetic information from 2457 patients and healthy subjects (HS) across 5 test sites over 3.5 years. Analysis of the first "wave" (W1) of 1400 subjects identified prepulse inhibition (PPI) deficits in patients vs. HS. Data from the second CO...

Background Measures of social cognition are increasingly being applied to psychopathology, including studies of schizophrenia and other psychotic disorders. Tests of social cognition present unique challenges for international adaptations. The Mayer–Salovey–Caruso Emotional Intelligence Test, Managing Emotions Branch (MSCEIT-ME) is a commonly-used...

Background: Postmortem and imaging studies provide converging evidence that the frontal lobe myelination trajectory is dysregulated in schizophrenia (SZ) and suggest that early in treatment, antipsychotic medications increase intracortical myelin (ICM). We used magnetic resonance imaging to examine whether the ICM trajectory in SZ is dysregulated...

Background: Working memory (WM) deficits are part of the constellation of cognitive impairments associated with schizophrenia (SZ). Although WM efficiency may be especially important for patients functioning within academic and employment settings, much of the research on WM in SZ neglects the social context of cognitive performance and fails to co...

Background: No prior study of morbid risk in relatives of schizophrenia probands has, to our knowledge, focused solely on those with a recent onset of illness. Given that studies starting with chronic schizophrenia probands may exclude some individuals who have a more benign illness course, the examination of morbid risks among first-degree relativ...

Background: Systematic cognitive training has led to significant gains in cognition in schizophrenia, but methods of enhancing learning during such training could greatly increase its impact. Aerobic exercise stimulates synaptic plasticity and may be an effective way to enhance learning during cognitive training. We hypothesize that combining aerob...

Background: Converging evidence suggests that the degree of intracortical myelination (ICM), which is thought to be responsible for high-frequency synchronization of electrical activity across the cerebral cortex, is dysregulated in schizophrenia (SZ) and that consistent treatment with antipsychotic medications can increase ICM or stabilize loss of...

Background: The presence of altered white matter microstructure in disorders involving psychosis is well established, but the nature and developmental course of these changes are not well understood (Peters & Karlsgodt, 2015). It is not clear whether the presence of attenuated frontal white matter anisotropy at any phase of illness indexes a pathop...

Background: People with schizophrenia show impaired performance on specific tests of visual perception, such as visual masking tasks that assess perception of objects, and these impairments have been linked to functional outcomes. People with bipolar disorder also show deficits on some visual masking tasks to a lesser degree than in schizophrenia....

Irving Gottesman was one of the leading psychopathologists and behavior geneticists of our time, greatly influencing our basic conceptualization of the transmission of schizophrenia and other major mental disorders in ways that impacted research programs around the world. Here we highlight his landmark twin studies of schizophrenia, his introductio...

The current study sought to expand on prior reports of the validity and reliability of the CAINS (CAINS) by examining its performance across diverse non-academic clinical settings as employed by raters not affiliated with the scale's developers and across a longer test-retest follow-up period. The properties of the CAINS were examined within the Ma...

Importance: Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by dete...

Cognitive deficits are pervasive among people with schizophrenia and treatment options are limited. There has been an increased interest in the neurocognitive benefits of exercise, but a comprehensive evaluation of studies to date is lacking. We therefore conducted a meta-analysis of all controlled trials investigating the cognitive outcomes of exe...

Background: Individuals with schizophrenia exhibit marked and disproportional impairment in social cognition, which is associated with their level of community functioning. However, it is unclear whether social cognitive impairment is stable over time, or if impairment worsens as a function of illness chronicity. Moreover, little is known about th...

Cognitive training (CT) and aerobic exercise have separately shown promise for improving cognitive deficits in schizophrenia. Aerobic exercise releases brain-derived neurotrophic factor, which promotes synaptic plasticity and neurogenesis. Thus, aerobic exercise provides a neurotrophic platform for neuroplasticity-based CT. The combination of aerob...

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the firs...

Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks durin...

Aim: This study examined whether expressed emotion (EE) predicts the emergence of depressive symptoms over a 1-year period in 109 individuals with recent-onset schizophrenia. Methods and results: Cox proportional hazards regression analyses indicated that EE did not predict the emergence of depressive symptoms. The results also indicated that th...