Dolores Malaspina

Icahn School of Medicine at Mount Sinai | MSSM · Psychiatry, Neuroscience and Genetics & Genomics

Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants...

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other...

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 ×...

We developed a “gut-brain-axis questionnaire” (GBAQ) to obtain standardized person-specific “review of systems” data for microbiome-gut-brain-axis studies. Individual items were compared to PANSS symptom measures using dimensional, transdiagnostic and traditional categorical approaches. Method : Forty psychotic participants, independent of diagnos...

Background A proportion of those who contract COVID-19 will develop long COVID (i.e., symptoms that persist for three months or more). Childhood trauma contributes to a pro-inflammatory state in adulthood evidenced by high morbidity and early mortality, but it has not yet been investigated as a risk factor for long COVID. Methods Participants (N=3...

The global emergence of novel pathogenic viruses presents an important challenge for research, as high biosafety levels are required to process samples. While inactivation of infectious agents facilitates the use of less stringent safety conditions, its effect on other biological entities of interest present in the sample is generally unknown. Here...

The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-sect...

Objective We conducted a systematic review of the published literature to test the hypothesis that maternal exposure to extremes of ambient temperatures during pregnancy is associated with the risk for psychiatric disorders or congenital malformations in offspring, both of which are indicative of perturbations of fetal neurodevelopment. Method Thi...

Polygenic risk scores (PRS) summarize genetic liability to a disease at the individual level, and the aim is to use them as biomarkers of disease and poor outcomes in real-world clinical practice. To date, few studies have assessed the prognostic value of PRS relative to standards of care. Schizophrenia (SCZ), the archetypal psychotic illness, is a...

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristi...

Sudden olfactory loss in the absence of concurrent nasal congestion is now a well‐recognized symptom of COVID‐19. We examined olfaction using standardized objective tests of odor detection, identification, and hedonics collected from asymptomatic university students before and as SARS‐CoV‐2 emerged locally. Olfactory performance of students who wer...

Objective: To investigate the prevalence and features of protracted COVID-19 symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness. Participants: COVID-19 positive participants with symptoms ≥ 28 days (N = 22), herein referred to as post-COVID syndrome, were compared to those who fully recovered (N = 21)...

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, par...

Daniele C Parise,1 Caitlin Gilman,2 Matthew A Petrilli,3 Dolores Malaspina4 1Scope Anesthesia of North Carolina, Charlotte, NC, USA; 2Department of Pediatrics, Montefiore Children’s Hospital, Einstein Medical School, New York, NY, USA; 3Sentara Behavioral Health Specialists, South Boston, VA, USA; 4Department of Psychiatry, Icahn School of Medicine...

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, par...

Objective: To assess the prevalence of early trauma in individuals with onset of schizophrenia at early (≤ 18 years) and adult (> 18 years) ages (EOP and AOP, respectively). and explore relationship between the onset of disease and clinical variables, including traumatic events, psychotic and mood symptoms. Methods: Subjects with SZ (n=71) and EOP...

Background: Studying the phenotypic and genetic characteristics of age and polarity at onset (AAO, PAO) in bipolar disorder (BD) can provide new insights into disease pathology and facilitate the development of screening tools. Aims: To examine the genetic architecture of AAO and PAO and their association with BD disease characteristics. Methods: G...

Schizophrenia (SCZ) is the archetypal severe mental illness and one of the most deeply characterized human genetic traits. Like most common diseases SCZ is highly polygenic, and as such its genetic liability can be summarized at the individual level by a polygenic risk score (PRS). Polygenic risk scores are a cornerstone of the precision medicine v...

Objective: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gy...

The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica­tion is prescribed, with second‐generation antipsychotics usually preferred to first‐generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is eviden...

What are the underlying causes of psychosis? Why do certain members of the general population experience hallucinations but remain functional while other members enter the psychosis prodrome, and still others go on to experience full-fledged psychosis? In this chapter we will review the putative risk factors associated with psychosis and explore cu...

