Low plasma BDNF is associated with suicidal behavior in major depression

Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, has a known association with the pathophysiology of anxiety and depression. However, the role of BDNF in suicide has not been well investigated to date. This study examined plasma BDNF levels in 32 major depressive disorder (MDD) patients who had recently attempted suicide, 32 non-suicidal MDD patients, and 30 normal controls. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS). Plasma BDNF levels were measured by enzyme linked immunosorbent assay. BDNF levels were significantly lower in suicidal MDD patients (430.5+/-397.0 pg/ml) than non-suicidal MDD patients (875.80+/-663.02 pg/ml) or normal controls (889.4+/-611.3 pg/ml) (F=6.682, p=0.002). The most suitable cut-off point of BDNF level between suicidal depression and non-suicidal depression groups was 444.58 pg/ml. At this cut-off point, the sensitivity=68.7%, specificity=78.1%, positive predictive value=75.9%, and negative predictive value=71.4%. However, there was no significant difference in BDNF levels between the depressive control and normal control groups (p=0.996). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal patients. In addition, BDNF levels were not different between fatal and non-fatal suicide attempts. These results suggest that reduction of plasma BDNF level is related to suicidal behavior in major depression and that BDNF level may be a biological marker of suicidal depression.     

Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients

BACKGROUND: Several studies have suggested that there is a substantial genetic contribution to suicidal behavior. Genes encoding proteins involved in serotonergic transmission are major candidates in association studies of suicidal behavior. In this study, we aimed to investigate the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for association with suicidal behavior in depressive patients. METHODS: Patients with major depression who had recently attempted suicide (n=191) and control subjects (n=193) were genotyped for 5HTR2A 102T/C, and TPH 218A/C. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured using the Hamilton Depression Rating Scale (HDRS). RESULTS: There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. CONCLUSIONS: We concluded that these polymorphisms may not be associated with susceptibility to suicidal behavior in our Korean population. Our results were in line with most previous studies. More work is needed to replicate these findings. Our future studies aim at identifying other genetic associations.     

TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression

Background

Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior.

Methods

One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by χ² statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype.

Results

There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the lethality of suicidal behavior in suicidal depressed patients according to the genotypes of three polymorphisms.

Conclusion

Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.     

Cytokine levels in the blood may distinguish suicide attempters from depressed patients

Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressed patients, as well as healthy controls.Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS).We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication.These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.     

Reduced platelet BDNF level in patients with major depression

Serum and plasma brain-derived neurotrophic factor (BDNF) levels as well as brain BDNF have previously been shown to be decreased in patients with major depressive disorder (MDD). We explored whether platelet BDNF levels, circulating stored BDNF, would be lower in MDD patients than in normal controls. BDNF levels were examined in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in 20 hospitalized non-suicidal MDD patients, 20 recent-suicidal MDD patients, and 20 normal controls. Platelet BDNF content was calculated by subtracting PPP BDNF level from PRP BDNF level, and dividing the result by the total platelet count, and it was expressed as pg/10⁶ platelets. Individuals were evaluated using a Structured Clinical Interview for DSM-IV and a Hamilton Depression Rating Scale. Platelet BDNF contents were significantly lower in non-suicidal patients (3.09 ± 2.53 pg/10⁶ platelets) and recent-suicidal MDD patients (3.16 ± 1.99 pg/10⁶ platelets) than in healthy controls (6.17 ± 2.64 pg/10⁶ platelets) (p < 0.01). However, platelet BDNF contents had no significant differences between non-suicidal and recent-suicidal patients. PRP BDNF levels were also significantly lower in non-suicidal and suicidal MDD patients than in healthy controls (p = 0.029), while PPP BDNF had no significant difference between 3 groups (p = 0.971). Our findings suggest that there is a decrease in the platelet BDNF of patients with major depression. Reduced platelet BDNF contents as circulating stored BDNF could be associated with lower serum BDNF level in patients with major depression.     

