Search

Background: Depression is commonly conceptualized as corticolimbic dysregulation. Due to insufficient studies in normal aged populations especially subcortical sources of disconnection are unclear in contrast to potentially general parietal white matter (WM) deficits. This may be due to important influences of variable patient characteristics, most importantly episode severity. Especially thalamic disconnections have been functionally revealed, however, their structural correlates have not been distinctly investigated for its highly diverse subnuclei. Methods: We compared 20 major depressive disorder (MDD) patients with mixed Hamilton depression rating scale (HAMD) severity to matched controls in fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Robust acquisition of 4 repetitions restricted to twelve directions, also to match the same parameters used by Eckert et al. (2011) who described a preferential architecture of centromedian (CM) and mediodorsal (MD) thalamic connections. Second to whole brain analysis, we tested for group differences within the preferred structural network of these two nuclei using a tract of interest (TOI) approach. Results: Significant FA deficits in a whole brain analysis were only found in right parietal WM (po 0.05, corrected). Effects of severity were found for increasing thalamic FA. Post hoc analysis revealed this effect to be restricted to CM specific tracts. In contrast, we found MD to dorsolateral prefrontal cortex (DLPFC) tracts to be decreased in FA. Unspecific decreases between MD and CM towards amygdala were paralleled by primary amygdala FA reductions. Limitations: Specificity of the TOI approach and heterogenous sample. Conclusions: Robust parietal FA reductions, controlled for age effects were found in MDD. Further we revealed subcortical disease state dependency of FA in thalamic tracts, specific to predescribed preferential connections.

Background Alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme of GABA synthesis. Methods Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLC), the entorhinal cortex (EC), the hippocampal formation, and the medial dorsal and lateral dorsal thalamic nuclei, with consecutive determination of GAD-immunoreactive (-ir) neuropil relative density. The study was performed on paraffin-embedded brains from 21 depressed patients (14 of whom had committed suicide) and 18 matched controls. The data were tested using Kruskal–Wallis, Mann–Whitney ( U ) and Spearman statistical procedures. Results As shown by post-hoc U -tests, an increase in the relative density of GAD-ir neuropil was present in the hippocampal formation, specific for suicidal patients. The EC was the only area where non-suicidal patients also revealed an increase compared with controls. On the contrary, the DLC was the only area where a significant decrease existed, specific for non-suicidal patients. Numerous negative correlations were found between the investigated parameter and psychotropic medication. Limitations A major limitation of this study is the relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. The possible impact of unipolar–bipolar dichotomy of mood disorders on the obtained results should also be considered. Conclusion The study, revealing predominantly an increased relative density of GAD-ir neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients.

Background : The biological basis of unipolar-bipolar dichotomy of mood disorders was investigated in this postmortem study by morphological comparison of the locus coeruleus (LC) as the main source of noradrenergic transmission in the brain. Methods : Numbers and the rostro-caudal as well as ventro-dorsal distribution of neuromelanin-containing neurones in the LC were determined in brainstem of 12 patients with bipolar disorder ( n =6) or major depression ( n =6), and 12 normal comparison subjects. Results : Bipolar patients had significantly more neurones on both sides of the LC as a whole than patients with major depression. Topographical analysis revealed that this difference was restricted to the rostral two thirds and the dorsal part of the LC, in which bipolar patients showed at least a trend to higher neurone numbers as compared to unipolar patients or to controls. Limitations : Small case numbers. Conclusions : Results suggest differences of innervation arising from the LC of bipolar patients as compared to patients with major depression. These first data of brainstem transmitter system morphology in unipolar and bipolar disorder are in line with neuroanatomical studies of other brain regions indicating a biological basis of the unipolar-bipolar dichotomy of mood disorders.

Regional planimetric measurements of internal and external CSF spaces were performed in CT scans of 23 patients with endogenous depression (ICD 9, 296.1) and 28 patients with neurotic depression (ICD 9, 300.4) as compared to 56 control individuals without neuropsychiatric disorder. In female patients with endogenous depression, but not in men, the bilateral upper cortical sulci were widened, especially in the frontal regions, and the third ventricle was enlarged. In contrast, the female neurotic depressed group showed no enlargement of CSF spaces, but a narrowing of the Sylvian fissure and of the basal frontal lobe reaching level of significance in the right fronto-temporal region ( P =0.005). No narrowing of CSF spaces was observed in women with endogenous depression. A discriminant analysis of significantly changed CSF regions resulted in a correct classification in 82.4% of depressed women in either the endogenous or the neurotic group. Determination of divergent types of brain pathology might prove as a useful tool in validating the differential classification of these two main subtypes of affective disorders.

