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Dolores Malaspina

Publications and source records attributed to Dolores Malaspina.

At least 19 recordsLinked to original sources
PubMed2026

Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.

Bipolar disorder's (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder-and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic-GABAergic gradient along the psychotic factor. BD's genetic architecture appears hierarchical-a general liability resolving into dimensions of course and comorbidity, beyond subtypes.

Journal Article↗
PubMed2025

Mediterranean and standard American diet consumption in psychosis and non-psychosis affective disorders groups: Symptoms and cognition.

UNLABELLED: Research supports an association between diet and health, and emerging evidence suggests that diet is associated with neuropsychiatric symptoms. However, no human study has examined an anti-inflammatory diet across rigorously defined psychiatric diagnoses and its associations with symptom severity and cognition. As inflammation is implicated in mental illness, we investigated adherence to the Mediterranean diet (MD), an anti-inflammatory diet, and the standard American diet (SAD), and examined cross-sectional relationships with psychiatric symptoms and cognition. METHOD: Participants included 54 individuals with psychotic disorders, 30 with non-psychosis affective disorders and 40 healthy controls. Participants underwent diagnostic interviews, PANSS symptom ratings, and MATRICS cognitive assessments. The self-report GBAQ was used to assess adherence to the MD versus SAD. RESULTS: The psychosis group was significantly more likely to consume the SAD than healthy controls (p&#xa0;=&#xa0;0.007), with MD adherence predicting better working memory (r&#xa0;=&#xa0;0.461, p&#xa0;<&#xa0;0.001). In the non-psychosis affective disorders group, MD adherence predicted slower processing speed (r&#xa0;=&#xa0;-0.376, p&#xa0;=&#xa0;0.049). In the non-psychosis affective disorders group, MD predicted reduced PANSS General Psychopathology scale (r&#xa0;=&#xa0;-0.449, p&#xa0;=&#xa0;0.013), as well as the Activation (r&#xa0;=&#xa0;-0.362, p&#xa0;=&#xa0;0.049), and Dysphoric Mood factors (r&#xa0;=&#xa0;-0.403, p&#xa0;=&#xa0;0.027). DISCUSSION: This first-of-its kind study identified poor dietary choices in persons with psychosis, showing significantly lower symptoms and better cognition in association with the MD in transdiagnostic analyses. It supports the study of dietary interventions for prevention and treatment of psychiatric conditions.

Humans↗
PubMed2007

Revisiting the backward masking deficit in schizophrenia: individual differences in performance and modeling with transcranial magnetic stimulation.

BACKGROUND: Deficits in backward masking have been variably reported in schizophrenia patients, but individual differences in the expression of these deficits have not been explicitly investigated. In addition, increased knowledge of the visual system has opened the door for new techniques such as transcranial magnetic stimulation (TMS) to explore these deficits physiologically. METHODS: Patients with schizophrenia and healthy controls were tested using a backward masking paradigm. In order to examine the functionality of visual pathways involved in backward masking, subjects were retested on a backward masking paradigm using single pulse TMS applied to occipital cortex in lieu of the masking stimuli. RESULTS: Compared with controls, patients had significantly delayed recovery from visual backward masking. However, 23.5% of patients (compared to 5% of controls) never recovered to levels approaching unmasked performance. When these subjects were segregated from the analysis, group differences vanished. In addition, stimulus masking with occipital TMS followed the same pattern in both patients and controls. CONCLUSIONS: Observations of individual differences in visual masking performance may identify a subgroup of schizophrenia patients. The TMS data suggest that this deficit may not localize to the occipital cortex. However, TMS can be a useful tool for localizing processing deficits in schizophrenia.

Adult↗
PubMed2006

Tetrachloroethylene exposure and risk of schizophrenia: offspring of dry cleaners in a population birth cohort, preliminary findings.

Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia.

Adult↗
PubMed2006

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia.

