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Papers by David Fogelson

Research paper thumbnail of Schizophrenia and Schizophrenia-Spectrum Personality Disorders in the First-Degree Relatives of Children With Schizophrenia

Results: There was an increased lifetime morbid risk for schizophrenia (4.95%±2.16%) and schizoty... more Results: There was an increased lifetime morbid risk for schizophrenia (4.95%±2.16%) and schizotypal personal- ity disorder (4.20%±2.06%) in the parents of COS pro- bands compared with parents of ADHD (0.45%±0.45%, 0.91%±0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophre- nia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder

Research paper thumbnail of Interrater reliability of the structured clinical interview for DSM-III-R, Axis II: Schizophrenia spectrum and affective spectrum disorders

Psychiatry Research, 1991

Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical In... more Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical Interview for DSM-III-R, Axis II (SCID-II) administered to the first degree relatives of probands with either DSM-III-R schizophrenia, schizoaffective disorder, or bipolar disorder, for a total of 45 second ratings. Interrater reliability was determined using the intraclass correlation coefficient and ranged from 0.60 to 0.84. The previous studies of the reliability of structured interviews for diagnosing personality disorders are summarized and compared to the present findings. We conclude that the SCID-II can be reliably used to diagnose schizophrenia-spectrum and affective spectrum disorders in the first degree family members of probands with schizophrenic or bipolar affective disorders.

Research paper thumbnail of The factor structure of schizophrenia spectrum signs and symptoms in first-degree relatives of schizophrenic patients from the ucla family members study

Schizophrenia Research, 1997

Selective attention was investigated in chronic schizophrenics and their first-degree relatives, ... more Selective attention was investigated in chronic schizophrenics and their first-degree relatives, classified as schizotypal and non-schizotypal according to DSM-III-R criteria, using two learning procedures. Latent Inhibition (LI) and the Kamin Blocking Effect (KBE). Based on previous findings, schizotypal relatives were predicted to show abolished LI and KBE, and the remaining groups, including a group of normal controls, intact effects. Although changes in the effect of preexposure in both procedures were observed in varying degrees in the clinical group, a surprising finding was a d~lay. in associative leamin~, regardless of diagnostic status, which IS not usually found m normal controls. Results suggest that membership of a schizophrenia-affected kin is associ~t~d~th reduce~~I and~E effects as well as with a deficit m simple associative learning, as compared to the usual performance of normal controls in the same procedures.

Research paper thumbnail of The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study

Schizophrenia Research, 2002

Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate... more Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate in the relatives of schizophrenic patients, supporting the view that both are likely to reflect genetic contributions to liability to schizophrenia. Within the relatives of schizophrenic patients, however, the interrelationships between these potential indicators of liability to schizophrenia are not well known. Using data from the UCLA Family Study, we examine the interrelationships between personality disorder symptoms and neurocognitive functioning in nonpsychotic first-degree relatives of schizophrenic patients. Factor analyses indicate that several dimensions of schizotypy can be identified. A neurocognitive dysfunction dimension includes loadings from measures of sequential visual conceptual tracking, rapid perceptual encoding and search, and focused, sustained attention as well as the rating of odd and eccentric behavior from schizotypal personality disorder. Other aspects of schizotypal personality disorder form separate positive schizotypy and negative schizotypy dimensions. These analyses support the view that schizotypy is multidimensional in relatives of schizophrenic patients and indicate that neurocognitive deficits in perception and attention are associated with particular schizotypal personality features. D

Research paper thumbnail of Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands

Schizophrenia Research, 2004

This study examined the validity of the family history method for diagnosing schizophrenia, schiz... more This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses.

Research paper thumbnail of Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: The UCLA family study

Schizophrenia Research, 2010

Whether avoidant personality disorder symptoms are related to neurocognitive impairments that agg... more Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models. Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent. Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

Research paper thumbnail of Neurocognitive functioning and schizophrenia spectrum disorders can be independent expressions of familial liability for schizophrenia in community control children: the UCLA family study

Schizophrenia Research, 2002

This study provided a further test of the hypothesis that certain neuromotor, language and verbal... more This study provided a further test of the hypothesis that certain neuromotor, language and verbal memory dysfunctions reflect genetic predisposition to schizophrenia, by examining the effects of family loading for schizophrenia (FLS) in normal controls without personal histories of schizophrenia or attention deficit hyperactivity disorder. In a case control design, 11 community controls (CC) with FLS were compared to 47 CC without FLS on tests of expressive and receptive language, visual motor coordination, full scale intelligence and verbal memory. In this study, FLS primarily reflects the incidence of schizophrenia spectrum diagnoses in the second-degree relatives of CC probands. CC probands with FLS had significantly poorer general intelligence, expressive and receptive vocabulary abilities, visual motor coordination and slower motor speed than CC probands without FLS. The variance in neurocognitive functioning associated with FLS is not due to the presence of any psychiatric disorders in CC probands, nor the presence of schizophrenia spectrum disorders in their parents. The relation between FLS and neurocognitive and neuromotor functioning in CC probands was moderated by the parent's cognitive functioning. The results of the present study indicate that familial liability to schizophrenia can be transmitted across two generations, independent of the presence of schizophrenia spectrum disorders in either the parent or proband, and account for significant variance in proband neurocognitive and neuromotor functioning. These findings suggest the neurocognitive and neuromotor functioning and schizophrenia spectrum disorders can be relatively independent expressions of familial liability to schizophrenia. D

