Alcohol dependence-related increase of glial cell density in the anterior cingulate cortex of suicide completers.

BACKGROUND: Suicide is the most serious consequence of major depressive disorder (MDD). Although the anterior cingulate cortex (ACC; Brodmann area [BA] 24) has been increasingly investigated for its role in the etiology of MDD, there is surprisingly very little information about the possible implication of this brain region in suicide. We hypothesized that changes in BA24 cell densities occur in depressed individuals who commit suicide, possibly reflecting an altered state of cortical plasticity that is thought to occur in depression. METHODS: We investigated cell densities and sizes in BA24 among suicide completers and matched sudden-death controls. We examined a 1-cm(3) tissue block from BA24a of the supracallosal ACC in 26 human postmortem brain specimens (13 depressed individuals who committed suicide and 13 controls). We assessed neuronal and glial cell densities as well as neuronal soma sizes in the upper and lower cortical layers using optical fractionator and nucleator 3-dimensional stereological probes. RESULTS: Glial densities, neuronal densities and soma sizes measured in BA24a did not differ significantly between controls and suicide completers. Secondary analyses showed a significant and robust increase in glial cell densities in BA24a of alcohol-dependent depressed suicide completers compared with depressed suicide completers who were not alcohol-dependent (38%) and, to a lesser extent, controls (30%). LIMITATIONS: Our study, conducted with tissue samples from men only, made use of a nonspecific stain that does not distinguish between neuronal or glial cell subtypes. Furthermore, the quantitative analysis concerned upper and lower cortical contours rather than individual cortical layers. CONCLUSION: Our results indicate that in BA24, glial density, neuronal density and soma size are not affected in MDD and suicide. They also suggest that alcohol dependence has an important influence on glial densities in this key limbic structure.

Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene in suicide.

Altered stress reactivity is considered to be a risk factor for both major depressive disorder and suicidal behavior. The authors have sought to expand their previous findings implicating altered expression of spermidine/spermine N(1)-acetyltransferase 1 (SAT1), the rate-limiting enzyme involved in catabolism of the polyamines spermidine and spermine in the polyamine stress response (PSR), across multiple brain regions between control individuals and depressed individuals who have died by suicide. Microarray expression of probesets annotated to SAT1 were examined across 17 brain regions in 13 controls and 26 individuals who have died by suicide (16 with a diagnosis of major depression and 10 without), all of French-Canadian origin. Profiling conducted on the Affymetrix U133A/B chipset was further examined on a second chipset (U133 Plus 2.0) using RT-PCR, and analyzed in a second, independent sample. A reduction in SAT1 expression identified through multiple probesets was observed across 12 cortical regions in depressed individuals who have died by suicide compared with controls. Of these, five cortical regions showed statistically significant reductions which were supported by RT-PCR and analysis on the additional chipset. SAT1 cortical expression levels were also found to be significantly lower in an independent sample of German subjects with major depression who died by suicide in comparison with controls. These findings suggest that downregulation of SAT1 expression may play a role in depression and suicidality, possibly by impeding the normal PSR program or through compensation for the increased polyamine metabolism accompanying the psychological distress associated with depressive disorders.

Implication of SSAT by gene expression and genetic variation in suicide and major depression.

CONTEXT: A large body of evidence suggests that predisposition to suicide, an important public health problem, is mediated to a certain extent by neurobiological factors. OBJECTIVE: To investigate patterns of expression in suicide with and without major depression and to identify new molecular targets that may play a role in the neurobiology of these conditions. DESIGN: Brain gene expression analysis was performed using the Affymetrix HG-U133 chipset in the orbital cortex (Brodmann area [BA] 11), the dorsolateral prefrontal cortex (BA8/9), and motor cortex (BA4). Subsequent studies were carried out in independent samples from adjacent areas to validate positive findings, confirm their relevance at the protein level, and investigate possible effects of genetic variation. SUBJECTS: We investigated 12 psychiatrically normal control subjects and 24 suicide victims, including 16 with and 8 without major depression, in the brain gene expression analysis, validation, and protein studies. The genetic studies included 181 suicide completers and 80 psychiatrically normal controls. All subjects investigated were male and of French Canadian origin. MAIN OUTCOME MEASURES: Gene expression measures from microarray, semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses. RESULTS: Twenty-six genes were selected because of the consistency of their expression pattern (fold change, >1.3 in either direction [P

Anterior cingulate pyramidal neurons display altered dendritic branching in depressed suicides.

