Suicidal Subjects Research Articles

Regulation of GRK 2 and 6, β-arrestin-2 and associated proteins in the prefrontal cortex of drug-free and antidepressant drug-treated subjects with major depression

G protein-coupled receptor kinases (GRKs) and β-arrestin-2 play a crucial role in the regulation of neurotransmitter receptors in brain. In this study, GRK 2, GRK 6, β-arrestin-2 and associated proteins (Gβ proteins and protein phosphatase (PP)-2A) were quantitated in parallel (immunodensity with specific antibodies) in brains of depressed subjects (drug-free and antidepressant-treated) to investigate the effect of major depression and antidepressant drugs on these receptor regulatory proteins. Specimens of the prefrontal cortex (Brodmann’s area 9) were collected from 19 suicide and non-suicide depressed subjects and 13 control subjects. In drug-free ( n=9), but not in antidepressant-treated ( n=10), depressed subjects an increase in the density of membrane-associated GRK 2 (30%, n=9, P=0.005) was found compared with that in sex-, age-, and PMD-matched controls. Comparison between drug-free and antidepressant-treated depressed subjects showed that GRK 2 was reduced in membrane (39%, n=10, P=0.008) and cytosolic (44%, n=10, P=0.09) preparations after antidepressant drug treatment. In contrast, membrane-associated GRK 6 (drug-free and antidepressant-treated depressed subjects) was found unchanged when compared with that in matched controls. Similarly, the densities of β-arrestin-2, PP-2A, and Gβ proteins were not significantly different from those in matched controls. There was a positive correlation between the immunodensities of GRK 2 and β-arrestin-2 in membrane preparations ( r=0.48, n=19, P=0.04), suggesting that both proteins are regulated in a coordinated manner in brains of depressed subjects. The results of this study indicate that major depression is associated with upregulation of brain GRK 2, but not GRK 6, and that antidepressant drug treatment appears to induce downregulation of GRK 2 protein.

Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide

A variety of postmortem brain studies and clinical investigations have provided evidence that reduced serotonin neurotransmission is associated with suicidal behavior and depression, and several serotonergic parameters have been found to be altered in the prefrontal cortex of suicide victims. However, the integrity of the serotonin innervation of the prefrontal cortex in mood disorders has not been directly investigated. The present study used immunocytochemical methods and an antibody against the serotonin transporter to examine the relative density of serotonin axons in the dorsolateral prefrontal cortex of suicide victims with a diagnosis of major depression. The mean total length of serotonin transporter-immunoreactive axons per unit area was unchanged in layers 2 and 4 of area 46 in the depressed suicide subjects compared to controls, but was significantly ( P<0.01) decreased by 24% in layer 6 in the depressed suicide group. The total length of serotonin transporter-positive axons in layer 6 was reduced in eight of the 12 depressed suicide subjects compared to their matched control subjects. These findings reveal that depressed subjects who have committed suicide exhibit a lamina-specific reduction in a marker of serotonin axons in the dorsolateral prefrontal cortex that may reflect an alteration in cortical serotonin neurotransmission.

MRNA and Protein Expression of Selective Alpha Subunits of G Proteins are Abnormal in Prefrontal Cortex of Suicide Victims

The present investigation was undertaken to examine whether there is an abnormality in the expression of α and βγ subunits of G proteins both at the transcriptional and translational level in postmortem brain of adult and teenage suicide subjects and whether these abnormalities are related to mental disorders or suicide per se. In addition, an attempt has been made to investigate whether these abnormalities are similar or dissimilar in teenage and adult suicide, because the etiology of teenage suicide may be different than that of adults.A significant decrease in both mRNA and protein levels of Gi2α and GOα and a significant increase in levels of Gsα-S were observed in prefrontal cortex of suicide subjects (n = 43) compared with non-psychiatric control subjects (n = 38). When subjects were grouped according to age, a significantly decreased expression of Gi2α and GOα and significantly increased expression of Gsα-S were observed in adult suicide subjects (age ⩾ 20 yrs; n = 20) as compared with age-matched controls (n = 27). These changes were present in all adult suicide subjects regardless of psychiatric diagnosis. On the other hand, although there were no significant differences in any α or βγ subunits in teenage suicide subjects (age ⩽ 19 yrs; n = 16) when compared with matched control subjects (n = 18); however, mRNA and protein levels of Gi2α and GOα were significantly decreased and of Gsα-S were significantly increased only in those teenage suicide subjects who had a history of mental illness (n = 11). Our results suggest that there are defects in the expression of selective G protein α subunits in prefrontal cortex of adult and teenage suicide subjects, which appear to be related to mental disorders.