Serum lipid levels and suicidality among male patients with schizoaffective disorder

Suicidal behavior in schizoaffective disorder is a serious problem and suicide risk during lifetime ranges between 5%-10%. Neurobiology of suicidal behavior has not been studied sufficiently, and a high number of studies are oriented toward lipid investigation. The aim of our study was to investigate whether there were differences in the level of lipids (cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) in hospitalized suicidal (n=20) and non-suicidal (n=20) patients with schizoaffective disorder. The study also included male healthy control subjects (n=20). Hamilton Depression Rating Scale (HDRS-17), and Positive and Negative Syndrome Scale (PANSS) were used to confirm the level of psychopathology in patients with schizoaffective disorder. Severity of suicidality was measured by Scale for Suicide Ideation (SSI) at time of admission. Results of the study indicated significantly lower concentrations of cholesterol (p<0.001), LDL-cholesterol (p<0.01) and HDL-cholesterol (p<0.01). There were no differences in the number of previous hospitalization and previous suicide attempts between suicidal and non-suicidal patients (p>0.05). Duration of the illness was significantly (p<0.05) shorter in suicidal patients. Suicidal patients also had a significantly higher score on HDRS-17 (p<0.001) and PANSS (p<0.01) compared to non-suicidal patients.     

Platelet serotonin concentration and suicidal behavior in combat related posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a serious and global problem, a psychiatric disorder that frequently occurs with different comorbidities, and is associated with a high suicide rate. Pathophysiologically, both PTSD and suicidal behavior are related to disturbances in the central serotonergic system. Serotonin (5-hydroxytryptamine, 5-HT) controls emotional behavior, anxiety, impulsivity and aggression, and nearly all known antidepressants and antianxiety drugs affect 5-HT transmission. Platelet 5-HT can be used as a limited peripheral marker of the central serotonergic synaptosomes, since it is related to particular basic psychopathological characteristics of several psychiatric disorders. Platelet 5-HT concentration has been reported to be similar in PTSD subjects and healthy controls, but suicidal patients across different psychiatric diagnoses have reduced platelet 5-HT concentration. This study examined platelet 5-HT concentration by the spectrofluorimetric method in male subjects: 73 suicidal and 47 non-suicidal veterans with current and chronic combat related PTSD, 45 suicidal and 30 non-suicidal comparative non-PTSD subjects and 147 healthy men. The presence of suicidal behavior (score=0, non-suicidal; scores > or =1, suicidal) was assessed with the Hamilton Depression Rating Scale-17 (HDRS). Platelet 5-HT concentration was significantly lower in suicidal PTSD and non-PTSD patients compared to non-suicidal patients or healthy controls. Since the majority of patients scored very low on item 3 of HDRS, no significant correlation between suicidal scores and platelet 5-HT concentration was found. These results show that reduced platelet 5-HT concentration is related to suicidal behavior in PTSD, and suggest that platelet 5-HT concentration might be used as a peripheral marker to predict suicidal behavior across psychiatric diagnoses.     

Cytokine imbalance in the pathophysiology of major depressive disorder

OBJECTIVE: A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. METHODS: Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. CONCLUSION: We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.     

Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder

Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.     

Left orbitofrontal and superior temporal gyrus structural changes associated to suicidal behavior in patients with schizophrenia

Suicidal attempts are relatively frequent and clinically relevant in patients with schizophrenia. Recent studies have found gray matter differences in suicidal and non-suicidal depressive patients. However, no previous neuroimaging study has investigated possible structural abnormalities associated to suicidal behaviors in patients with schizophrenia. A whole-brain magnetic resonance voxel-based morphometric examination was performed on 37 male patients meeting the DSM-IV criteria for schizophrenia. Thirteen (35.14%) patients had attempted suicide. A non-parametric permutation test was computed to perform the comparability between groups. An analysis of covariance (AnCova) model was constructed with a statistical threshold of p<0.05 corrected for multiple comparisons. After controlling for age and severity of illness, results showed significant gray matter density reduction in left superior temporal lobe (p=0.03) and left orbitofrontal cortex (p=0.04) in patients who had attempted suicide when comparing with non-suicidal patients. Although sample size limitations and potential clinical heterogeneity preclude definitive conclusions, these data point to structural differences in key cerebral areas. Neuroimaging studies are necessary to expand our knowledge of biological mechanisms underlying suicide in schizophrenia.     