BACKGROUND: Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans. METHOD: We investigated whether prenatal exposure to household crowding was associated with the risk of schizophrenia in a sub-cohort of the Jerusalem Perinatal Study (JPS) consisting 11,015 individuals born between 1964 and 1976. During these years mothers participated in face to face interviews in early pregnancy. The prenatal and birth data, including the number of rooms and individuals living in the mothers' household, was cross-linked with the Israel Psychiatric Registry by ministry personnel. RESULTS: 104 schizophrenia cases were identified in the cohort. Offspring who, while in utero, their mother resided in a household with five or more individuals had RR of 1.47 (95% CI: 0.99-2.16, p=0.05) to develop schizophrenia, compared to those whose mother resided with four or fewer individuals. However, when adjusted for paternal age, the RR was reduced to 1.18 (95% CI: 0.76-1.84, p=0.46). The number of rooms in the household and the household crowding during pregnancy did not significantly impact the offspring's risk to develop schizophrenia. CONCLUSION: The link between maternal household crowding during pregnancy and the offspring's risk of schizophrenia was explained primarily by the impact of paternal age. The authors discuss the results in view of findings from animal and human studies.

Cohort Studies↗
PubMed2006

Does unwantedness of pregnancy predict schizophrenia in the offspring? Findings from a prospective birth cohort study.

BACKGROUND: We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring. METHOD: The study was conducted using a large, prospectively collected birth cohort as part of the Prenatal Determinants of Schizophrenia study (PDS). Attitude toward the pregnancy was assessed at the time of the mother's first visit to the prenatal clinic. Cases of schizophrenia and other schizophrenia spectrum disorders in the offspring of these mothers were subsequently ascertained and diagnosed. In univariate and multivariate analyses, we examined the relationship between attitude toward the pregnancy and risk of adult schizophrenia and other schizophrenia spectrum disorders. RESULTS: The unadjusted hazard ratio for the association between ambivalent or negative maternal attitude toward the pregnancy and the risk of schizophrenia spectrum disorders was 1.75, (95% CI=0.97, 3.17, P=0.06). This result was unchanged after adjustment for social class, paternal age, race/ethnicity and other potential confounders. Similar results were observed when only cases with schizophrenia were included in the analysis. CONCLUSIONS: We did not find a statistically significant association in favor of the hypothesis that unwantedness of pregnancy is a risk factor for adult schizophrenia. On the other hand, the magnitude of the observed association was similar to the findings of the only previous study of this question and the confidence limits overlap those findings. Whether unwantedness of pregnancy is a risk factor for adult schizophrenia remains an open question that may be resolved by future research.

Adult↗
PubMed2006

Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey.

Depriving healthy subjects of sleep has been shown to acutely increase blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension through extended exposure to raised 24-hour blood pressure and heart rate, elevated sympathetic nervous system activity, and increased salt retention. Such forces could lead to structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium. Sleep disorders are associated with cardiovascular disease, but we are not aware of any published prospective population studies that have shown a link between short sleep duration and the incidence of hypertension in subjects without apparent sleep disorders. We assessed whether short sleep duration would increase the risk for hypertension incidence by conducting longitudinal analyses of the first National Health and Nutrition Examination Survey (n=4810) using Cox proportional hazards models and controlling for covariates. Hypertension incidence (n=647) was determined by physician diagnosis, hospital record, or cause of death over the 8- to 10-year follow-up period between 1982 and 1992. Sleep durations of < or =5 hours per night were associated with a significantly increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in subjects between the ages of 32 and 59 years, and controlling for the potential confounding variables only partially attenuated this relationship. The increased risk continued to be significant after controlling for obesity and diabetes, which was consistent with the hypothesis that these variables would act as partial mediators. Short sleep duration could, therefore, be a significant risk factor for hypertension.

Adult↗
PubMed2006

Advancing paternal age and autism.

CONTEXT: Maternal and paternal ages are associated with neurodevelopmental disorders. OBJECTIVE: To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD). DESIGN: Historical population-based cohort study. SETTING: Identification of ASD cases from the Israeli draft board medical registry. PARTICIPANTS: We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses. MAIN OUTCOME MEASURES: Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data. RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Adult↗
PubMed2006

Etiological heterogeneity and intelligence test scores in patients with schizophrenia.