Research paper thumbnail of Avoidant personality disorder increases the detection of first degree relatives affected by a schizophrenia spectrum diagnosis

Schizophrenia Research, 2003

Research paper thumbnail of Schizophrenia and schizophrenic spectrum disorders among the first degree relatives of child and young adult onset schizophrenic patients

Schizophrenia Research, 1995

Serotonin (5-HT) receptors are thought to be involved in a range of behaviours including appetite... more Serotonin (5-HT) receptors are thought to be involved in a range of behaviours including appetite, sleep, mood and sexual behaviour and are candidates for aetiological involvements in psychosis and affective disorders. Serotonin receptors have been identified by pharmacological and molecular methods (the 5-HT1, 5-HT2, and 5-HT3 families, 5-HT 4 and the recently described 5-HTs, 5-HT6 and 5-HT7). Atypical neuroleptics show high occupancy of serotonin receptors, specially the 5-HT2 receptor (and the structurally similar 5-HTlc). These 5-HT2 receptors are G-protein-coupled, and share a significant number of molecular, pharmacological and biochemical characteristics. Clozapine, a potent atypical neuroleptic, with up to 60% success in patients refractory to other drugs, has high affinity for 5-HT 2 receptors. We wish to test the hypothesis that a mutation in the genes coding for these receptors could potentially be involved in drug response. A sample of clozapine treated patients (n=l16), including responders and nonresponders to clozapine, was typed for a 5-HT 2 polymorphism described by Warren et al. (1993). This polymorphism, a T/C change at position 102 of the 5-HTz gene has two alleles (C1 and C2) at a frequency of 0.42 and 0.58, respectively. A higher number of homozygous C2/C2 than expected was observed in the group of non-responders (significance p<0.05) suggesting a possible relation between this allele and failure to respond to clozapine. We are currently replicating this study in a larger sample.

Research paper thumbnail of Are schizophrenic deficits in signal detection during vigilance and span of apprehension vulnerability or episode indicators?

Schizophrenia Research, 1989

Research paper thumbnail of MMPI differences among firstdegree relatives of probands with childhood-onset schizophrenia, attention deficit disorder, and normal control children

Schizophrenia Research, 1997

Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree rela... more Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree relatives of pro bands with a recent-onset of schizophrenia to determine whether certain MMPI scales might serve as psychometric indicators of vulnerability to schizophrenia. The first-degree relatives (parents and siblings) were participants in the UCLA Family Members Study, a family genetic study of psychiatric symptoms and information processing anomalies that may be associated with a predisposition to schizophrenia. Only valid profiles of first-degree relatives Ig years and older were examined. All of the mean scores on MMPI basic clinical scales were in the nonpathological range. However, all of the basic clinical scales, with the exception of Si, were significantly elevated in relation to the standardization norms for adults. The highest mean scores were on scales Pd and Sc, which are associated with hostility and schizophrenia. The relatives of the schizophrenia probands were more likely to score in the clinical range (T-score > 70) on scales Pd and Sc than would be expected based on the normative sample. These two scales have previously been shown to be elevated in MZ twins of schizophrenia probands (Gottesman and Shields, 1972) and thus may represent personality traits associated with a genetic predisposition to schizophrenia.

Research paper thumbnail of MMPI profiles of first-degree relatives of recent-onset schizophrenia probands

Schizophrenia Research, 1997

Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree rela... more Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree relatives of pro bands with a recent-onset of schizophrenia to determine whether certain MMPI scales might serve as psychometric indicators of vulnerability to schizophrenia. The first-degree relatives (parents and siblings) were participants in the UCLA Family Members Study, a family genetic study of psychiatric symptoms and information processing anomalies that may be associated with a predisposition to schizophrenia. Only valid profiles of first-degree relatives Ig years and older were examined. All of the mean scores on MMPI basic clinical scales were in the nonpathological range. However, all of the basic clinical scales, with the exception of Si, were significantly elevated in relation to the standardization norms for adults. The highest mean scores were on scales Pd and Sc, which are associated with hostility and schizophrenia. The relatives of the schizophrenia probands were more likely to score in the clinical range (T-score > 70) on scales Pd and Sc than would be expected based on the normative sample. These two scales have previously been shown to be elevated in MZ twins of schizophrenia probands (Gottesman and Shields, 1972) and thus may represent personality traits associated with a genetic predisposition to schizophrenia.

