Stephen Zvi Levine

University of Haifa | haifa · School of Public Health

Background: Lower cognitive functioning has been documented across psychiatric disorders and hypothesized to be a core deficit of mental disorders. Situating psychopathology and cognition as part of a unitary construct is therefore important to understanding the etiology of psychiatric disorders. The current study aims to test competing structural...

Background: Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. Methods: We in...

This cross-sectional study uses electronic health record data to compare monthly incidence rates of spontaneous abortion in Israel before and during the COVID-19 pandemic.

Background Mental and physical health conditions are frequently comorbid. Despite the widespread physiological and behavioral changes during pregnancy, the pattern of comorbidities among women in pregnancy is not well studied. This study aimed to systematically examine the associations between mental and somatic disorders before and during pregnanc...

The identification of demographic factors of vulnerability and resilience in communities facing belligerent conflicts is increasingly relevant today. This representative study aims to examine the effect of protracted violence on the level of fear of the overall Israeli-Jewish population, and the role of the conflict on the connection between socioe...

Background Interrupted time series (ITS) analysis is a time series regression model that aims to evaluate the effect of an intervention on an outcome of interest. ITS analysis is a quasi-experimental study design instrumental in situations where natural experiments occur, gaining popularity, particularly due to the Covid-19 pandemic. However, chall...

Background: There exists substantial evidence of the effects of maternal mental health on birth outcomes. However, the roles of (1) comorbidity between mental and physical health, and (2) familial confounding underlying this association, remain unclear. Methods: This cohort study included a random sample of 19.5% children born between January 1, 19...

Introduction The Young Mania Rating Scale (YMRS) is the gold standard to assess manic symptoms of bipolar disorder, yet the clinical meaning of scores is unknown. To clinically understand and interpret YMRS scores, we examined linkages between the total and change scores of YMRS with the Clinical Global Impression (CGI) ratings. Methods Individual...

Background There is growing interest in the potential effects of maternal health in pregnancy on the risk for autism spectrum disorder (ASD) in the offspring. Studies to date have examined only a few maternal diagnoses in pregnancy and did not account for the potential effects of co-occurring conditions. This study systematically investigates the a...

Background The COVID-19 pandemic has been associated with increased levels of depression and anxiety with implications for the use of antidepressant medications. Methods The incident rate of antidepressant fills before and during the COVID-19 pandemic were compared using interrupted time-series analysis followed by comprehensive sensitivity analyse...

Objectives : To examine the association between prescription opioid use and the risk of dementia in old-age, since existing studies of the association are few, and the evidence is inconsistent. Design Prospective national cohort study (N=91,307, aged 60 years and over), without a dementia diagnosis for ten years, followed-up for incident dementia...

Psychometric network analysis is an alternative theoretically-driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer's disease differently than was previously assumed and consequently detect unknown treatment effects. Based on individual participant data, extracted from three double-blind, randomized plac...

The number needed to treat (NNT) is an efficacy index commonly used in randomized clinical trials. The NNT is the average number of treated patients for each undesirable patient outcome, for example, death, prevented by the treatment. We introduce a systematic theoretically‐based framework to model and estimate the conditional and the harmonic mean...

Background The association between serum folate deficiency and the risk of dementia in old age is unclear, perhaps owing to small sample sizes, the competing risk of mortality or reverse causation. Objective To examine the associations between serum folate deficiency and the risks of incident dementia and all-cause mortality in a large national sa...

Background Evidence from various sources suggests that females with schizophrenia tend to report lower quality of life than males with schizophrenia despite having a less severe course of the disorder. However, studies have not examined this directly. Aims To examine gender differences in the association between quality of life and the risk of sub...

The association between early improvement and subsequent change in cognition is unexamined in antidementia clinical trials. We aimed to examine the consequences of early-response to antidementia medication in Alzheimer's disease. Participant-level data were analyzed from five pivotal clinical trials of donepezil for Alzheimer's disease lasting up t...

Background: Studies of COVID-19 pandemic biopsychosocial exposure and schizophrenia risk showed contradictory results, were undertaken early in the pandemic, and did not consider lockdowns or COVID-19 infection. Hence, we examined the association between COVID-19 biopsychosocial exposure and incident schizophrenia. Methods: An interrupted time-s...

