Schizophrenia Research Forum - A Catalyst for Creative Thinking

Rimol LM, Hartberg CB, Nesvåg R, Fennema-Notestine C, Hagler DJ, Pung CJ, Jennings RG, Haukvik UK, Lange E, Nakstad PH, Melle I, Andreassen OA, Dale AM, Agartz I. Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder. Biol Psychiatry. 2010 Jul 1 ; 68(1):41-50. Pubmed Abstract

Comments on News and Primary Papers

Primary Papers: Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder.

Comment by:  Matthew J. Smith
Submitted 31 August 2010
Posted 31 August 2010

Schizophrenia and psychotic mood disorders such as bipolar disorder share a common genetic susceptibility (Lichtenstein et al., 2009) and several clinical characteristics (Glahn et al., 2006; Barch, 2009) that make the confirmation of diagnosis rather difficult. In order to identify whether schizophrenia and bipolar disorder share a similar pathophysiology, research must compare their neurobiology. Rimol and colleagues (2010) recently published an elegant study comparing cortical thickness and subcortical volumes among individuals with schizophrenia and bipolar disorder. Using a sound methodology, they did not conclude that cortical thinning in any region was specific to schizophrenia. This was somewhat surprising, given that the schizophrenia group had significant thinning when compared to controls, while the bipolar group did not differ from controls. However, the bipolar group did not differ from the schizophrenia group, either. The authors acknowledged that the schizophrenia group was significantly younger than the bipolar group. Thus, given that gray matter loss is progressive in schizophrenia, the authors also acknowledged that the age difference may have confounded the results.

I would like to suggest that an additional confounding factor may be the influence of substance abuse or dependence. Substance abuse is highly comorbid with schizophrenia and bipolar disorder (Roick et al., 2007; Swann, 2010), and is associated with gray matter loss (Sachdev et al., 2008; Matochick et al., 2005). However, although the current study excludes controls with recent cannabis abuse or dependence, this exclusion criteria was not applied to the patient groups. Furthermore, the types of substances and their rates of abuse or dependence in the patient groups were not reported. Hence, future studies comparing patient groups need to either examine the influence of substance abuse or group match the clinical samples by some measure of current or past substance use.

In addition, Rimol and colleagues understandably concluded that schizophrenia and bipolar disorder have a common underlying pathophysiology in the subcortical structures based on their evidence that the two groups did not differ on measures of volume. However, future studies may want to consider additional methods when comparing the pathophysiology between two clinical populations. In addition to using volumetry, our group recently used shape analysis to compare localized volume change across the surfaces of subcortical structures between individuals with schizophrenia and psychotic mood disorders (Mamah et al., 2010; Smith et al., 2010). Specifically, we found that, despite a trend level volume difference, the surface shape of the hippocampus differed between the schizophrenia group and the bipolar disorder group (Mamah et al., 2010). We also found that, although individuals with schizophrenia and individuals with schizoaffective disorder shared similar thalamic volumes, each patient group had distinct thalamic surface shape abnormalities (Smith et al., 2010).

Thus, despite some potential confounding factors, this study is an excellent initial step to investigate neurobiological factors that may differentiate schizophrenia from psychotic mood disorders such as bipolar or schizoaffective disorder.


Barch DM (2009). Neuropsychological abnormalities in schizophrenia and major mood disorders: similarities and differences. Current Psychiatry Reports, 11, 313-319. Abstract

Glahn DC, Bearden CE, Cakir S, Barrett JA, Najt P, Serap Monkul E, Maples N, Velligan DI, Soares JC. (2006). Differential working memory impairment in bipolar disorder and schizophrenia: effects of a lifetime history of psychosis. Bipolar Disorders, 8, 117-123. Abstract

Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study. Lancet, 373, 234-239. Abstract

Mamah D, Wang L, Csernansky JG, Rice JP, Smith MJ, Barch DM. (2010). Morphometry of the hippocampus and amygdala in bipolar disorder and schizophrenia, Bipolar Disorders, 12, 341-343. Abstract

Matochik JA, Eldreth DA, Cadet JL, Bolla KI, (2005). Altered brain tissue composition in heavy marijuana users. Drug and Alcohol Dependence, 77, 23-30. Abstract

Roick, C., Fritz-Wieacker, A., Matschinger, H., Heider, D., Schindler, J., Riedel-Heller, S., Angermeyer, M., 2007. Health habits of patients with schizophrenia. Social Psychiatry and Psychiatric Epidemiology, 42, 268-276. Abstract

Sachdev P, Chen X, Wen W, Anstry KJ (2008) Light to moderate alcohol use is associated with increased cortical gray matter in middle-aged men: a voxel-based morphometric study. Psychiatry Res 163(1):61-69. Abstract

Smith MJ, Wang L, Cronenwett W, Mamah D, Barch DM, Csernansky JG. (in press). Thalamic morphology in schizophrenia and schizoaffective disorder. J Psychiatr Res. 2010 Aug 24. Abstract

Swann AC. (2010). The strong relationship between bipolar and substance-use disorder. The Annals of the New York Academy of Sciences, 1187, 276-93. Abstract

View all comments by Matthew J. Smith