Research paper thumbnail of Cognitive/neuropsychological abnormalities in the parents of children with a schizophrenic disorder

Schizophrenia Research, 1997

Research paper thumbnail of Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression

Psychopharmacology, 2000

Rationale: The utility of fluphenazine levels during maintenance treatment of schizophrenia is st... more Rationale: The utility of fluphenazine levels during maintenance treatment of schizophrenia is still unclear. Objectives: This study investigated the relationship between fluphenazine levels and a variety of clinical measures during maintenance treatment of schizophrenia. Methods: Fluphenazine levels, side effects, depression and psychosocial outcome were measured at five time points over approximately 1 year in 59 recent onset schizophrenic patients treated with a maintenance dose of injectable fluphenazine decanoate. Negative symptoms were evaluated at the 1-year endpoint. Results: Fluphenazine levels showed marked intraindividual variability even when measurements were restricted to the second 6 months of treatment, by which time steady state levels should have been achieved. No consistent relationship was found between fluphenazine levels and any of the outcome measures.

Research paper thumbnail of Persistence of Fluphenazine in Plasma after Decanoate Withdrawal

Journal of Clinical Psychopharmacology, 1988

We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12... more We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12 recent onset clinically stable schizophrenics who had been given fluphenazine decanoate 12.5 mg intramuscularly every 2 weeks for at least 1 year prior to drug withdrawal. Each condition (drug or placebo) lasted 12 weeks. Using a radioimmunoassay verified by comparison to a gas chromatographic-mass spectrometric method, plasma fluphenazine levels were measured every 2 weeks during drug continuation and drug withdrawal conditions. No patient relapsed over the 24-week period of the study. Mean fluphenazine levels between drug continuation and withdrawal conditions showed a progressively larger difference over time, although significant differences were not seen until week 8. By week 12 after drug withdrawal, 33% of subjects still showed notable plasma fluphenazine levels. On the basis of our preliminary findings, we suggest that 2-week intervals between injections may be too short and that wider intervals may achieve similar clinical results.

Research paper thumbnail of The factor structure of schizophrenia spectrum personality disorders: signs and symptoms in relatives of psychotic patients from the UCLA family members study

Psychiatry research, 1999

The dimensions and limits of the concept of schizotypy are examined using an exploratory factor a... more The dimensions and limits of the concept of schizotypy are examined using an exploratory factor analysis of the 36 signs and symptoms in the Cluster A DSM-III-R personality disorders as well as those in Borderline Personality Disorder and Avoidant Personality Disorder in the 307 first-degree relatives and half-siblings of 123 probands with schizophrenia/schizoaffective disorder. The personality disorders examined were assessed using sections of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and hospital and clinic records. Interviewers were blind to the proband diagnosis. The resulting six-factor solution accounted for 40% of the variance. The results of the six-factor solution accounted for the greatest variance and gave the most easily interpretable simple structure of all the solutions examined. The six factors are labeled as (1) Borderline Symptoms, (2) Schizoid Symptoms, (3) Paranoid Symptoms, (4) Avoidant Symptoms, (5) Positive Schizotypy Symptoms, and (6) Disorganized Symptoms. The Schizotypal Personality items are spread across all but the &#39;Borderline Symptoms&#39; factor. We conclude schizotypy is a multidimensional construct that is not adequately characterized by any one DSM-III-R personality disorder. It appears to consist of six distinct dimensions, which, interestingly, parallel current thinking on dimensions in schizophrenia.

Research paper thumbnail of 130. Risperidone is associated with better work recovery after onset of schizophrenia

Biological Psychiatry, 2000

Most studies suggest that atypical neuroleptics are about equivalent in subjective measures of ef... more Most studies suggest that atypical neuroleptics are about equivalent in subjective measures of efficacy, extrapyramidal side effects, and tardive dyskinesia. We are comparing and contrasting the effects of olanzapine 5-20 mg/day and risperidone 2-8 mg/day in outpatients with schizophrenia. Our hypothesis is that risperidone will cause more hand force instability, tremor, and bradykinesia as compared to olanzapine on computerized objective measures because of its greater ex vivo D-2 receptor occupancy. Preliminary analysis (n ϭ 18 total) shows that the hand force instability prior to study initiation was 6.03 (3.3) for the risperidone group and 6.56 (5.4) for the olanzapine group. The hand force instability after two months of treatment reduced to 4.77 (2.1), 29% and 2.99 (0.9), 57%; respectively (F ϭ 4.125, p ϭ 0.05). Hand tremor changed Ϫ10.02db to Ϫ5.93db with risperidone treatment and 4.35db to Ϫ3.03db with olanzapine treatment. Examination of bradykinesia with measures of velocity scaling demonstrates a transition from 2.28 to 2.23 for risperidone treatment vs. 1.54 to 1.67 for olanzapine treatment. These data show that both risperidone and olanzapine improve hyperkinesia and bradykinesia when compared to their status prior to beginning the study. However, olanzapine treatment demonstrated more improvement in hyperkinesia measures, greater decrease in instability and tremor scores, and greater improvement in bradykinesia ie. increased velocity. We will discuss the implications of these data as well as our analysis of the larger 40 patient data set in this presentation.

