To our knowledge, this is the first morphometric study to compare volume of frontal cortex, temporal cortex and amygdala volume in SPD and BPD patients to determine which regions are important in differentiating these two disorders. This is the first study to report that (a) smaller-than-normal STG volume is specific to SPD and not found in BPD and (b) smaller STG volume in SPD is associated with greater overall symptom severity. Our finding of reduced STG volume in SPD compared with both healthy controls and BPD patients remained significant even when we controlled for history of prior psychoactive medication and comorbid MDD, suggesting it is not due to these factors. Our STG finding is consistent with previous reports of reduced STG volume in SPD compared with healthy individuals (Buchsbaum et al., 1997
; Dickey et al., 1999
; Hazlett et al., 2008
; Kawasaki et al., 2004
; Takahashi et al., 2006
). Consistent with the work of Dickey et al. (2003)
, we also found that smaller STG volume in SPD was associated with greater odd speech. Lastly, BA42 volume was significantly larger in BPD patients compared with healthy controls, and between-group differences in the other temporal lobe regions included in our analysis (BA41 and dorsal/ventral amygdala) were not significant.
From a functional perspective, prior work indicates that STG/BA22 has wide connections to the hippocampus-amygdala complex, cortical association areas in the frontal and parietal lobe and the thalamus, and it has been proposed that this part of the temporal cortex is involved in higher-order auditory perception (Binder et al., 1994
; Engelien et al., 1995
; Rajarethinam et al., 2000
; Pandya, 1995
). This includes phonemic discrimination and processing, the fusing of multiple sound features and analysis of temporal acoustic features of speech. Additionally, lesioning of this region produces receptive aphasia and deficits in comprehension of verbal language (Demonet et al., 2005
). Considered together with these anatomical findings, the posterior STG localization of our results in both patient groups fits well with work showing that both SPD and BPD individuals exhibit auditory information processing deficits that are similar to one another, as measured by P300 auditory evoked potentials (Kutcher et al., 1989
As such, our finding demonstrates that volumetric abnormalities in BA22 are unique to SPD and may be an important tool for differential diagnosis between these two disorders. Although it is still unclear how abnormalities in this region can affect auditory processing, it would be worthwhile to investigate the relationship between alterations in BA22 volume and socially-related functions since auditory processing plays a crucial role in social function and may be one way to distinguish between the groups clinically. For example, BA22 is located on the caudal two-thirds of the STG, an area that Gallagher and Frith (2003)
found to be activated during “mentalizing” tasks involving interpretation of mental states of others. Thus, our finding may help differentiate between “mentalizing” deficits experienced by both patient groups.
The finding of reduced gray matter volume in BA22 is the most widely-replicated finding in schizophrenia (reviewed by Shenton et al., 2001
). Therefore, our finding of reduced STG volume in SPD provides additional evidence for the similarity between SPD and schizophrenia patients. Our prior work showed a schizophrenia spectrum pattern for reduced STG volume with schizophrenia patients exhibiting the largest reduction compared with healthy controls, and SPD patients intermediate (Hazlett et al., 2008
). This observation is consistent with prior work indicating that individuals with SPD share a broad range of similarities with schizophrenia patients in terms of genetics and neurobiology (Siever and Davis, 2004
Our other interesting finding is that, among the SPD patients, smaller relative BA22 gray matter volume was associated with greater overall clinical (DSM) symptom severity, including greater impairment due to odd thinking and speech. These results are consistent with clinical correlates previously reported by Dickey et al. (2003)
and provide further evidence that STG abnormalities may underlie the pathophysiology of SPD. A better understanding of the relationship between structural and functional abnormalities in this key language processing area and psychopathology should be a top priority for future work.
We also found larger-than-normal BA42 gray matter volume in BPD patients. This area makes up part of the primary auditory cortex and lies in Heschl’s gyrus, a region shown to be involved in sensory auditory processing. As of April 2009, there were no publications reporting morphology of BA42 in BPD patients but it is possible that increased volume or alterations in this region reflect some type of compensatory mechanism for other dysfunctional regions involved in auditory-processing demands. In previous work, BA42 volume was found to be smaller in males with SPD compared with controls (Dickey et al., 2002a
). Even though BA42 makes up only a portion of Heschl’s gyrus and other work has shown preserved volume of this region in SPD (Takahashi et al., 2006
), it is important to note possible reasons for discrepancies between our failure to find healthy control-SPD differences in BA42 volume and findings of reduced left Heschl’s gyrus gray matter volume by Dickey et al. (2002a)
. Differences may be due to heterogeneity of sample characteristics and symptom severity, methodological techniques, normal variations in the distribution of auditory cortex (Dickey et al., 2008
) or medication differences. Understanding both structural and functional abnormalities in this region in BPD and SPD patients should remain a goal for future work such that measures of temporal lobe integrity may ultimately help us predict which patients will respond to different treatments.