Plasma Levels of IL-23 and IL-17 before and after Antidepressant Treatment in Patients with Major Depressive Disorder

Objective

Cytokines are believed to have a role in the pathophysiology of major depression. The alteration in levels of pro-inflammatory cytokines [interleukin 1β (IL-1β), IL-2, IL-6, IL-12, interferon γ, and tumor necrosis factor α] in major depression supports the cytokine hypothesis of this illness. IL-23 and IL-17 are also pro-inflammatory cytokines, but few studies have focused on their role in major depression. This study investigated the potential role of the IL-23 and IL-17 axis in major depression.

Methods

Plasma IL-23 and IL-17 levels were measured in 26 major depressive disorder (MDD) patients before and after 6-week treatment with antidepressants; these levels were measured in 28 age- and sex-matched normal controls. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). IL-23 and IL-17 plasma levels were estimated using quantitative enzyme-linked immunosorbent assay.

Results

Pre-treatment plasma levels of IL-23 and IL-17 in MDD patients were not significantly different from those of normal controls. In MDD patients, IL-23 and IL-17 levels after 6 weeks of antidepressant treatment were not different from the baseline levels. There was no significant correlation between changes in the cytokine levels and changes in the HDRS scores representing the severity of depression.

Conclusion

The present study does not support a potential involvement of IL-23 and IL-17 axis in major depression. Replication and extension using a larger sample are required.     

Increased plasma nitric oxide level associated with suicide attempt in depressive patients

BACKGROUND: Nitric oxide (NO) is known to influence cerebral monoaminergic activity, including the activity of serotonin. We evaluated plasma NO metabolite (NO(x)) levels in depressive patients with and without a recent history of suicide attempt. METHOD: Plasma NO(x) levels were measured in 39 depressive patients who had recently attempted suicide, 44 non-suicidal depressed patients, and 70 normal controls. The severity of depression was measured with the Hamilton's Depression Rating Scale. The lethality of the suicide attempt was scored using Weisman and Worden's risk-rescue rating scale and Lethality Suicide Attempt Rating Scale. RESULTS: Plasma NO(x) levels were significantly higher in suicidal depressive patients than non-suicidal depressive patients or normal control subjects (Z=-2.472, p=0.013). However, higher plasma NO(x) levels in suicidal depressive patients were significantly related to a lower lethality of suicide attempts and lower severity of depression. CONCLUSIONS: Our study suggests that increased plasma NO(x) level is associated with suicide attempts in depressive patients. Moreover, higher plasma NO(x) level is related with suicide attempts in mild depressed patients. However, further studies are required to understand the role of NO system in depression and suicidal behavior.     

Involvement of levels of Toll like receptor-4 in monocytes,CD4 + T-lymphocyte subsets,and cytokines in patients with immune thrombocytopenic purpura

Introduction

Toll-like receptors have been found to be associated with immune-mediated diseases but it is still not clear whether they play a role in immune thrombocytopenic purpura (ITP), especially TLR4. CD4 + T-lymphocyte abnormalities, including Th17, Th1, Th2, and regulator T cell (Treg), are considered important in ITP. There have been few studies regarding the expression of TLR4 and the relationships between TLR4 and Th17 levels in ITP.

Materials and Methods

In this study, we evaluated the expression of TLR4 in monocytes, the plasma concentrations of IL-23, IL-17 and the profiles of Th17, Th1, Th2 cells in 70 patients with ITP and 31 healthy controls. In addition, we evaluated IL-2 and Treg cells in 46 cases of 70 patients with ITP and the same 31 controls.

Results

Higher levels of TLR4 expression, higher relative numbers of Th17 and Th1 cells and lower levels of Treg cells were observed in patients when compared with controls (p = 0.001 for TLR4; p < 0.001 for Th17; p = 0.014 for Th1; p = 0.001 for Treg). The levels of IL-23 and IL-2 were increased (p = 0.022 for IL-23; p = 0.025 for IL-2), the relative levels of Th2 and concentrations of IL-17 were similar across both groups (p = 0.446 for Th2; p = 0.316 for IL-17). A significant negative correlation was observed between levels of TLR4 and Treg(r = -0.544, p < 0.001), but a significantly positive correlation was observed between IL-2 and IL-23 concentration in patients (r = 0.441, p = 0.004). Neither the correlation between TLR4 and the other CD4⁺ T cells and cytokines nor the correlation between the three cytokines and CD4+ T cells was found to be statistically significant.