Social phobia, panic disorder and suicidality in subjects with pure and depressive mania

Background: The objective of this study is to ascertain the rates of social phobia, panic disorder and suicidality in the midst of the manic state among subjects with pure and depressive mania. Methods: Subjects received evaluations entailing the use of serial standard clinical interviews, the Schedule for Affective Disorders and Schizophrenia (SADS) and a structured interview to determine whether they met the criteria for intra-episode social phobia (IESP) and panic disorder (IEPD). The diagnoses of major depressive disorder and mania were rendered using the Research Diagnostic Criteria. The diagnoses of IESP and IEPD were rendered using DSM-III-R criteria. Categorization as being suicidal was based on the SADS suicide subscale score. Results: Twenty-five (56.8%) subjects had pure and 19 (43.2%) subjects had depressive mania. None of the subjects with pure and 13 (68.4%) with depressive mania had IESP ( P<0.0001). One (4.0%) subject with pure and 16 (84.2%) subjects with depressive mania had IEPD ( P<0.0001). One (4.0%) subject with pure and 12 (63.2%) subjects with depressive were suicidal. Twelve of 13 (92.3%) subjects with depressive mania met the criteria for IESP and IEPD concurrently ( P<0.0001). All were suicidal. Limitations: The study suffers limitations imposed by small sample sizes and non-blind methods of identifying subjects with IESP, IEPD and who were suicidal. Conclusions: Subjects with depressive but not pure mania exhibited high rates of both IESP and IEPD. Concurrence of the disorders is the rule. The findings suggest that databases disclosing a relationship between panic disorder and suicidality merit, where possible, reanalysis directed at controlling for the effect of social phobia.

Cholesterol, essential fatty acids, and suicide

Epidemiological and clinical studies have described an association between lower serum cholesterol concentrations and increased suicide risk that is not entirely attributable to depression-related malnutrition and weight loss. Recent epidemiological studies with greater samples and longer follow-up periods, however, have even shown a positive correlation between cholesterol concentrations and suicide risk after controlling for potential confounding variables. A meta-analysis of earlier intervention trials suggested that cholesterol lowering could cause or worsen depressive symptoms and increase the risk of suicide. Large trials of statins (simvastatin, lovastatin, and pravastatin) did not show an increase of suicide mortality. The aim of this selective review is to critically discuss the current evidence for a potential link between cholesterol, essential fatty acids, depression, suicide, impulsivity, and aggression. Preclinical data support the hypothesis that cholesterol reduction may contribute to the serotonergic abnormalities that have been postulated in suicidal subjects. Recently, it was hypothesised that a decreased consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, may be a risk factor for depression and suicide. Currently, we do not have sufficient evidence that cholesterol-lowering therapies increase the risk of depression and suicide. Increasing the dietary intake of omega-3 fatty acids may increase central serotonergic activity and reduce impulsive and aggressive behaviours.