Our frontal lobe analyses were not statistically significant, indicating the three groups did not differ in anterior-orbital-dorsolateral or cingulate gyrus gray matter volume. These prefrontal cortex results are consistent with our previous findings and other observations showing prefrontal volumes largely preserved in SPD in contrast to widespread prefrontal reductions in schizophrenia (Buchsbaum et al., 2002
; Suzuki et al., 2005
). Contrary to our hypothesis, neither patient group showed significantly smaller ACC volume compared with healthy controls. We previously reported significantly reduced cingulate (BA24, 31, 23) gray matter volume in a sample of 79 patients meeting DSM criteria for SPD compared with healthy controls (Hazlett et al., 2008
). However, it should be noted that in our prior study, the SPD group may have had comorbid BPD; this was not examined because the SPD group was compared with schizophrenia patients. We have also previously shown that, compared with healthy controls, individuals with a diagnosis of both SPD and BPD exhibit greater BA24 reduction than those with only BPD (Hazlett et al., 2005
). In contrast, our current sample included SPD patients without BPD. Thus, patient sample characteristics such as SPD-BPD comorbidity appear to play an important role in anterior cingulate volume abnormalities and may explain discrepancies across studies.
In the prefrontal cortex, the BPD patients showed no significant gray matter volume difference which is consistent with previous work by our group and others (Hazlett et al., 2005
; Rusch et al., 2003
). Nonetheless, as mentioned above, the current study did not replicate our previous findings of normal-BPD differences in anterior cingulate gray volume (Hazlett et al., 2005
) which has also been reported by Tebartz van Elst et al (2003)
. This inconsistency may be due to sample differences in clinical symptom characteristics and severity (e.g., 50% of current sample had past history of MDD versus 76% of Hazlett et al 2005
To the best of our knowledge, this is the first volumetric study to compare SPD patients with BPD patients and healthy controls. Although all patients were unmedicated at the time of their MRI, a unique feature of the study since many MRI studies to date examine medicated patients, a primary limitation is that some had previously received psychoactive medications. However, it is important to note that when we controlled for prior medication history, our finding of smaller STG volume in SPD compared with healthy controls and BPD patients remained significant. A second limitation is that, due to power considerations, we did not include participants with a comorbid diagnosis of both BPD and SPD. This is an important group to include in future studies. Additionally, given the common comorbidity between BPD and MDD, half of the BPD patients in our study met criteria for past MDD, although it was required to be in full remission for at least two months prior to their scan. It is imperative that future BPD studies recruit large enough sample sizes so that individuals with and without past MDD can be compared. As such, it is important to note that our finding of smaller-than-normal STG volume in SPD remained significant when we controlled for past MDD (only 18% of the SPD patients had past MDD). Also, although our diagnostic groups were matched on age and gender, it is possible that gender differences exist between groups in morphometry. Unfortunately, given our current sample size, we were unable to examine whether gender effects play a role in our STG findings. Future MRI studies with larger sample sizes will allow a much-needed examination of gender effects in SPD and BPD. Lastly, we do not have family history records for our patients. It would be worthwhile to know how many SPD and BPD patients have a first-degree relative in the schizophrenia spectrum and/or bipolar spectrum and whether there is overlap in family history. Nevertheless, our STG findings suggest that future work addressing the genetic link between reduced STG volume and schizophrenia-spectrum disorders may be fruitful.
Our results showed that SPD individuals exhibit abnormalities in STG volume that are not evidenced in BPD patients, supporting the hypothesis that they are two separate disorders. Of note, neither previous use of psychoactive medications nor past history of MDD explained smaller STG in SPD patients. Our findings are consistent with the concept that SPD is in the schizophrenia spectrum. STG volumetric abnormalities may serve as important biological markers or endophenotypes which may ultimately help diagnose and/or predict treatment response in schizophrenia-spectrum illnesses.