Conclusions

Our data showed that TLR4, CD4 + T cells (Th1, Th17 and Treg cells) and related cytokines (IL-23, IL-2) may take part in the pathogenesis of ITP. TLR4 may play a role through the TLR4-cytokine-CD4+ T lymphocyte cell pathway.     

Suicidal ideation and attempts among psychiatric patients with major depressive disorder

BACKGROUND: Few studies have investigated risk factors for suicidal ideation and attempts, or possible variations in them, among representative samples of psychiatric patients with major depressive disorder. METHOD: As part of the Vantaa Depression Study in Vantaa, Finland, 269 patients with DSM-IV major depressive disorder (MDD), diagnosed by interview using semistructured World Health Organization Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and Structured Clinical Interview for DSM-III-R Personality Disorders, were thoroughly investigated. Information was gathered on patients' levels of depression, anxiety, hopelessness, perceived social support, social and occupational functioning, and alcohol use. Suicidal behavior was assessed by interviews, including the Scale for Suicidal Ideation, and by information from psychiatric records. Data were gathered from Feb. 1, 1997, to May 31, 1998. RESULTS: During the current MDD episode, 58% of all patients had experienced suicidal ideation; among the 15% of the total who had attempted suicide, almost all (95%) had also had suicidal ideation. In nominal regression models predicting suicidal ideation, hopelessness, alcohol dependence or abuse, low level of social and occupational functioning, and poor perceived social support were found to be significant (p < .05) independent risk factors. High severity of depression and current alcohol dependence or abuse in particular, but also younger age and low level of social and occupational functioning, predicted suicide attempt. CONCLUSION: Suicidal ideation is prevalent and appears to be a precondition for suicide attempts among psychiatric patients with MDD. The risk factors for suicidal ideation and attempts locate in several clinical and psychosocial domains. While these risk factors largely overlap, the overall level of psychopathology of suicide attempters is higher compared with that in patients with ideation, and substance use disorders and severity of depression may be of particular importance in predicting suicide attempts.     

A meta-analysis of cytokines in suicidal behavior

Background: We conducted the first meta-analysis of studies comparing the plasma and CSF concentrations of cytokines in suicidal patients vs. non-suicidal patients or healthy controls. Methods: We searched Medline, Web of Science, and PsycINFO from 1965 to November 2014 for relevant studies. Manual searches of references and unpublished data were also included. Suicidal patients included severe suicide ideators and suicide attempters. Results: Eleven articles were available for the meta-analysis, for a total sample size of 494 suicidal patients, 497 non-suicidal patients and 398 healthy controls. Levels of 6 independent plasma cytokines (IL2, IL6, TNFalpha, IFNgamma, IL4, TGFbeta) were meta-analyzed for plasma studies comparing suicidal vs. both controls. IL8 level was meta-analyzed for cerebrospinal fluid studies comparing suicidal patients with healthy controls. We reported with medium effect size, that suicidal patients had: (1) lower IL2 plasma levels than both non-suicidal patients and healthy controls (medium effect size); (2) lower IL4 and higher TGFbeta plasma levels than healthy controls. Conclusion: Our results promote the hypothesis of altered inflammatory markers in suicidal patients, for both pro-inflammatory (IL2) and anti-inflammatory (IL4 and TGFbeta) cytokines.     

Executive functioning in depressed patients with suicidal ideation

OBJECTIVE: Suicidal thinking has been associated with cognitive rigidity, however, not all depressed patients contemplate suicide. Therefore, we hypothesized that compared with depressed subjects without suicidal ideation, depressed individuals with suicidal ideation would display poorer performance on measures of executive functioning that involve mental flexibility. METHOD: In-patients with a current major depressive episode who had no current suicidal ideation (n=28) were compared with those who had current suicidal ideation (n=5) on measures of executive functioning and two neurocognitive tests that predominantly assess non-frontal regions. RESULTS: Compared with non-suicidal depressed patients, depressed suicidal patients performed significantly worse on several measures of executive functioning after controlling for age, IQ, severity of depression and prior suicide attempts. The two groups performed similarly on tests that predominantly assess non-frontal regions. CONCLUSION: Depressed individuals contemplating suicide have cognitive rigidity, which does not appear to be a global brain dysfunction. Suicidal mental states may result from dysfunctional executive decision-making that is associated with the frontal lobe.     

