Patients with Poor Response to Antipsychotics Have a More Severe Pattern of Frontal Atrophy: A Voxel-Based Morphometry Study of Treatment Resistance in Schizophrenia

Abstract

Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.

Classification of multi-site MR images in the presence of heterogeneity using multi-task learning

“…However cerebellar findings should be interpreted cautiously, since segmentation between GM and WM in that region is difficult and prone to errors, due to poor contrast at this imaging resolution. Finally, other brain sites showing volume abnormalities in our study, including the precuneus and lateral parietal cortical regions, fusiform, lingual and middle occipital gyri, have been variably implicated in previous neuroimaging studies of SCZ ( Borgwardt et al, 2010 ; Brunet-Gouet and Decety, 2006 ; Chou et al, 2014 ; Davatzikos et al, 2005 ; Di Rosa et al, 2009 ; Dong et al, 2006 ; Faget-Agius et al, 2012 ; Gaser et al, 1999 ; Herrmann et al, 2006 ; Johnston et al, 2005 ; Lee et al, 2002 ; Mashal et al, 2014 ; Nierenberg et al, 2005 ; Niznikiewicz et al, 2000 ; Onitsuka et al, 2005 ; Onitsuka et al, 2003 ; Quarantelli et al, 2014 ; Schultz et al, 2010 ; Seiferth et al, 2008 ; Shenton et al, 2001 ; Singh et al, 2014 ; Takahashi et al, 2011 ; Tanskanen et al, 2010 ; Walther et al, 2009 ; Whalley et al, 2006 ; Yoon et al, 2006 ). These brain regions are involved in a variety of cognitive operations of relevance to schizophrenia, including language, visual attention and emotional processing ( Cohen et al, 1996 ; Dong et al, 2006 ; Herrmann et al, 2006 ; Johnston et al, 2005 ; Kaas, 1995 ; Mashal et al, 2014 ; Nierenberg et al, 2005 ; Niznikiewicz et al, 2000 ; Seiferth et al, 2008 ; Walther et al, 2009 ; Whalley et al, 2006 ; Yoon et al, 2006 ).…”

Distinguishing Between Treatment-Resistant and Non-Treatment-Resistant Schizophrenia Using Regional Homogeneity

“…The left postcentral gyrus belongs to the parietal lobe and the auditory and sensorimotor networks; furthermore, this area might be related to abnormal feelings ( 21 ), social cognition ( 22 ), aggression ( 23 ), and even hallucination ( 24 , 25 ). Anderson et al ( 26 ) and Quarantelli et al ( 27 ) demonstrated that TRS had decreased GM volume in the left postcentral gyrus compared with NTRS. Furthermore, significantly decreased ReHo values in this area were observed in patients with schizophrenia ( 22 , 28 , 29 ), which indicated that abnormal regional activity in the left postcentral gyrus may be associated with the etiology of schizophrenia.…”

Progressive Grey Matter Volume Changes in Patients with Schizophrenia over 6 Weeks of Antipsychotic Treatment and Their Relationship to Clinical Improvement

“…Several studies have focused on this topic, but the findings are inconsistent. Some have reported that reductions in total and regional GMV, such as in prefrontal, middle frontal, hippocampal, and caudate volumes, are associated with a relatively poor response to treatment [ 16 , 17 ]. A voxel-wise volume study on first-episode drug-naive patients with schizophrenia found a significant GMV increase in the right putamen after 6 weeks of antipsychotic treatment, and this increase was associated with an improvement in positive symptoms [ 18 ].…”

“…The baseline temporal GMV was positively correlated with an improvement in positive symptoms, whereas a high baseline GMV in the dorsolateral prefrontal cortex was associated with an improvement of the negative symptoms in treatment-resistant patients [ 21 ]. Only poor-outcome patients, and not good-outcome patients, displayed a significantly smaller frontal GMV [ 17 , 22 ]. Further, a study also showed different interactive effects between brain structure and the treatment responses to clozapine and haloperidol; the right prefrontal cortex GMV was positively correlated with changes in the total brief psychiatric rating scale score in the haloperidol group, while the opposite was found in the clozapine group [ 22 ].…”