Optimal use of electroconvulsive therapy: choosing a treatment schedule.

Choice of treatment schedule is an important component of the ongoing efforts to optimize electroconvulsive therapy (ECT) administration and thereby maximize therapeutic benefit while reducing cognitive adverse effects. Frequency of ECT administration (that is, the spacing between treatments) and the total number of treatments in a series are the two factors that define the ECT schedule. Available evidence supports the view that a schedule of twice weekly ECT with a total of six to eight treatments is an effective therapeutic regiment that potentially reduces cognitive morbidity associated with more frequent administration and a larger number of treatments. More frequent administration, however, may accelerate antidepressant response and may be indicated in cases in which rapidity of therapeutic effect is a significant clinical consideration. This consideration may be at the cost of greater cognitive impairment, which could be reduced by limiting the number of treatments administered. Aside from their clinical relevance, these issues have important implications for understanding the mechanisms of action of ECT.     

The impact of preoperative skin disinfection on preventing intraoperative wound contamination

The efficacy of total body showering and incision site scrub with disinfectant agents was evaluated in a randomized, prospective study of 575 patients undergoing selected surgical procedures. Patients who showered twice with 4% chlorhexidine gluconate had lower mean colony counts of skin bacteria at the surgical incision site in the operating room prior to the final scrub than patients who showered twice with povidone-iodine solution or medicated bar soap. Patients in the chlorhexidine group had no growth on 43% of the incision site skin cultures compared with 16% in the povidone-iodine group and 6% in the soap and water group. Patients who showered and who were scrubbed with chlorhexidine also had lower rates of intraoperative wound contamination. Bacteria were recovered from the wounds of 4% of patients using this regimen compared with 9% for patients who used povidone-iodine and 15% for patients who showered with medicated soap and water and were scrubbed with povidone-iodine. We noted no difference in surgery-specific infection rates among patients in the three treatment groups; however, our sample sizes were too small to evaluate this outcome parameter adequately. These data suggest that preoperative showering and scrubbing with chlorhexidine is an effective regimen to reduce extrinsic intraoperative contamination of the surgical wound from skin bacteria. The efficacy of this regimen to prevent postoperative wound infection needs to be evaluated in a well-designed, carefully controlled prospective trial with adequate numbers of patients to achieve statistically valid conclusions.     

Medication Outcome in ECT-Resistant Depression

The outcome of antidepressant treatment in 12 cases of electroconvulsive therapy (ECT)-resistant depression is presented. Eight patients had been refractory to a clinically adequate course of ECT (Hamilton Depression Scale improvement <20%) and four were partial responders (improvement 20-49%). All remitted completely on antidepressant medication within 2.2 +/- 1.1 (mean +/- SD) months of the ECT course. Remission was associated with clomipramine treatment (139 +/- 49.7 mg/day) in seven cases and maprotiline (125 mg/day) in one case. Four patients who did not respond to a tricyclic antidepressant alone remitted following supplementation (of clomipramine in 2 cases, clomipramine + haloperidol in 1 case, and imipramine in 1 case) with lithium carbonate. Although a delayed therapeutic response to ECT cannot be excluded, the results suggest that ECT may alter the sensitivity of refractory patients to antidepressant medication.     

A follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22

Evidence for linkage between bipolar affective disorder (BP) and 21q22 was first reported by our group in a single large pedigree with a lod score of 3.41 with the PFKL locus. In a subsequent study, with denser marker coverage in 40 multiplex BP pedigrees, we reported supporting evidence with a two-point lod score of 2.76 at the D21S1260 locus, about 6 cM proximal to PFKL. For cost-efficiency, the individuals genotyped in that study comprised a subset of our large pedigree sample. To augment our previous analysis, we now report a follow-up study including a larger sample set with an additional 331 typed individuals from the original 40 families, improved marker coverage, and an additional 16 pedigrees. The analysis of all 56 pedigrees (a total of 862 genotyped individuals vs. the 372 genotyped previously), the largest multigenerational BP pedigree sample reportedly analyzed to date, supports our previous results, with a two-point lod score of 3.56 with D21S1260. The 16 new pedigrees analyzed separately gave a maximum two-point lod score of 1.89 at D21S266, less than 1 cM proximal to D21S1260. Our results are consistent with a putative BP locus on 21q22.     

A large deletion mutation in the CFTR gene (3120+1Kbdel8.6Kb): a founder mutation in the Palestinian Arabs. Mutation in brief no. 231. Online

A deletion mutation of 8.6Kb in the CFTR gene, spanning the exons 17a, 17b and 18 was identified in 4 homozygous unrelated Palestinian CF patients. The patients were of various ethnic subgroups including Muslims, Christians and Druze. The deletion breakpoint occurred within an identical 4bp sequence in introns 16 and 18, and the mutation was defined as 3120+1Kbdel8.6Kb. A simple PCR based assay was designed and using this assay two compound heterozygote patients with the 3120+1Kbdel8.6Kb were identified. The 3120+1Kbdel8.6Kh hearing chromosomes had a common intragenic haplotype and variable flanking polymorphic markers, indicating that it is an ancient founder mutation.     