Research paper thumbnail of MMPI Vulnerability Indicators for Schizophrenia and Attention Deficit Disorder: UCLA Family Study of Biological Parents of Offspring with Childhood-Onset Schizophrenia or ADHD

Behavior Genetics, 2005

Minnesota Multiphasic Personality Inventory (MMPI) scores were examined for 50 parents of childre... more Minnesota Multiphasic Personality Inventory (MMPI) scores were examined for 50 parents of children with an onset of schizophrenia prior to 14 years of age, 153 parents of children with attention deficit hyperactivity disorder (ADHD), and 168 parents of community comparison children. The parents were participants in the UCLA Family Study. The mean scores on all standard MMPI scales were within normal limits for all three groups of participants. Parents of schizophrenia probands were significantly higher on scale Sc than parents of community comparison children. Previous research has shown that scale Sc may be associated with a genetic liability to developing schizophrenia. Thus, scale Sc shows promise as an indicator of a heightened risk for the development of schizophrenia. The parents of the ADHD probands were significantly higher on standard clinical scale Pd than community comparison parents. Mothers of both schizophrenia and ADHD probands shared some personality indicators of stress reactivity. Although this study, like all non-adoptee family studies, cannot disentangle genetic effects on the development of these personality characteristics from environmental effects, we speculate that the emotional distress resulting in higher levels of the MMPI characteristics seen in the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; mothers reflects the impact of raising a psychiatrically ill offspring.

Research paper thumbnail of Neurocognitive Impairments in Nonpsychotic Parents of Children With Schizophrenia and Attention-Deficit/Hyperactivity Disorder

Archives of General Psychiatry, 2002

We tested the hypotheses that certain neurocognitive impairments index genetic liability to schiz... more We tested the hypotheses that certain neurocognitive impairments index genetic liability to schizophrenia and that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining whether parents of COS probands show the types of neurocognitive impairments found in relatives of AOS probands.

Research paper thumbnail of Relationship Between Positive and Negative Symptoms of Schizophrenia and Schizotypal Symptoms in Nonpsychotic Relatives

Archives of General Psychiatry, 2001

Continuous rather than categorical measures of psychopathology may provide greater statistical po... more Continuous rather than categorical measures of psychopathology may provide greater statistical power to detect susceptibility loci for schizophrenia. However, it has not been established that the dimensions of schizophrenic symptomatology and personality traits in nonpsychotic individuals share etiological factors. We therefore sought to clarify the relationship between positive and negative symptoms of schizophrenic probands and dimensions of schizotypy in their first-degree relatives. In the Roscommon Family Study, we examined the ability of positive and negative symptoms in probands to predict 7 factors of schizotypy in nonpsychotic relatives using regression analysis. These consisted of positive, negative, and avoidant symptoms; odd speech; suspicious behavior; social dysfunction; and symptoms of borderline personality disorder. We examined 3 proband groups: schizophrenia (n = 127); schizophrenia, simple schizophrenia, and schizoaffective disorder (n = 178); and all nonaffective psychoses (n = 216), and their nonpsychotic relatives (n = 309, 477, and 584, respectively). Positive symptoms in all nonaffective psychoses probands predicted positive schizotypy (beta = 0.1972, P =.0004), social dysfunction (beta = 0.0719, P =.0489), and borderline personality disorder symptoms (beta = 0.1327, P =.0084) in relatives, while negative symptoms predicted negative schizotypy (beta = 0.2069, P =.0002), odd speech (beta = 0.2592, P =.0001), suspicious behavior (beta = 0.2749, P =.0001), and social dysfunction (beta =.2398, P =.0002). Proband negative symptoms and borderline personality disorder symptoms in relatives in the schizophrenia, simple schizophrenia, and schizoaffective disorder group were inversely related (beta = -0.1185, P =.05). Positive and negative symptoms in schizophrenia predict corresponding schizotypal symptoms in relatives. This provides evidence that these schizophrenic symptom factors (1) are etiologically distinct from each other and (2) occur on an etiological continuum with their personality-based counterparts.

