F Bernardini ͣ ᵇ , C Ramsay Wan ͨ , A Crisafio ͩ , SH Massey ᵉ, MT Comptonᵇ ᶠ

1. Maternal Smoking During Pregnancy and Symptom Severity among Offspring during their First Episode of Psychosis* 4th Schizophrenia International Research Society Conference Florence, Italy, 5-9 April 2014 F Bernardiniͣ ᵇ, C Ramsay Wan ͨ , A Crisafioͩ , SH Massey ᵉ, MT Comptonᵇ ᶠ a University of Perugia, School of Psychiatry, Perugia, ITALY. b Lenox Hill Hospital, Department of Psychiatry, New York, NY, USA. c Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA. d The George Washington University School of Medicine and Health Sciences, Department of Psychiatry and Behavioral Sciences, Washington, DC, USA. e Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences and Department of Medical Social Sciences, Chicago, IL, USA. f Hofstra North Shore–LIJ School of Medicine at Hofstra University, Department of Psychiatry, Hempstead, NY, USA. *RelatedarticlecurrentlysubmittedtoSchizophreniaResearch METHODS INTRODUCTION • Maternal smoking during pregnancy is associated with a number of adverse perinatal outcomes and far-reaching neurobehavioral consequences for exposed children • Chronic prenatal exposure to nicotine is thought to result in the up-regulation of fetal central and peripheral nervous system nicotinic acetylcholine receptors • Subsequent alterations in the regulation of acetylcholine, norepinephrine, dopamine, serotonin, glutamate, and gamma-aminobutyric acid then translate to the physical deficits, as well as deficits in learning, memory, and behavior • It seems plausible that the above neurodevelopmental effects of prenatal exposure to maternal smoking could also be associated with an increased vulnerability to psychotic symptoms or psychotic disorders such as schizophrenia; yet little research is available • Fetal exposure to maternal smoking during pregnancy could conceivably impact illness manifestation among individuals with schizophrenia and related psychotic disorders • 247 participants recruited in 2 cities in the United States between August 2008 and May 2013, among them 93 also had data from their biological mothers • Habits and health conditions during the prenatal period, including prenatal tobacco exposure, were assessed via mothers’ self-reports using a questionnaire regarding prenatal illnesses, habits, and complications during labor and delivery • Data on recent symptom severity were collected with the Positive and Negative Syndrome Scale (PANSS) • Psychiatric diagnoses were determined using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) • Comparisons between those unexposed and exposed to prenatal maternal cigarette smoking were made using independent samples Student’s t-tests. Factorial analyses of variance (ANOVAs) were used to examine the effects of the exposure, as well as gender and current smoking status. All analyses were conducted using IBM SPSS Statistics 19.0, using two-tailed hypothesis tests with p<.05 considered statistically significant RESULTS • See Table 1 for sociodemographic characteristics of the first-episode patients • SCID-diagnosed psychotic disorders included: schizophreniform disorder (9, 9.7%), schizophrenia (56, 60.3%), schizoaffective disorder (5, 5.4%), delusional disorder (2, 2.1%), brief psychotic disorder (1, 1.1%), and psychotic disorder NOS (20, 21.5%) • See Table 2 for sociodemographic and substance use during pregnancy of the mothers • The average number of cigarettes smoked per month was 113.7 (range, 2–900, with 9 smoking less than 1 cigarette per day on average, and 10 smoking more than 1 cigarette per day) • PANSS positive symptoms (Table 3): patients exposed to prenatal tobacco smoke did not significantly differ on mean PANSS positive symptoms severity from those not exposed. However, they had a greater severity of reality distortion: 13.6±2.8, compared to 11.6±3.0; t=2.64, df=91, p=.01. This appeared to be driven by a greater severity of hallucinations (5.2±1.3, compared to 4.0±1.6; t=3.06, df=91, p=.003) • Controlling for potential effects of patients’ gender and smoking status did not eliminate the effect of prenatal tobacco smoke exposure on reality distortion severity. • PANSS negative symptoms (Table 3): Patients exposed to prenatal tobacco smoke did not differ significantly in mean PANSS negative symptoms severity from those not exposed. However, they had a lower severity of deficit symptoms: –7.1±3.1, compared to –4.0±3.3; t=3.69, df=91, p<.001. This appeared to be driven by a lower severity of blunted affect (2.6±1.5, compared to 3.4±1.5; t=2.18, df=91, p=.03), a lower severity of lack of spontaneity and flow of conversation (2.3±1.8, compared to 3.2±1.6; t=1.96, df=91, p=.05), and a greater severity of guilt feelings (2.7±1.6, compared to 1.9±1.2; t=2.29, df=91, p=.02) • Controlling for potential effects of patients’ gender and smoking status did not eliminate the effect of prenatal tobacco smoke exposure on severity of deficit symptoms DISCUSSION • Although these initial results require replication, there appears to be an association between fetal tobacco smoke exposure and greater hallucination severity at the time of the initial hospitalization for first-episode psychosis. This finding is consistent with the limited prior studies indicating that prenatal exposure to maternal smoking elevates risk for psychotic symptoms and psychotic disorders • Interestingly, a significant association was not observed for the PANSS positive symptom subscale as a whole, and our post-hoc tests suggest that the effect might be specific to hallucinations rather than positive symptoms more generally • Our findings suggest that, in addition to potentially increasing risk for psychotic symptoms and psychotic disorders as suggested by prior literature, this fetal environmental exposure might also worsen the severity of hallucinations among those with early-course schizophrenia and related disorders • Further research is needed to confirm this initial finding, and additional work is required to clarify the mixed findings to date on the effects of prenatal exposure to maternal smoking on negative/deficit symptoms • This work was supported by a grant from the National Institute of Mental Health (R01 MH081011) to the last author.