Seclusion treatment measures and serum cholesterol levels among Finnish male forensic psychiatric patients

Low total serum cholesterol (TC) concentrations have been found to be linked with violent and suicidal behavior among mentally ill patients and also in the general population. However, it has remained unclear if this correlation is non-linear, which would allow the determination of a cutoff TC level to differentiate violent or suicidal subjects from non-violent and non-suicidal subjects. We studied, in 397 Finnish forensic male patients, by using ROC analysis, the optimal cut-off point for TC level to differentiate between those who had been secluded because of acute acts, including violent and suicidal behaviors, and those who had not. According to ROC analysis, the observed cut-off points of the TC levels (5.3 mmol/l) for differentiating between those patients that had been secluded and those that were nonsecluded were below the mean TC levels of the Finnish general male population, and moderate sensitivities and specificities were achieved. The low (below 5.3 mmol/l) TC level seems to be a marker for an increased risk of violent and suicidal behavior among Finnish forensic male patients.

Onset of grip- and pinch-strength impairment after acute poisonings with organophosphate insecticides.

The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans has not been quantitatively measured in epidemiologic studies. This study evaluated the association of acute OP poisonings with motor neurologic impairment. Hand grip and pinch strength were evaluated among 62 Nicaraguan men hospitalized for acute OP poisoning between 1992 and 1996; 39 cattle ranchers and fishermen who had never experienced pesticide poisoning were controls. Exposure categories were moderate and severe poisonings with neuropathic and non-neuropathic OPs. Strength was measured at hospital discharge and seven weeks after poisoning. Grip and pinch strength were impaired among all OP-poisoned subjects at both examinations, more noticeably among those poisoned with OPs with suspected neuropathic effects, methamidophos and chlorpyrifos. In those with severe poisonings with neuropathic OPs, impairments were more marked among intentional than among occupational poisonings. The performances of suicidal subjects worsened at the second examination, consistent with OPIDP. Early motor impairment at the time of hospital discharge is consistent with cholinergic depolarization blockade after acute poisoning. The persistence of deficits in motor strength in all severely poisoned patients regardless of pesticide type was unexpected, and may reflect persistent cholinergic blockade or intermediate syndrome, neuropathy, or a combination of these.

Body attitudes and body experiences in suicidal adolescents.

The relationships between cognitive and affective attitudes toward the body, body experiences (dissociation, insensitivity, and lack of control), and suicidal tendencies were examined as a derivative of the hypothesis that bodily attitudes and experiences may facilitate suicidal acting out. Three groups of adolescents (aged 14-18), including suicidal (made a suicide attempt) and nonsuicidal inpatients and controls, were compared with regard to suicidal tendencies, various body aspects, and depression and anxiety. A series of MANOVAs, discriminant analysis, Pearson correlations, and regressions were employed. The results show that the suicidal group differed from the two nonsuicidal groups in feelings toward the body, body protection, and body dissociation. Some aspects of bodily measures discriminated between suicidal and nonsuicidal subjects. In addition, various bodily measures were associated with and statistically predicted suicidal tendencies. The discussion focuses on the web of associations between body attitudes and experiences and their role in suicidal behavior.

Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects.

The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post-mortem brain tissue obtained from non-psychiatric control subjects (n = 11) and age- and the post-mortem interval-matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a 'dual function' ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post-mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.

A retrospective study of general hospital patients who commit suicide shortly after being discharged from the hospital.

To assess the scope of diagnostic screening for suicide prevention in general hospital patients. Retrospective medical record review of general hospital patients who committed suicide and matched-control subjects who did not commit suicide shortly after being discharged from the hospital. The suicide rate was 32 per 100 000 patient-years. Eight (73%) of 11 patients who committed suicide were diagnosed with depression, substance use disorder, or both at their last hospital admission compared with 11 (33%) of the controls (P<.05). Only 1 of 44 patients (both cases and controls) was referred for psychiatric consultation. The suicide rate in general hospital patients was almost 3-fold higher than in the general population. Depression and/or substance use disorders were risk factors for suicide. Screening for those disorders may be beneficial for suicide prevention in the general hospital population, but will likely benefit more patients who will not commit suicide.

Attempted and completed suicide in older subjects: results from the WHO/EURO Multicentre Study of Suicidal Behaviour.

