Biomedical subjects

Jeremy M Silverman

Publications and source records attributed to Jeremy M Silverman.

At least 37 records · Page 2Linked to original sources

PubMed2004

Effects of acute metabolic stress on the dopaminergic and pituitary-adrenal axis activity in patients with schizotypal personality disorder.

BACKGROUND: Stress has been associated with the onset of schizophrenia and exacerbation of psychotic symptoms. Patients with schizotypal personality disorder (SPD), the prototypic schizophrenia spectrum disorder, do not develop the frank psychosis of schizophrenia and appear clinically to be less reactive to stress than schizophrenic patients. Schizophrenic patients demonstrate increased dopaminergic (DA) and hypothalamic-pituitary-adrenal-axis (HPA) activation following 2-deoxyglucose (2-DG), an acute metabolic (glycopyruvic) stressor, compared to healthy volunteers (HV). We hypothesized that SPD patients would demonstrate comparable or lower DA and HPA responses after 2-DG to HV. METHODS: Fifteen SPD patients and 13 HV were administered 2-DG (40 mg/kg, i.v.) in a double-blind, placebo-controlled, randomized protocol. The area under the curve (AUC) was determined for plasma HVA, ACTH and cortisol (utilizing baseline and post infusion indices). RESULTS: 2-DG induced significant increases in ACTH, cortisol and HVA concentrations in both groups and cortisol elevations were significantly lower in patients with SPD than in HV. CONCLUSIONS: Patients with SPD have a blunted cortisol and a normal dopaminergic response to 2-DG. These results are consistent with the hypothesis that SPD patients are better buffered against DA and HPA overactivation in response to stress.

Acute Disease↗

PubMed2004

Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia.

Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia--and, more recently, for bipolar disorder--on chromosome 6q13-q26. We genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the MOXD1-STX7-TRARs gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (P=.0014) within the TRAR4 (trace amine receptor 4) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the TRAR4 region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.

Black or African American↗

PubMed2004

Familial symptom domains in monozygotic siblings with autism.

Autism is characterized by a triad of symptom domains (impaired social interaction, communication deficits, and repetitive behaviors) that vary significantly in their clinical presentation across the population. Within families with more than one affected member, however, discrepant findings exist with regard to symptom variability. Reduced intrafamily variance is of particular importance because it supports an underlying model of genetic heterogeneity in the transmission of autism, and the identification of familial clinical subtypes can be used to select more homogeneous samples for linkage analysis in the future. This study examines whether there are specific features of autism that show decreased variance within 16 families with monozygotic siblings concordant for autism. Evidence for familiality was defined as significantly decreased variance of symptom levels within monozygotic siblingships as compared to between siblingships. Using regression analysis, we demonstrated significant aggregation of symptoms within monozygotic siblingships for two of the three main symptom domains in autism: impairments in communication and social interaction showed significant familiality. Within the repetitive behavior domain, only the categories of circumscribed interests and preoccupation with part-objects showed reduced variance within siblingships. In addition, with the exception of a negative association between the social and behavior domains, partial correlation coefficients did not reveal significant associations between the levels of different symptom domains within families, suggesting that the levels of clinical features seen in autism may be a result of mainly independent genetic traits. Because of presumed genetic heterogeneity and the wide clinical variation seen in autism and other pervasive developmental disorders, selecting probands according to specific features known to show reduced variance within families may provide more homogeneous samples for genetic analysis and strengthen the power to detect the specific genes involved in autism.

Autistic Disorder↗

PubMed2004

Tolerance of MRI procedures by the oldest old.

OBJECTIVES: The study aimed to evaluate the feasibility and discomfort of magnetic resonance imaging (MRI) procedures in the oldest-old subjects (age > 90 years) using a survey design in a university-affiliated neuroimaging research center. PARTICIPANTS: Forty-one community-dwelling, elderly subjects were considered for participation. Twenty-nine of them underwent voluntary, extensive MRI scanning (up to 1 h) as part of a project on brain function in the oldest old. Thirteen oldest old (OO, range 90-93 years, mean 92 years) were compared to 16 young old (YO, range 72-80 years, mean 76 years). MEASUREMENTS: Likert-style questionnaire on satisfaction following extensive MRI scanning session (up to 1 h) was administered. Data were analyzed by an analysis of variance (gender by age group). RESULTS: All subjects reported positive experiences with no significant difficulties or concerns. There were minor differences in some rated items, with the OO and males slightly less comfortable than YO and females, respectively. Overall, the OO tolerated the procedures as well as the YO. CONCLUSION: Very long MRI sessions are feasible, even in the oldest-old subjects, and are not associated with any significant discomfort. Prior screening and thorough education of the subjects probably help to minimize anxiety and dropout.

Adolescent↗

PubMed2004

Context-processing deficits in schizotypal personality disorder.