Research paper thumbnail of Schizophrenia and Schizophrenia-Spectrum Personality Disorders in the First-Degree Relatives of Children With Schizophrenia

Results: There was an increased lifetime morbid risk for schizophrenia (4.95%±2.16%) and schizoty... more Results: There was an increased lifetime morbid risk for schizophrenia (4.95%±2.16%) and schizotypal personal- ity disorder (4.20%±2.06%) in the parents of COS pro- bands compared with parents of ADHD (0.45%±0.45%, 0.91%±0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophre- nia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder

Research paper thumbnail of Interrater reliability of the structured clinical interview for DSM-III-R, Axis II: Schizophrenia spectrum and affective spectrum disorders

Psychiatry Research, 1991

Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical In... more Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical Interview for DSM-III-R, Axis II (SCID-II) administered to the first degree relatives of probands with either DSM-III-R schizophrenia, schizoaffective disorder, or bipolar disorder, for a total of 45 second ratings. Interrater reliability was determined using the intraclass correlation coefficient and ranged from 0.60 to 0.84. The previous studies of the reliability of structured interviews for diagnosing personality disorders are summarized and compared to the present findings. We conclude that the SCID-II can be reliably used to diagnose schizophrenia-spectrum and affective spectrum disorders in the first degree family members of probands with schizophrenic or bipolar affective disorders.

Research paper thumbnail of The factor structure of schizophrenia spectrum signs and symptoms in first-degree relatives of schizophrenic patients from the ucla family members study

Schizophrenia Research, 1997

Selective attention was investigated in chronic schizophrenics and their first-degree relatives, ... more Selective attention was investigated in chronic schizophrenics and their first-degree relatives, classified as schizotypal and non-schizotypal according to DSM-III-R criteria, using two learning procedures. Latent Inhibition (LI) and the Kamin Blocking Effect (KBE). Based on previous findings, schizotypal relatives were predicted to show abolished LI and KBE, and the remaining groups, including a group of normal controls, intact effects. Although changes in the effect of preexposure in both procedures were observed in varying degrees in the clinical group, a surprising finding was a d~lay. in associative leamin~, regardless of diagnostic status, which IS not usually found m normal controls. Results suggest that membership of a schizophrenia-affected kin is associ~t~d~th reduce~~I and~E effects as well as with a deficit m simple associative learning, as compared to the usual performance of normal controls in the same procedures.

Research paper thumbnail of The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study

Schizophrenia Research, 2002

Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate... more Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate in the relatives of schizophrenic patients, supporting the view that both are likely to reflect genetic contributions to liability to schizophrenia. Within the relatives of schizophrenic patients, however, the interrelationships between these potential indicators of liability to schizophrenia are not well known. Using data from the UCLA Family Study, we examine the interrelationships between personality disorder symptoms and neurocognitive functioning in nonpsychotic first-degree relatives of schizophrenic patients. Factor analyses indicate that several dimensions of schizotypy can be identified. A neurocognitive dysfunction dimension includes loadings from measures of sequential visual conceptual tracking, rapid perceptual encoding and search, and focused, sustained attention as well as the rating of odd and eccentric behavior from schizotypal personality disorder. Other aspects of schizotypal personality disorder form separate positive schizotypy and negative schizotypy dimensions. These analyses support the view that schizotypy is multidimensional in relatives of schizophrenic patients and indicate that neurocognitive deficits in perception and attention are associated with particular schizotypal personality features. D

Research paper thumbnail of Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands

Schizophrenia Research, 2004

This study examined the validity of the family history method for diagnosing schizophrenia, schiz... more This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses.

Research paper thumbnail of Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: The UCLA family study

Schizophrenia Research, 2010

Whether avoidant personality disorder symptoms are related to neurocognitive impairments that agg... more Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models. Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent. Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

Research paper thumbnail of Neurocognitive functioning and schizophrenia spectrum disorders can be independent expressions of familial liability for schizophrenia in community control children: the UCLA family study

Schizophrenia Research, 2002

This study provided a further test of the hypothesis that certain neuromotor, language and verbal... more This study provided a further test of the hypothesis that certain neuromotor, language and verbal memory dysfunctions reflect genetic predisposition to schizophrenia, by examining the effects of family loading for schizophrenia (FLS) in normal controls without personal histories of schizophrenia or attention deficit hyperactivity disorder. In a case control design, 11 community controls (CC) with FLS were compared to 47 CC without FLS on tests of expressive and receptive language, visual motor coordination, full scale intelligence and verbal memory. In this study, FLS primarily reflects the incidence of schizophrenia spectrum diagnoses in the second-degree relatives of CC probands. CC probands with FLS had significantly poorer general intelligence, expressive and receptive vocabulary abilities, visual motor coordination and slower motor speed than CC probands without FLS. The variance in neurocognitive functioning associated with FLS is not due to the presence of any psychiatric disorders in CC probands, nor the presence of schizophrenia spectrum disorders in their parents. The relation between FLS and neurocognitive and neuromotor functioning in CC probands was moderated by the parent's cognitive functioning. The results of the present study indicate that familial liability to schizophrenia can be transmitted across two generations, independent of the presence of schizophrenia spectrum disorders in either the parent or proband, and account for significant variance in proband neurocognitive and neuromotor functioning. These findings suggest the neurocognitive and neuromotor functioning and schizophrenia spectrum disorders can be relatively independent expressions of familial liability to schizophrenia. D

