Schizophrenia Center (Trainee) Publications

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Publications Related to the Center and Publications from Center Trainees
Updated: 37 weeks 1 day ago

Fears SC(1), Service SK(1), Kremeyer B(2), Araya C(3), Araya X(3), Bejarano J(3), Ramirez M(3), Castrillón G(4), Gomez-Franco J(5), Lopez MC(5), Montoya G(5), Montoya P(5), Aldana I(1), Teshiba TM(1), Abaryan Z(1), Al-Sharif NB(1), Ericson M(1), Jalbrzik

2014, July 16 - 15:24
IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN, SETTING, AND PARTICIPANTS Multigenerational pedigree study in 2 closely related, genetically isolated populations: the Central Valley of Costa Rica and Antioquia, Colombia. A total of 738 individuals, all from Central Valley of Costa Rica and Antioquia pedigrees, participated; among them, 181 have BP-I. MAIN OUTCOMES AND MEASURES Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging, and diffusion tensor imaging phenotypes. RESULTS Of 169 phenotypes investigated, 126 (75%) were significantly heritable and 53 (31%) were associated with BP-I. About one-quarter of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions as well as volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE To our knowledge, this is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I association within families that is consistent with expectations from case-control studies. Together, these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder.

Tsai KH(1), López S, Marvin S, Zinberg J, Cannon TD, O'Brien M, Bearden CE. Perceptions of family criticism and warmth and their link to symptom expression in racially/ethnically diverse adolescents and young adults at clinical high risk for psychosis. 1.

2014, July 16 - 15:24
AIM: Little is known about the role of expressed emotion (EE) in early symptom expression in individuals at clinical high risk (CHR) for psychosis. In patients with established schizophrenia, the effects of EE on clinical outcomes have purportedly varied across racial/ethnic groups, but this has not yet been investigated among CHR patients. Furthermore, studies have traditionally focused upon caregiver levels of EE via interview-based ratings, whereas the literature on patient perceptions of caregiver EE on psychosis symptoms is relatively limited. METHODS: Linear regression models were conducted to examine the impact of criticism and perceived warmth in the family environment, from the CHR patient's perspective, on positive and negative symptom expression in non-Latino white (NLW; n?=?38) and Latino (n?=?11) adolescents and young adults at CHR for developing psychosis. RESULTS: Analyses examining the sample as a whole demonstrated that perceived levels of maternal criticism were negatively associated with negative CHR symptomatology. Additional analyses indicated that race/ethnicity moderated the relationship between criticism/warmth and clinical symptomatology. We found evidence of a contrasting role of patient perceived criticism and warmth depending upon the patient's race/ethnicity. CONCLUSION: Family processes shown to impact the course of schizophrenia among NLWs may function differently among Latino than NLW patients. These findings have important implications for the development of culturally appropriate interventions and may aid efforts to improve the effectiveness of mental health services for diverse adolescents and young adults at CHR for psychosis. Given the small sample size of this study, analyses should be replicated in a larger study before more definitive conclusions can be made.

Jalbrzikowski M, Jonas R, Senturk D, Patel A, Chow C, Green MF, Bearden CE. Structural abnormalities in cortical volume, thickness, and surface area in 22q11.2 microdeletion syndrome: Relationship with psychotic symptoms. 1. Neuroimage Clin. 2013 Oct 14;3

2014, July 16 - 15:24
INTRODUCTION: 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins. METHODS: High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10-25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed. RESULTS: Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS. CONCLUSION: Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population.

