Schizophrenia is a disorder characterised by positive symptoms (hallucinations and delusions), thought disorder and negative symptoms (such as apathy). Brain imaging studies have identified structural changes both early in the presentation of the illness and more extensive changes later in the course of the illness
]. The distribution of changes has been replicated between studies
], and may be considered a ‘structural signature’ of schizophrenia within the brain. However, an adequate explanation for this spatial distribution remains elusive. Models have been proposed involving genetic factors coding neuro-protein variants resulting in abnormal development of limbic and frontal-temporal-subcortical networks
]. However, it remains uncertain which neuro-chemical pathways are responsible and how they cause the spatial changes.
FTLD is characterised by declines in social function, interpersonal conduct, emotional blunting, speech and language abnormalities and loss of insight
]. It is associated with degeneration of the prefrontal and anterior temporal cortices
]. However, the topographical distribution of structural brain changes is heterogeneous amongst different patient groups, reflecting behavioral and pathological variants. Although the most common histological feature is tauopathy
], over half of all patients, including those with a family history of the condition, have no abnormality in the tau gene or protein
], consistent with pathological and aetiological heterogeneity.
In this study, we investigate whether there is overlap in the distribution of brain changes in First Episode Schizophrenia (FES) and Fronto-Temporal Lobar Degeneration (FTLD). There is evidence for similarities in clinical, neuropsychological and neuroimaging findings in patients with FTLD and schizophrenia
]. In some cases, patients with FTLD have been diagnosed with a schizophrenia-like psychotic illness years before the dementia diagnosis is made
]. Echopraxia, echolalia, aprosody of speech, utilisation behavior, ‘negative’ symptoms, self-neglect, and bizarre, compulsive, and stereotyped behaviors are well recognised in both disorders. Executive dysfunction with relative preservation of visual perception and spatial skills
] and deficits in social cognition, theory of mind, empathy and affect recognition have been identified in both disorders
Frontal, temporal and hippocampal atrophy
] and regionally specific reductions in the anterior corpus callosum
] and anterior hippocampus
] have been described in MRI studies of both FTLD and schizophrenia. Frontal hypoperfusion on single photon emission tomography or positron emission tomography constitutes one of the imaging criteria for the diagnosis of frontotemporal dementia
], and is also one of the most robust functional imaging findings in the schizophrenia literature in patients with chronic and first-episode illness
]. There is also recent evidence that schizophrenia and FTLD co-occur in some families, suggesting the possibility of a common vulnerability to these disorders
]. While the pathology of schizophrenia remains uncertain, there have been considerable advances in elucidating the complex and heterogeneous pathology of FTLD
]. We have chosen to examine FES rather than chronic schizophrenia because the structural changes in FES may more accurately reflect the pathological changes of the disorder, and may minimize the confounding effects of long-term medication and other aspects of chronic illness. Different antipsychotics have individual volumetric effects on brain structure
] and therefore, patients with FES were used in order to reduce heterogeneity.
The aim of this review is to determine the distribution of brain changes in FTLD and FES, by employing an established meta-analytic technique (anatomical likelihood estimation, ALE)
] that is widely used for coordinate-based meta-analyses of neuroimaging data by converting the co-ordinates of peak gray matter changes from multiple published studies into spatial probability maps. However, the accuracy and extent of these maps is dependent on the total number of peak co-ordinates available from published studies. Therefore, this study employs a new statistical approach to investigate the degree of spatial correspondence between the two disorders, taking into account the greater availability of data co-ordinates for FTLD than FES. The comparison of brain changes between an individual MRI scan and maps for different disorders may become increasingly important for early diagnosis, as currently, diagnoses of psychiatric disorders are made on the basis of clinical manifestations and associated psychosocial disturbances. There are current initiatives to encourage the classification of mental disorders for research purposes, such as the RDoC (Research Domain Criteria) approach
]. Several MRI-based studies have attempted to distinguish between patients and healthy subjects with high accuracy (ranging from 75 to 92%)
]. Therefore, the statistical technique described in this paper for assessing spatial overlap may have wider clinical utility in the future.