P2RX7 polymorphisms Gln460Arg and His155Tyr are not associated with major depressive disorder or remission after SSRI or ECT

Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) gene polymorphism, has been suggested to be associated with major depressive disorder (MDD). The association between P2RX7 gene polymorphism and remission after serotonin selective reuptake inhibitors (SSRI) or electroconvulsive therapy (ECT) has not previously been studied. The aims of the present study were to test for an association between P2RX7 polymorphisms Gln460Arg (rs2230912) and His155Tyr (rs208294) and MDD in two patient populations compared to controls. The first patient sample consisted of 119 subjects with treatment-resistant major depressive disorder, who were treated with ECT and the second of 99 depressive outpatients treated with SSRI. Genotype frequencies were also compared between remitters (Montgomery and Åsberg Depression Rating Scale (MADRS) < 8) and non-remitters (defined as MADRS ≥ 8) to SSRI or ECT treatment. There were no differences in allele or genotype frequencies of either rs2230912 or rs208294 between patient groups and controls. Neither rs2230912 nor rs208294 was associated with MDD or remission after SSRI or ECT. The results suggest that P2RX7 gene polymorphisms Gln460Arg (rs2230912) and His155Tyr (rs208294) are not associated with MDD or remission after SSRI or ECT.     

Association between major depressive disorder and the norepinephrine transporter polymorphisms T-182C and G1287A: A meta-analysis

Background

Previous studies have implicated norepinephrine transporter (NET) gene polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide NET polymorphisms, T-182C (rs2242446) in the promoter region and G1287A (rs5569) in exon 9, were found to be associated with MDD in different populations. However, inconsistent and inconclusive results have also been obtained.

Methods

In this study, we examined whether rs2242446 and rs5569 genetic variants are related to the etiology of MDD using a meta-analysis. Relevant case-control studies were retrieved by database searching and selected according to established inclusion criteria.

Results

Eight articles were identified that tested the relationship between the NET T-182C and/or G1287A polymorphism and MDD. Statistical analyses revealed no significant association between these polymorphisms and MDD (OR=1.23, 95% CI=0.77−1.97, P=0.38 for T-182C; OR=1.00, 95% CI=0.78−1.29, P=0.99 for G1287A).

Limitations

The results must be treated with caution because of the small sample sizes of several included studies.

Conclusions

Our findings suggest that the NET T-182C and G1287A polymorphisms are not susceptibility factors for MDD.     

Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder

Background

Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge.

Methods

This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6–1.2 mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS.

Results

At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were −2.32 (−4.6, −0.05) and −0.97 (−3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥50% reduction in total score), MADRS remission (total score ≤10, add-on quetiapine XR only) and Clinical Global Impressions (‘much’/‘very much’ improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments.

Limitations

Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase.

Conclusions

Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.     

Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese

Background

A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.

Methods

We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.

Results

The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06–1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.

Limitations

The relative small sample size in BD group should be considered a limitation of this study.

Conclusions

Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.     

Trajectories of individual symptoms in remitters versus non-remitters with depression

Background

It remains unclear regarding the contribution of each individual symptom in predicting the outcome in major depressive disorder (MDD). The objective of this analysis was to evaluate trajectories of individual symptoms over time to identify which specific depressive item(s) could predict subsequent clinical response.

Methods

The data of 2874 outpatients with nonpsychotic MDD who received citalopram for up to 14 weeks in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. Average trajectories of individual symptoms over time were estimated for remitters and non-remitters. Moreover, specific symptoms whose improvement at week 2 predicted remission were identified, using binary logistic regression analysis.

Results

Trajectories were significantly different between remitters and non-remitters in all depressive symptoms. All depressive symptoms in the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR₁₆) in the two groups, except for hypersomnia and weight change in non-remitters, substantially improved within 2 weeks and gradually continued to improve thereafter throughout the 14 weeks. Early improvements in the following five symptoms, in order of magnitude, in the QIDS-SR₁₆ were significantly associated with remission: sad mood, negative self-view, feeling slowed down, low energy, and restlessness (P<0.001, P<0.001, P=0.001, P=0.004, P=0.021).

