Several lines of evidence suggest that the thalamus is abnormal in patients with neuropsychiatric disorders. In both schizophrenic and unipolar depressed patients, some structural MRI studies indicate a reduction in the volume of the thalamus. We have recently used stereological cell counting procedures to estimate total neuron number in 5 thalamic nuclei from postmortem schizophrenic and control brains. Our data indicate that numbers of neurons in MD, the anteroventral and anteromedial thalamic nuclei (AV/AM) and the laterodorsal thalamic nucleus (LD) are decreased by more than 20 percent in schizophrenics. In the same brains, neuron number is unaffected in the ventroanterior/ventrolateral nuclear complex (VA/VL) and the reticular (R) nucleus. These data are noteworthy because the MD, AV/AM and LD thalamus provide input to areas of the cortex where functional deficits are consistently observed not only in patients with schizophrenia but also in patients with affective disorders. Since neuron cell counts have never been performed in affective disorder cases, nor in many regions in the thalamus in schizophrenia, it is unclear whether: a) the MD and the anterior nuclei are the only regions in the thalamus that are abnormal in schizophrenia, and b) similar thalamic neuron number reductions are present in affective disorder patients. Using stereological cell counting methods, we propose to measure thalamic neuron number in 9 thalamic nuclei in postmortem brains from schizophrenics, bipolar and unipolar depressed subjects, and age-matched controls. There are two specific aims:
Aim 1 : Are thalamic neuron number abnormalities in schizophrenia confined to MD, AV/AM and LD nuclei? It is predicted that significant neuron number reductions will be observed in schizophrenics in thalamic nuclei that communicate with prefrontal and limbic cortical regions, specifically, the MD, LD and AV/AM.
Aim 2 : Are thalamic neuron number abnormalities that characterize schizophrenia also found in affective (mood) disorder patients? Based on observations that there are similar abnormalities in the the function of prefrontal and limbic cortex in both schizophrenia and affective disorder, it is predicted that significant neuron number reductions will be observed in the MD, LD and AV/AM of unipolar and bipolar subjects. The study will provide information about whether there are similar or different thalamic abnormalities in schizophrenia and affective disorders.
| Young, Keith A; Bonkale, Willy L; Holcomb, Leigh A et al. (2008) Major depression, 5HTTLPR genotype, suicide and antidepressant influences on thalamic volume. Br J Psychiatry 192:285-9 |
| Young, Keith A; Holcomb, Leigh A; Bonkale, Willy L et al. (2007) 5HTTLPR polymorphism and enlargement of the pulvinar: unlocking the backdoor to the limbic system. Biol Psychiatry 61:813-8 |
| Young, Keith A; Holcomb, Leigh A; Yazdani, Umar et al. (2004) Elevated neuron number in the limbic thalamus in major depression. Am J Psychiatry 161:1270-7 |