Research paper thumbnail of Avoidant personality disorder increases the detection of first degree relatives affected by a schizophrenia spectrum diagnosis

Schizophrenia Research, 2003

Research paper thumbnail of Schizophrenia and schizophrenic spectrum disorders among the first degree relatives of child and young adult onset schizophrenic patients

Schizophrenia Research, 1995

Serotonin (5-HT) receptors are thought to be involved in a range of behaviours including appetite... more Serotonin (5-HT) receptors are thought to be involved in a range of behaviours including appetite, sleep, mood and sexual behaviour and are candidates for aetiological involvements in psychosis and affective disorders. Serotonin receptors have been identified by pharmacological and molecular methods (the 5-HT1, 5-HT2, and 5-HT3 families, 5-HT 4 and the recently described 5-HTs, 5-HT6 and 5-HT7). Atypical neuroleptics show high occupancy of serotonin receptors, specially the 5-HT2 receptor (and the structurally similar 5-HTlc). These 5-HT2 receptors are G-protein-coupled, and share a significant number of molecular, pharmacological and biochemical characteristics. Clozapine, a potent atypical neuroleptic, with up to 60% success in patients refractory to other drugs, has high affinity for 5-HT 2 receptors. We wish to test the hypothesis that a mutation in the genes coding for these receptors could potentially be involved in drug response. A sample of clozapine treated patients (n=l16), including responders and nonresponders to clozapine, was typed for a 5-HT 2 polymorphism described by Warren et al. (1993). This polymorphism, a T/C change at position 102 of the 5-HTz gene has two alleles (C1 and C2) at a frequency of 0.42 and 0.58, respectively. A higher number of homozygous C2/C2 than expected was observed in the group of non-responders (significance p<0.05) suggesting a possible relation between this allele and failure to respond to clozapine. We are currently replicating this study in a larger sample.

Research paper thumbnail of Are schizophrenic deficits in signal detection during vigilance and span of apprehension vulnerability or episode indicators?

Schizophrenia Research, 1989

Research paper thumbnail of MMPI differences among firstdegree relatives of probands with childhood-onset schizophrenia, attention deficit disorder, and normal control children

Schizophrenia Research, 1997

Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree rela... more Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree relatives of pro bands with a recent-onset of schizophrenia to determine whether certain MMPI scales might serve as psychometric indicators of vulnerability to schizophrenia. The first-degree relatives (parents and siblings) were participants in the UCLA Family Members Study, a family genetic study of psychiatric symptoms and information processing anomalies that may be associated with a predisposition to schizophrenia. Only valid profiles of first-degree relatives Ig years and older were examined. All of the mean scores on MMPI basic clinical scales were in the nonpathological range. However, all of the basic clinical scales, with the exception of Si, were significantly elevated in relation to the standardization norms for adults. The highest mean scores were on scales Pd and Sc, which are associated with hostility and schizophrenia. The relatives of the schizophrenia probands were more likely to score in the clinical range (T-score > 70) on scales Pd and Sc than would be expected based on the normative sample. These two scales have previously been shown to be elevated in MZ twins of schizophrenia probands (Gottesman and Shields, 1972) and thus may represent personality traits associated with a genetic predisposition to schizophrenia.

Research paper thumbnail of MMPI profiles of first-degree relatives of recent-onset schizophrenia probands

Schizophrenia Research, 1997

Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree rela... more Minnesota MUltiphasic Personality Inventory (MMPI) scores were examined for 150 first-degree relatives of pro bands with a recent-onset of schizophrenia to determine whether certain MMPI scales might serve as psychometric indicators of vulnerability to schizophrenia. The first-degree relatives (parents and siblings) were participants in the UCLA Family Members Study, a family genetic study of psychiatric symptoms and information processing anomalies that may be associated with a predisposition to schizophrenia. Only valid profiles of first-degree relatives Ig years and older were examined. All of the mean scores on MMPI basic clinical scales were in the nonpathological range. However, all of the basic clinical scales, with the exception of Si, were significantly elevated in relation to the standardization norms for adults. The highest mean scores were on scales Pd and Sc, which are associated with hostility and schizophrenia. The relatives of the schizophrenia probands were more likely to score in the clinical range (T-score > 70) on scales Pd and Sc than would be expected based on the normative sample. These two scales have previously been shown to be elevated in MZ twins of schizophrenia probands (Gottesman and Shields, 1972) and thus may represent personality traits associated with a genetic predisposition to schizophrenia.

