ABSTRACT
Genetically, bipolar disorder is a complex genetic illness, in which both genes and environmental factors play an important role in pathogenesis. Linkage studies have reported suggestive evidence for genomic regions, especially on chromosome 18, but in most cases they have been inconclusive. A total of 12 pedigrees, from the islands of Majorca and Minorca (Balearic Archipelago), with a high expression of mental illness, have been studied. A scan of 29 polymorphic short tandem repeat markers was performed, spanning chromosomes 17 and 18 for bipolar and other affective disorder susceptibility loci. Narrow (only bipolar I disorder) and broad (bipolar plus other affective disorders) diagnosis criteria were employed. The loci D18S63, D18S452, D18S53, D18S61, D18S1161 and D17S831 showed LOD score values of less than -2. Thus, the positive linkage found by other authors on the regions 18p11.2 and 18p11.3 has not been reproduced in the families studied. The data obtained in chromosome 17 suggested two possible regions that could contain a bipolar disorder susceptibility gene: 17q11 (D17S1857, D17S798) and especially 17q24-qter (D17S949, D17S928). The maximum significant linkage was to D17S949 (17q24), following a recessive mode of inheritance. We have also found a positive LOD score value for D18S478 marker located in the region 18q12.
Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 18 , Genetic Linkage , Mental Disorders/genetics , Adolescent , Adult , Age of Onset , Atlantic Islands , Child , Chromosome Mapping , Family , Female , Genetic Markers , Humans , Male , Middle Aged , Pedigree , SpainABSTRACT
Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have found antidepressant effects when high frequency stimulation (HF-rTMS; >1 Hz) is applied over the left prefrontal cortex (LPF). A few studies have also reported success with low frequency stimulation (LF-rTMS) to the right prefrontal cortex (RPF). Both HF-rTMS and LF-rTMS have been reported to work better in areas with cerebral hypometabolism or hypermetabolism, respectively. Thirty medication-resistant patients with major depression were randomized into three groups. The first group received sham rTMS and the second group received active rTMS (20-Hz rTMS to the LPF and 1-Hz rTMS to the RPF). The third group, however, received active rTMS that was focused on different regions of the brain after examination with single photon emission computed tomography (20-Hz rTMS to an area of relatively low activity and 1-Hz rTMS to an area showing relatively high activation). Patients and raters were blind to the treatment condition. Comparison of the sham rTMS group with the overall group that received active rTMS revealed statistically significant changes on the Hamilton Rating Scale for Depression after 10 sessions. This study demonstrated that combined 20+1-Hz rTMS was effective, but no additional advantages were obtained by focusing rTMS on areas identified by single photon emission tomography as showing high versus low levels of functional activity.
