High-risk research in schizophrenia: A summary of what has been learned

Erlenmeyer‐Kimling, L.; Cornblatt, Barbara A.

doi:10.1016/0022-3956(87)90087-2

Cited by 111 publications

(56 citation statements)

References 45 publications

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“…Incidence rates of schizophrenia-related or not otherwise specified psychosis in offspring of schizophrenia patients range from 8 to 20%, that is up to twenty times higher than the incidence in the general population (Erlenmeyer-Kimling & Cornblatt, 1987). While conversion rates may be seen as relatively low, other measures point to pervasive deficits in neuropsychological and brain function during childhood and adolescence.…”

Section: Discussionmentioning

confidence: 96%

The neural correlates of performance in adolescents at risk for schizophrenia: Inefficiently increased cortico-striatal responses measured with fMRI

Diwadkar

Pruitt

Zhang

et al. 2012

Journal of Psychiatric Research

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Background fMRI studies indicate that schizophrenia patients and their adult relatives require greater prefrontal activation to maintain performance at levels equal to controls, but studies have not established if this pattern of inefficiency is observed in child and adolescent offspring of schizophrenia patients (SCZ-Off). Methods Using a task with visual working memory demands, we investigated activation in cortico-striatal networks and dorsal prefrontal modulation of regions underlying visual working memory in a group of SCZ-Off (n=19) and controls with no family history of psychosis (n=25 subjects) using an event-related design. Trials were divided based on memory performance (correct vs. incorrect) to specifically identify the neural correlates of correct working memory performance. Results Whereas groups did not differ in terms of behavioral accuracy, SCZ-Off demonstrated significantly increased fMRI-measured activation in dorsal prefrontal cortex and the caudate nucleus during correct, relative to incorrect memory performance. Whereas activation in SCZ-Off was high and independent of performance in each region, in controls the fMRI response was related to behavioral proficiency in the caudate. Further, exploratory analyses indicated that this inefficiency in the dorsal prefrontal cortex response increased with age in SCZ-Off (but in no other regions or group). Finally, these differences were not based in differences in dorsal prefrontal modulation of other regions during successful performance. Discussion These results are consistent with observed patterns in adult patients and first-degree relatives. Inefficient fronto-striatal responses during working memory may characterize the schizophrenia diathesis and may reflect the effects of the illness and vulnerability for the illness.

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Section: Discussionmentioning

confidence: 96%

The neural correlates of performance in adolescents at risk for schizophrenia: Inefficiently increased cortico-striatal responses measured with fMRI

Diwadkar

Pruitt

Zhang

et al. 2012

Journal of Psychiatric Research

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“…SPEMD was first reported in schizophrenia patients in 1908 by Diefendorf and Dodge (Diefendorf & Dodge, 1908); because of its impact on oculomotor research, this paper gave rise to the current centenary special issue. SPEMD has since been viewed as one of the most promising candidate endophenotypes to assist in our search for schizophrenia genes (Erlenmeyer-Kimling & Cornblatt, 1987; Holzman, 1987; Iacono, 1983, 1988, 1998; Iacono & Grove, 1993; Lee & Williams, 2000; Siever & Coursey, 1985; Siever, Coursey, Alterman, Buchsbaum, & Murphy, 1982; Venables, 1991). In addition to SPEMD, several other forms of eye movement dysfunction (EMD) have been implicated as candidate endophenotypes of schizophrenia (e.g., Broerse, Holthausen, van den Bosch, & den Boer, 2001; Calkins & Iacono, 2000; Clementz, 1998; Curtis, Calkins, & Iacono, 2001).…”

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confidence: 99%

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: A meta-analytic evaluation of candidate endophenotypes

Calkins

Iacono

Ones

2008

Brain and Cognition

110

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Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 16 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.

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“…Since its inception, the CPT has been modified many times, but usually the subject responds to identify a single target stimulus (e.g., "0") or a series of target stimuli (e.g., "A" followed by "X") which remains constant throughout a testing session. These CPT procedures have been used to identify and characterize attentional deficits in a variety of subject populations including attention deficit disorder in children and adults (Halperin, Wolf, Greenblatt, & Young, 1991), schizophrenics and persons at-risk for schizophrenia (see reviews by Erlenmeyer-Kimling & Cornblatt, 1987;Nuechterlein & Dawson, 1984), as well as persons with learning disabilities (Dykman, Ackerman, & Oglesby, 1979;Swanson, 1981).…”

mentioning

confidence: 99%

A Comparison Between Adults With Conduct Disorder And Normal Controls on a Continuous Performance Test: Differences in Impulsive Response Characteristics

Dougherty¹,

Bjork²,

Marsh³

et al. 2000

Psychol Rec

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Continuous Performance Test (CPT) responding was compared between 15 adults with a history (childhood/adolescent) of Conduct Disorder (CD) and 15 normal controls. Of particular interest was whether response latencies and commission errors, which have been suggested to be measures of impulsivity, would differ between the groups. The CPT procedure used included two conditions: Immediate Memory Task and Delayed Memory Task (IMT/DMT; Dougherty et aI., 1998). Both the IMT (0.5-s delay) and DMT (3.5-s delay with distracter stimuli at 0.5-s intervals) required the subject to respond if a briefly displayed number was identical to the one presented before it. Stimuli included target (identical match), catch (four of five digits matched), and novel (no match). Participants completed six 22-min testing sessions scheduled across a single day. The most significant findings were that the CD group (compared to the control group) had (a) elevated commission errors (responses to catch stimuli); (b) lower stimulus discriminability (between target and catch stimuli); and (c) shorter response latencies. These results are consistent with the few previous studies indicating that these parameters are related to impulsive behaviors.A number of different approaches have been used to study impulsive responding in the laboratory. One of the most popular methods is the operant model, which defines impulsive responding as a choice for a smaller immediate reinforcer over a larger delayed reinforcer. The advantages of this approach are its rich history from which comparisons can be made and the clearly defined responses that are amenable to statistical and theoretical analyses (see Anslie, 1975, for a review). As a result, the operant conditioning perspective remains a popular model for investigating impulsive choice behavior in both humans and nonhumans

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High-risk research in schizophrenia: A summary of what has been learned

Cited by 111 publications

References 45 publications

The neural correlates of performance in adolescents at risk for schizophrenia: Inefficiently increased cortico-striatal responses measured with fMRI

The neural correlates of performance in adolescents at risk for schizophrenia: Inefficiently increased cortico-striatal responses measured with fMRI

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: A meta-analytic evaluation of candidate endophenotypes

A Comparison Between Adults With Conduct Disorder And Normal Controls on a Continuous Performance Test: Differences in Impulsive Response Characteristics

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