Medial temporal lobe structure and cognition in individuals with schizophrenia and in their non-psychotic siblings

Abstract

Medial temporal lobe (MTL) structures play a central role in episodic memory. Prior studies suggest that individuals with schizophrenia have deficits in episodic memory as well as structural abnormalities of the medial temporal lobe (MTL). While correlations have been reported between MTL volume loss and episodic memory deficits in such individuals, it is not clear whether such correlations reflect the influence of the disease state or of underlying genetic influences that might contribute to risk. We used high resolution magnetic resonance imaging and probabilistic algorithms for image analysis to determine whether MTL structure, episodic memory performance and the relationship between the two differed among groups of 47 healthy control subjects, 50 control siblings, 39 schizophrenia subjects, and 33 siblings of schizophrenia subjects. High-dimensional large deformation brain mapping was used to obtain volume measures of the hippocampus. Cortical distance mapping was used to obtain volume and thickness measures of the parahippocampal gyrus (PHG) and its substructures: the entorhinal cortex (ERC), the perirhinal cortex (PRC), and the parahippocampal cortex (PHC). Neuropsychological data was used to establish an episodic memory domain score for each subject. Both schizophrenia subjects and their siblings displayed abnormalities in episodic memory performance. Siblings of individuals with schizophrenia, and to a lesser extent, individuals with schizophrenia themselves, displayed abnormalities in measures of MTL structure (volume loss or cortical thinning) as compared to control groups. Further, we observed correlations between structural measures and memory performance in both schizophrenia subjects and their siblings, but not in their respective control groups. These findings suggest that disease-specific genetic factors present in both patients and their relatives may be responsible for correlated abnormalities of MTL structure and memory impairment. The observed attenuated effect of such factors on MTL structure in individuals with schizophrenia may be due to non-genetic influences related to the development and progression of the disease on global brain structure and cognitive processing.

Medial temporal lobe default mode functioning and hippocampal structure as vulnerability indicators for schizophrenia: A MRI study of non-psychotic adolescent first-degree relatives

“…Thus, the hippocampus proper is abnormal in young individuals at FHR, consistent with results observed in older relatives. The parahippocampal gyrus (PHG) has been studied less frequently and the only published study of PHG in young relatives has shown thinner cortex in nonpsychotic relatives than in controls (Karnik-Henry et al, 2012). We had found smaller PHG volume in older relatives .…”

“…We had found morphometric abnormalities in PHG in a prior larger study of adult relatives using these methods . To date, two studies of young relatives have shown excessive cortical thinning in FHR (Byun et al, 2012;Karnik-Henry et al, 2012) but there were no significant differences in parahippocampus in the one study that measured volumes.…”

“…review by Thermenos et al, 2013) with few negative findings (Karnik-Henry et al, 2012). Early studies demonstrated a smaller "amygdala-hippocampal complex" in youth at familial high-risk (FHR), in which the amygdala and hippocampus were not separated due to existing limitations of anatomical resolution and segmentation procedures (Keshavan et al, 1997(Keshavan et al, , 2002Schreiber et al, 1999;Lawrie et al, 2001).…”

Neural activity changes in unaffected children of patients with schizophrenia: A resting-state fMRI study

“…Interestingly, neuroimaging evidence has suggested aberrations in this region in previous studies of schizophrenia patients and their first-degree relatives, particularly left-lateralized deficits (Friston et al, 1992;Karnik-Henry et al, 2012;Meisenzahl et al, 2008). Hoptman et al (2010) also found increased ALFF in the left hippocampus and parahippocampal gyrus in subjects with schizophrenia.…”

Spatial-memory deficit in schizophrenia spectrum disorders under viewpoint-independent demands in the virtual courtyard task

“…On a backdrop of a generalized cognitive impairment, deficits in declarative memory appear particularly severe among persons with chronic and first-episode schizophrenia spectrum disorders (SSD; Aleman, Hijman, de Haan & Kahn, 1999;Heinrichs & Zakzanis, 1998;Karnik-Henry et al, 2012;Mesholam-Gately, Giuliano, Goff, Faraone, & Seidman, 2009;Weiss & Heckers, 2001). Moreover, memory performance is one of the strongest predictors of functional outcome, as compared to a host of other cognitive measures, clinical symptoms, and demographic variables (Ranganath, Minzinberg, & Ragland, 2008).…”