The authors present an analysis of findings for the 65 years and over age group from the WHO/EURO Multicentre Study of Suicidal Behaviour (1989-93). Multinational data on non-fatal suicidal behaviour is derived from 1518 subjects in 16 European centres. Local district data on suicide were available from 10 of the collaborating centres. Stockholm (Sweden), Pontoise (France) and Oxford (UK) had the highest suicide attempts rates. In most centres, the majority of elderly who attempted suicide were widow(er)s, often living alone, who used predominantly voluntary drug ingestion. Non-fatal suicidal behaviour decreased with increasing age, whereas suicide rates rose. The ratio between fatal and non-fatal behaviours was 1:2, that for males/females almost 1:1. In the years considered, substantial stability in suicide and attempted suicide rates was observed. As their age increased, suicidal subjects displayed only a limited tendency to repeat self-destructive acts. Moreover, there was little correlation between attempted suicide and suicide rates, which carries different clinical implications for non-fatal suicidal behaviour in the elderly compared with younger subjects in the same WHO/EURO study.

Cholesterol, omega-3 fatty acids, and suicide risk: empirical evidence and pathophysiological hypotheses

Studies in psychiatric patients described an association between lower serum cholesterol concentrations, suicidality, depression, impulsivity, and aggression which is not entirely attributable to depression-related malnutrition and weight-loss. Several lines of evidence suggest that a serotonergic deficit in the prefrontal cortex may predispose vulnerable subjects to impulsive, autoaggressive, and suicidal behaviour in stressful life-events. In-vitro studies, animal experiments, and human in-vivo studies support the hypothesis that cholesterol reduction may contribute to the serotonergic abnormalities which have been postulated in suicidal subjects. Recently it was hypothesized that decreased consumption of polyunsaturated fatty acids, especially omega-3 fatty acids, may be a risk factor for depression and suicide. Data from human studies in healthy volunteers suggest that increasing the dietary intake of omega-3 fatty acids may increase central serotonergic activity and reduce impulsive and aggressive behaviours. Earlier epidemiological studies showed an association between low cholesterol concentrations and increased suicide risk. Recent epidemiological studies with greater samples and longer follow-up periods, however, even showed a positive correlation between cholesterol concentrations and suicide risk after controlling for potential confounding variables. Large trials of statins (simvastatin, lovastatin, pravastatin) did not show an increase of suicide mortality.

Dr. Turecki and Colleagues Reply

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Turecki and Colleagues ReplyGUSTAVO TURECKI, M.D., PH.D., RICHARD BRIÈRE, PH.D., KAREN DEWAR, PH.D., ALAIN D. LESAGE, M.D., MONIQUE SÉGUIN, PH.D., NADIA CHAWKY, M.SC., CLAUDE VANIER, M.D., MARTIN ALDA, M.D., RIDHA JOOBER, M.D., CHAWKI BENKELFAT, M.D., and GUY A. ROULEAU, M.D., PH.D., GUSTAVO TURECKISearch for more papers by this author, M.D., PH.D., RICHARD BRIÈRESearch for more papers by this author, PH.D., KAREN DEWARSearch for more papers by this author, PH.D., ALAIN D. LESAGESearch for more papers by this author, M.D., MONIQUE SÉGUINSearch for more papers by this author, PH.D., NADIA CHAWKYSearch for more papers by this author, M.SC., CLAUDE VANIERSearch for more papers by this author, M.D., MARTIN ALDASearch for more papers by this author, M.D., RIDHA JOOBERSearch for more papers by this author, M.D., CHAWKI BENKELFATSearch for more papers by this author, M.D., and GUY A. ROULEAUSearch for more papers by this author, M.D., PH.D., Verdun, Que., CanadaPublished Online:1 Jan 2001https://doi.org/10.1176/appi.ajp.158.1.148AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Drs. Hrdina and Du report the results they observed in a study (unpublished) in which they attempted to replicate our findings. In observing 17 depressed suicide subjects and 35 comparison subjects, they failed to find a relationship between variation at the T102C 5-HTR2A polymorphism and 5-HTR2A binding. As previously discussed (1), a possible explanation for this inconsistency may be related to the characteristics of the subjects included in our study, who were of French Canadian descent. This is a relatively young and isolated population that has a large background linkage disequilibrium (2). Thus, it is possible that a functional genetic variant located in a different coding or regulatory region of the 5-HTR2A gene, rather than the T102C silent polymorphism, may in fact be responsible for our positive results.This may not have been the case in the study by Drs. Hrdina and Du because they investigated subjects of Hungarian origin. Although they did not provide details about the specific ethnic composition of their study group, the Hungarian general population is composed of several different ethnic groups with admixture among most of them. The population is not known to have undergone any event leading to the presence of the relatively large linkage disequilibrium that may be observed in subjects chosen at random (3, 4).An additional point relates to ascertainment differences between the studies. Drs. Hrdina and Du have focused their attention on depressed suicide victims (Du et al., 1999). Our findings are not related to the phenotype, but rather to a relationship between genetic variation and 5-HTR2A binding. However, if there is less variation among binding levels in depressed patients, this group may have lower power to detect a positive association.

