The stability of inhibitory and working memory deficits in children and adolescents who are children of parents with schizophrenia.

Cognitive deficits are a central feature of schizophrenia and occur in first-degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives. This report focuses on 25 children (ages 6-15 years), all with at least one schizophrenic parent. The children were assessed twice, utilizing inhibitory and working memory tasks, with a mean 2.6 years between visits. Stop reaction time (a measure of motor inhibition) and performance on a counting span task (a measure of verbal working memory) were borderline to mildly impaired (compared with a typically developing comparison group) at both visits with similar effect sizes (stopping task time 1, effect size = 0.46, time 2 effect size = 0.50; counting span time 1 effect size = 0.53, time 2 effect size = 0.42). For these 2 tasks, individual age-adjusted scores also correlated across both time points (r = 0.41-0.76) suggesting that individual children maintained deficits across time. As etiologically driven strategies are developed for the cognitive deficits of schizophrenia, expansion of these treatments to relatives who share the cognitive but not the psychotic symptoms may be worth exploring.

High rates of comorbidity are found in childhood-onset schizophrenia.

BACKGROUND: For adults with schizophrenia, comorbidity is common and contributes to impairment. Thus, there has been an increasing effort to identify and treat comorbid symptoms. This report extends that work by examining comorbidity in children and young adolescents with childhood-onset schizophrenia. METHODS: Eighty-two children, ages 4-15 years, with schizophrenia or schizoaffective disorder received structured diagnostic instruments for symptoms and pharmacological treatment history. DSM-IV diagnoses were identified using a non-hierarchical approach. RESULTS: Eighty-one (99%) of the children with schizophrenia or schizoaffective disorder had at least one comorbid psychiatric illness: attention deficit hyperactivity disorder (84%), oppositional defiant disorder (43%), depression (30%), and separation anxiety disorder (25%) were the most common comorbid conditions identified. Pharmacological treatment of the comorbid conditions was uncommon. DISCUSSION: Comorbid syndromes are common in children and young adolescents with schizophrenia or schizoaffective disorder. Pharmacological treatment of the comorbid conditions is rare; however it is unclear if this is due to DSM-IVs hierarchical diagnostic system or to a lack of empirically driven guidelines for appropriate treatment. Additional efforts focused on comorbidity in very-early-onset schizophrenia are warranted.

Neuropsychological deficits in children associated with increased familial risk for schizophrenia.

By studying neuropsychological performance in children genetically at-risk for schizophrenia, greater understanding may be obtained regarding the developmental processes of schizophrenia and associated cognitive weaknesses. A variety of cognitive deficits in genetically at-risk children have been reported. The present study was designed to examine cognitive tasks that have traditionally differentiated children genetically at-risk for schizophrenia (e.g. working memory) from normal children, while also assessing abilities that have received scant attention in this population. Aspects of emotional perception, verbal abilities, inhibition, visuo-spatial skills, and working memory were assessed in children of schizophrenic parents and normal children. Significant differences in performances were identified in at-risk children on measures of verbal skills, working memory and inhibition. Findings suggest that children genetically at-risk for developing schizophrenia exhibit neurocognitive weaknesses generally consistent with those noted in the literature. However, inhibition also appeared to be a cognitive process that significantly differentiated the groups. The possibility of a developmental expression of neurocognitive deficits is discussed.

Creating school-age versions of semistructured interviews for the prodrome to schizophrenia: lessons from case reviews.

There is an increasing emphasis on identifying individuals with schizophrenia earlier and earlier in their disease process, with the assumption that earlier identification translates into earlier treatment, which translates into improved outcome. Unfortunately, one age cohort, children under 13 years of age, have been excluded from this critical alteration in clinical intervention strategy, and its associated improved clinical outcome. One of the barriers to inclusion of younger children is the lack of knowledge about diagnostic issues related to attenuated psychotic symptoms in this age sample. This report focuses on our experience with evaluating attenuated psychotic symptoms in young children, in particular subthreshold hallucinations and delusions, using semistructured interviews. The inclusion of both Caregiver and Child report sections and the addition of concrete, detailed examples of clear-conscience, non-stress-related subthreshold psychotic symptoms are likely to be necessary.

Saccadic eye movement task identifies cognitive deficits in children with schizophrenia, but not in unaffected child relatives.

BACKGROUND: The delayed oculomotor response (DOR) task requires response inhibition followed by movement of gaze towards a known spatial location without a current stimulus. Abnormalities in response inhibition and in the spatial accuracy of the eye movement are found in individuals with schizophrenia and in many of their relatives, supporting the use of these saccadic abnormalities as endophenotypes in genetic studies. It is unknown whether school-age children, either with psychosis or as relatives of a schizophrenic proband, can be included. METHOD: One hundred eighty-seven children, ages 5.8-16.0 years - 45 children with childhood-onset schizophrenia, 64 children with a first-degree relative with schizophrenia, and 84 typically developing children - completed DOR tasks with 1 and 3 second delays. RESULTS: Children with childhood-onset schizophrenia demonstrated impaired response inhibition and impaired spatial accuracy compared to both relatives and typicals; however, relatives and typicals did not differ from each other. CONCLUSIONS: Children with childhood-onset schizophrenia have saccadic abnormalities similar to those found in adults with schizophrenia, supporting the continuity of executive function deficits in childhood-onset with adolescent and adult-onset schizophrenia. However, saccadic tasks are not sensitive to genetic risk in non-psychotic children and 6-15-year-old children should not be included in genetic studies utilizing this endophenotype.

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes.

Abnormalities during a smooth pursuit eye movement task (SPEM) are common in schizophrenic patients and their relatives. This study assessed various components of SPEM performance in first-degree unaffected relatives of schizophrenic patients. One hundred individuals with schizophrenia, 137 unaffected first-degree relatives, and 69 normal controls completed a 16.7 degrees/s SPEM task. Smooth pursuit gain, catch-up saccades (CUS), large anticipatory saccades, and leading saccades (LS) were identified. Groups were compared with parametric and admixture analyses. Schizophrenic patients performed more poorly than unaffected relatives and normals on gain, CUS, and LS. Unaffected relatives were more frequently impaired than normals only on gain and LS. Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset schizophrenia.