Knowledge is limited regarding the association between very‐late onset schizophrenia and the risks of risks of death and dementia. We aimed examine the associations between very‐late onset schizophrenia and the risks of death and dementia. A prospective Israeli cohort study (N=94,120) of persons without either dementia or schizophrenia (2002 to 201...

Background: The current study aims to overcome past methodological limitations and capture adolescents in need of psychiatric care with psychopathological symptoms in a cohort with unrestricted access to mental health professionals. Methods: The study source population consisted of a random sample of adolescents aged 16-17 years (N=1,369) assess...

Background To characterize the association between the protracted biopsychosocial coronavirus disease 2019 (COVID-19) pandemic exposures and incident suicide attempt rates. Methods Data were from a nationally representative cohort based on electronic health records from January 2013 to February 2021 ( N = 852 233), with an interrupted time series...

It is biologically plausible that risk of autism spectrum disorder (ASD) is elevated by both short and long interpregnancy intervals (IPI). We conducted a retrospective cohort study of singleton, non-nulliparous live births, 1998–2007 in Denmark, Finland, and Sweden (N = 925,523 births). Optimal IPI was defined as the IPI at which minimum risk was...

Background: In patients with Alzheimer's disease, global assessment scales, such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Clinician's Interview-Based Impression Plus Caregiver Input (CIBI plus), and the Clinical Global Impression (CGI) are commonly used. Objective: To clinically understand and interpret the associations between...

The association between exposure to terror and psychiatric rehabilitation service utilization (i.e., of housing, employment, and education) is yet to be examined in persons with schizophrenia, yet it is relevant to public health policy during emergencies. Accordingly, the current study aims to examine the association between exposure to terror and...

This study aimed to examine the contribution of ethnic group status and social support to posttraumatic growth (PTG) among widows after sudden spousal loss. Participants included 184 widows from three ethnic groups: 59 (32.3%) Jewish, 58 (31.7%) Muslim, and 66 (36%) Druze. Information was gathered via a demographic questionnaire, PTG Inventory, and...

Background Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagno...

IMPORTANCE Comorbidity between mental and physical health is a frequent problem, resulting in greater morbidity than the sum of the effects of individual diseases. Despite pervasive physiological and behavioral changes during pregnancy, the pattern of comorbidities among pregnant women is not well-understood. OBJECTIVE Systematically examine the a...

Background: Quality-adjusted life years (QALYs) are widely used to measure the impact of various diseases on both the quality and quantity of life and in their economic valuations. It will be clinically important and informative if we can estimate QALYs based on measurements of depression severity. Objective: To construct a conversion table from t...

Background Quality-adjusted life years (QALYs) are widely used to measure the impact of various diseases on both the quality and quantity of life and in their economic valuations. It will be clinically important and informative if we can estimate QALYs based on measurements of depression severity. Objective To construct a conversion table from the...

Objective We aim to explain the unadjusted, adjusted and marginal number needed to treat (NNT) and provide software for clinicians to compute them. Methods The NNT is an efficacy index that is commonly used in randomised clinical trials. The NNT is the average number of patients needed to treat to obtain one successful outcome (ie, response) due t...

Background: The extent and profiles of heterogeneity in cognitive functioning among participants in clinical trials of antidementia medication are unknown. We aimed to quantify and identify profiles of heterogeneity of cognition in Alzheimer's disease. Methods: Individual-level participant data were analyzed from five pivotal clinical trials of...

Background: The Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Severe Impairment Battery (SIB) are widely used rating scales to assess cognition in Alzheimer's disease. Objective: To understand the correspondence between these rating scales, we aimed to examine the linkage of...

In memory of Dr. Dennis John McFarland, who passed away recently, our objective is to continue his efforts to compare psychometric networks and latent variable models statistically. We do so by providing a commentary on his latest work, which he encouraged us to write, shortly before his death. We first discuss the statistical procedure McFarland u...

Knowledge is limited regarding the risks of death and dementia in very-late onset schizophrenia-like psychosis (VLOS). This study aims to scrutinize the associations between VLOS with the risks of death and dementia. Based on a prospective Israeli cohort study with national coverage, 94,120 persons without dementia or schizophrenia diagnoses aged 6...

Background Cumulative evidence suggests that health-related risk factors during midlife and old-age are associated with cognitive impairment. However, studies are needed to clarify the association between early-life risk factors and impaired cognitive functioning to increment existing knowledge. Objective To examine the association between childho...