Suicide by police: a proposed typology of law enforcement officer‐assisted suicide

A typology of suicide by police was created by separating 143 such incidents from a database of 174 police shooting incidents. The 143 incidents were found to consist of three main categories: Direct Confrontations, in which suicidal subjects instigated attacks on police, Disturbed Interventions, in which potentially suicidal subjects took advantage of police intervention, and Criminal Interventions, in which subjects preferred death to submission. These three categories were then subdivided into nine types. Two judges obtained a reliability coefficient of 0.87 for distinguishing suicide by cop, and 0.58 for placement into the nine types. Meaningful distinctions among the types were found on three variables: subject age, real danger, and lethality.

Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder.

There is evidence indicating that density of 5-HT2A receptors is altered in brain regions of depressed suicide victims and in platelets of suicidal subjects with major depression or schizophrenia. Recent studies have also shown an association between the allele C of 102T/C polymorphism in the 5-HT2A receptor gene and schizophrenia. The present investigation tested the hypothesis that the observed changes in 5-HT2A receptor density in platelets of patients with major depression are a trait rather than state phenomenon and are associated with the 102 C allele in 5-HT2A receptor gene in a sample of 120 patients with major depression and a group of 131 control subjects comparable with respect to age, sex, and ethnic background. The allele and genotype frequencies of 102T/C polymorphism in 5-HT2A receptor gene were compared between patients and control subjects and between suicidal and non-suicidal patient groups. The major finding of this study was a significant association between the 102 C allele in 5-HT2A receptor gene and major depression, chi(2) = 4.5, df = 1, P = 0.03, particularly in patients with suicidal ideation, chi(2) = 8.5, df = 1, P < 0.005. Furthermore, we found that patients with a 102 C/C genotype had a significantly higher mean HAMD item 3 score (indication of suicidal ideation) than T/C or T/T genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:56-60, 2000.

A study of suicides in Ballarat, Victoria, Australia.

To study suicides occurring in Ballarat with regard to incidence, demographic variables, possible causal factors, and association with psychiatric disorders over a period of 5 years. A detailed review of the coroner's record of every suicide occurring during 1992-1996 was undertaken. Information was obtained on socio-demographic variables, method and circumstances of suicide, and associated psychiatric disorders in each case and subjected to psychological autopsy. 75 suicides were recorded. The male to female ratio was 4:1 and average age was 43 years. 60% had associated psychiatric illnesses, mainly affective disorders. Carbon monoxide self-poisoning accounted for 40%, firearms for 30%, and hanging, overdose, asphyxia and other methods for the remaining 30%. It was statistically significant that the younger age group preferred firearms to other methods, and that their suicides were precipitated by interpersonal conflicts. Social and personal difficulties were associated in 33%, and triggering factors were present in 40%. Previous suicide attempts were present in 28%, while 32% had manifest behavior changes preceding suicides or verbalized their intent to suicide. Suicide rates in Ballarat were higher than the average overall Victorian and Australian rates. After a consistent decline over 4 years an increase occurred in 1996. The preferred method of suicide was carbon monoxide, although the young preferred firearms. Demographic and other psychosocial factors were similar to the rest of Australia. Unemployment was not a significant factor. Psychiatric conditions, personal and social problems figured prominently as factors of etiological significance in suicide subjects.