Limitations

The participants were limited to the nonpsychotic MDD outpatients who received citalopram. Further, symptomatology was not evaluated at the very beginning of treatment.

Conclusions

While the data pertain to citalopram and replication is necessary for other antidepressants, early improvements in certain core depressive symptoms may serve as a predictor of subsequent remission.     

Homocysteine,depression and cognitive function in older adults

Background

Depression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression.

Methods

We recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery.

Results

Individuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1–3.3), immediate (OR 1.9, 95%CI 1.1–3.5) and delayed (OR 1.9, 95%CI 1.1–3.4) word recall after adjusting for age, gender, IHD and MADRS score.

Limitations

The presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study.

Conclusions

Elevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.     

Association between the so-called “activation syndrome” and bipolar II disorder,a related disorder,and bipolar suggestive features in outpatients with depression

Background

Activation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression.

Methods

The frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively.

Results

Of 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS.

Limitations

This is a retrospective and naturalistic study; therefore, patient selection bias could have occurred.

Conclusions

Cautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar–bipolar dichotomy. Prospective studies are needed to confirm these results.     

Dimensional endophenotypes in bipolar disorder: Affective dysregulation and psychosis proneness

Background

The clinical phenotype of bipolar disorder (BPD) is heterogeneous and the genetic architecture of the disorder is complex and not well understood. Given these complications, it is possible that the identification of intermediate phenotypes (“endophenotypes”) will be useful in elucidating the complex genetic mechanisms that result in the disorder. The examination of unaffected relatives is critical in determining whether a particular trait is genetically-relevant to BPD. However, few dimensional traits related to BPD have been assessed in unaffected relatives of patients.

Methods

We assessed affective temperament and schizotypy in 55 discordant sibling pairs and 113 healthy controls (HCs) using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) to assess affective temperament and the Schizotypal Personality Questionnaire (SPQ) to assess schizotypy.

Results

BPD patients scored significantly higher than HCs on all subscales of the SPQ and on all but one subscale (hyperthymic) of the TEMPS-A (all p<0.01). Siblings demonstrated scores that were significantly intermediate to patients and HCs on the anxious subscale of the TEMPS-A and on the interpersonal deficits and disorganized subscales of the SPQ.

Limitations

We did not investigate the BPD spectrum as most patients were diagnosed with BPD I (n=47). Most of the patients had experienced psychosis (n=42) and so we were unable to examine whether psychosis status impacted upon affective temperament or schizotypy in patients or their siblings.

Conclusion

These data suggest that schizotypy and affective temperament represent dimensional traits that are likely to underlie the genetic risk for BPD.     

Treating anxious depression using repetitive transcranial magnetic stimulation

Background

A subset of patients given a clinical diagnosis of major depressive disorder (MDD) are described as having “anxious depression,” a presentation that, in some studies, has been an indicator of poor response to pharmacotherapy. The aim of this study was to determine if anxious depression is associated with attenuated response to repetitive transcranial magnetic stimulation (rTMS), an FDA-approved treatment for MDD.

Methods

Participants were 32 adult outpatients with treatment resistant MDD who were referred for rTMS. The Hamilton Rating Scale for Depression (HAMD) was administered to assess treatment response, and anxious depression was defined as a score of seven or above on the anxiety/somatization factor of the HAMD. A quarter of the sample met the anxious depression criterion at pretreatment.

Results

Both depression (total score) and anxiety symptoms improved from pre- to post-treatment with moderate to large treatment effects. Patients with and without anxious depression demonstrated similar rates of improvement in depression. Patients with versus without anxious depression demonstrated larger improvements in anxiety.

Limitations

The sample size was small, and assessments did not include structured diagnostic interview or independent measures of anxiety symptoms.

Conclusions

For the sample as a whole, there were significant improvements in both depression and anxiety. Anxious depression was not associated with attenuated treatment response to rTMS.     

Probing for depression and finding diabetes: a mixed-methods analysis of depression interviews with adults treated for type 2 diabetes

Background

Depression has increased prevalence and consistently predicts poor health outcomes among patients with diabetes. The impact of stressors related to diabetes and its treatment on depression assessment is infrequently considered.

