Kristen A. Woodberry

Premorbid IQ in Schizophrenia: A Meta-Analytic Review

OBJECTIVE Over the past three decades, there have been significant changes in the diagnostic criteria for schizophrenia as well as changes in measurement of IQ. The last quantitative review of the literature on premorbid IQ in schizophrenia was published more than two decades ago. Since that time, there have been many published studies of data sets pertaining to this issue. The purpose of the present review was to provide an updated meta-analysis of premorbid IQ in individuals who later develop schizophrenia. METHOD The authors performed a systematic literature search, which yielded 18 studies that met criteria for the meta-analysis. Inclusion criteria were 1) premorbid psychometric measures of IQ in subjects who were later diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder, 2) similar comparison data, and 3) sufficient data for calculation of an effect size. The analogue to the analysis of variance method was used to model between-study variance due to key study-design features. RESULTS Overall, schizophrenia samples demonstrated a reliable, medium-sized impairment in premorbid IQ. The heterogeneity of effect sizes was minimal and almost exclusively the result of one study. Methodological differences, such as diagnostic criteria, type of IQ measure, sample ascertainment, and age at premorbid testing, contributed minimally to the effect size variance. A cross-sectional analysis of all studies by age and a descriptive review of studies that used repeated measures of IQ in a single sample did not support the presence of a relative decline in IQ during the premorbid period in individuals with schizophrenia. However, all studies with pre- and post-onset testing within the same sample suggested that a significant decline in the IQ of individuals with schizophrenia, relative to comparison subjects, was associated with the onset of frank psychosis. CONCLUSIONS Years before the onset of psychotic symptoms, individuals with schizophrenia, as a group, demonstrate mean IQ scores approximately one-half of a standard deviation below that of healthy comparison subjects.

Neuropsychological Profiles in Individuals at Clinical High Risk for Psychosis: Relationship to Psychosis and Intelligence

BACKGROUND Characterizing neuropsychological (NP) functioning of individuals at clinical high risk (CHR) for psychosis may be useful for prediction of psychosis and understanding functional outcome. The degree to which NP impairments are associated with general cognitive ability and/or later emergence of full psychosis in CHR samples requires study with well-matched controls. METHODS We assessed NP functioning across eight cognitive domains in a sample of 73 CHR youth, 13 of whom developed psychotic-level symptoms after baseline assessment, and 34 healthy comparison (HC) subjects. Groups were matched on age, sex, ethnicity, handedness, subject and parent grade attainment, and median family income, and were comparable on WRAT-3 Reading, an estimate of premorbid IQ. Profile analysis was used to examine group differences and the role of IQ in profile shape. RESULTS The CHR sample demonstrated a significant difference in overall magnitude of NP impairment but only a small and nearly significant difference in profile shape, primarily due to a large impairment in olfactory identification. Individuals who subsequently developed psychotic-level symptoms demonstrated large impairments in verbal IQ, verbal memory and olfactory identification comparable in magnitude to first episode samples. CONCLUSIONS CHR status may be associated with moderate generalized cognitive impairments marked by some degree of selective impairment in olfaction and verbal memory. Impairments were greatest in those who later developed psychotic symptoms. Future study of olfaction in CHR samples may enhance early detection and specification of neurodevelopmental mechanisms of risk.

Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

IMPORTANCE Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

White Matter Microstructure in Individuals at Clinical High Risk of Psychosis: A Whole-Brain Diffusion Tensor Imaging Study

BACKGROUND The study of individuals at clinical high risk (CHR) for psychosis provides an important opportunity for unraveling pathological mechanisms underlying schizophrenia and related disorders. A small number of diffusion tensor magnetic resonance imaging (DTI) studies in CHR samples have yielded anatomically inconsistent results. The present study is the first to apply tract-based spatial statistics (TBSS) to perform a whole-brain DTI analysis in CHR subjects. METHODS A total of 28 individuals meeting CHR criteria and 34 healthy controls underwent DTI. TBSS was used for a group comparison of fractional anisotropy (FA), as well as axial, radial, and mean diffusivity (AD, RD, and MD). Conversion to psychosis was monitored during a mean follow-up period of 12.3 months. RESULTS The rate of conversion to psychosis was relatively low (4%). TBSS revealed increased MD in several clusters in the right hemisphere, most notably in the superior longitudinal fasciculus (SLF), posterior corona radiata, and corpus callosum (splenium and body). Increased RD was restricted to a smaller area in the posterior parietal lobe. CONCLUSION We present further evidence that white matter microstructure is abnormal in CHR individuals, even in a sample in which the vast majority do not transition to psychosis over the following year. In accord with previous studies on CHR individuals and patients with early-onset schizophrenia, our findings suggest an important pathological role for the parietal lobe and especially the SLF. The latter is known to undergo particularly dynamic microstructural changes during adolescence and early adulthood, a critical phase for the development of psychotic illness.