Jalbrzikowski M, Krasileva KE, Marvin S, Zinberg J, Andaya A, Bachman P, Cannon TD, Bearden CE. Reciprocal social behavior in youths with psychotic illness and those at clinical high risk. 1. Dev Psychopathol. 2013 Nov;25(4 Pt 1):1187-97. doi: 10.1017/S09

2014, July 16 - 15:24
Youths at clinical high risk (CHR) for psychosis typically exhibit significant social dysfunction. However, the specific social behaviors associated with psychosis risk have not been well characterized. We administer the Social Responsiveness Scale (SRS), a measure of autistic traits that examines reciprocal social behavior, to the parents of 117 adolescents (61 CHR individuals, 20 age-matched adolescents with a psychotic disorder [AOP], and 36 healthy controls) participating in a longitudinal study of psychosis risk. AOP and CHR individuals have significantly elevated SRS scores relative to healthy controls, indicating more severe social deficits. Mean scores for AOP and CHR youths are typical of scores obtained in individuals with high functioning autism (Constantino andamp; Gruber, 2005). SRS scores are significantly associated with concurrent real-world social functioning in both clinical groups. Finally, baseline SRS scores significantly predict social functioning at follow-up (an average of 7.2 months later) in CHR individuals, over and above baseline social functioning measures (p andlt; .009). These findings provide novel information regarding impairments in domains critical for adolescent social development, because CHR individuals and those with overt psychosis show marked deficits in reciprocal social behavior. Further, the SRS predicts subsequent real-world social functioning in CHR youth, suggesting that this measure may be useful for identifying targets of treatment in psychosocial interventions.

Karlsgodt KH, van Erp TG, Bearden CE, Cannon TD. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis. 1. Psychiatry Res. 2013 Oct 18. pii: S0925-4927(13)00217-5. doi: 10.1016/j.pscychresns.

2014, July 16 - 15:24
Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant.

Golembo-Smith S, Bachman P, Senturk D, Cannon TD, Bearden CE. Youth-caregiver Agreement on Clinical High-risk Symptoms of Psychosis. 1. J Abnorm Child Psychol. 2013 Oct 4. [Epub ahead of print]

2014, July 16 - 15:24
Early identification of individuals who will go on to develop schizophrenia is a difficult endeavor. The variety of symptoms experienced by clinical high-risk youth make it difficult to identify who will eventually develop schizophrenia in the future. Efforts are being made, therefore, to more accurately identify at-risk individuals and factors that predict conversion to psychosis. As in most assessments of children and adolescents, however, both youth and parental report of symptomatology and resulting dysfunction are important to assess. The goals of the current study were to assess the extent of cross-informant agreement on the Structured Interview for Prodromal Symptoms (SIPS), a widely-used tool employed to determine clinical high-risk status. A total of 84 youth-caregiver pairs participated. Youth and caregiver raters displayed moderate overall agreement on SIPS-rated symptoms. Both youth and caregiver ratings of youth symptomatology contributed significantly to predicting conversion to psychosis. In addition, youth age and quality of youth-caregiver relationships appear to be related to cross-informant symptom ratings. Despite differences on individual SIPS domains, the majority of dyads agreed on youth clinical high-risk status. Results highlight the potential clinical utility of using caregiver informants to determine youth psychosis risk.

Jalbrzikowski M, Sugar CA, Zinberg J, Bachman P, Cannon TD, Bearden CE. Coping styles of individuals at clinical high risk for developing psychosis. 1. Early Interv Psychiatry. 2012 Nov 19. doi: 10.1111/eip.12005. [Epub ahead of print]

2014, July 16 - 15:24
AIM: There is a wealth of evidence suggesting that patients with schizophrenia tend to respond to life stressors using less effective coping skills, which are in turn related to poor outcome. However, the contribution of coping strategies to outcome in youth at clinical high risk (CHR) for developing psychosis has not been investigated. METHODS: This longitudinal study followed CHR youth over a 12-month period, using the Brief COPE questionnaire. CHR subjects (n?=?88) were compared at baseline with a healthy control sample (n?=?53), and then mixed models were used to explore the relationship of coping strategies to clinical and psychosocial outcomes in CHR subjects over time (n?=?102). RESULTS: Cross-sectional analyses revealed that, in comparison with healthy controls, CHR youth reported using more maladaptive coping strategies (P?andlt;?0.001) and fewer adaptive coping strategies (P?andlt;?0.01). Longitudinal analyses within the CHR group showed significant decreases in maladaptive coping and symptom severity over time, with corresponding improvements in social and role functioning. Adaptive coping was associated with better concurrent social functioning and less severe symptomatology (both P?andlt;?0.001). Over time, more maladaptive coping was associated with more severe positive and negative symptoms (both P?andlt;?0.005). CONCLUSIONS: Youth at risk for psychosis report using fewer adaptive and more maladaptive coping strategies relative to healthy controls. Over 1-year follow-up, more adaptive coping styles are associated with less severe clinical symptomatology and better social functioning. These findings suggest that teaching adaptive coping styles may be an important target for intervention in youth at high risk for psychosis.

