[show abstract][hide abstract] ABSTRACT: Schizophrenia (SZ) is a heterogeneous disease with a spectrum of symptoms, risk factors, and etiology. Abnormalities in mitochondria, the energy-producing organelles of the cell, have been observed in mixed cohorts of subjects with SZ. The purpose of the present study was to determine if striatal mitochondria were differentially affected in two different DSM-IV subgroups of SZ. Postmortem striatal tissue was examined from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was processed for calbindin immunohistochemistry to identify striosomal compartments, prepared for electron microscopy and analyzed using stereological methods. In both caudate and putamen, the density of mitochondria in the neuropil was decreased in SZP compared to both NCs and SZU. In the putamen, both the SZP and the SZU subgroups had fewer mitochondria per synapse than did NCs. When examining patch matrix compartments, striatal compartments associated with different circuitry and function, only the matrix exhibited changes. In the caudate matrix, the SZP subgroup had fewer mitochondria in the neuropil than did the SZU and NCs. In the putamen matrix, the SZP had fewer mitochondria in the neuropil as compared to NCs, but not the SZU. The numbers of mitochondria per synapse in both the SZP and the SZU groups were similar to each other and fewer than that of NCs. A decrease in mitochondrial density in the neuropil distinguishes the SZP from the SZU subgroup, which could be associated with the symptoms of paranoia and/or could represent a protective mechanism against some of the symptoms that are less pronounced in this subtype than in the SZU subgroup such as cognitive and emotional deficits.
[show abstract][hide abstract] ABSTRACT: Schizophrenia (SZ) is a severe mental illness with neuropathology in many regions, including the striatum. The typical symptoms of this disease are psychosis (such as hallucinations and delusions), cognitive impairments, and the deficit syndrome. Not all patients respond to treatment and, in those who do, only psychotic symptoms are improved. Imaging studies support a biological distinction between treatment response and resistance, but postmortem examinations of this issue are rare. This study tests the hypotheses that abnormalities in mitochondria, the energy producing organelles in the cell, may correlate with treatment response. Postmortem striatal tissue was obtained from the Maryland Brain Collection. The density of mitochondria (in various neuropil compartments) and the number of mitochondria per synapse (all types of synapses combined) were tallied using electron microscopy and stereology in striatum from SZ subjects (rated treatment responsive or not) and normal controls. The number of mitochondria per synapse was significantly different among groups for both the caudate nucleus (P < 0.025) and putamen (P < 0.002). Compared to controls, treatment-responsive SZ subjects had a 37-43% decrease in the number of mitochondria per synapse in the caudate nucleus and putamen. In the putamen, treatment-responsive subjects also had decreases in this measure compared to treatment-resistant subjects (34%). Our results provide further support for a biological distinction between treatment response and treatment resistance in SZ. Because treatment responders have fewer mitochondria per synapse than controls, although the treatment-resistant subjects have similar results to that of controls, fewer mitochondria per synapse may be related to treatment response.
[show abstract][hide abstract] ABSTRACT: Schizophrenia is a severe mental illness that manifests pathology in many brain regions, including the striatum. Among the abnormalities in schizophrenia are those related to mitochondria. The present study sought to determine whether the number of mitochondria was affected at the level of the synapse.
Human postmortem striatum from schizophrenia subjects and controls was examined at the ultrastructural level. The density of mitochondria and synapses were tabulated using stereology.
There were similar overall numbers of mitochondria in the caudate nucleus and putamen of schizophrenia subjects vs. controls, but a differential distribution of existing mitochondria. Schizophrenia subjects had 26?30% fewer mitochondria per synapse compared to controls. This may contribute to the pathophysiology of the illness, may be a medication effect, or an adaptive response to normalize the high number of striatal synapses we have previously found. The higher density of mitochondria in dendrites in the caudate nucleus in certain subgroups of schizophrenia vs. controls (>34%) may be related to more synaptic inputs.
The role of mitochondria in the various symptoms of schizophrenia is still unclear. A comparison of schizophrenia subjects with differing symptoms or treatment response might shed light on whether differences in mitochondrial density are abnormal or adaptive.
The World Journal of Biological Psychiatry 02/2011; 12(1):48-56. · 3.57 Impact Factor