Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide.
OBJECTIVE
Suicide has a high prevalence in patients with schizophrenia and affective disorder. Our recent postmortem study [Steiner J, Mawrin C, Ziegeler A, Bielau H, Ullrich O, Bernstein HG, Bogerts B. Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathologica (Berl) 2006;112:305-16.] revealed increased microglial densities in two schizophrenic patients who had committed suicide. Therefore, the hypothesis of microglial activation during acute psychosis was proposed. Alternatively, "suicide" could be a diagnosis-independent factor leading to microgliosis.


METHODS
To clarify this question, microglial HLA-DR expression was analyzed by immunohistochemistry in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), mediodorsal thalamus (MD) and hippocampus of 16 schizophrenics, 14 depressed patients with affective disorder and 10 matched controls. A subgroup of six schizophrenics and seven patients with affective disorder who committed suicide was included.


RESULTS
ANOVA revealed no effect of diagnosis on microglial density (DLPFC: P=0.469; ACC: P=0.349; MD: P=0.569; hippocampus: P=0.497). However, significant microgliosis was observed in the DLPFC (P=0.004), ACC (P=0.012) and MD (P=0.004) of suicide patients. A similar trend was seen in the hippocampus (P=0.057).


CONCLUSIONS
In conclusion, immunological factors may play a hitherto underestimated role in suicide. First, microglial activation might be interpreted as a consequence of presuicidal stress. Second, one might speculate a causal link between microglial activation and suicidal behaviour, such as neuroendocrine factors, cytokines, and nitric oxide, which are released from microglial cells and are known to modulate noradrenergic or serotonergic neurotransmission and thus may trigger suicidality.
Steiner
Johann
J
Department of Psychiatry, University of Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany. johann.steiner@medizin.uni-magdeburg.de
Bielau
Hendrik
H
Brisch
Ralf
R
Danos
Peter
P
Ullrich
Oliver
O
Mawrin
Christian
C
Bernstein
Hans-Gert
HG
Bogerts
Bernhard
B
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000276:immunology* / Q000473:pathology; D001921:Brain / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D003865:Major Depressive Disorder / Q000276:immunology* / Q000473:pathology; D005260:Female; D005911:Gliosis / Q000276:immunology / Q000473:pathology; D006179:Gyrus Cinguli / Q000276:immunology / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis*; D006624:Hippocampus / Q000276:immunology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000276:immunology / Q000473:pathology; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D012559:Schizophrenia / Q000276:immunology* / Q000473:pathology; D013405:Suicide / Q000523:psychology*
D006684:HLA-DR Antigens