Mittal VA, Willhite R, Daley M, Bearden CE, Niendam T, Ellman LM, Cannon TD. Obstetric complications and risk for conversion to psychosis among individuals at high clinical risk. 1. Early Interv Psychiatry. 2009 Aug;3(3):226-30. doi: 10.1111/j.1751-7893.2

2014, July 16 - 15:24
AIM: Examining risk factors among high-risk populations stands to inform treatment and to elucidate our understanding of the pathophysiology of schizophrenia. Despite substantial evidence implicating the incidence of obstetric complications (OCs) as a risk factor for schizophrenia, little is known about the relationship between OCs and risk for conversion among high-risk individuals. METHODS: We prospectively followed individuals at high risk for developing psychotic disorders for a two-year period to determine if a history of OCs is associated with conversion. RESULTS: Individuals who converted to psychosis had significantly more OCs when compared to non-converting participants; a history of OCs was associated with increased odds of conversion (odds ratio = 4.90, confidence interval :1.04/22.20). OCs were positively associated with prodromal symptomatology. CONCLUSIONS: To date, this report represents the first empirical evidence suggesting that OCs confer increased risk of conversion to psychosis. It is possible that OCs interact with brain maturational processes in the pathophysiology of schizophrenia and can serve as a risk marker.

Niendam TA, Jalbrzikowski M, Bearden CE. Exploring predictors of outcome in the psychosis prodrome: implications for early identification and intervention. 1. Neuropsychol Rev. 2009 Sep;19(3):280-93. Epub 2009 Jul 14.

2014, July 16 - 15:24
Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth.

Mittal VA, Jalbrzikowski M, Daley M, Roman C, Bearden CE, Cannon TD. Abnormal movements are associated with poor psychosocial functioning in adolescents at high risk for psychosis. 1. Schizophr Res. 2011 Aug;130(1-3):164-9. Epub 2011 Jun 1.

2014, July 16 - 15:24
The period immediately preceding the onset of overt psychosis is characterized by a range of symptoms and behaviors including emerging attenuated psychosis, spontaneous movement abnormalities, and a broad decline in role and social functioning. Recent evidence suggests that basal ganglia dysfunction, which is implicated in the development of psychotic symptomatology, may manifest in the form of both movement abnormalities and deficits in processes integral to psychosocial functioning. However, little is known about the relationship between abnormal movement function and the observed psychosocial deficits. In the present study, 40 clinical high-risk participants meeting criteria for a prodromal syndrome were assessed for movement abnormalities and global role and social functioning at baseline. Role and social functioning were then followed up after a one-year period. At baseline, the severity of spontaneous movement abnormalities was associated with poor role functioning. Further, when controlling for baseline functioning, movement abnormalities predicted changes in social functioning one-year later, with a trend in the same direction for role functioning. Exploratory analyses also indicated that elevated baseline movement abnormalities distinguished those at-risk participants who eventually converted to psychosis and that this was also the case for poorer baseline global role functioning (at the trend level). Taken together, the results suggest that movement abnormalities are closely associated with deficits in psychosocial functioning. Elucidating the link between these phenomena may serve to refine etiological models of frontal-subcortical circuit dysfunction and inform understanding of functioning and outcome of these affected youth.

