Heterogeneity Of Major Depressive Disorder Research Articles

Sertoli cell therapy: A novel possible treatment strategy for treatment-resistant major depressive disorder

By the year 2020, depression will be the 2nd most common health problem in the world. Current medications to treat depression are effective in less than 50% of patients. There is the need for novel treatments for depression to address the high rates of resistance to current treatment and the chronic residual symptoms in many patients treated for depression. The heterogeneity of major depressive disorder suggests that multiple neurocircuits and neurochemicals are involved in its pathogenesis thus, finding an alternative to neurotransmitter agonist- or antagonist-based treatments offers an important new approach. Cellular therapy is an emerging treatment strategy for multiple diseases, including depression. Based upon their in vivo function as “nurse cells” within the testis and the documented viability, efficacy, and safety of Sertoli cells transplanted into multiple tissues, including brain, the potential for these cells to provide a neuroprotective, anti-inflammatory, and trophic environment for neurons should be considered. It is proposed that the combination of self-protective, immunoregulatory and trophic properties of Sertoli cells may confer a unique potential for depression treatment and avoid many of the risks and challenges associated with stem cell therapies. At the very least, studies of the effects of Sertoli cell transplantation will add substantially to our understanding of the cellular and molecular processes that underlie depression.

Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication

There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R). The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview. Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypo-mania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder. These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice.

FMRI BOLD responses to negative stimuli in the prefrontal cortex are dependent on levels of recent negative life stress in major depressive disorder

It is poorly understood how stressors modulate neurobiological mechanisms that may contribute to the heterogeneity of major depressive disorder (MDD). Unmedicated patients diagnosed with MDD ( n = 15) and individually matched healthy controls ( n = 15) completed stress questionnaires and were studied with functional magnetic resonance imaging while viewing emotional words. Significant effects of recent negative life stressors, but not early life stress/trauma, were observed on regional blood oxygen level dependent activity during presentation of negative words in patients with MDD. No significant effects of stress on brain activation to negative words were found in controls. In MDD patients, positive correlations were found bilaterally in orbitofrontal areas 11 l/47/12 m, which are involved in representing negatively valenced stimuli. Negative correlations were also found in the right ventrolateral prefrontal area 45, subgenual cingulate area 25, and nucleus accumbens, all of which are implicated in the pathophysiology of MDD. Negative memory bias was additionally positively associated with recent negative life stress and negatively associated with subgenual cingulate activation, suggesting a mechanism by which stress may contribute to these abnormalities. The severity of recent negative life stressors is an important modifier of neurobiological and cognitive function in MDD and may help explain heterogeneity in the disorder.

Heterogeneity in Comorbidity Between Major Depressive Disorder and Generalized Anxiety Disorder and Its Clinical Consequences

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly comorbid and, as diagnoses, problematic because they are heterogeneous, may impair functioning even in subclinical manifestations, and may not predict important external criteria as well as empirically-derived classifications. The present study employed a latent class analysis using data from National Comorbidity Survey (1990-1992) and focused on respondents who endorsed at least 1 screening question for MDD and 1 for GAD (N = 1009). Results revealed 4 symptom domains (somatic anxiety, somatic depression, psychological anxiety, and psychological depression) reflecting the heterogeneity of MDD and GAD, and 7 respondent classes. Analysis revealed that people in classes with a high prevalence of either somatic anxiety or somatic depression symptoms presented with the highest levels of disability, distress, and service utilization. Evidence also was found for clinically meaningful subthreshold comorbid conditions. Anxiety-related and depression-related symptoms can be meaningfully differentiated, but differentiating between somatic and psychological symptoms has the greatest practical significance.

Major Depressive Disorder: Barriers to Treatment

There are a variety of barriers to major depressive disorder (MDD) treatment which may impede access to professional help and prevent best patient outcome. These barriers include the heterogeneity of MDD, societal factors, and clinician-patient relationship as well as issues of concordance, compliance, and adherence.

Effect of the 5-HTTLPR polymorphism in the serotonin transporter gene on major depressive disorder and related comorbid disorders

The serotonin transporter gene (5-HTT) has been proposed as a candidate gene for major depressive disorder (MDD). Association studies, however, have revealed inconsistent results. This could be because of the phenotypic heterogeneity of MDD, as it often presents with comorbid disorders such as generalized anxiety disorder (GAD), alcohol-related disorders, and dysthymia. In this exploratory study, we performed regression analyses with generalized estimating equations in patients with familial MDD (n=233) in order to explore whether a polymorphism in the serotonin transporter gene (5-HTTLPR) is differentially associated with MDD and a comorbid disorder compared with MDD without that particular comorbidity. As in general, GAD is more common in females and alcohol-related disorders are more common in males, the analyses were stratified for sex. Comorbid dysthymia was less common in s-allele carriers with MDD (P<0.05) than in patients homozygous for the long allele. In the sex-specific analyses, an association between the 5-HTTLPR and comorbid alcohol use disorders was observed in females, with s-carriers reporting significantly less alcohol use disorders. The relationship with comorbid GAD differed by sex with male s-carriers reporting more comorbid GAD than female s-carriers. The effect of the 5-HTTLPR polymorphism on MDD is co-dependent on the presence of comorbid disorders and sex. In this study, the s-allele of the 5-HTTLPR polymorphism was associated with significantly lower rates of particular lifetime comorbid disorders. Therefore, the presence of comorbid psychiatric disorders should be taken into account to clarify the association of the 5-HTTLPR polymorphism with MDD phenotypes.

Biological heterogeneity of major depressive disorder: indications by sleep EEG and TRH stimulation test findings.

A group of 27 patients with definite (n = 20) or probable (n = 7) RDC major depressive disorder underwent 2 sleep EEGs and 1 TRH test while in a drug-free depressive phase. A short mean REM latency (less than 60 min) identified 55.5% of major depressives while added use of blunted TSH responses (delta max. less than 5 microU/ml) increased that percentage by 11%. When patients were subdivided into RDC endogenous and nonendogenous, mean REM latency and global depression scores distinguished the 2 groups, while delta TSH did not. A short mean REM latency identified endogenous depression with 80% specificity and 76% sensitivity. The combination of REM latency and delta TSH reduced the specificity to 60%, and therefore cannot be recommended for differentiating endogenous from nonendogenous depression.