Research suggests that schizotypal personality disorder (SPD) is a part of the spectrum of schizophrenia-related illnesses. This article hypothesizes that a deficit in the representation and maintenance of context is a core cognitive disturbance in schizophrenia and that SPD individuals should demonstrate context-processing deficits. To test this hypothesis, the authors administered 3 versions of their AX-CPT task, designed to assess context processing, to 35 healthy controls and 26 individuals with DSM-IV SPD. They also administered working memory and selective attention tasks. SPD individuals displayed context representation deficits similar to those found in schizophrenia but did not show the same additional deficits in context maintenance. Context processing was strongly associated with working memory and selective attention performance in the SPD individuals.

Adult↗

PubMed2004

Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism.

OBJECTIVE: Autism/autistic disorder (MIM number 209850) is a complex, largely genetic psychiatric disorder. The authors recently mapped a susceptibility locus for autism to chromosome region 2q24-q33 (MIM number 606053). In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region. METHOD: Mutation screening of positional candidate genes was performed in two stages. The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). In the second stage, the two SNPs in SLC25A12 were further genotyped in 411 autistic families, and linkage and association tests were carried out in the 197 informative families. RESULTS: Linkage and association were observed between autistic disorder and the two SNPs, rs2056202 and rs2292813, found in SLC25A12. Using either a single affected subject per family or all affected subjects, evidence for excess transmission was found by the Transmission Disequilibrium Test for rs2056202, rs2292813, and a two-locus G*G haplotype. Similar results were observed using TRANSMIT for the analyses. Evidence for linkage was supported by linkage analysis with the two SNPs, with a maximal multipoint nonparametric linkage score of 1.57 and a maximal multipoint heterogeneity lod score of 2.11. Genotype relative risk could be estimated to be between 2.4 and 4.8 for persons homozygous at these loci. CONCLUSIONS: A strong association of autism with SNPs within the SLC25A12 gene was demonstrated. Further studies are needed to confirm this association and to decipher any potential etiological role of AGC1 in autism.

Aspartic Acid↗

PubMed2003

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Bipolar Disorder↗

PubMed2003

Obsessive-compulsive behaviors in parents of multiplex autism families.

Parents of autistic probands with high and low rates of repetitive behaviors were compared for rates of obsessive-compulsive traits and disorder. The rate of repetitive behaviors was assessed using the Autism Diagnostic Interview-Revised (ADI-R) in 176 autistic probands from 57 multiplex families. Obsessive-compulsive disorder (OCD) in parents was determined by direct interview using a parental history questionnaire, with screening for obsessive-compulsive traits using the Yale-Brown Obsessive-Compulsive Scale checklist. Children who had high total scores on the repetitive behavior domain of the ADI-R were significantly more likely to have one or both parents with obsessive-compulsive traits or disorder compared with children who had low total scores on this domain. Children with high scores on D1/D2 of the ADI-R (narrow restricted interests and rituals) were significantly more likely to have one or both parents with OCD, especially fathers, than those with low D1/D2. The occurrence of obsessive-compulsive traits or disorder in parents of autistic children in multiplex families is significantly more likely if autistic children have a high occurrence of repetitive behaviors. Dichotomizing autistic probands by severity and type of repetitive behaviors (circumscribed interests and compulsive rituals) may yield more homogenous groups, which could be helpful in genetic linkage studies.

Adult↗

PubMed2003

Familial patterns of risk in very late-onset Alzheimer disease.

BACKGROUND: The incidence of Alzheimer disease (AD) peaks after 85 years of age. Although genetic factors are implicated in AD with substantially earlier onset, the familial characteristics of high-incidence very late-onset AD (VLOAD, defined here as AD with onset age >/=85 years) remain unknown. METHODS: We collected information pertaining to the cognitive status and demographics of 809 parents and siblings of 144 VLOAD probands, 4235 parents and siblings of 793 earlier-onset AD probands, and 7646 parents and siblings of 1493 nondemented elderly probands. Cumulative risks and 5-year interval-specific hazard rate ratios were calculated for AD in relatives of the 2 AD proband groups and relatives of the nondemented elderly group. RESULTS: The cumulative risk for AD in the relatives of VLOAD probands was significantly different than that in the relatives of earlier-onset AD probands (P<.001), but not in the relatives of nondemented elderly probands. Also, the relatives of earlier-onset AD probands had hazard rate ratios ranging from 19.7 in those aged 50 to 54 years to 1.2 in those aged 90 to 94 years. Rates successively dropped as age intervals increased. CONCLUSIONS: At least through the middle of the ninth decade of life, relatives of VLOAD probands have a lower risk for AD than those of earlier-onset AD probands. In addition, the relatively increased risk of relatives of earlier-onset AD probands is highest at younger ages and diminishes with increasing age. In counseling family members of patients with AD concerned about their own risk, the onset age of the patient and the age of the concerned relative should be considered. Very late-onset AD may be a good target for investigating environmental factors associated with AD.

Age Factors↗

PubMed2003

Neurobiologic function and temperament in subjects with personality disorders.

