Emeritus Faculty, Acad Council, Psychiatry and Behavioral Sciences - Behavioral Medicine
Current research centers on the use of human genetic haploid systems, e.g. the Y chromosome, to understand the prehistory of human migrations particularly since the Holocene. This work includes investigating correlations with human symbolic material culture, focusing on the visual artistic realm. Also being explored are the issues and ethical implications of the social construction of race and ethnicity vis a vis the enhanced capacity to differentiate populations using genotypes.
The process of Greek colonization of the central and western Mediterranean during the Archaic and Classical Eras has been understudied from the perspective of population genetics. To investigate the Y chromosomal demography of Greek colonization in the western Mediterranean, Y-chromosome data consisting of 29 YSNPs and 37 YSTRs were compared from 51 subjects from Provence, 58 subjects from Smyrna and 31 subjects whose paternal ancestry derives from Asia Minor Phokaia, the ancestral embarkation port to the 6th century BCE Greek colonies of Massalia (Marseilles) and Alalie (Aleria, Corsica).19% of the Phokaian and 12% of the Smyrnian representatives were derived for haplogroup E-V13, characteristic of the Greek and Balkan mainland, while 4% of the Provencal, 4.6% of East Corsican and 1.6% of West Corsican samples were derived for E-V13. An admixture analysis estimated that 17% of the Y-chromosomes of Provence may be attributed to Greek colonization. Using the following putative Neolithic Anatolian lineages: J2a-DYS445 = 6, G2a-M406 and J2a1b1-M92, the data predict a 0% Neolithic contribution to Provence from Anatolia. Estimates of colonial Greek vs. indigenous Celto-Ligurian demography predict a maximum of a 10% Greek contribution, suggesting a Greek male elite-dominant input into the Iron Age Provence population.Given the origin of viniculture in Provence is ascribed to Massalia, these results suggest that E-V13 may trace the demographic and socio-cultural impact of Greek colonization in Mediterranean Europe, a contribution that appears to be considerably larger than that of a Neolithic pioneer colonization.
View details for DOI 10.1186/1471-2148-11-69
View details for Web of Science ID 000289414700002
View details for PubMedID 21401952
Human Y-chromosome haplogroup structure is largely circumscribed by continental boundaries. One notable exception to this general pattern is the young haplogroup R1a that exhibits post-Glacial coalescent times and relates the paternal ancestry of more than 10% of men in a wide geographic area extending from South Asia to Central East Europe and South Siberia. Its origin and dispersal patterns are poorly understood as no marker has yet been described that would distinguish European R1a chromosomes from Asian. Here we present frequency and haplotype diversity estimates for more than 2000 R1a chromosomes assessed for several newly discovered SNP markers that introduce the onset of informative R1a subdivisions by geography. Marker M434 has a low frequency and a late origin in West Asia bearing witness to recent gene flow over the Arabian Sea. Conversely, marker M458 has a significant frequency in Europe, exceeding 30% in its core area in Eastern Europe and comprising up to 70% of all M17 chromosomes present there. The diversity and frequency profiles of M458 suggest its origin during the early Holocene and a subsequent expansion likely related to a number of prehistoric cultural developments in the region. Its primary frequency and diversity distribution correlates well with some of the major Central and East European river basins where settled farming was established before its spread further eastward. Importantly, the virtual absence of M458 chromosomes outside Europe speaks against substantial patrilineal gene flow from East Europe to Asia, including to India, at least since the mid-Holocene.
View details for DOI 10.1038/ejhg.2009.194
View details for Web of Science ID 000275726900017
View details for PubMedID 19888303
The earliest Neolithic sites of Europe are located in Crete and mainland Greece. A debate persists concerning whether these farmers originated in neighboring Anatolia and the role of maritime colonization. To address these issues 171 samples were collected from areas near three known early Neolithic settlements in Greece together with 193 samples from Crete. An analysis of Y-chromosome haplogroups determined that the samples from the Greek Neolithic sites showed strong affinity to Balkan data, while Crete shows affinity with central/Mediterranean Anatolia. Haplogroup J2b-M12 was frequent in Thessaly and Greek Macedonia while haplogroup J2a-M410 was scarce. Alternatively, Crete, like Anatolia showed a high frequency of J2a-M410 and a low frequency of J2b-M12. This dichotomy parallels archaeobotanical evidence, specifically that while bread wheat (Triticum aestivum) is known from Neolithic Anatolia, Crete and southern Italy; it is absent from earliest Neolithic Greece. The expansion time of YSTR variation for haplogroup E3b1a2-V13, in the Peloponnese was consistent with an indigenous Mesolithic presence. In turn, two distinctive haplogroups, J2a1h-M319 and J2a1b1-M92, have demographic properties consistent with Bronze Age expansions in Crete, arguably from NW/W Anatolia and Syro-Palestine, while a later mainland (Mycenaean) contribution to Crete is indicated by relative frequencies of V13.
