Biomedical subjects

Jill M Goldstein

Publications and source records attributed to Jill M Goldstein.

At least 19 recordsLinked to original sources

PubMed2006

Neuroanatomic substrates of sex differences in language dysfunction in schizophrenia: a pilot study.

OBJECTIVE: This pilot study investigated whether our previous findings of disrupted normal sexual brain dimorphisms in language-associated regions in schizophrenia were linked with our previously reported sex differences in language dysfunction in schizophrenia. METHOD: Nineteen adults with schizophrenia and 15 normal comparisons were tested on phonology, semantics and grammar and underwent structural MRI. RESULTS: Among males, left hippocampal and left planum temporale (PT) abnormalities were associated with phonological, semantic and grammar deficits, accounting for 17-52% and 27-33%, respectively, of variance in diagnostic group differences. Anterior cingulate gyrus was significantly associated with semantics. Among females, right Heschl's Gyrus (HG) and left PT were significantly associated with phonology, right HG with semantics and grammar and right hippocampus with semantics. CONCLUSIONS: These preliminary findings suggest disrupted sexual brain dimorphisms in schizophrenia are associated with sex-specific language deficits, and left hippocampal abnormalities, in particular, contribute to language dysfunction among men. Abnormalities in right cortical temporal regions showed stronger associations with language dysfunction among females.

Adolescent↗

PubMed2006

Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability.

BACKGROUND: This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. METHODS: Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. RESULTS: Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. CONCLUSIONS: Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities.

Adult↗

PubMed2006

Sex, hormones and affective arousal circuitry dysfunction in schizophrenia.

Women with schizophrenia express affective disturbances disproportionately more than men. Brain regions implicated in the affective arousal circuitry also regulate the hypothalamic-pituitary-adrenal and -gonadal systems, which are dysfunctional in schizophrenia. This review will argue that understanding the etiology of affective arousal deficits in schizophrenia is intimately connected with characterizing the role of neuroendocrine dysfunction and sex effects in schizophrenia. Further, the etiology of these neuroendocrine deficits begins during fetal development, during a period of time that coincides with the sexual differentiation of the brain and the vulnerability for schizophrenia. Studying the links between deficits in neuroendocrine systems and the affective arousal system in schizophrenia will provide clues to understanding the development of sex differences in schizophrenia and thereby its etiology.

Animals↗

PubMed2006

Decreased volume of left and total anterior insular lobule in schizophrenia.

The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.

Adolescent↗

PubMed2006

Fear conditioning and extinction: influence of sex and menstrual cycle in healthy humans.

Although sex differences have been demonstrated in behavioral paradigms of fear conditioning, the findings have been inconsistent, and fear extinction has been little studied. The present study investigated the influence of sex and menstrual cycle phase on the recall of fear extinction. Three groups of healthy adult participants were studied: women at 2 different phases of the menstrual cycle (early follicular [early cycle] and late follicular [midcycle]) and men. Participants underwent a 2-day fear conditioning and extinction protocol. The paradigm entailed habituation, fear conditioning, and extinction learning on Day 1 and extinction recall and fear renewal on Day 2. Skin conductance served as the dependent variable. During fear acquisition on Day 1, men showed significantly larger conditioned responses relative to women; early cycle and midcycle women did not differ. No significant group differences were found during extinction learning. On Day 2, men and early cycle women expressed greater extinction memory than midcycle women. These data confirm sex differences in conditioned fear acquisition and suggest that midcycle hormones attenuate extinction recall.

Adult↗

PubMed2006

Intellectual decline in schizophrenia: evidence from a prospective birth cohort 28 year follow-up study.

It is well established that IQ is lower among persons with schizophrenia than in the general population. However, it remains unclear if there is deterioration beyond a premorbid deficit. In order to assess the question of IQ deterioration, we assessed persons pre- and-post psychosis, comparing those who developed schizophrenia with those who did not. Twenty six patients with schizophrenia and 59 normal controls, evaluated at age 7 in the prospective, longitudinal, National Collaborative Perinatal Project (NCPP), were re-tested approximately 28 years later. We assessed change in an estimate of IQ based on the Vocabulary and Block Design tests from the Wechsler intelligence scales. Persons who later developed schizophrenia were significantly impaired on IQ compared to controls at age 7, especially on measures of attention. At age 35, persons with schizophrenia demonstrated significant impairment and deterioration on both IQ sub-tests compared to controls. Because impairment occurs by early childhood and subsequent deterioration occurs at an unknown period, designs with more frequent assessment of IQ through the premorbid, prodromal and early phases of illness are required to identify the key period of decline. Future research on this sample will evaluate the prospective roles of family history and perinatal complications on cognition, and assess the specificity of these findings.

Achievement↗

PubMed2006

Sex differences in language dysfunction in schizophrenia.