Background Post-COVID syndrome is increasingly recognized by the medical community but has not been studied exclusively in young adults. This preliminary report investigates the prevalence and features of protracted symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness. Methods 148 students completed an on...

Background and purpose: Previous hippocampal proton MR spectroscopic imaging distinguished patients with schizophrenia from controls by elevated Cr levels and significantly more variable NAA and Cho concentrations. This goal of this study was to ascertain whether this metabolic variability is associated with clinical features of the syndrome, poss...

Background Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world’s population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping o...

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbor...

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic and calcium signaling pathways and brain-expressed genes, particularly those with high...

By meta-analyzing the whole-exomes of 24,248 cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in ten genes as conferring substantial risk for schizophrenia (odds ratios 3 - 50, P < 2.14 x 10^-6), and 32 genes at a FDR < 5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular...

The underpinnings of poor decision-making in schizophrenia could reflect excessively risky or inhibited behaviors. This study employed the Balloon Analogue Risk Task (BART) to compare decision-making in schizophrenia cases to that of healthy controls. Individuals with schizophrenia performed significantly differently across three trials, failing to...

Background Anosmia is a recognized symptom of COVID-19, but the relationship of SARS-CoV-2 exposure with olfactory dysfunction remains enigmatic. This report adds unique data from healthy students tested as the virus emerged locally. Methods Psychometrically validated measures assessed odor detection, identification and hedonics in healthy universi...

Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypot...

Background Rare variants in the TRIO gene are associated with schizophrenia and autism spectrum disorders (ASD), which are commonly comorbid. ASD may define a specific schizophrenia subtype. This study examined person-specific hippocampal metabolite concentrations for 4 schizophrenia cases harboring rare variants in TRIO or its interaction partner...

As global temperatures increased by 0.5 °C to 1 °C during the last half century, the number and severity of heat waves also increased. Headlines pronounced the huge mortality tolls: more than 1000 deaths in the US East Coast and Midwest heat wave of July 1995 and up to 70 000 in the 2003 European heat wave.

Emotion Regulation (ER) difficulties are ubiquitous among individuals with schizophrenia and have been hypothesized to contribute to stress sensitivity and exacerbation of psychotic symptoms in this population. However, the evidence supporting this link is equivocal, potentially due to previous studies’ reliance on retrospective assessments of ER a...

Background: Previous studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic l...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilep...

Objective: Eating disorders (ED) and schizophrenia are frequently comorbid and schizophrenia shares genetic susceptibility with anorexia. Many factors associated with schizophrenia can disrupt eating, but ED can present years before schizophrenia. If premorbid ED distinguishes a particular subtype of schizophrenia, then phenotypic features may dif...

In the original article, there was a small error. We did not add an acknowledgement section, which is required in order to acknowledge a financial contribution we recently received.A correction has therefore been made to the original article and the section ACKNOWLEDGEMENTS has been added:“Sergio Eduardo de Carvalho Machado, was supported by a gran...

Clinical high-risk (CHR) individuals have been increasingly utilized to investigate the prodromal phases of psychosis and progression to illness. Research has identified medial and lateral temporal lobe abnormalities in CHR individuals. Dysfunction in the medial temporal lobe, particularly the hippocampus, is linked to dysregulation of glutamate an...

Aim: The following work aims to investigate the putative correlation between early trauma and cognitive functions, as well as psychotic symptoms and cognitive functions, in individuals diagnosed with schizophrenia. Methods: A quantitative assessment was performed with 20 individuals diagnosed with schizophrenia according to the 5th edition of the D...

Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage. Method: Relative Risks (RR) for schizophrenia were estima...

This study used machine-learning algorithms to make unbiased estimates of the relative importance of various multilevel data for classifying cases with schizophrenia (n = 60), schizoaffective disorder (n = 19), bipolar disorder (n = 20), unipolar depression (n = 14), and healthy controls (n = 51)into psychiatric diagnostic categories. The Random Fo...

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals...

Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, ma...

he association of early trauma exposure with current cognition was examined in a research series of 56 schizophrenia cases with respect to the BDNF Val66Met polymorphism (rs6265, Val66Val, Val66Met, Met66Met), as met allele carriers have reduced neurotrophic activity. The Perceptual Organization Index had a significant negative correlation with tra...

The ability to mentalize, or theory of mind (ToM), is sexually dimorphic in humans and impaired in schizophrenia. This sex-stratified study probed cognitive (indexed by intelligence) and affective (indexed by olfactory tasks) contributions to ToM performance in 37 individuals with schizophrenia and 31 healthy controls. The schizophrenia group showe...

Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. BD subtypes schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I) and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania and depress...

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophr...

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural eq...

Objective To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. Methods Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) underwent retrospective symp...

The purpose of this article is to determine the risk of schizophrenia in offspring of women exposed to x-ray radiation during pregnancy. The risk of schizophrenia was evaluated using cohort data collected in The Jerusalem Perinatal Study. The cohort of 92,408 births from 1964 to 1976 was linked to Israel’s National Psychiatric Registry of all indiv...

Background: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex e...

Mounting evidence supports a genetic-vascular-inflammatory etiology of schizophrenia. The retina provides an indirect assessment of inflammation and degeneration in the brain. In particular, the use of spectral domain optical coherence tomography (SD-OCT) has emerged as a powerful tool for examining single retinal nerve cell layers and the choroid,...

Objective: This study compared health care access and utilization among adults with serious psychological distress by race-ethnicity and gender in years surrounding implementation of the Affordable Care Act. Methods: Data for adults ages 18 to 64 with serious psychological distress in the 2006-2015 National Health Interview Survey (N=8,940) were...

Objective: There is limited research on metabolic abnormalities in psychotropic-naïve patients with serious mental illness (SMI). Our study examined metabolic conditions in a large, ethnically diverse sample of psychotropic-naïve and non-naïve adults with SMI at an urban public hospital. Methods: In this cross-sectional study of 923 subjects, th...

Zinc dysregulation is linked to neuropsychiatric disorders and a beneficial response to zinc supplementation has been demonstrated for depression. In this case series, we examined serum zinc levels with respect to clinical factors among 20 acutely ill psychiatric cases admitted to a large urban public hospital. The results showed frank clinical zin...

Although the Positive and Negative Syndrome Scale (PANSS) is widely used in clinical research, factor analytic studies of the scale have been inconsistent and questions remain about the underlying factor structure of schizophrenia symptoms. The purpose of this study was to examine whether the factor structure of the PANSS differs in men and women w...

Early trauma (ET), though broadly and inconsistently defined, has been repeatedly linked to numerous psychological disturbances, including various developmental stages of psychotic disorders. The prodromal phase of psychosis highlights a unique and relevant population, that provides insight into the critical periods of psychosis development. As suc...

Background: Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relations...

The risk for diabetes risk is significantly elevated in persons who are older, overweight and have serious mental illness. However, primary care practitioners (PCP) tend to underestimate this risk. Although there are few opportunities for early detection of diabetes, blood exuded during routine oral exams in dental settings can be used to assess gl...

Twenty patients with DSM5 schizophrenia were comprehensively and formally assessed by an experienced psychiatrist. All subjects were assessed for: positive and negative psychotic symptoms; social anxiety; panic anxiety; obsessive compulsive disorder, atypical depression; major depression; suicide risk; and global assessment of functioning. Differen...

Brain Derived Neurotrophic Factor (BDNF) gene has a functional variant resulting in a Valine (VAL) to Methionine (MET) substitution at codon 66 of the pro-BDNF. The low active MET variant is related to reduced BDNF release (Egan et al., 2003). BDNF's expression in adult life may be modulated by exposures during childhood development, with reduced e...

Zinc participation is essential for all physiological systems, including neural functioning, where it participates in a myriad of cellular processes. Converging clinical, molecular, and genetic discoveries illuminate key roles for zinc homeostasis in association with clinical depression and psychosis which are not yet well appreciated at the clinic...