Neil Laufer

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients.

Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance.1 Family and twin studies indicate a significant genetic contribution2,3 and pharmacological data suggest possible dysfunction of the serotonergic4,5 and dopaminergic6–9pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism10 and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles.11 Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% χ2 = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemars χ2 = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: A case-control study of female patients and several ethnic groups in the Israeli Jewish population

The human small‐conductance Ca2+‐activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family‐based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co‐morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case‐control analysis that has demonstrated a significant over‐representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co‐morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive‐compulsive disorder (OCD) co‐morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.

Involvement of GABAA receptor modulating neuroactive steroids in patients with social phobia

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S), neurosteroids synthesized in the brain, are weak gamma-aminobutyric acid (GABA) A receptor allosteric antagonists that may be involved in anxiety disorders. In the present study we measured the circulatory [corrected] levels of DHEA, DHEA-S, pregnenolone and cortisol in [corrected] untreated patients (n=26) diagnosed with social phobia (SP) compared with sex- and age-matched healthy controls (n=21). No significant differences in neurosteroids were observed in [corrected] untreated SP patients and [corrected] compared with healthy controls. The findings may reflect an absence of involvement of the GABA(A) modulators DHEA, DHEA-S and pregnenolone in SP.

Lifetime psychiatric comorbidity rate in Israeli non-help-seeking patients with combat-related post-traumatic stress disorder.

BACKGROUND Most of the data on lifetime psychiatric comorbidity in combat-related posttraumatic stress disorder (CR-PTSD) were collected in help-seeking patients. METHODS In the present study we used the Schedule for Affective Disorder and Schizophrenia-Lifetime Version to examine a relatively large sample (n=80) of Israeli non-help-seeking CR-PTSD patients. The diagnosis of PTSD was based on the DSM-III-R criteria. RESULTS We found a low rate of lifetime psychiatric comorbidity, especially drug dependence (2.25%), alcoholism (2.25%) and major depressive disorders (5%). CONCLUSION It seems that in contrast to help-seeking CR-PTSD, non-help-seeking CR-PTSD is associated with a low frequency of comorbid psychiatric disorders. LIMITATION Only non-help seeking CR-PTSD patients who agreed to participate in the study were included in this investigation. CLINICAL RELEVANCE The detection and diagnosis of CR-PTSD comorbidity is important for establishing appropriate psychotherapeutic and pharmacological treatment.

Platelet vesicular monoamine transporter density in untreated patients diagnosed with social phobia.

The vesicular monoamine transporter (VMAT2) is important in the storage and release of monoamines. Platelet VMAT2 was characterized using high-affinity [(3)H]dihydrotetrabenazine ([(3)H]TBZOH) binding in untreated social phobia (SP) patients (n=20) compared with sex- and age-matched healthy controls (n=15). No significant differences in VMAT2 density (B(max)) and affinity constants (K(d)) were observed.

Erratum to “Involvement of GABAA receptor modulating neuroactive steroids in patients with social phobia” [Psychiatry Res. 137 (2005) 131–136]

a Laboratory of Biological Psychiatry, Felsenstein Medical Research Cente, Beilinson Campus, Petah Tiqva, Israel b Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel c Adult Outpatient Department, Geha Psychiatric Hospital, Beilinson Campus, Petah Tiqva, Israel d Beer Yaakov Mental Health Centre, Beer Yaakov, Israel e Research Unit, Geha Psychiatric Hospital, Beilinson Campus, P.O.B. 102 Petah Tiqva 49100, Israel