Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described.

Background: The habenular complex is composed of important relay nuclei linking the limbic forebrain to the midbrain and brain stem nuclei. Based on clinical observations, experiments with animals and theoretical considerations, it has been speculated that this brain area might be involved in psychiatric diseases (i.e. schizophrenia and depression). However, evidence in favour of this hypothesis is still lacking because the human habenular complex has rarely been studied with regard to mental illness.Method: We examined habenular volumes in post-mortem brains of 17 schizophrenia patients, 14 patients with depression (six patients with major depression and eight patients with bipolar depression) and 13 matched controls. We further determined the neuronal density, cell number and cell area of the medial habenular nuclei of the same cohorts using a counting box and a computer-assisted instrument.Results: Significantly reduced habenular volumes of the medial and lateral habenula were estimated in depressive patients in comparison to normal controls and schizophrenia patients. We also found a reduction in neuronal cell number and cell area in depressive patients for the right side compared to controls and schizophrenia patients. No such changes were seen in schizophrenia.Conclusions: Our anatomical data argue against prominent structural alterations of the habenular nuclei in schizophrenia but demonstrate robust alterations in depressive patients. We are currently applying immunohistochemical markers to better characterize neuronal subpopulations of this brain region in schizophrenia and depression.

In the last 10 years, structural, molecular and functional changes in glial cells have become a major focus of interest in the search for the neurobiological foundations of schizophrenia. While neuronal degeneration, as seen in typical degenerative brain diseases, cannot be found in post-mortem brains of psychotic disorders called 'schizophrenia', many studies show abnormalities in the connecting elements between the nerve cell bodies (synapses, dendrites and axons) and in all three types of glial cells. There is accumulating evidence of reduced numbers of oligodendrocytes and altered gene expression of myelin/oligodendrocyte-related genes that might explain white matter abnormalities and disturbed inter- and intra-hemispheric connectivity, which have frequently been described in schizophrenia. Earlier reports of increased astrocyte densities as a sign of gliosis could not be confirmed by later studies; however, the expression of several astrocyte-related genes is abnormal. Since astrocytes play a key role in the synaptic metabolism of glutamate and monamines, astrocyte dysfunction may well be related to the current transmitter theories of schizophrenia. Results in increased densities of microglial cells, which act as the main cells for immune defence in the brain, are more controversial. There are, however, higher microglial cell numbers in psychotic patients dying from suicide, and several studies reported altered expression of microglia-related surface markers in schizophrenia, suggesting that immunological/inflammatory factors may be relevant for the pathophysiology of psychosis. Searches for future therapeutic options should aim at compensating disturbed functions of oligodendrocytes, astrocytes and microglial cells, by which at least some aspects of the pathophysiology of the very inhomogeneous clinical syndrome of schizophrenia might be explained.

The aetiology of suicide is complex and still not completely understood. The present communication, which consists of two parts, aims to shed some light on the role of amino acidergic neurotransmission in suicide. In the first part we provide an overview of the literature showing that with the exception of certain gamma-aminobutyric acid transporters, virtually all components of the glutamate-glutamine- gamma-aminobutyric acid cycle are, in some way or other, abnormal in suicide victims, which indicates a prominent involvement of the glutamatergic and gammaaminobutyric acidergic neurotransmitter systems in suicidal behaviour. In the second part we present own immunohistochemical findings showing that densities of glutamine synthetase expressing glial cells in the mediodorsal thalamus as well as in the dorsolateral prefrontal and orbitofrontal cortex of schizophrenic suicide completers are significantly elevated compared with controls and non-suicide individuals with schizophrenia, thus calling into question the belief that cerebral glutamine synthetase deficit is indicative of suicidal behaviour.