The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, “activated” cAMP signaling activity in BPD and “blunted” cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.

Our data suggest that FEZ1 may play important roles in human astrocytes, and that mood stabilizers might exert their cytoprotective and mood-stabilizing effects by inducing FEZ1 expression in astrocytes.

The right to be heard has little value, however, to those who lack the knowledge to exercise their right in a meaningful or skillful way. The notion of a meaningful right to be heard has been linked to access to counsel. 3 In Powell v. Alabama, the Supreme Court noted, "[t]he right to be heard would be, in many cases, of little avail if it did not comprehend the right to be heard by counsel. Even the intelligent and educated layman has small and sometimes no skill in the science of law." ' Several commen-I. See 28 U.S.C. § 1654 (1982) ("parties may plead and conduct their own cases personally or by counsel"). 2. In some states, the right to be heard is defined explicitly in terms of a right to prosecute or defend in person. See, e.g., At.A. CONST. art. I, § 10 ("no person shall be barred from prosecuting or defending before any tribunal in this state, by himself or counsel, any civil cause to which he is a party"); GA. CONS'r. art I, para. XII; MiCaH. CONS-r. art. I, § 13; Miss. CONST. art. 3, § 25; UTAH CoNSr. art I, § 11; WIs. CONSr. art I, § 21(2). In other states, the right to prosecute or defend in person arises by statute.