Brain structure abnormalities

Khorram et al. (2006) found that conventional antipsychotics caused a dose-dependent increase in the volume of the thalamus compared to normal volunteers. The thalamic volumes returned to normal when the patients were switched from the older antipsychotic drugs to olanzapine. However, the doses of olanzapine are not provided. The authors conclude, Antipsychotic medication could contribute to the wide range of thalamic volumes reported in schizophrenia (p. 2007). In other words, the drugs and not the disorder are causing the brain structure abnormalities. This, of course, confirms the brain-disabling principles of neuroleptic effects. 

Sparks BE, Friedman SD, Shaw DW, Aylward E, Echelard D, Artm AA, MaraviUa KR, Giedd IN, Munson 1, Dawson G, Dager SR (2002) Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59 184-192. 

Mann, J. J. and Arango, V. Abnormalities of brain structure and function in mood disorders. In Neurobiology of Mental Illness. Ed. Bunney, B. S. New York Oxford University Press,... 

Fig. 12. X-ray crystal structure of complex 72, Na[Gd(DOTA)(H20)], an MRI contrast agent used clinically for detection of blood-brain barrier abnormalities. Adapted from (306).

Consistent with this proposal, some post-mortem analyses of the brains of patients have shown either an increased concentration of dopamine or an increase in the number of dopamine receptors in the forebrain. These analyses have provided no indication of degeneration of neurones in the brain, but gross structural abnormalities are present the ventricles are enlarged and the cortex is thinner compared with normal brains. This suggests a disorder of development of the brain but how this could give rise to overactivity of the dopamine system in the forebrain is not known. 

In epilepsy certain neurons and/or groups of neurons become hyperexcitable and begin firing bursts of action potentials that propagate in a synchronous manner to other brain structures (and in the case of generalized seizures, to practically all areas of the brain). These may be the result of abnormalities in neuronal membrane stability or in the connections among neurons. It is known that the epileptic bursts consist of sodium-dependent action potentials and a calcium-dependent depolarizing potential. 

Strakowski, S.M., DelBello, M.P., Sax, K.W., et al. (1999) Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 56 254-260. 

Measurements of structural abnormalities using CT or MRI brain scans Measurements of functional or physiological abnormalities using PET, EEG, evoked potentials, or magnetoencephalography... 

The exact cause of schizophrenia has been the subject of extensive research. It appears that genetic factors (i.e., chromosomal abnormalities that cause deviations in brain structure and function) are the primary risk factors in the majority of people with schizophrenia (70% to 80%).15,23 Environmental factors (social stresses, prenatal or childhood brain injury, and so forth) seem to be the underlying cause in the remaining 20% to 30% of people with schizophrenia.23 The precise role of these factors, and the interplay between genetic and environmental factors, continues to be elucidated.28,50 61... 

The most frequently cited possible cause of mental illnesses is an abnormal hyperactivity of the dopamine neurotransmitter system in the brain. Neuroleptics inhibit dopamine nerve transmission in the frontal lobes and in the limbic system—the emotion-regulating brain structures. Inhibiting this portion of the brain causes diffuse CNS depression and disrupts an individual s behavior entirely—reducing psychotic thoughts, perceptions, and agitation. 

Several brain scan studies have claimed to demonstrate brain abnormalities associated with ADHD (Giedd et al., 1994 Hynd et al., 1991 Lou et al., 1984). Most of the studies have found relatively small brain structures in various parts of the frontal lobes and basal ganglia in children diagnosed with ADHD. The differences were based on comparisons between groups of normals and groups of children labeled ADHD. The findings are not perceptible on a case-by-case basis and cannot be used for diagnostic purposes. 

Andreason NC, Ehrhardt JC, Swayze II VW, Alliger RJ, Yuh WT, et al. 1990. Magnetic resonance imaging of the brain in schizophrenia The pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry 47 35-44. 

Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED. Structural abnormalities in the brain of human subjects who use methamphetamine. J Neurosci 2004 24 6028-36. 

Although the nature of the brain abnormalities seen in schizophrenia is not clearly known at present, certain pieces of the puzzle are being identified. Overall, schizophrenic patients appear to have some degree of cerebral atrophy (about 5% loss of cerebral mass), enlarged cerebral ventricles, and decreased size of certain other brain structures. From a functional perspective, the prefrontal and medial temporal brain appear to be particularly affected. Several neurochemical abnormalities are also associated with the disorder, and several neurotransmitter systems have been implicated (Table 5.5). 

Chronically impaired perfusion reserve tends to occur when one or both internal carotid arteries are stenosed by at least 50% of the luminal diameter (Brice et al. 1964 DeWeese et al. 1970 Schroeder 1988), or are occluded, and the collateral circulation is inadequate (Powers et al. 1987 Kluytmans et al. 1999). In this situation, the brain is vulnerable to any fiirtber fall in cerebral perfusion pressure and cerebral metabolism is begiiming to become impaired, with the appearance of structural abnormalities on MRI (van der Grond et aL 1996 Isaka et al. 1997 Derdeyn et al. 1999). 

---