Factors related to the incidence of stomach cancer in the Pittsburgh Standard Metropolitan Statistical Area.

This report presents an analysis of several demographic discriminants of stomach cancer incidence for residents of the Pittsburgh Standard Metropolitan Statistical Area (SMSA) with the use of data collected as part of the Third National Cancer Survey, 1969-71. The Pittsburgh SMSA, one of nine areas included in the Third National Cancer Survey, was of particular interest in the study of stomach cancer, since area residents showed the highest age-adjusted incidence rate for cancer of this site while showing the fifth highest rate for all sites. To examine the data in greater detail, we used the variables of sex, race, nativity, and median income level to classify the cancer patients into homogeneous subgroups of census tracts of residence to allow comparisons of the average annual age-adjusted incidence rates among the groups. The data indicated that Pittsburgh SMSA residents showed stomach cancer incidence patterns that were generally consistent with earlier published reports; particularly when contrasted with appropriate population subgroups, higher rates appeared for males, for blacks, for lower income areas, and for areas with "large" proportions of foreign-born and foreign-stock residents. Furthermore, when one considered interactions among the factors, the relationship between ethnic composition and incidence appeared to supercede that of income among white males.     

Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings

The serotonergic (5-HT) system has been implicated in the etiopathogenesis of psychoses. Since the 5-HT transporter plays an important role in regulation of 5-HT transmission, its gene can be considered as a candidate for vulnerability to psychiatric disorders. Two polymorphic sites of the 5-HT transporter gene-5-HTTLPR, a VNTR in the 5' regulatory region, and a VNTR in the second intron-were studied in a sample of 61 families with schizophrenia for transmission disequilibrium. Each family contained at least two siblings affected with schizophrenia or schizoaffective disorder (mainly schizophrenic). One hundred and thirty-nine affected offspring with parental information for genotyping, were available for analysis. No preferential transmission of either short or long alleles of the promoter polymorphism was observed. However, a transmission distortion was detected for alleles of the intronic VNTR polymorphism (chi2TDT max =14.33; P = 0.0002; corrected P value = 0.0003) resulting in more frequent than expected transmission of the 12 repeat allele. This finding adds additional evidence to the idea that the serotonergic system may be involved in development of psychoses. Molecular Psychiatry (2000) 5, 91-95.     

Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy

Depression has been shown in some studies to be associated with a reduction in hypothalamic 5-HT(1A) receptor function, as indicated by reduced hormone and/or hypothermic responses to 5-HT(1A) agonists such as ipsapirone. The hypothermic response to ipsapirone was reduced in depressed patients treated with amitriptyline. Hormone and hypothermic responses to 5-HT(1A) agonists were reduced in normal subjects administered specific serotonin reuptake inhibitors. Effects of electroconvulsive therapy (ECT) on 5-HT(1A) receptor-mediated responses in humans have not been reported. In the present work, ten depressed patients and 15 control subjects were challenged with placebo and with 0.3 mg/kg ipsapirone, administered 48 h apart in a randomised double blind design. Hypothermic, growth hormone (GH) and cortisol responses were measured. Seven of the depressed patients were treated with a course of ECT, and placebo and ipsapirone challenges were repeated 24 and 72 h after the last treatment. The cortisol response to ipsapirone was significantly reduced in the depressed patients compared with controls. The hypothermic response to ipsapirone was totally abolished in the depressed patients. When tested after a course of ECT, the seven depressed patients again showed reduced or blunted responses. We conclude that hypothalamic 5-HT(1A) receptor function is reduced in depression. In contrast to the effects of electroconvulsive shock (ECS) on post-synaptic 5-HT(1A) receptor function in animals, which have chiefly been measured in the hippocampus using electrophysiological techniques, ECT in humans does not induce an increase in sensitivity of post-synaptic 5-HT(1A) receptors in the hypothalamus.     

An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline

We assessed whether the efficacy of plant-source derived phosphatydilserine (one of the phospholipids which play an important functional role in membrane-related processes in the brain) for treatment of age related cognitive decline is consistent with previous (placebo controlled) positive findings with bovine derivative of PS (BC-PS). Eighteen healthy elderly volunteers meeting Age Associated Memory Impairment inclusion and exclusion criteria were treated for 12 weeks with plant-source derived phosphatydilserine (PS) (100 mg x 3/day p.o.) and evaluated at base line, after 6 weeks of treatment and at the end of the trial. Fifteen concluded the study. All but two outcome measures elicited a significant drug over time effect. Post-hoc paired t-tests showed that the significant effect was attributable to an improvement from base line to week 6 and that effect was maintained at week 12. These results are encouraging. However, they await double-blind controlled verification in a large sample before suggesting that this may be a viable approach to the treatment of age-related cognitive decline, without exposing the patients to possible hazards involved in the treatment with bovine derivative of PS (BC-PS).