BACKGROUND: Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects. METHODS: A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria) participated in these studies. The prolactin response to fenfluramine (a measure of serotonin function) was obtained for 110 subjects; growth hormone response to clonidine (a measure of noradrenergic function) was obtained for 77 subjects, while homovanillic acid (HVA) at baseline, an index of dopaminergic function, was available for 103 subjects. Measures of central neurotransmitter function (dopaminergic, serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylglycol, respectively) were available for 36 subjects. Separate regression analyses utilizing each of the hypothesized associations, where the TPQ total scores were used as the dependent measures and the biologic indices were the independent measures were conducted. Exploratory correlational analyses between these biologic measures and the four dimensions of the TPQ (and its subscales) were also conducted. (Correlations are reported if they would remain significant at P<.01 level after Bonferroni correction for multiple comparisons across the six neuroendocrine measures). RESULTS: In the regression analyses, there was a trend association between CSF and plasma HVA in predicting novelty-seeking (P<.07). No other significant associations were found in the other three measures. Regarding the individual correlational analyses, the persistence scale of the TPQ was significantly positively correlated with the growth hormone response to clonidine (r=.30, P<.008). The sentimentality subscale (reward dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45, P<.001), while the attachment subscale (also reward dependence) was correlated with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002). CONCLUSION: Limited support was provided for a relationship between monoamines, particularly dopamine and novelty-seeking as well as norepinephrine and reward dependence but other hypothesized relationships were not supported by these measures.

Brain↗

PubMed2003

Abuse and neglect in childhood: relationship to personality disorder diagnoses.

BACKGROUND: Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples. METHODS: This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for ~2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution. RESULTS: Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men. CONCLUSION: These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder.

Adult↗

PubMed2003

The role of childhood trauma in differences in affective instability in those with personality disorders.

BACKGROUND: This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174). METHODS: Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure. RESULTS: A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21-.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores. CONCLUSION: This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder.

Adolescent↗

PubMed2003

Reduced processing resource availability in schizotypal personality disorder: evidence from a dual-task CPT study.

Performance on a dual-task information processing task was investigated in 23 schizotypal personality disorder patients (SPD), 29 patients with other noncluster A personality disorders (OPD) and 8 non-psychiatric healthy controls (NC). All participants were assessed using a computer-based visual continuous performance test (CPT) and an auditory CPT individually, and administered again simultaneously in a dual-task condition. The SPD group showed a greater increase in the number of errors of omission than the OPD group or normal controls on the CPT tasks in the dual-task conditions. Performance operating characteristics indicated that the SPD patients did not allocate their attention in a manner different from the healthy controls, suggesting that poorer performance was due to resource limitations in the dual task condition and not strategic failures. These results are similar to previous studies of patients with schizophrenia, where performance deficits on information processing tests have been shown to be related to resource limitations more than failures in effective allocation of attention.

Acoustic Stimulation↗

PubMed2003

The relationship of borderline personality disorder to posttraumatic stress disorder and traumatic events.

OBJECTIVE: The authors examined the relationship of borderline personality disorder to posttraumatic stress disorder (PTSD) with respect to the role of trauma and its timing. METHOD: The Trauma History Questionnaire and the PTSD module of the Structured Clinical Interview for DSM-III-R were administered to 180 male and female outpatients with a diagnosis of one or more DSM-III-R personality disorders. Path analysis was used to evaluate the relationship between borderline personality disorder and PTSD. RESULTS: High rates of early and lifetime trauma were found for the subject group as a whole. Compared to subjects without borderline personality disorder, subjects with borderline personality disorder had significantly higher rates of childhood/adolescent physical abuse (52.8% versus 34.3%) and were twice as likely to develop PTSD. In the path analysis of the relationship between borderline personality disorder and PTSD, none of the different types of paths (direct path, indirect paths through adulthood traumas, paths sharing the antecedent of childhood abuse) was significant. The associations with both trauma and PTSD were not unique to borderline personality disorder; paranoid personality disorder subjects had an even higher rate of comorbid PTSD than subjects without paranoid personality disorder, as well as elevated rates of physical abuse and assault in childhood/adolescence and adulthood. CONCLUSIONS: The associations of personality disorder with early trauma and PTSD were evident, but modest, in borderline personality disorder and were not unique to this type of personality disorder. The results do not appear substantial or distinct enough to support singling out borderline personality disorder from the other personality disorders as a trauma-spectrum disorder or variant of PTSD.

Adolescent↗

PubMed2003

Deficient attentional modulation of the startle response in patients with schizotypal personality disorder.

OBJECTIVE: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. METHOD: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. RESULTS: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. CONCLUSIONS: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with schizophrenia.

Acoustic Stimulation↗

PubMed2002

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity.

BACKGROUND: Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS: We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS: Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS: Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Adult↗

PubMed2002

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample.

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Africa↗

PubMed2002

Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

Adult↗