OBJECTIVE: Normal sex differences in language functions are disrupted in schizophrenia. However, identification of specific language components most vulnerable in schizophrenia and how they may differ by sex remain unexamined. The current study investigated this issue in the domains of phonology, semantics, and grammar, which have been closely linked with neuroanatomic regions for which sex differences have been identified. METHOD: Thirty-one outpatients with DSM-III-R schizophrenia and 27 healthy subjects comparable within sex on age, handedness, parental socioeconomic status, and ethnicity were systematically ascertained from a Boston catchment area. The subjects were administered an extensive language battery in the context of a comprehensive neuropsychological battery that included measures of phonology, semantics, and grammar. RESULTS: Male patients performed significantly worse than their healthy counterparts on all three domains, with phonology least affected. In contrast, language function was relatively preserved in the female patients, compared to their healthy counterparts, with phonology most affected. Across domains, the effect sizes in comparisons of male patients and healthy male subjects had a twofold difference, whereas the difference in effect sizes in comparisons of female patients and healthy female subjects was less in all areas. CONCLUSIONS: Findings were consistent with prior evidence of overall language dysfunction in schizophrenia and may have implications for understanding sex differences in neuroanatomic abnormalities in regions associated with phonological processing.

Adult↗

PubMed2005

Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging.

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.

Adult↗

PubMed2005

The effect of working memory performance on functional MRI in schizophrenia.

INTRODUCTION: Studies of prefrontal cortical (PFC) function in schizophrenia have been inconsistent, with studies showing both increased and decreased PFC activation compared to healthy controls. Discrepant findings may be due to task performance effects or demographic differences between samples. We report functional magnetic resonance imaging (fMRI) data comparing subjects with schizophrenia and healthy controls performing a 2-back working memory (WM) task, addressing the effects of task performance. METHODS: Twenty-two controls and 14 patients with DSM-IV schizophrenia, scanned on a Siemens 1.5 T scanner, performed a visual letter 2-back task and control task (CPT-X) during fMRI. Data were analyzed using Statistical Parametric Mapping (SPM)-99. RESULTS: After statistical adjustment for performance differences, persons with schizophrenia showed significantly greater activation than controls in the right medial frontal gyrus and left inferior parietal lobule/medial temporal gyrus region (BA 39/40), and a trend toward greater activation in the left ventrolateral PFC. This pattern was also observed in demographically matched subgroups of participants. CONCLUSIONS: Data are consistent with findings reported in recent studies showing increased PFC and parietal activation in schizophrenia when the effects of reduced WM task performance in patients with schizophrenia are addressed. Further studies are needed to clarify the pathophysiological basis of WM load sensitivity in schizophrenia and its relationship to genes.

Adult↗

PubMed2005

Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory.

Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results.

Acoustic Stimulation↗

PubMed2004

The retrospective measurement of prenatal and perinatal events: accuracy of maternal recall.

Adverse obstetric events have been implicated as risk factors for schizophrenia. Many studies have relied on retrospective recall of these events, given typical adult onset of schizophrenia, when most studies ascertain their samples. The goal of this study was to assess the validity of an interview for the long-term recall of prenatal and perinatal events. Ninety-six women from the Providence and Boston cohorts of the National Collaborative Perinatal Project were administered a brief structured telephone interview regarding their recall of pregnancy-related events that had occurred 22 years or more prior to interview. Women accurately reported major medical events such as cesarean section, breech delivery, and multiple birth (kappa=1) and demographic items, such as age at birth and parity. Medical interventions and major medical conditions such as placental (kappa=-0.01) and cord (kappa=-0.10) difficulties were not accurately reported. Estimated birthweight, low birthweight, and length of gestation were recalled with reasonable accuracy. Women who completed high school generally recalled events more accurately than those who did not. It is therefore important to attend to the sources of information, the mode of interviewing, the specific type of event, and sociodemographic characteristics of the informant to improve the accuracy of retrospective data on obstetric events, and to increase the validity of findings relating these to the onset of schizophrenia.

Adolescent↗

PubMed2004

Decreased absolute amygdala volume in cocaine addicts.

The amygdala is instrumental to a set of brain processes that lead to cocaine consumption, including those that mediate reward and drug craving. This study examined the volumes of the amygdala and hippocampus in cocaine-addicted subjects and matched healthy controls and determined that the amygdala but not the hippocampus was significantly reduced in volume. The right-left amygdala asymmetry in control subjects was absent in the cocaine addicts. Topological analysis of amygdala isosurfaces (population averages) revealed that the isosurface of the cocaine-dependent group undercut the anterior and superior surfaces of the control group, implicating a difference in the corticomedial and basolateral nuclei. In cocaine addicts, amygdala volume did not correlate with any measure of cocaine use. The amygdala symmetry coefficient did correlate with baseline but not cocaine-primed craving. These findings argue for a condition that predisposes the individual to cocaine dependence by affecting the amygdala, or a primary event early in the course of cocaine use.

Adult↗

PubMed2004

Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study.

BACKGROUND: First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks. We used functional magnetic resonance imaging (fMRI) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex (PFC), thalamus, hippocampus, and anterior cingulate during a working memory task requiring interference resolution. METHODS: Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory, verbal working memory version of the Continuous Performance Test during fMRI. An asymmetric, spin-echo, T2*-weighted sequence (15 contiguous, 7-mm axial slices) was acquired on a full-body MR scanner. Data were analyzed by Statistical Parametric Mapping (SPM). RESULTS: Compared with control subjects, relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus. When task performance was controlled, relatives showed significantly greater activation in the anterior cingulate. When effects of other potentially confounding variables were controlled, relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate. CONCLUSIONS: This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis. These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia.