Methods

We used mixed methods to evaluate depressive symptoms in adults with type 2 diabetes. We categorized responses related to diabetes and its treatment during interviews (n=70) using the Montgomery–Åsberg Depression Rating Scale (MADRS) and administered questionnaires to measure diabetes-related distress and depressive symptoms.

Results

Participants (M age=56, SD=7; 67% female; 64% Black; 21% Latino) had mild depression on average (MADRS M=10, SD=9). Half of those with symptoms spontaneously mentioned diabetes context; 61% said diabetes contributed to their symptoms when questioned directly. Qualitative themes included: overlapping symptoms of diabetes and depression; burden of diabetes treatment; emotional impact of diabetes; and the bidirectional influence of depression and diabetes. Diabetes was mentioned more often at higher levels of depression severity (r=.38, p=.001). Higher HbA1c was associated with mentioning diabetes as a context for depressive symptoms (r=.32, p=.007). Insulin-users mentioned diabetes more often than those on oral medications only (p=.005).

Limitations

MADRS is not a traditional qualitative interview so themes may not provide an exhaustive view of the role of diabetes context in depression assessment.

Conclusions and clinical implications

The burden of type 2 diabetes and its treatment often provide an explanatory context for depressive symptoms assessed by structured clinical interviews, the gold standard of depression assessment. Diabetes context may influence accuracy of assessment and should inform intervention planning for those needing treatment.     

Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples

Background

Major depressive disorder (MDD) is a universally prevalent, genetic, and environment dependent mental condition that disables people of every culture, race, gender, and age. While the gender differences for MDD have been widely reported in literature, few genome-wide analyses of gender differences have been reported to date.

Methods

We conducted a genome-wide association analysis of gender differences for MDD using the Netherlands NESDA and NTR population-based samples (1726 cases and 1630 controls). PLINK software was used to analyze the genome-wide association data of Perlegen 600 K SNP Chips.

Results

We identified 40 male-specific and 56 female-specific MDD associated SNPs with P-values less than 10^− 4. The best male-specific SNP was rs9352774 (P = 2.26 × 10^− 6) within LGSN gene while the best female-specific SNP was rs2715148 (P = 5.64 × 10^− 7) within PCLO gene. We also found 38 SNPs showing gene × gender interactions in influencing MDD (P < 10^− 4). The best SNP was rs12692709 (P = 5.75 × 10^− 6) near FIGN gene at 2q24.3 while the next best SNP was rs11039588 (P = 1.16 × 10^− 5) within OR4B1 gene.

Limitations

The findings from this study need be replicated in other populations.

Conclusions

These results provide genetic basis for gender differences in MDD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in MDD.     

Dissociation of regional activity in the default mode network in first-episode,drug-naive major depressive disorder at rest

Background

Major depressive disorder (MDD) is associated with altered neural activity in the default mode network (DMN). In the present study, we used a fractional amplitude of low-frequency fluctuations (fALFF) approach to directly investigate the features of spontaneous brain activity of the DMN in patients with the first-episode, drug-naive MDD at rest.

Methods

Twenty-four first-episode, drug-naive patients with MDD and 24 age-, gender-, and education-matched healthy subjects participated in the study. The fALFF and independent component analysis (ICA) approaches were utilized to analyze the data.

Results

Patients with MDD exhibited a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the left dorsal medial prefrontal cortex (MPFC) and decreased fALFF in the left parahippocampal gyrus (PHG). The increased fALFF values of the left dorsal MPFC were positively correlated to the Hamilton Rating Scale for Depression (HRSD) scores.

Conclusions

Our results first suggested that there was a dissociation pattern of resting-state fALFF in the DMN in patient with MDD, which highlighted the importance of the DMN in the pathogenesis of MDD.     

Meta-analytic evidence for neuroimaging models of depression: State or trait?

Background

Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. With the rapid growth of neuroimaging research on relatively small samples, meta-analytic techniques are becoming increasingly important. Here, we aim to clarify the support in fMRI literature for three leading neurobiological models of MDD: limbic–cortical, cortico–striatal and the default mode network.