Schlosser DA, Jacobson S, Chen Q, Sugar CA, Niendam TA, Li G, Bearden CE, Cannon TD. Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis. 1. Schizophr Bull. 2012 Nov;38(6):1225-33. d

2014, July 16 - 15:24
Background: The "clinical high risk" (CHR) construct was developed to identify individuals at imminent risk of developing psychosis. However, most individuals identified as CHR do not convert to psychosis, and it is unknown whether these nonconverting individuals actually recover from an at-risk state. Methods: Eighty-four prospectively identified patients meeting CHR criteria, and 58 healthy comparison subjects were followed in a 2-year longitudinal study. Analyses examined rates of conversion, clinical, and functional recovery. Proportional cause-specific hazard models were used to examine the effects of baseline and time-varying predictors on conversion and remission. Trajectories of symptoms and psychosocial functioning measures were compared across outcome groups. Results: Competing risk survival analyses estimated that 30% of CHR subjects convert to psychosis by 2 years, while 36% symptomatically remit and 30% functionally recover by 2 years. Lower levels of negative and mood/anxiety symptoms were related to increased likelihood of both symptomatic and functional recovery. CHR subjects who remitted symptomatically were more similar to healthy controls in terms of both their baseline and longitudinal symptoms and functioning than the other outcome groups. Conclusions: Nonconverting CHR cases represented a heterogeneous group. Given that nonconverted subjects who remitted symptomatically also presented initially with less severe prodromal symptomatology and showed a distinct normative trajectory of both symptoms and psychosocial functioning over time, it may be possible to refine the CHR criteria to reduce the number of "false positive" cases by eliminating those who present with less severe attenuated positive symptoms or show early improvements in terms of symptoms or functioning.

Bachman P, Kim J, Yee CM, Therman S, Manninen M, Lönnqvist J, Kaprio J, Huttunen MO, Näätänen R, Cannon TD. Efficiency of working memory encoding in twins discordant for schizophrenia. 1. Psychiatry Res. 2009 Nov 30;174(2):97-104. Epub 2009 Oct 23.

2014, July 16 - 15:24
It has been proposed that patients with schizophrenia and some of their relatives suffer from reduced neurocognitive efficiency, increasing their sensitivity to experimental task demands. The present study evaluated such a possibility during performance of a working memory task by schizophrenia patients and their co-twins along with a healthy control sample. Electrophysiological data were obtained from sets of nine twin pairs (monozygotic and dizygotic pairs collapsed) discordant for a diagnosis of schizophrenia and from nine matched healthy control twin pairs, during administration of a variable-load spatial working memory task. Event-related potentials (ERPs) were measured immediately after memory set onset and during a delay period. For correctly performed trials, slow-wave ERP activity measured during the late stimulus encoding and delay periods exhibited a significant Diagnostic Group-by-Memory Load interaction, with schizophrenia patients showing a differentially strong load effect. Patients' co-twins displayed an intermediate level of load sensitivity while healthy controls showed no significant load effect. These results support an inefficiency model of neurocognitive dysfunction in schizophrenia, a pattern that appears to be related to the pathogenesis and inheritance of the disorder. Furthermore, this inefficiency appeared during the late stimulus encoding stage of working memory functioning, possibly reflecting disruptions in stimulus representation consolidation.

Cannon TD, Glahn DC, Kim J, Van Erp TG, Karlsgodt K, Cohen MS, Nuechterlein KH, Bava S, Shirinyan D. Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia. 1. Arch Gen P

2014, July 16 - 15:24
CONTEXT: It remains unclear whether altered regional brain physiological activity in patients with schizophrenia during working memory tasks relates to maintenance-related processes, manipulation-related (ie, executive) processes, or both. OBJECTIVE: To examine regional functional activations of the brain during maintenance- and manipulation-related working memory processing in patients with schizophrenia and in healthy comparison subjects. DESIGN: Functional images of the brain were acquired in 11 schizophrenic patients and 12 healthy control subjects (matched for age, sex, handedness, and parental education) during 2 spatial working memory paradigms, one contrasting maintenance-only processing with maintenance and manipulation processing and the other contrasting parametrically varying maintenance demands. RESULTS: Patients and controls showed activation of a large, spatially distributed network of cortical and subcortical regions during spatial working memory processing. When task demands required explicit manipulation of information held in memory, controls recruited right dorsolateral prefrontal cortex (Brodmann areas 45 and 46) to a significantly greater extent than patients. A similar effect was observed for the larger memory set sizes of the memory set size task. No other brain regions showed activation differences between groups for either task. These differences persisted when comparing activation maps for memory set sizes in which the 2 groups were equivalent in behavioral accuracy and when comparing subgroups of patients and controls matched for behavioral accuracy on either task. CONCLUSIONS: Physiological disturbances in the dorsolateral prefrontal cortex contribute differentially to patients' difficulties with maintaining spatial information across a brief delay, as well as with manipulating the maintained representation. These differences persisted when comparing conditions in which the 2 groups were equivalent in behavioral accuracy.