Previous research has indicated that patients with a family history of schizophrenia show a greater degree of cognitive and neuropsychological impairment than patients without a family history. We examined the neurocognitive performance, using the WAIS-R, of 51 patients with a family history (familial) and 103 patients without a family history (sporadic) to determine if differences exist that may help to explain the heterogeneous neuropsychological profile of the illness. The family history groups did not differ with respect to gender, diagnosis, ethnicity, age, age of onset, education or duration of illness. Multivariate analyses, covarying for age of onset and education, showed the sporadic group performed significantly better than the familial group on the digit symbol and object assembly subtests, with a trend level difference in overall performance IQ score. Additionally, we identified significant gender differences in favor of males for full scale and verbal IQ, the information, digit span, block design, and arithmetic subtests, and at a trend level, the picture assembly subtest. The family history group differences reflect relative dysfunction in visual attention and scanning, visuomotor control, and spatial processing and reasoning. Overall, the results suggest that sporadic patients have better perceptual-organizational skills and faster speed of processing.

Adult↗
PubMed2006

Schizophrenia: a neurodevelopmental or a neurodegenerative disorder.

The functional decline and onset of psychosis that individuals with schizophrenia experience suggests that schizophrenia has a neurodegenerational origin. However, current research favors a neurodevelopmental model in which individuals with schizophrenia develop abnormalities during brain development. The abnormality that leads to psychosis and deterioration remains latent as the brain develops but emerges concurrently with the brain's normal development or after an outside event that leads to changes in brain function. Prenatal adversity may underlie the neurodevelopmental process and neurodegeneration of schizophrenia. Because psychosis may be a clinically identifiable marker of an underlying neuropathologic process associated with deterioration, the best way to treat the illness is to reduce the duration of untreated psychosis, aim for full remission of psychosis, and combine medication with other therapies.

Antipsychotic Agents↗
PubMed2006

Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection.

Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia.

Adolescent↗
PubMed2005

Computerized experience sampling method (ESMc): assessing feasibility and validity among individuals with schizophrenia.

The Experience Sampling Method (ESM) is an ecologically valid, time-sampling of self-reports developed to study the dynamic process of person-environment interactions. ESM with digital wristwatch and booklets (paper-based ESM; ESMp) has been used extensively to study schizophrenia. The present study is designed to test the feasibility and validity of using Computerized ESM (ESMc) among individuals with schizophrenia. ESMc is advantageous in allowing for recording of precise time-stamps of responses. We used PDAs ("Personal Digital Assistant"; Palm handheld computers) to collect data on momentary psychotic symptoms, mood, and thoughts over a one day period among 10 hospitalized schizophrenia patients and 10 healthy controls. ESMc was equally acceptable to both groups, with similar ratings of comfort carrying the PDAs and operating them, interference with daily activities, as well as response rates. The schizophrenia patients reported significantly higher ratings of auditory and visual hallucinations, suspiciousness, sense of unreality, lack of thought control, fear of losing control, difficulty expressing thoughts, as well as depression/sadness, loneliness and less cheerfulness. Significant inverse relationships were found among both groups between ratings of feeling cheerful and being stressed, irritated, and sad/depressed. Among the schizophrenia subjects, the correlation between ratings of suspiciousness on ESMc and Scale for Assessment of Positive Symptoms (SAPS) approached significance, as well as the link between suspiciousness and stress. Our results support the feasibility and validity of using ESMc for assessment of momentary psychotic symptoms, mood, and experiences among individuals with schizophrenia. The authors discuss the potential applications of combining ESMc with ambulatory physiological measures.

Adolescent↗
PubMed2005

Delusions in individuals with schizophrenia: factor structure, clinical correlates, and putative neurobiology.

BACKGROUND: Delusions are a central feature of schizophrenia, yet our understanding of their neurobiology is limited. Attempt to link dimensions of psychopathology to putative neurobiological mechanisms depends on careful delineation of symptoms. Previous factor analytic studies of delusions in schizophrenia were limited by several methodological problems, including the use of patients medicated with antipsychotics, inclusion of nondelusion symptoms in the analyses, and/or inclusion of patients with psychotic disorders other than schizophrenia. These problems may have possibly biased the resulting factor structure and contributed to the inconclusive findings regarding the neurobiology of positive symptoms. Our goal is to examine the factor structure of delusions in antipsychotic-free individuals with diagnoses of schizophrenia/schizoaffective disorder. SAMPLING AND METHODS: We assessed 83 antipsychotic-free individuals with DSM-IV diagnoses of schizophrenia/schizoaffective disorder. A principal component analysis was conducted on the delusions symptoms of the SAPS. RESULTS: The principal component analysis resulted in three distinct and interpretable factors explaining 58.3% of the variance. The Delusions of Influence factor was comprised by delusions of being controlled, thought withdrawal, thought broadcasting, thought insertion, and mind reading. The Self-Significance Delusions factor was comprised by delusions of grandeur, reference, religious, and delusions of guilt/sin. The Delusions of Persecution factor was comprised solely by persecutory delusions. The three factors displayed distinct associations with hallucinations, bizarre behavior, attention, positive formal thought disorder, and avolition/apathy. CONCLUSIONS: The results indicate that delusions are best described by three distinct subtypes. The authors propose a novel model linking the three delusion subtypes, attributions to self/other, and putative neurobiological mechanisms. Implications for future research are discussed, as well as links to cognitive-behavioral conceptualizations of delusions.