Prodromal psychosis detection in a counseling center population in China: An epidemiological and clinical study

BACKGROUND To investigate through a two-stage clinic-based screening, the frequency and clinical features of risk for psychosis syndromes in a Chinese help-seeking sample. METHOD 2101 consecutive new patients ages 15-45 were recruited at their first visit to the Shanghai Mental Health Center (SMHC) and screened with the Prodromal Questionnaire-Brief version (PQ-B) and questions about genetic risk. The Structured Interview for Prodromal Syndromes (SIPS) was administered to a sub-sample to estimate rates of psychosis and clinical high risk (CHR) for psychosis syndromes. RESULTS The frequency estimate of CHR syndromes in the total sample was 4.2%. Among 89 CHR patients, more than two-thirds met the criteria for Attenuated Positive Symptom Syndrome (APSS); and nearly a quarter met the criteria for Genetic Risk and Deterioration Syndrome (GRDS). The frequency of CHR syndromes peaked between the ages of 16 and 21years old and declined with subsequent age. The mean total and distress scores on the PQ-B in subjects with APSS and psychosis were significantly higher than in individuals with GDRS and patients without psychosis or CHR. High frequencies and strong correlations were found among some positive and non-specific symptoms in SIPS interviews. Among the 53 CHR participants who were followed-up for two years, 14 (26.4%) converted to psychosis. Of the non-converters, 53.8% were diagnosed with Axis I disorders. CONCLUSIONS This two stage screening method can enhance detection of Chinese CHR patients in clinical settings. The validity of the procedures for detecting CHR is supported by rates of transition to psychosis and of non-converter Axis I disorders that are comparable to those reported in meta-analyses.

The role of general intelligence as an intermediate phenotype for neuropsychiatric disorders

Introduction. Neurocognitive impairment is common to several neuropsychiatric disorders. The growing use of cognitive impairment as an intermediate phenotype, or “endophenotype”, in psychiatry raises the issue of whether global measures of cognition, such as IQ, or assays of more specific cognitive domains, such as working memory, will best serve to enhance power in detecting susceptibility loci in molecular genetic studies. Methods. This paper will review the research on general intelligence in schizophrenia and bipolar disorder and evaluate its strengths and weaknesses as a candidate intermediate phenotype. Results. Although global measures of cognition may not be optimal as intermediate phenotypes in bipolar disorder, certain clinical traits that overlap between schizophrenia and bipolar disorder, such as psychosis, may be predictive of poor performance on global measures, regardless of DSM-IV categorisation. Conclusions. Global measures of cognition represent good intermediate phenotypes in schizophrenia. Current research does not support the use of global measures of cognition as intermediate phenotypes for bipolar disorder. Assays of specific neurocognitive domains may have greater potential to detect genetic markers for bipolar disorder.

A randomized trial of family focused therapy with populations at clinical high risk for psychosis: Effects on interactional behavior

OBJECTIVE This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. METHOD This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions on categories of calm-constructive and critical-conflictual behavior. RESULTS Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month reassessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC. Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger, complaints and criticism, and off-task comments compared to participants in EC. These changes occurred equally in high-risk participants and their family members. CONCLUSIONS A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents. Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk.

Change in neuropsychological functioning over one year in youth at clinical high risk for psychosis.

Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d = -1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms.

Neuropsychological Impairment in Prodromal, First-Episode, and Chronic Psychosis: Assessing RBANS Performance.

Background Cognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis. Method We administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis. Results Performance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis. Conclusions Cognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease.

An experimental pilot study of response to invalidation in young women with features of borderline personality disorder

One of the leading biosocial theories of borderline personality disorder (BPD) suggests that individuals with BPD have biologically based abnormalities in emotion regulation contributing to more intense and rapid responses to emotional stimuli, in particular, invalidation [Linehan, M.M., 1993. Cognitive-Behavioral Treatment of Borderline Personality Disorder. Guilford, New York.]. This study used a 2 by 2 experimental design to test whether young women with features of BPD actually show increased physiological arousal in response to invalidation. Twenty-three women ages 18 to 29 who endorsed high levels of BPD symptoms and 18 healthy controls were randomly assigned to hear either a validating or invalidating comment during a frustrating task. Although we found preliminary support for differential response to these stimuli in self-report of valence, we found neither self-report nor physiological evidence of hyperarousal in the BPD features group, either at baseline or in response to invalidation. Interestingly, the BPD features group reported significantly lower comfort with emotion, and comfort was significantly associated with affective valence but not arousal. We discuss implications for understanding and responding to the affective intensity of this population.