Cornblatt BA, Auther AM, Niendam T, Smith CW, Zinberg J, Bearden CE, Cannon TD. Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia. 1. Schizophr Bull. 2007 May;33(3):688-702. Epub 2007 Apr 17.

2014, July 16 - 15:24
INTRODUCTION: Research on prediction and prevention of schizophrenia has increasingly focused on prodromal (prepsychosis) social and role dysfunction as developmentally early, stable, and treatment-resistant illness components. In this report, 2 new measures, Global Functioning: Social and Global Functioning: Role, are presented, along with preliminary findings about psychometric properties and course of social and role (academic/work) functioning in the prodromal phase of psychosis. METHODS: Subjects included 69 participants from the Recognition and Prevention program and 52 from the Center for the Assessment and Prevention of Prodromal States. Ages ranged from 12 to 29 years, and all met criteria for Attenuated Positive Symptom syndrome. Retrospective (past year) and baseline data are reported for all 121 prodromal subjects and for 44 normal controls (NCs). Prospective follow-up data are reported for a subsample of patients reevaluated at both 6 and 12 months (N = 44). RESULTS: For both scales, interrater reliability was high, and preliminary data supported construct validity. Relative to NCs, prodromal individuals displayed impaired social and role functioning at baseline. Analyses of change over time indicated that role functioning declined over the year before ascertainment and improved over 12-month follow-up, presumably with treatment. Social impairment, by contrast, was constant across time and predicted later psychosis (P = .002). DISCUSSION: Using 2 new global measures, social functioning was found to be a stable trait, unchanged by treatment, with considerable potential to be a marker of schizophrenia. Role functioning, by contrast, may be a more direct barometer of clinical change and may be responsive to treatment and environmental change.

Ellman LM, Yolken RH, Buka SL, Torrey EF, Cannon TD. Cognitive functioning prior to the onset of psychosis: the role of fetal exposure to serologically determined influenza infection. 1. Biol Psychiatry. 2009 Jun 15;65(12):1040-7. Epub 2009 Feb 5.

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BACKGROUND: Previous studies have linked prenatal influenza exposure to increased risk of schizophrenia; however, no study has examined the neurodevelopmental sequelae of this prenatal insult before the onset of psychotic symptoms using serological evidence of infection. This study sought to examine the contribution of prenatal influenza A and B exposure to cognitive performance among children who developed psychoses in adulthood versus nonpsychiatric control children. METHODS: Subjects were 111 cases (70 with schizophrenia and 41 with affective psychoses) and 333 matched control subjects followed from gestation until age 7 through the Collaborative Perinatal Project. The Wechsler Intelligence Scale for Children (age 7) was administered and adult psychiatric morbidity was assessed by medical records review and confirmed by a validation study. Assays were conducted from archived prenatal maternal sera collected at birth, and influenza infection was determined by immunoglobulin G (IgG) antibody titers andgt;75th percentile. RESULTS: Significant decreases in verbal IQ and the information subtest, as well as similar nonsignificant reductions in full scale IQ scores and vocabulary, comprehension, digit span, and picture arrangement subtests were found among cases who were prenatally exposed to influenza B versus cases who were not exposed. Fetal exposure to influenza B did not lead to any significant differences in cognitive performance among control children. CONCLUSIONS: Cumulatively, these findings suggest that a genetic and/or an environmental factor associated with psychosis rendered the fetal brain particularly vulnerable to the effects of influenza B, leading to poorer cognitive performance even before symptom onset.