Adult↗

PubMed2003

A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

Adult↗

PubMed2002

Antipsychotic medication, prolactin elevation, and ovarian function in women with schizophrenia and schizoaffective disorder.

Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic with prolactin-elevating potential (five with typical antipsychotics and three with risperidone) and eight treated with an antipsychotic with prolactin-sparing potential (seven with olanzapine and one with clozapine), were studied for eight weeks. Data were collected on menstrual functioning and on serum prolactin, estradiol, and progesterone levels, and were compared between subjects who received an antipsychotic with prolactin-elevating potential and an antipsychotic with prolactin-sparing potential, and between subjects with hyperprolactinemia (N=6) and normoprolactinemia (N=10). Additionally, peak ovarian hormone levels were compared to normal values. While mean prolactin levels of subjects who received an antipsychotic with prolactin-elevating potential were significantly greater than those of subjects who received an antipsychotic with prolactin-sparing potential, there were no differences in rates of menstrual dysfunction or in ovarian hormone values between the two groups. Additionally, similar rates of menstrual dysfunction and ovarian hormone values were observed between the hyperprolactinemic and normoprolactinemic subjects. Moreover, irrespective of medication type or prolactin status, most subjects had peak estradiol levels below normal reference values for the periovulatory phase of the menstrual cycle. While our sample size is small, warranting the need for further investigation, the findings of this preliminary study suggest that antipsychotic-induced hyperprolactinemia, alone, may not adequately explain the observed ovarian dysfunction in women with schizophrenia.

Adult↗

PubMed2002

Sex differences in clinical response to olanzapine compared with haloperidol.

There is current disagreement over whether men and women respond differently to typical or atypical antipsychotic medications. This study reanalyzed a large international clinical trial of olanzapine (Olz) compared with haloperidol (Hal) to test for sex differences in treatment response, controlling for illness chronicity and menopausal status. We hypothesized that women would show a greater response to either medication than men, particularly among first admission, premenopausal women. DSM-III-R schizophrenia inpatients (700 women and 1295 men) were randomly assigned to a 6-week trial of Olz vs. Hal. Longitudinal random effect models were used to test for interactions of sex with medication, chronicity and menopausal status on treatment response. Findings showed that women on olanzapine had a greater drop in overall symptomatology by week 4 than any other group, and their level of symptomatology remained lower throughout the 6-week trial. The sex differences in treatment response in olanzapine compared with haloperidol were, in part, dependent on chronicity and, in women, menopausal status. That is, first episode women on haloperidol exhibited an increase in symptomatology over the 6-week trial compared to their male counterparts, while multiply hospitalized women had a better treatment response on haloperidol than their male counterparts. Women on olanzapine had a significantly better treatment response than men, regardless of chronicity. Finally, premenopausal women had a significantly better treatment response than postmenopausal women, regardless of treatment and chronicity.

Adult↗

PubMed2002

A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses.

Evidence for neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia, patients with chronic psychotic bipolar disorder and normal controls. Groups were comparable on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also relatively similar on age at onset and number of hospitalizations. Using multivariate analyses of variance with sex and parental SES as covariates (our primary analyses), patients with schizophrenia were significantly more impaired than controls on seven of eight neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on declarative verbal memory, and showed moderate-to-large effect size decrements on abstraction, perceptual-motor speed and vigilance. Results were not attenuated when IQ was controlled, which was significantly lower in patients with schizophrenia. Analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.

Adult↗

PubMed2002

Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging.

BACKGROUND: Previous studies suggest that the impact of early insults predisposing to schizophrenia may have differential consequences by sex. We hypothesized that brain regions found to be structurally different in normal men and women (sexual dimorphisms) and abnormal in schizophrenia would show significant sex differences in brain abnormalities, particularly in the cortex, in schizophrenia. METHODS: Forty outpatients diagnosed as having schizophrenia by DSM-III-R were systematically sampled to be comparable within sex with 48 normal comparison subjects on the basis of age, ethnicity, parental socioeconomic status, and handedness. A comprehensive assessment of the entire brain was based on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate general linear models for correlated data were used to test for sex-specific effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal fluid brain volumes, adjusted for age and total cerebrum size. Sex x group interactions were also tested on asymmetries of the planum temporale, Heschl's gyrus, and superior temporal gyrus, additionally controlled for handedness. RESULTS: Normal patterns of sexual dimorphisms were disrupted in schizophrenia. Sex-specific effects were primarily evident in the cortex, particularly in the frontomedial cortex, basal forebrain, cingulate and paracingulate gyri, posterior supramarginal gyrus, and planum temporale. Normal asymmetry of the planum was also disrupted differentially in men and women with schizophrenia. There were no significant differential sex effects in subcortical gray matter regions or cerebrospinal fluid. CONCLUSION: Factors that produce normal sexual dimorphisms may be associated with modulating insults producing schizophrenia, particularly in the cortex.

Adult↗