Adolescent↗
PubMed2005

The factorial structure of the schedule for the deficit syndrome in schizophrenia.

Deficit schizophrenia (DS) is considered a distinct subtype within the diagnosis of schizophrenia. While the common assumption is that DS represents a single, cohesive domain of psychopathology, the factorial structure of DS has not been investigated. We assessed 52 individuals with DSM-IV diagnoses of schizophrenia with DS. A principal component analysis (PCA) was conducted on the symptoms of the Schedule for the Deficit Syndrome. The PCA resulted in 2 distinct factors explaining 73.8% of the variance. Factor 1 (avolition) is made up of symptoms of curbing of interests, diminished sense of purpose, and diminished social drive. Factor 2 (emotional expression) is made up of symptoms of restricted affect, diminished emotional range, and poverty of speech. The results indicate that DS is best characterized by these 2 factors. The great majority of participants (86%) displayed DS symptoms from both factors. On average, participants had 4.19 (S.D. = 1.39) symptoms that were primary, enduring, and at least moderate in severity. The mean severity of symptoms was 2.25 (S.D. = 1.06). We discuss possible links between the obtained factors and putative neurobiological mechanisms, as well as directions for future research.

Adolescent↗
PubMed2005

Olfactory deficits, cognition and negative symptoms in early onset psychosis.

BACKGROUND: Smell identification deficits (SID) are common in adult schizophrenia, where they are associated with negative symptoms and lower intelligence. However, smell identification has not been examined in adolescents with early onset psychosis, wherein diagnosis is often obscure, and there are few prognostic predictors. METHOD: We examined smell identification, diagnosis, neuropsychological performance and symptoms in 26 well characterized adolescents with early onset psychosis, age 11-17 years. RESULTS: SID existed in the sample and were more common in patients with schizophrenia and psychotic depression than in patients with psychosis NOS and bipolar disorder. As in adults, SID were significantly associated with greater negative symptoms and lower verbal IQ. However, the associations of verbal IQ (and other verbal tasks) to smell identification in this pediatric sample were explained by the relation of both of these types of variables to negative symptoms. CONCLUSIONS: SID existed across this sample of youths with psychotic disorder, and were specifically related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder, such as grandiosity. SID is a characteristic of early onset psychosis that may be useful for prognostic purposes.

Adolescent↗
PubMed2005

Lack of evidence for elevated obstetric complications in childhood onset schizophrenia.

BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to "earlier" age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings. METHODS: We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia.

Adult↗
PubMed2005

Prodromal interventions for schizophrenia vulnerability: the risks of being "at risk".

Given the morbidity and difficulty of treating psychotic disorders, including schizophrenia, there has been a move toward identifying and treating adolescents and young adults who appear to be clinically at risk or "prodromal" to psychosis. The field now has greater specificity in identification, with rates of 40-50% conversion to frank psychosis within 1-2 years. There is further evidence that medications and other treatments may have some efficacy for "prodromal" patients, though with variable side effects. However, controversy remains about some of the inherent risks in prodromal research, such as medication exposure and stigma among false-positives. In this paper, we add to this discussion through an analysis of ethics in prodromal research from the more established field of predictive genetic testing. Issues are raised about the effects of information on patients, families, and institutions, as well as future insurability, the limits of confidentiality (as it relies on discretion of patients and families), the autonomy of minors with psychiatric symptoms, and even the risks for the true-positive patient.

Confidentiality↗