Methods

Searches of PubMed and Web of Knowledge, and manual searches, were undertaken in early 2011. Data from 34 case-control comparisons (n=1165) and 6 treatment studies (n=105) were analysed separately with two meta-analytic methods for imaging data: Activation Likelihood Estimation and Gaussian-Process Regression.

Results

There was broad support for limbic–cortical and cortico–striatal models in the case-control data. Evidence for the role of the default mode network was weaker. Treatment-sensitive regions were primarily in lateral frontal areas.

Limitations

In any meta-analysis, the increase in the statistical power of the inference comes with the risk of aggregating heterogeneous study pools. While we believe that this wide range of paradigms allows identification of key regions of dysfunction in MDD (regardless of task), we attempted to minimise such risks by employing GPR, which models such heterogeneity.

Conclusions

The focus of treatment effects in frontal areas indicates that dysregulation here may represent a biomarker of treatment response. Since the dysregulation in many subcortical regions in the case-control comparisons appeared insensitive to treatment, we propose that these act as trait vulnerability markers, or perhaps treatment insensitivity. Our findings allow these models of MDD to be applied to fMRI literature with some confidence.     

Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population

Background

Previous candidate gene studies of major depressive disorder (MDD) have provided inconclusive evidence of association for genes with strong biological rationale for MDD. In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population.

Methods

Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder were recruited for the study. 371 normal controls were recruited from local community. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants by polymerase chain reaction. Male and female subjects were analyzed separately.

Results

No differences were found in the frequencies of the single alleles and genotypes of the tested polymorphisms between MDD patients and normal group. The frequency of the A-A haplotype was significantly higher in female MDD compared to healthy female controls (P < 0.05). No significant association with treatment response was discovered in haplotype and single-marker analysis.

Limitations

This study lacks a placebo control and we cannot definitively exclude the possibility that some patients in the responder group responded to the placebo effect alone.

Conclusion

The result suggests that TPH2 gene may have a gender dependent effect on susceptibility to MDD but not with its treatment response in Chinese Han population. Further studies are needed to replicate the association that we observed.     

Transcranial direct current stimulation (tDCS) for depression: Analysis of response using a three-factor structure of the Montgomery–Åsberg depression rating scale

Background

There is growing evidence that transcranial direct current stimulation (tDCS) may be an effective treatment for depression. However, no study to date has profiled the antidepressant effects of tDCS using items or factors on depression symptom severity rating scales. This could potentially provide information about the mechanisms by which tDCS achieves its antidepressant effects and also identify clinical predictors of response.

Methods

The present study analysed scores on the Montgomery–Åsberg depression rating scale (MADRS) from a randomised, sham-controlled trial of tDCS (Loo et al., 2012. British Journal of Psychiatry. 200, 52–59) using a three-factor model of MADRS items (Suzuki et al., 2005. Depression and Anxiety. 21, 95–97) encompassing dysphoria, retardation and vegetative symptoms.

Results

Participants in the active tDCS treatment group showed significant improvement in dysphoria while participants in the sham treatment group did not. While both groups showed improvement in retardation symptoms, improvement was significantly greater in the active tDCS group. Both groups also showed improvement in vegetative symptoms but there were no between-group differences.

Limitations

Further studies with larger sample sizes are warranted to investigate the generalisability of results and whether the MADRS factor structure may change as a result of the specific treatment used.

Conclusions

tDCS appears to be particularly effective in treating dysphoria and retardation, but not vegetative symptoms of depression. This may have implications for selection of types of depression most likely to respond to this treatment.     

VEGF plasma level variations in duloxetine-treated patients with major depression

Background

The vascular endothelial growth factor (VEGF) signaling, which modulates angiogenesis and neurogenesis within the neurovascular unit, might play an important role in the neuro-endocrine-immune (NEI) stress-adaptation system. Recent evidence suggests that VEGF is involved in the pathophysiology of a number of diseases including major depressive disorder (MDD) and is affected by some treatments, including antidepressants. The objective of the study was to investigate the VEGF level variations in MDD patients during antidepressant treatment with duloxetine, a relatively new SNRI.

Methods

A total of 30 MDD patients and 32 healthy controls were assessed using the Hamilton Depression Scale (HAM-D) and monitored for VEGF plasma levels at baseline, week 6 and week 12 of duloxetine treatment (60 mg/day) and at baseline, respectively.