View details for DOI 10.1111/j.1469-1809.2007.00414.x
View details for Web of Science ID 000252928000007
View details for PubMedID 18269686
We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation.
View details for DOI 10.1186/gb-2008-9-7-404
View details for Web of Science ID 000258773600005
View details for PubMedID 18638359
Analysis of 89 biallelic polymorphisms in 523 Turkish Y chromosomes revealed 52 distinct haplotypes with considerable haplogroup substructure, as exemplified by their respective levels of accumulated diversity at ten short tandem repeat (STR) loci. The major components (haplogroups E3b, G, J, I, L, N, K2, and R1; 94.1%) are shared with European and neighboring Near Eastern populations and contrast with only a minor share of haplogroups related to Central Asian (C, Q and O; 3.4%), Indian (H, R2; 1.5%) and African (A, E3*, E3a; 1%) affinity. The expansion times for 20 haplogroup assemblages was estimated from associated STR diversity. This comprehensive characterization of Y-chromosome heritage addresses many multifaceted aspects of Anatolian prehistory, including: (1) the most frequent haplogroup, J, splits into two sub-clades, one of which (J2) shows decreasing variances with increasing latitude, compatible with a northward expansion; (2) haplogroups G1 and L show affinities with south Caucasus populations in their geographic distribution as well as STR motifs; (3) frequency of haplogroup I, which originated in Europe, declines with increasing longitude, indicating gene flow arriving from Europe; (4) conversely, haplogroup G2 radiates towards Europe; (5) haplogroup E3b3 displays a latitudinal correlation with decreasing frequency northward; (6) haplogroup R1b3 emanates from Turkey towards Southeast Europe and Caucasia and; (7) high resolution SNP analysis provides evidence of a detectable yet weak signal (<9%) of recent paternal gene flow from Central Asia. The variety of Turkish haplotypes is witness to Turkey being both an important source and recipient of gene flow.
View details for DOI 10.1007/s00439-003-1031-4
View details for Web of Science ID 000186954300001
View details for PubMedID 14586639
Studies in younger patients with panic disorder suggest greater somatization compared to similarly aged normal controls. Thus, we compared the degree of somatization in young versus older female patients with panic disorder to ascertain whether similarly high levels of somatization exist in older panic disorder patients.Community-dwelling subjects were recruited for clinical trials for panic disorder and met Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for panic disorder as a primary diagnosis. Our sample (N = 64) contained 42 younger females (< 55 years of age; age range 21-54, mean age 34.6) who were compared to 22 older females (> or = 55 years of age; age range 55-73, mean age 60.8). Subjects were evaluated at baseline using the Self-Report Inventory for Somatic Symptoms (SISS). Statistical analysis of total somatization disorder scores (TSDS) was accomplished by t-tests for independent groups.Older patients showed statistically significantly higher total somatization disorder scores (TSDS) (X = 11.54, SD = 7.45) than did younger patients (X = 8.07, SD = 4.77; t(62) = 2.27, p = < 0.05).Our results are suggestive of a higher degree of somatization in older compared to younger female panic disorder patients.
View details for Web of Science ID 000075551900009
View details for PubMedID 9733338
View details for PubMedID 8784861
Studies of panic attacks in older adults are virtually nonexistent. The authors surveyed 520 adults with panic attacks; 445 were younger than age 55, 57 were 55 years old or older but had their first panic attack before age 55, and 18 were 55 years old or older and had their first panic attack at age 55 or later. The respondents with late-onset panic attacks reported fewer symptoms during their attacks and were less avoidant than both groups of respondents with early-onset panic attacks.
View details for Web of Science ID A1991GD55200018
View details for PubMedID 1883003
Recent studies have linked impulsivity with CSF concentrations of both 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). One work found a negative correlation between the MMPI psychopathic deviate (Pd) scale and 5-HIAA in personality disordered men (Brown et al., 1982). We found that the 5-HIAA/Pd correlation extends (P less than 0.05) to unmedicated depressed patients (n = 21). A trend was found between HVA and Pd in depression. There was no relationship between either metabolite and the Pd scale in unmedicated schizophrenics (n = 24). A significant inverse correlation was found between the MMPI depression scale and CSF HVA but not 5-HIAA in the depressed patients.
View details for Web of Science ID A1991GD38100007
View details for PubMedID 1939932
To assess the relationship between complexity preference as measured by the Barron-Welsh Revised Art Scale and models of arousal and personality, 36 male substance abusers and 24 community controls were given this tool as well as a battery of personality tests. Some support was found for the notion that emotionality, as measured by the Test of Emotional Styles, was associated with preference for complexity. Relevant neurobiological models of affective expression and hemispheric asymmetry are discussed in light of these findings.