Research paper thumbnail of Cognitive/neuropsychological abnormalities in the parents of children with a schizophrenic disorder

Schizophrenia Research, 1997

Research paper thumbnail of Fluphenazine levels during maintenance treatment of recent-onset schizophrenia: relation to side effects, psychosocial function and depression

Psychopharmacology, 2000

Rationale: The utility of fluphenazine levels during maintenance treatment of schizophrenia is st... more Rationale: The utility of fluphenazine levels during maintenance treatment of schizophrenia is still unclear. Objectives: This study investigated the relationship between fluphenazine levels and a variety of clinical measures during maintenance treatment of schizophrenia. Methods: Fluphenazine levels, side effects, depression and psychosocial outcome were measured at five time points over approximately 1 year in 59 recent onset schizophrenic patients treated with a maintenance dose of injectable fluphenazine decanoate. Negative symptoms were evaluated at the 1-year endpoint. Results: Fluphenazine levels showed marked intraindividual variability even when measurements were restricted to the second 6 months of treatment, by which time steady state levels should have been achieved. No consistent relationship was found between fluphenazine levels and any of the outcome measures.

Research paper thumbnail of Persistence of Fluphenazine in Plasma after Decanoate Withdrawal

Journal of Clinical Psychopharmacology, 1988

We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12... more We discontinued fluphenazine decanoate using a double-blind, crossover random order design, in 12 recent onset clinically stable schizophrenics who had been given fluphenazine decanoate 12.5 mg intramuscularly every 2 weeks for at least 1 year prior to drug withdrawal. Each condition (drug or placebo) lasted 12 weeks. Using a radioimmunoassay verified by comparison to a gas chromatographic-mass spectrometric method, plasma fluphenazine levels were measured every 2 weeks during drug continuation and drug withdrawal conditions. No patient relapsed over the 24-week period of the study. Mean fluphenazine levels between drug continuation and withdrawal conditions showed a progressively larger difference over time, although significant differences were not seen until week 8. By week 12 after drug withdrawal, 33% of subjects still showed notable plasma fluphenazine levels. On the basis of our preliminary findings, we suggest that 2-week intervals between injections may be too short and that wider intervals may achieve similar clinical results.

Research paper thumbnail of The factor structure of schizophrenia spectrum personality disorders: signs and symptoms in relatives of psychotic patients from the UCLA family members study

Psychiatry research, 1999

The dimensions and limits of the concept of schizotypy are examined using an exploratory factor a... more The dimensions and limits of the concept of schizotypy are examined using an exploratory factor analysis of the 36 signs and symptoms in the Cluster A DSM-III-R personality disorders as well as those in Borderline Personality Disorder and Avoidant Personality Disorder in the 307 first-degree relatives and half-siblings of 123 probands with schizophrenia/schizoaffective disorder. The personality disorders examined were assessed using sections of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and hospital and clinic records. Interviewers were blind to the proband diagnosis. The resulting six-factor solution accounted for 40% of the variance. The results of the six-factor solution accounted for the greatest variance and gave the most easily interpretable simple structure of all the solutions examined. The six factors are labeled as (1) Borderline Symptoms, (2) Schizoid Symptoms, (3) Paranoid Symptoms, (4) Avoidant Symptoms, (5) Positive Schizotypy Symptoms, and (6) Disorganized Symptoms. The Schizotypal Personality items are spread across all but the &#39;Borderline Symptoms&#39; factor. We conclude schizotypy is a multidimensional construct that is not adequately characterized by any one DSM-III-R personality disorder. It appears to consist of six distinct dimensions, which, interestingly, parallel current thinking on dimensions in schizophrenia.

Research paper thumbnail of 130. Risperidone is associated with better work recovery after onset of schizophrenia

Biological Psychiatry, 2000

Most studies suggest that atypical neuroleptics are about equivalent in subjective measures of ef... more Most studies suggest that atypical neuroleptics are about equivalent in subjective measures of efficacy, extrapyramidal side effects, and tardive dyskinesia. We are comparing and contrasting the effects of olanzapine 5-20 mg/day and risperidone 2-8 mg/day in outpatients with schizophrenia. Our hypothesis is that risperidone will cause more hand force instability, tremor, and bradykinesia as compared to olanzapine on computerized objective measures because of its greater ex vivo D-2 receptor occupancy. Preliminary analysis (n ϭ 18 total) shows that the hand force instability prior to study initiation was 6.03 (3.3) for the risperidone group and 6.56 (5.4) for the olanzapine group. The hand force instability after two months of treatment reduced to 4.77 (2.1), 29% and 2.99 (0.9), 57%; respectively (F ϭ 4.125, p ϭ 0.05). Hand tremor changed Ϫ10.02db to Ϫ5.93db with risperidone treatment and 4.35db to Ϫ3.03db with olanzapine treatment. Examination of bradykinesia with measures of velocity scaling demonstrates a transition from 2.28 to 2.23 for risperidone treatment vs. 1.54 to 1.67 for olanzapine treatment. These data show that both risperidone and olanzapine improve hyperkinesia and bradykinesia when compared to their status prior to beginning the study. However, olanzapine treatment demonstrated more improvement in hyperkinesia measures, greater decrease in instability and tremor scores, and greater improvement in bradykinesia ie. increased velocity. We will discuss the implications of these data as well as our analysis of the larger 40 patient data set in this presentation.