Results

According to early clinical response to duloxetine (defined at week 6 by reduction>50% of baseline HAM-D score), the MDD patients were divided into early responders (ER) and early non-responders (ENR). During duloxetine treatment, we found an opposite trend in the VEGF levels between ER and ENR: in ER the VEGF levels significantly increased in association with clinical response at W6, while in ENR the VEGF levels significantly decreased in association with an overall clinical response at W12.

Limitations

Small sample size.

Conclusions

The opposite trends in VEGF levels, increasing in ER and decreasing in ENR, might reflect differential Norepinephrine/Serotonin effects of duloxetine on differential neurobiological backgrounds of depressive syndromes. Overall, the modulation of VEGF signaling within the neurovascular unit during antidepressant treatment could hypothetically favor the remodeling of neural circuitry, contributing to adaptive adjustment of the NEI stress-adaptation system.     

Age of onset and corpus callosal morphology in major depression

Background

The corpus callosum and related white matter projections have been implicated in major depressive disorder (MDD). Previously, we found a smaller genu in adolescents with MDD as compared to controls. To date, no study has examined the age of depression onset (adult vs. pediatric) as it relates to genu area in adults with MDD.

Methods

The area of the corpus callosum and its sub-regions were measured in 21 MDD subjects with pediatric age of onset (≤18 years) (29.48±7.62 years; 16 female, 5 male) and 31 MDD subjects with adult age of onset (≥19 years) (41.42±8.85; 17 female, 14 male) and 19 healthy controls (32.89±years 9.98; 11 female, 8 male) using magnetic resonance imaging (MRI).

Results

A difference in genu area was noted between groups (p=0.03), after co varying for age with post-hoc tests revealing that the difference was driven by the subjects with an MDD onset of pediatric age (p=0.035). No other sub-regions or total corpus callosum area demonstrated a significant difference. Genu area correlated with age in controls (p=0.02) but not in MDD patients (p=0.35). No significant correlation was found between the confound illness duration and genu area in MDD subjects with pediatric age of onset.

Limitations

Confirmation and extension of our findings requires a larger sample size and usage of diffusion tensor imaging.

Conclusions

Our findings provide additional evidence of abnormalities in the genu of the corpus callosum in early onset depression that persist into adulthood.     

TNF-alpha −308G>A polymorphism is associated with suicide attempts in major depressive disorder

Background

Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) −308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) −1082A>G are associated with increased risk for suicide attempts in MDD.

Methods

Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD.

Results

The GG genotype of the TNF-alpha −308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 −1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types.

Limitations

Limitations include a relatively small sample size and a cross-sectional design.

Conclusions

TNF-alpha −308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha −308G>A influences suicide in MDD.     

The relationship between positive and negative automatic thought and activity in the prefrontal and temporal cortices: A multi-channel near-infrared spectroscopy (NIRS) study

Background

Recently, neurobiological studies of the cognitive model of depression have become vastly more important, and a growing number of such studies are being reported. However, the relationship between the proportion of positive and negative automatic thought and activity in the prefrontal and temporal cortices has not yet been explored. We examined the relationship between brain activity and the proportion of positive and negative automatic thought in patients with major depressive disorder (MDD), using multi-channel near-infrared spectroscopy (NIRS).

Methods

We recruited 75 individuals with MDD (36 females; mean age=39.23±12.49). They completed the Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire-Revised, Japanese version of the National Adult Reading Test, and the State-Trait Anxiety Inventory. Brain activation was measured by 52-channel NIRS.

Results

We found that activation in the vicinity of the right superior temporal gyrus is related to a deviation to negative of the proportion of positive and negative thoughts in individuals with MDD. Left dorsolateral prefrontal cortex activity was higher in the group with comparatively frequent positive thought.

Limitations

Our participants were patients taking antidepressant medication, which is known to influence brain activity. Second, the poor spatial resolution of NIRS increases the difficulty of identifying the measurement position.

Conclusions

We found that activation of the prefrontal and temporal cortices is related to the proportion of automatic thoughts in the cognitive model of depression.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.