Abnormal Functional and Structural Asymmetry as Biomarker for Schizophrenia

Abstract

The hemispheres of the human brain are anatomically and functionally asymmetric. Many cognitive and motor functions such as language and handedness are lateralized. In this review, we discuss the principles of laterality and brain asymmetry in relation to schizophrenia. Schizophrenia is one of the most disabling forms of mental illness. One important challenge is to develop and set up biological markers, which can accurately identify at-risk individuals in preclinical stages and thus improve the effects of early intervention strategies. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential use as biological marker for the illness. The review is an overview of literature from the 1990's on cerebral asymmetry in schizophrenia. We critically discuss the use of cerebral asymmetry for biomarker research, regarding diagnosis improvements, the improvement of psychopharmacology and the prediction of conversion in at-risk individuals. We propose that abnormal cerebral asymmetry is an attractive biomarker candidate for schizophrenia that could index changes in a range of pathophysiological pathways.

Hemispheric lateralization abnormalities of the white matter microstructure in patients with schizophrenia and bipolar disorder

“…Third, our study was crosssectional in design. Although hemispheric lateralization occurs during perinatal stages, 4 we could not fully establish whether the white matter hemispheric lateral ization anomalies found across participants with schizophre nia and BD were due to neurodevelopmental aberrance or whether they were a consequence of the onset or chronicity of illness. To confirm its neurodevelopmental origins, prospec tive longitudinal studies on prodromal and firstepisode psych osis patients would be required to determine that the white matter hemispheric abnormalities are present before psychosis onset.…”

“…1,3 Hemispheric lateralization occurs early during the perinatal stages and is genetically associated within fam ilies. 4 As such, the loss of hemispheric lateralization has long been proposed to be a consequence of disrupted neuro develop ment in individuals with psychotic disorders. 2,4,5 The interest in hemispheric lateralization in individuals with psych osis dates back more than 3 decades, with the field dominated by theories of preferential left hemisphere dys function in people with schizophrenia and right hemisphere dysfunction in those with bipolar disorder (BD).…”

“…4 As such, the loss of hemispheric lateralization has long been proposed to be a consequence of disrupted neuro develop ment in individuals with psychotic disorders. 2,4,5 The interest in hemispheric lateralization in individuals with psych osis dates back more than 3 decades, with the field dominated by theories of preferential left hemisphere dys function in people with schizophrenia and right hemisphere dysfunction in those with bipolar disorder (BD). 6 The advent of noninvasive neuroimaging MRI techniques ushered in a series of structural and taskbased fMRI studies in patients with schizophrenia that demonstrated loss of left ward volume asymmetry of specific brain regions involved in auditory and language processing.…”

On the other hand: including left-handers in cognitive neuroscience and neurogenetics

“…LRRTM1 regulates the differentiation of excitatory synapses [107][108][109][110][111][112] and binds to neurexin proteins across the synaptic cleft [107][108][109][110][111][112] . Genetic deletion mapping strongly implicates neurexins in a range of major neuropsychiatric disorders, including autism and schizophrenia, both of which are associated with increased rates of lefthandedness and alterations of structural and functional brain asymmetry [113][114][115][116][117][118][119][120][121][122][123][124][125] (although not in all clinical populations 126 ). However, it…”

Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI neurofeedback training

“…However, it is unclear whether such effect may result from or contribute to better learning. Nevertheless, the feasibility of learning control over the interhemispheric balance between homologous brain areas opens new perspectives for potential therapeutic approaches in neuropsychiatric diseases characterized by abnormal asymmetries in hemispheric processing, including but not limited to spatial neglect (Driver and Mattingley, 1998;Driver and Vuilleumier, 2001;Halligan et al, 2003;Husain and Rorden, 2003;Milner and McIntosh, 2005), dyslexia (Bishop, 2013), schizophrenia (Oertel-Knochel et al, 2012), and mood disorders (Herrington et al, 2010;Sackeim et al, 1982).…”