Tryptophan hydroxylase gene polymorphisms are not associated with suicide.

Several lines of evidence suggest a serotonergic dysfunction involved in the biological susceptibility of suicide. Abnormalities of serotonergic markers such as 5-hydroxyindoleacetic acid and prolactin response to fenfluramine have been demonstrated in suicide subjects. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified and some of these polymorphisms have been suggested to be associated with suicide, but the results are still inconsistent. We examined whether the -6526A/G polymorphism in the promoter region and the 218A/C polymorphism in intron 7 of the TPH gene were associated with suicide using 132 Japanese suicide victims. No significant difference in genotype distribution and allele frequencies of these polymorphisms was found between the suicide victims and the controls. We concluded neither the -6526A/G polymorphism nor the 218A/C polymorphism of the TPH gene is likely to have a major effect on the susceptibility of suicide. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:861-863, 2000.

Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.

The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects. PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique. Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects. Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.

Reduced adenylyl cyclase immunolabeling and activity in postmortem temporal cortex of depressed suicide victims

Background: Previous studies have found altered receptor/G protein-modulated adenylyl cyclase (AC) activity in subjects with mood disorders. Methods: To investigate whether these effects are associated with altered levels of specific isoforms of AC, we measured AC isoform I, IV and V/VI immunoreactivities in postmortem temporal cortex from nine depressed suicide victims, nine subjects with bipolar disorder (BD) and 18 age-matched non-psychiatric controls. Basal, GTPγS- and forskolin-stimulated AC activities were measured in the temporal cortex from the nine depressed suicide victims and their controls. Results: Western blotting revealed significant reductions in immunolabeling in AC type IV (−49%; p<0.05) in depressed suicide subjects compared to age-matched controls, but no differences were found in AC type I or type V/VI. There were no statistically significant differences in AC type I, IV or V/VI immunoreactivities between BD and matched control subjects. Functionally, there was a significant reduction in forskolin-stimulated AC activity in depressed suicide subjects compared to controls, which may be, in part, related to higher basal AC activity in the former group. Limitations: Our sample size was small with diverse subject characteristics. Conclusions: These preliminary findings suggest altered levels and/or function in AC type IV may contribute to disturbances in the postreceptor cAMP signaling cascade in depression.

Coupling efficiency of brain beta-adrenergic receptors to Gs protein in suicide, alcoholism and control subjects.

Abnormal beta-adrenergic receptor (betaAR) density in the brains of suicide victims has been reported, although results of studies are inconsistent. Ethanol modifies betaAR-mediated signal transduction. Moreover abnormal betaAR function has been implicated in alcoholism. BetaAR antagonists, which were used as ligands in previous betaAR binding studies, also bind to 5-HT1B/1Dbeta receptors; hence, their estimates of betaAR density are confounded by binding to 5-HT1B/1Dbeta receptors. More importantly, previous studies did not examine betaAR agonist affinity or coupling efficiency to Gs protein. We investigated agonist affinity and coupling efficiency of betaAR to Gs protein in the brains of ten suicide victims, six subjects with alcoholism, and eight controls. There were no differences in betaAR density in either the frontal cortex or hippocampus of suicide victims or alcoholic subjects compared to controls. Preliminary results indicate betaAR supercoupling in suicide victims in both brain regions and uncoupling in alcoholic subjects in the frontal cortex. These results are discussed in view of the existing literature on the role of betaAR in suicide and alcoholism and the mechanism of action of antidepressants.