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients

Noradrenergic neurons of the locus coeruleus (LC) have been implicated in the neurobiology of depression and suicidal behavior. The current postmortem study determined numbers of noradrenergic neurons by immunostaining the synthesizing enzyme tyrosine hydroxylase in the LC of 12 non-elderly depressed patients with a mood disorder as compared to 12 age- and sex-matched normal controls. Six patients were suicide victims, the other six patients died of natural causes. Non-suicidal patients had fewer neurons immunoreactive for tyrosine hydroxylase (TH-ir) than suicide victims or controls. No difference appeared between the number of TH-ir neurons in suicide patients and controls. Numbers of pigmented LC neurons were equal in patients and controls. The differences of TH-immunoreactivity could neither be attributed to drug influences nor to polarity of depressive disorder (i.e., unipolar/bipolar). Numbers of TH-ir neurons correlated positively with mean doses of tri- or tetracyclic antidepressants. Results of this study suggest a presynaptic noradrenergic deficit of the LC in depressed non-suicidal patients. Indirect evidence is provided that suicide is not related to decreased noradrenergic function and that traditional antidepressants may enhance noradrenergic activity of the LC in depressed patients. Received: 29 January 1999 / Accepted: 27 May 1999     

The prediction of suicidal intent in depressed patients

The aim of the present study was to examine the relationships between suicidal ideation or suicidal attempts and severity of depression, presence of personality disorders, and sociodemographic factors in a population of depressed in-patients. A total of 338 adult depressed psychiatric in-patients were examined and classified according to DSM-III criteria as having major depression with or without melancholic or psychotic features, adjustment disorder with depressed mood or dysthymic disorder. Scores on the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and Zung Self-Rating Depression and Anxiety Scales (SDS and SAS) were measured. We found that suicidal ideation was significantly related to severity of depression (according to the HDRS and all self-rating scales), a lower global assessment of functioning the year before hospitalization, and previous psychiatric hospitalizations. The items with the strongest predictive value for suicidal ideation were hopelessness, depressed mood, feelings of guilt, loss of interest and low self-esteem. These symptoms predicted 43% of the variance in suicidal ideation. None of the above predictors of suicidal ideation was related to suicidal attempts. Depressed patients with a personality disorder attempted significantly more suicidal attempts and showed more suicidal ideation than depressed patients without personality disorder. No significant correlations were found between suicidal ideation or suicide attempts and gender, marital status, employment status or psychosocial stressors during the previous 6 months.     

REM sleep,dream variables and suicidality in depressed patients

To examine the relationship between the emotional quality of dreams, REM sleep variables and suicidal tendency in depressed individuals, 26 depressed volunteers (10 males and 16 females) were assessed with the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and underwent 3 nights of polysomnography. There was a significant negative correlation between suicidality scores and REM latency and a positive correlation between suicidality and REM percent. Suicidal subjects had a significantly shorter mean REM latency and a higher mean REM percentage than the non-suicidal subjects. As expected in normal subjects, 20 subjects had an increase in dream-like quality (DLQ) of REM reports between the first and second halves of the night. The six subjects with a negative DLQ difference also scored as suicidal. A reduction in dream-like quality of the REM content reports between the first and second halves of the night was found to be associated with suicidal tendency. The findings may indicate that these subjects fail to self-regulate mood and integrate affect into long-term memory networks during sleep. Theoretical and clinical implications of these findings in depression are discussed.     

Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder

Objective

The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD).

Methods

Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal controls. Hamilton''s 17-item Depression Rating Scale (HDRS), the Risk-Rescue rating system (RRR) and the Lethality Suicide Attempt Rating Scale updated (LSARS-II) were assessed for the depressed patients.

Results

Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. Comparing allele frequency, those with a 10 allele or 10 allele carriers were higher in suicidal subjects than in control subjects. No difference was noted in 5-HTTLPR genotypes and haplotype distribution between the suicidal subjects and control subjects. The RRR scores in subjects with the 10/10 5-HTTVNTR genotype or 10 5-HTTVNTR allele were significantly lower than those in subjects with other genotypes.

Conclusion

These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.