IMPORTANCE: Many maternal diagnoses in pregnancy have been linked with offspring ASD risk. However, pregnant women receive many other diagnoses, most of which have not been evaluated for an association with offspring ASD. OBJECTIVE: Systematically test the associations between maternal diagnoses around pregnancy, and ASD risk in offspring, filterin...

Background Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcom...

Aim: Substantial research has focused on the examination of factors that contribute to the development of psychiatric problems. However, much less is known about factors early in life that may protect from poor mental health outcomes in midlife. This study aimed to identify the extent to which a set of key perinatal demographic variables and adole...

The number needed to treat is often used to measure the efficacy of a binary outcome in randomized clinical trials. There are three different available measures of the number needed to treat. Two of these measures, Furukawa and Leucht’s and Kraemer and Kupfer’s, focus on converting Cohen’s δ index into the number needed to treat, while Laupacis et...

Importance: Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, where most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and out...

Importance The origins and development of autism spectrum disorder (ASD) remain unresolved. No individual-level study has provided estimates of additive genetic, maternal, and environmental effects in ASD across several countries. Objective To estimate the additive genetic, maternal, and environmental effects in ASD. Design, Setting, and Particip...

Competing hypotheses stating that past genocide exposure reduces (owing to resilience) versus increases (owing to vulnerabilities) the risk of dementia are yet to receive empirical support. This study tested these competing hypotheses. Registry data were extracted on 51,752 Israeli residents without dementia from September 2002 to January 2012; ind...

Background: Childhood trauma increases the risk of schizophrenia, yet the role of adult sexual assault in the course of schizophrenia is unknown. This study aims to examine the associations between substance use and sexual assault severity characteristics with the course of schizophrenia among adult sexual assault victims using an epidemiologic st...

Objective: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia. Methods: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017....

Objective: Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex. Method: Population-based cohort study of 1998-2007 livebirths...

Background Mixed effects models have been widely applied in clinical trials that involve longitudinal repeated measurements, which possibly contain missing outcome data. In meta-analysis of individual participant data (IPD) based on these longitudinal studies, joint synthesis of the regression coefficient parameters can improve efficiency, especial...

Prisoners are at risk of self-harm during incarceration, yet national estimates of the rate and risk factors of self-harm are rare. We aimed to examine the rate and risk factors of self-harm on aggregate and by sex using a national population-based study design. Israel Prison Service data were examined on all persons incarcerated for a criminal off...

Importance Prenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed. Objective To investigate the association of early-life interference with different neurotransmitter systems by pr...

Background Along with the key clinical features of major psychiatric disorders such as psychosis, mania, and depression, these disorders are also associated with cognitive, social, and functional deficits. A growing body of evidence suggests that these disorders exist at the extreme end of a continuum of symptoms rather than as binary entities, so...

Background: Age of onset is considered central to understanding the course of schizophrenia, yet little is known regarding its association with quality of life in general, and specifically among males and females. Aims: To examine the association between the age of schizophrenia onset and quality of life, in general, and among males and females,...

Objective To examine the association between paternal antidepressant use at conception and offspring preterm birth, malformations, autism spectrum disorder, and intellectual disability. Design Observational prospective cohort study with regression methods, and negative control comparison. Setting Sweden nationwide. Participants 170 508 children...

Web appendix: Supplementary material

We aimed to examine the effects of infertility treatments on the risk of Autism Spectrum Disorder (ASD). Data were from a representative national registry on 110,093 male live births in Israel (born: 1999-2008; and ASD: 975, 0.9%). Infertility treatments included In Vitro Fertilization (IVF), and five hormone treatments. Relative risk (RR) was esti...

Objective: The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta-analysis. Method: We identified al...

This study tested the hypothesis that maternal exposure to terror attacks during pregnancy is associated with the risk of schizophrenia in the offspring. A population-based study was conducted of Israeli children born between 1975 and 1995 and that were registered in the Ministry of Interior and followed up in the Ministry of Health from birth to 2...

Background: Disparities between mental health patients and their professional caregivers in quality of life appraisals have been identified, however, the structure that such disparities assume is unknown. Aims: To examine the network structure of quality of life appraisals and disparities using network analysis. Methods: Participants were 1639...

