A fabulous new edition of Encephalon has arrived at Neurontic (not to be confused with The Neurocritic).
The sequel to my post included there, Differences in Auditory Cortex Neurons and Prefrontal microRNA Expression in Schizophrenia, begins below with a figure illustrating a striking amount of gray matter loss in early-onset schizophrenia (Thompson et al., 2001).
from Thompson et al. 2001: MRI image of an averaged profile of brain tissue loss from a group of patients with early-onset schizophrenia. These brain maps depict striking anatomical characteristics of accelerated gray matter loss and unsuspected patterns of brain structure defects. Red and pink indicate the regions with the fastest gray matter loss, green colors slower loss, and blue colors no loss.
The comparison group was a set of individuals who were matched for age, IQ, and medication.
Medication-Matched Subjects. To address the possibility that neuroleptic exposure and/or lower IQ could have determined differential gray matter loss in the schizophrenics, we mapped 10 serially imaged subjects referred to the childhood schizophrenia study who did not meet diagnostic criteria for schizophrenia [labeled psychosis NOS, in DSM terms]. These subjects received medication identical to that of the patients in this study through adolescence, primarily for control of aggressive outbursts, and at follow-up, none had progressed to schizophrenia but all continued to exhibit chronic mood and behavior disturbance.Thus, the gray matter changes can be attributed to the illness, rather than to typical or atypical antipsychotic treatment.
Now let's go one step further and examine what differences (if any) might occur in the brains of individuals with schizophrenia who are relatively drug-naive. These folks have been treated with antipsychotic medication for only a short duration [it's not particularly ethical to scan floridly psychotic patients before stabilizing them, so complete drug-naivety is not usually observed]. For example, structural MRI morphometric studies have demonstrated reduced volumes in the thalamus (Crespo-Facorro et al., 2007), in the left planum temporale (Takahashi et al., 2007) showing an inverse correlation with the duration of untreated psychosis, and in the left middle and inferior temporal gyri (Lappin et al., 2006), also showing an inverse correlation with the duration of untreated psychosis. A SPECT study in completely drug-naive patients showed abnormal dopaminergic D2 receptor binding (Corripio et al., 2006). Finally, increases in gray matter volume (along with improvements in clinical symptoms) have been obseved after treatment with atypical antipsychotics (Garver et al., 2005).
Caveats? Yes, there are caveats. Although genetic and neurodevelopmental factors influence brain structure and function, as I said before,
Certainly, one's environment, social circumstances, upbringing, stress levels, etc. do play a role in the expression of various mental illnesses...Plus, it's not as if the literature presents a neat and consistent picture (e.g., for volumes of the caudate nucleus; see Tauscher-Wisniewski, 2005). Nevertheless, the evidence for brain changes in early-onset schizophrenia (and in individuals who are relatively drug-naive, with long durations of untreated psychosis), compared to proper control groups, is compelling.
Crespo-Facorro B, Roiz-Santianez R, Maria Pelayo-Teran J, Manuel Rodriguez-Sanchez J, Perez-Iglesias R, Gonzalez-Blanch C, Tordesillas-Gutierrez D, Gonzalez-Mandly A, Diez C, Magnotta VA, Andreasen NC, Luis Vazquez-Barquero J. (2007). Reduced thalamic volume in first-episode non-affective psychosis: Correlations with clinical variables, symptomatology and cognitive functioning. Neuroimage Feb 13; [Epub ahead of print] .
Corripio I, Perez V, Catafau AM, Mena E, Carrio I, Alvarez E. (2006). Striatal D2 receptor binding as a marker of prognosis and outcome in untreated first-episode psychosis. Neuroimage 29:662-6.
Garver DL, Holcomb JA, Christensen JD. (2005). Cerebral cortical gray expansion associated with two second-generation antipsychotics. Biol Psychiatry 58:62-6.
Lappin JM, Morgan K, Morgan C, Hutchison G, Chitnis X, Suckling J, Fearon P, McGuire PK, Jones PB, Leff J, Murray RM, Dazzan P. (2006). Gray matter abnormalities associated with duration of untreated psychosis. Schizophr Res. 83:145-53.
Takahashi T, Suzuki M, Tanino R, Zhou SY, Hagino H, Niu L, Kawasaki Y, Seto H, Kurachi M. (2007). Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: A preliminary report. Psychiatry Res. 154:209-19.
Tauscher-Wisniewski S, Tauscher J, Christensen BK, Mikulis DJ, Zipursky RB. (2005). Volumetric MRI measurement of caudate nuclei in antipsychotic-naive patients suffering from a first episode of psychosis. J Psychiatr Res. 39:365-70.
Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci 98:11650-5.
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