Research paper thumbnail of MMPI Vulnerability Indicators for Schizophrenia and Attention Deficit Disorder: UCLA Family Study of Biological Parents of Offspring with Childhood-Onset Schizophrenia or ADHD

Behavior Genetics, 2005

Minnesota Multiphasic Personality Inventory (MMPI) scores were examined for 50 parents of childre... more Minnesota Multiphasic Personality Inventory (MMPI) scores were examined for 50 parents of children with an onset of schizophrenia prior to 14 years of age, 153 parents of children with attention deficit hyperactivity disorder (ADHD), and 168 parents of community comparison children. The parents were participants in the UCLA Family Study. The mean scores on all standard MMPI scales were within normal limits for all three groups of participants. Parents of schizophrenia probands were significantly higher on scale Sc than parents of community comparison children. Previous research has shown that scale Sc may be associated with a genetic liability to developing schizophrenia. Thus, scale Sc shows promise as an indicator of a heightened risk for the development of schizophrenia. The parents of the ADHD probands were significantly higher on standard clinical scale Pd than community comparison parents. Mothers of both schizophrenia and ADHD probands shared some personality indicators of stress reactivity. Although this study, like all non-adoptee family studies, cannot disentangle genetic effects on the development of these personality characteristics from environmental effects, we speculate that the emotional distress resulting in higher levels of the MMPI characteristics seen in the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; mothers reflects the impact of raising a psychiatrically ill offspring.

Research paper thumbnail of Neurocognitive Impairments in Nonpsychotic Parents of Children With Schizophrenia and Attention-Deficit/Hyperactivity Disorder

Archives of General Psychiatry, 2002

We tested the hypotheses that certain neurocognitive impairments index genetic liability to schiz... more We tested the hypotheses that certain neurocognitive impairments index genetic liability to schizophrenia and that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining whether parents of COS probands show the types of neurocognitive impairments found in relatives of AOS probands.

Research paper thumbnail of Relationship Between Positive and Negative Symptoms of Schizophrenia and Schizotypal Symptoms in Nonpsychotic Relatives

Archives of General Psychiatry, 2001

Continuous rather than categorical measures of psychopathology may provide greater statistical po... more Continuous rather than categorical measures of psychopathology may provide greater statistical power to detect susceptibility loci for schizophrenia. However, it has not been established that the dimensions of schizophrenic symptomatology and personality traits in nonpsychotic individuals share etiological factors. We therefore sought to clarify the relationship between positive and negative symptoms of schizophrenic probands and dimensions of schizotypy in their first-degree relatives. In the Roscommon Family Study, we examined the ability of positive and negative symptoms in probands to predict 7 factors of schizotypy in nonpsychotic relatives using regression analysis. These consisted of positive, negative, and avoidant symptoms; odd speech; suspicious behavior; social dysfunction; and symptoms of borderline personality disorder. We examined 3 proband groups: schizophrenia (n = 127); schizophrenia, simple schizophrenia, and schizoaffective disorder (n = 178); and all nonaffective psychoses (n = 216), and their nonpsychotic relatives (n = 309, 477, and 584, respectively). Positive symptoms in all nonaffective psychoses probands predicted positive schizotypy (beta = 0.1972, P =.0004), social dysfunction (beta = 0.0719, P =.0489), and borderline personality disorder symptoms (beta = 0.1327, P =.0084) in relatives, while negative symptoms predicted negative schizotypy (beta = 0.2069, P =.0002), odd speech (beta = 0.2592, P =.0001), suspicious behavior (beta = 0.2749, P =.0001), and social dysfunction (beta =.2398, P =.0002). Proband negative symptoms and borderline personality disorder symptoms in relatives in the schizophrenia, simple schizophrenia, and schizoaffective disorder group were inversely related (beta = -0.1185, P =.05). Positive and negative symptoms in schizophrenia predict corresponding schizotypal symptoms in relatives. This provides evidence that these schizophrenic symptom factors (1) are etiologically distinct from each other and (2) occur on an etiological continuum with their personality-based counterparts.