Background: The aim to find a morphological biomarker of disturbed activity of the lateral amygdaloid nucleus in depression was approached by a karyometric analysis of projection neurons. Methods: The study was performed on paraffin-embedded brains from 19 depressed patients from both the major depressive disorder (MDD) and the bipolar disorder (BD) diagnostic groups, including 10 suicides, and 24 matched controls. The karyometric parameters of the lateral amygdaloid nucleus (La) projection neurons bilaterally were evaluated by the argyrophilic nucleolar organiser region (AgNOR) silver staining method. Results: An increased AgNOR number was found in the right La in suicides compared to controls. The intra-group comparisons between the hemispheres suggest a disturbed amygdaloid lateralisation in depressed patients. The effects were independent from psychotropic medication. There was a strong positive correlation between the nuclear area in La projection neurons and prefrontal limbic areas pyramidal neurons in the right hemisphere specific for suicide and MDD. Limitations: A major limitation of this study is the relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the entire lifespan. Conclusion: The results suggest that depressed patients from both the MDD and BD diagnostic groups exhibit an increased activity of the La output neurons specific for suicidal patients. The distinctness of the diagnostic groups of mood disorders was accentuated in the correlation analysis. This putative hyperactivity was specific for the right hemisphere and psychotropic medication most likely did not counteract it.

Background The external globus pallidus (EGP) is thought to play the most important integrating and conveying role in the striatopallidal system involved in the transfer from motivation to action. The aim to find a morphological biomarker of disturbed EGP activity in depression was approached by the karyometric analysis of large projecting neurons. Methods The study was performed on paraffin-embedded brains from 19 depressed patients from both the major depressive disorder (MDD) and the bipolar disorder (BD) diagnostic groups encompassing 10 suicides and from 24 controls. The karyometric parameters of EGP neurons bilaterally were evaluated by argyrophilic nucleolar organiser (AgNOR) silver staining method. Results A significantly decreased AgNOR area was found in the left EGP neurons in depressed patients compared to controls. The distinctness of the diagnostic groups and suicidal vs non-suicidal patients was not shown in the statistical comparisons. The AgNOR parameter which was decreased correlated positively with the mean dose of benzodiazepines in non-suicidal patients. Limitations A major limitation of this study is the relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the whole lifespan of patients. Conclusion The results suggest disturbed, most likely decreased, activity of the left EGP projecting neurons in depressed patients, a disturbed activity that should hypothetically be counteracted by the applied pharmacotherapy in non-suicidal patients.

Background The aim to find the morphological biomarker of disturbed activity of the orbitofrontal cortex (OFC) in depression was approached by the karyometric analysis of pyramidal neurons. Methods The study was performed on paraffin-embedded brains from 19 depressed patients from both major depressive disorder (MDD) and bipolar disorder (BD) diagnostic groups, including 9 suicides, and 24 matched controls. The karyometric parameters of medial OFC layer III and V pyramidal neurons bilaterally were evaluated by argyrophilic nucleolar organiser region (AgNOR) silver staining method. Results The enlarged nuclear area was found in layer V pyramidal neurons in the right OFC in non-suicides compared to suicides and controls, which was most likely the effect of neuroleptics. The intra-group comparisons between the hemispheres suggest the disturbed orbitofrontal lateralisation in depressed patients (predominantly in suicides) with moderate distinctness of the MDD and the BD diagnostic groups. Limitations A major limitation of this study is a relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the whole lifespan. Conclusion The results suggest disturbed activity of OFC pyramidal neurons in depression, distinct in suicide and the diagnostic groups of mood disorders. The non-suicidal patients seem to benefit from neuroleptics, which most likely increase the activity of the subpopulation of OFC pyramidal neurons.

Background Suicide and depression are closely related yet distinct phenomena. In both these phenomena, research has focused on central serotonergic system disturbances. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of limbic structures crucial for the regulation of emotionally influenced behaviour. Methods The study was carried out on paraffin-embedded brains from 23 depressed patients (12 suicides and 11 non-suicides) and 26 matched controls without mental disorders. The karyometric parameters of DRN neurons were evaluated by the AgNOR silver staining method. Results The significant effect of suicide on the nuclear area was found in the cumulative analysis of all DRN subnuclei (ANOVA, P = 0.032). A decreased mean value of this parameter was observed in the suicides group versus controls (t-test, P = 0.032). This effect was especially pronounced in the violent suicide victims (t-test, P = 0.001), who also demonstrated a decreased AgNOR area versus controls (t-test, P = 0.007). No significant effect of depression or polarity on AgNOR parameters was found. Limitations A major limitation of this study is relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. Conclusion Our findings suggest that hypoactivity of DRN neurons is a distinct phenomenon in depression, specific only for suicidal subgroup of depressed patients.