Search

In patients with major depressive disorder or bipolar disorder, abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate and gamma-aminobutyric acid have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic-dose ketamine has led to a collection of studies that have examined neurochemical (e.g., glutamatergic and gamma-aminobutyric acidergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the relationship between structural brain abnormalities and dimensions of depressive symptomatology.Methods: In the current study, we examined the relationship between cortical structural abnormalities and specific behavioral dimensions relevant to depression in a sample of unmedicated patients with major depressive disorder (MDD, n=57) and demographically similar healthy control volunteers (HC, n=29). All subjects underwent diagnostic assessment with the SCID, MRI at 3T, and dimensional assessments using the visual analog scales (VAS). Cortical regions were extracted for each subject, and group comparisons of cortical volume (CV), surface area (SA), and cortical thickness (CT) were performed controlling for multiple comparisons using a bootstrapping technique. Regions demonstrating group differences were analyzed for correlation with specific dimensions assessments.Results: As compared with HC, MDD subjects exhibited reduced CV within the left supramarginal gyrus, right ventrolateral prefrontal cortex (VLPFC), entorhinal cortex, parahippocampal gyrus, fusiform gyrus and pericalcarine; reduced SA in the right VLPFC, cuneus, and left temporal pole; and reduced CT in the right rostral anterior cingulate cortex (rACC) (all p's<0.05, corrected). The largest effect occurred within the right VLPFC for CV and SA (MDDLimitations: Future studies will be required to further map the anatomical changes in depression to behavioral dimensions.Conclusions: Our results indicate that specific cortical abnormalities are associated with specific behavioral components linked to depression. [ABSTRACT FROM AUTHOR]

Over the last few decades, neuroimaging techniques have advanced the identification of structural, functional, and neurochemical brain abnormalities that are associated with the increased risk, clinical course, and treatment outcomes of major depressive disorder (MDD). This paper reviews specific neuroimaging abnormalities that, on the basis of early studies, may discriminate between MDD patients who do or do not respond to current therapeutic modalities, such as antidepressants, cognitive behavioral therapy, or novel therapies. Differences in gray matter volume, white matter coherence, brain activity via structural and functional magnetic resonance imaging techniques, and concentrations of specific brain metabolites (as measured with magnetic resonance spectroscopy), are potential biomarkers discussed in this review. Given the heterogeneity of MDD, larger, multisite studies with increased statistical power will be needed to identify more precise imaging biomarkers of treatment response in MDD. [ABSTRACT FROM AUTHOR]

Background: Due to the heterogeneity of depressive symptoms-which can include depressed mood, anhedonia, negative cognitive biases, and altered activity levels-researchers often use a combination of depression rating scales to assess symptoms. This study sought to identify unidimensional constructs measured across rating scales for depression and to evaluate these constructs across clinical trials of a rapid-acting antidepressant (ketamine).Methods: Exploratory factor analysis (EFA) was conducted on baseline ratings from the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Snaith-Hamilton Pleasure Rating Scale (SHAPS). Inpatients with major depressive disorder (n = 76) or bipolar depression (n = 43) were participating in clinical ketamine trials. The trajectories of the resulting unidimensional scores were evaluated in 41 subjects with bipolar depression who participated in clinical ketamine trials.Results: The best solution, which exhibited excellent fit to the data, comprised eight factors: Depressed Mood, Tension, Negative Cognition, Impaired Sleep, Suicidal Thoughts, Reduced Appetite, Anhedonia, and Amotivation. Various response patterns were observed across the clinical trial data, both in treatment effect (ketamine versus placebo) and in degree of placebo response, suggesting that use of these unidimensional constructs may reveal patterns not observed with traditional scoring of individual instruments.Limitations: Limitations include: 1) small sample (and related inability to confirm measurement invariance); 2) absence of an independent sample for confirmation of factor structure; and 3) the treatment-resistant nature of the population, which may limit generalizability.Conclusions: The empirical identification of unidimensional constructs creates more refined scores that may elucidate the connection between specific symptoms and underlying pathophysiology. [ABSTRACT FROM AUTHOR]

Higher rates of non-right-handedness (i.e. left- and mixed-handedness) have been reported in schizophrenia and have been a centrepiece for theories of anomalous lateralization in this disorder. We investigated whether non-right-handedness is (i) more prevalent in patients as compared with unaffected siblings and healthy unrelated control participants; (ii) familial; (iii) associated with disproportionately poorer neurocognition; and (iv) associated with grey matter volume asymmetries. We examined 1445 participants (375 patients with schizophrenia, 502 unaffected siblings and 568 unrelated controls) using the Edinburgh Handedness Inventory, a battery of neuropsychological tasks and structural magnetic resonance imaging data. Patients displayed a leftward shift in Edinburgh Handedness Inventory laterality quotient scores as compared with both their unaffected siblings and unrelated controls, but this finding disappeared when sex was added to the model. Moreover, there was no evidence of increased familial risk for non-right-handedness. Non-right-handedness was not associated with disproportionate neurocognitive disadvantage or with grey matter volume asymmetries in the frontal pole, lateral occipital pole or temporal pole. Non-right-handedness was associated with a significant reduction in left asymmetry in the superior temporal gyrus in both patients and controls. Our data neither provide strong support for ‘atypical’ handedness as a schizophrenia risk-associated heritable phenotype nor that it is associated with poorer neurocognition or anomalous cerebral asymmetries. [ABSTRACT FROM PUBLISHER]