BACKGROUND: It is hypothesized that mood disorders are accompanied by altered wiring and plasticity in key limbic brain regions such as the anterior cingulate cortex (ACC). To test this hypothesis at the cellular level, we analyzed basilar dendritic arborizations extended by layer VI pyramidal neurons in silver-impregnated postmortem ACC samples from well-characterized depressed suicide subjects (n=12) and matched sudden-death controls (n=7). METHODS: One cm(3) tissue blocks were stained using a Golgi preparation, cut on a microtome, and mounted on slides. Basilar dendritic arbors from 195 neurons were reconstructed, and the number, length, and diameter of branches were determined at each branch order. The size and number of spines borne by these branches were also assessed. RESULTS: Third-order branches were significantly reduced in number (24% fewer; p=0.00262) in depressed suicides compared to controls. The size and average length of these branches, as well as their number of spines/length were unaltered. On average, for each pyramidal neuron analyzed in depressed subjects, the fewer third-order branches resulted in a significant reduction in branch length (28% shorter; p=0.00976) at this branch order. CONCLUSIONS: These results provide the first evidence of altered cortical dendritic branching in mood disorders. Given that proximal dendritic branches grow during perinatal development, and that they are generally less plastic at maturity than distal segments, we speculate that these differences in dendritic branching may reflect a biological predisposition to depression and suicide.

Fatty acid composition in postmortem brains of people who completed suicide.

OBJECTIVE: Cholesterol levels have been reported to be lower in suicidal patients, and alterations in blood levels of polyunsaturated fatty acids have been found in people with depression. Given that the evidence for the link between lipid metabolism and psychopathology thus far has almost exclusively hinged on alterations of these variables in blood, this study aimed to address whether similar alterations in fatty acids would be evident in the brains of people who complete suicide. METHODS: Using gas chromatography, we measured 49 different fatty acids in the orbitofrontal cortex and the ventral prefrontal cortex of people who had completed suicide with (n = 16) and without (n = 23) major depression and in control subjects (n = 19) with no current psychopathology and whose cause of death was sudden. RESULTS: Comparisons of fatty acids between the 3 groups did not reveal significant differences. CONCLUSION: Further research is required to better understand the link between fatty acids in the peripheral circulation and those in the central nervous system before determining whether fatty acids play a mediating role in suicidal behaviour.

Cholesterol content in brains of suicide completers.

An association between low levels of serum cholesterol and violent or suicidal behaviour has frequently been reported, but it remains unclear how cholesterol in the peripheral system might be related to the brain functions involved in mediating suicidal behaviour. To our knowledge, there have been no previous studies aimed at answering the important question of whether there are differences in cholesterol within the brains of suicide completers. In the present study, cholesterol content was measured in cortical and subcortical tissue of brains from 41 male suicide completers and 21 male controls that died of sudden causes with no direct influence on brain tissue. No significant differences in cholesterol content were found between suicides and controls in the frontal cortex, amygdala or hippocampus. However, when the suicide completers were stratified into violent (n=31) or non-violent (n=10) groups based on the method of death, violent suicides were found to have lower grey-matter cholesterol content overall compared to non-violent suicides [F(1,111)=4.75, p=0.03], specifically in the frontal cortex (t=-4.16, d.f.=37, p<0.0005). Further exploration of the frontal cortex revealed that violent suicides had lower cholesterol content compared to non-violent suicides in the orbitofrontal cortex (t=-2.01, d.f.=36, p=0.05) and the ventral prefrontal cortex (t=-2.49, d.f.=37, p=0.02). This study represents the first direct examination of cholesterol content in brain tissue from suicide completers, and the present findings provide added support for the relationship between low cholesterol and violent or suicidal behaviour.

Tumores mixtos apocrinos de la piel: comunicación de ocho casos / Mixed apocrine tumors of the skin: report of 8 cases

Los tumores mixtos de la piel son neoplasias benignas constituídas por elementos epiteliales y mesenquimáticos que conforman estructuras túbulo-alveolares y ductales inmersas en un estroma mixoide o concroide. Se presentan 8 casos de tumores mixtos con diferenciación apocrina localizados en región de la cabeza cuyos diagnósticos clínicos fueron: quiste sebáceo, quiste dermoide, lipoma y mucocele. Histológicamente todos presentaron un patrón epitelial constituído por estructuras tubulares, ductales, túbulo-alveolares o áreas sólidas con diferenciación pilosebácea focal y áreas de metaplasia adiposa. Este último es un rasgo pocas veces referido en la literatura mundial. Los resultadsos de la inmunohistoquímica y los hallazgos morfológicos sugieren un origen común en la unidad folículo sebáceo-apocrina, existiendo una estrecha relación entre los componentes estromales y epiteliales que favorece la diferenciación hacia el aparato sudoríparo