View details for Web of Science ID A1991FD07200008
View details for PubMedID 2038532
Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.
View details for Web of Science ID A1990CX84900006
View details for PubMedID 2187912
Higher CSF 5-HIAA concentrations and lower CSF HVA concentrations have been associated with various measures of slowed motor behaviour and communication in schizophrenic patients. To derive a single, reliable measure of deficit characteristics in schizophrenic patients, we entered four items of the BPRS reflecting negative symptoms, a work history measure derived from the Strauss-Carpenter scale, and three subscale scores of the WAIS-R into a principal-components analysis to derive a single factor score. The CSF 5-HIAA concentrations were within the normal range of values, and correlated directly with this factor score, but CSF HVA concentrations were not associated with the deficit factor score. These findings add support to the hypothesis that brain serotonin function is associated with deficit schizophrenic characteristics.
View details for Web of Science ID A1990CY31800009
View details for PubMedID 1696842
A survey of 794 subjects volunteering for studies of panic disorder with or without phobic avoidance revealed that fewer than 15% had received imipramine and fewer than 15% had undergone in vivo exposure, although the majority had engaged in some form of counseling and had used benzodiazepines. Subjects with spontaneous panic attacks reported more avoidance than subjects with situational attacks. One-half of the subjects were unemployed. The authors recommend wider use of the available effective treatments for panic disorder and phobic avoidance.
View details for Web of Science ID A1989AX18500005
View details for PubMedID 2817112
Lumbar cerebrospinal fluid concentrations of phenylacetic acid were significantly elevated in paranoid vs. nonparanoid schizophrenics. Further, phenylacetic acid concentrations were correlated with hostility. These results are consistent with the hypothesis that phenylethylamine, the proposed precursor of phenylacetic acid, plays a role in schizophrenia.
View details for Web of Science ID A1989CF03100001
View details for PubMedID 2616681
Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.
View details for Web of Science ID A1989AD14300020
View details for PubMedID 2742017
Details are presented of an ultra-sensitive gas chromatographic/mass spectrometric assay for phenylacetic acid in plasma and cerebrospinal fluid based on measurements of the relative intensities of the carboxylate anions, derived from the penta- and tetrafluorobenzyl esters under electron capture chemical ionization conditions, of unlabeled and a (13C2)-labeled internal standard. The limits of detection for the penta- and tetrafluorobenzyl esters are 0.85 and 4.0 pg respectively, and the assay is capable of measuring phenylacetic acid concentrations in samples as small as 20 microliter of CSF and plasma. The penta- and tetrafluorobenzyl esters are chromatographically separated on the gas chromatograph column, which allows for their co-injection and independent measurement from the same chromatogram.
View details for Web of Science ID A1988P968500009
View details for PubMedID 3214675
Personality theorists have long predicted a relationship between personality traits and autonomic activation. In this study, 48 patients with panic disorder underwent personality assessment by questionnaire (Eysenck Personality Inventory: 48 patients) and by interview (Personality Disorders Examination: 35 patients). Ambulatory heart rate and activity were measured by the Vitalog method and were used as measures of activation and autonomic arousal. There was a significant positive correlation between histrionic traits and activity level and a significant negative correlation between sociability and heart rate. The findings are consistent with previous studies showing a negative relationship between sensation-seeking personality traits and cerebrospinal fluid levels of norepinephrine and a positive relationship between extroversion and cerebrospinal fluid levels of dopamine.
View details for Web of Science ID A1988P894700008
View details for PubMedID 3217468
Treadmill exercise test performance and ambulatory heart rate and activity patterns of 40 patients with panic attacks were compared with 20 age-matched controls (control group 1) and 20 nonexercising controls (control group 2). All patients underwent a symptom-limited exercise stress test. Panic attack patients and control group 1 wore an ambulatory heart rate/activity monitor for up to 3 days. Panic patients had a significantly higher heart rate at 4 and 6 METS than either control group. The max METS were 11.2 +/- 2.3, 13.5 +/- 2.3 and 11.2 +/- 1.8 for the panic attack patients and control groups 1 and 2, respectively. One panic patient had ischemia on the treadmill at 12 METS. Panic patients had a significantly higher standing heart rate than controls. Furthermore, 11 of 39 panic patients had tachycardia on standing compared with 3 of 40 controls. Panic attack patients had higher wake and sleep heart rates than control group 1, but the differences were not significant. These results are consistent with autonomic dysfunction in panic patients but may also be due to differences in physical conditioning. The treadmill can be useful for reassuring patients and for identifying the rare patient with ischemia on exercise.
View details for PubMedID 3425557