Importance The association of maternal use of folic acid and multivitamin supplements before and during pregnancy with the risk of autism spectrum disorder (ASD) in offspring is unclear. Objective To examine the associations between the use of maternal folic acid and multivitamin supplements before and during pregnancy and the risk of ASD in offsp...

Background: The efficacy of antipsychotics across the initial severity range in patients with acute mania remains unclear. Therefore, we examined the influence of baseline severity on the efficacy of olanzapine. Methods: We did an individual participant data meta-analysis of double-blind, randomised controlled trials that compared olanzapine wit...

Importance Maternal antidepressant medication use during pregnancy has previously been associated with adverse outcomes in offspring, but to our knowledge, the association with intellectual disability (ID) has not been investigated. Objectives To examine the association of maternal antidepressant medication use during pregnancy with ID in offsprin...

Objectives: Mood stabilizers administered for bipolar disorder during pregnancy, such as valproic acid, can increase the risk of congenital anomalies in offspring. Valnoctamide is a valproic acid derivative associated with a decreased risk for congenital abnormalities in animals. The present study evaluated the efficacy and safety of valnoctamide...

Background: Previous studies have examined if maternal antidepressant medication during pregnancy increase the risk of autism spectrum disorder (ASD) in the offspring, but the results have been conflicting. Methods: In a population-based cohort of 179 007 children born in 2006 and 2007 and followed through 2014 when aged 7 and 8, we estimated re...

Objectives: To examine the association between the extent of genocide exposure and subsequent suicide risk among Holocaust survivors. Methods: Persons born in Holocaust-exposed European countries during the years 1922-1945 that immigrated to Israel by 1965 were identified in the Population Registry (N = 209,429), and followed up for suicide (195...

Background: Reasons for the recent mixed success of research into negative symptoms may be informed by conceptualizing negative symptoms as a system that is identifiable from network analysis. Our objectives were to identify (1) negative symptom systems; (2) central negative symptoms within each system; and (2) differences between the systems, base...

Network analysis is yet to be used to examine patient-reported symptom severity and change during citalopram treatment for major depressive disorder. We aimed to identify: (I) network systems; (II) central symptoms; and (III) network differences, in patient-reported depression for baseline, endpoint and change scores. STAR*D data during citalopram...

Background: Reasons for the recent mixed success of research into negative symptoms may be informed by conceptualizing negative symptoms as a system that is identifiable from network analysis. We aimed to identify: (I) negative symptom systems; (I) central negative symptoms within each system; and (III) differences between the systems, based on ne...

Background: Hypotheses about the sequel of parental genocide exposures on the offspring's risk and course of schizophrenia remain untested. Aims: To test hypotheses related to the transgenerational transmission of parental genocide exposure on the risk and course of schizophrenia. Methods: Data were extracted from the National Population Regis...

Case management services for people with serious mental illness are generally found to be effective, but controlled and randomized studies assessing such services are scarce. The aim of the present study was to assess the effectiveness of a new strengths-based case management (SBCM) service in Israel, using a randomized controlled approach. The sam...

The association between periods of genocide-related exposures and suicide risk remains unknown. Our study tests that association using a national population-based study design. The source population comprised of all persons born during1922-1945 in Nazi-occupied or dominated European nations, that immigrated to Israel by 1965, were identified in the...

Cox regression model terms of the sex by likely exposure group interactions. Note. Female sex and indirect exposure were reference groups. (DOCX)

Background: Risperidone is a common psychopharmacological treatment for irritability in autism spectrum disorder (ASD). It is not well-established how effective risperidone is across the initial symptom severity range. This study aims to examine the influence of baseline severity on the efficacy of risperidone in the treatment of ASD. Methods: P...

Purpose: The Jerusalem study of resilience and environmental adversity in midlife health (STREAM) was established to examine the prevalence of common mental and physical health issues in mid-adulthood in the inner city of Jerusalem, and to examine their association with lifespan psychosocial factors of vulnerability and resilience. Method: Parti...

Background: No evidence exists on the association between genocide and the incidence of schizophrenia. This study aims to identify critical periods of exposure to genocide on the risk of schizophrenia. Method: This population-based study comprised of all subjects born in European nations where the Holocaust occurred from 1928 to 1945, who immigr...