Auditory Hallucinations in First-Episode Psychosis: a Voxel
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Schizophrenia Research 209 (2019) 148–155 Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Auditory hallucinations in first-episode psychosis: A voxel-based morphometry study María Jose Escarti a,b,o,⁎,1, Gracian Garcia-Marti c,o,1, Roberto Sanz-Requena c, Luis Marti-Bonmatí c,d, Bibiana Cabrera m,o, Eduard Vieta e,k,o, Antonio Lobo f,g,o,Josefina Castro-Fornieles h,o,AnaGonzález-Pintoi,o, Romina Cortizo j, Laura Pina-Camacho l,o,MaraParelladal,o, Miquel Bernardo m,o, Julio Sanjuan a,n,o,PEPs Group a Department of Psychiatry, Hospital Clinic, University of Valencia, INCLIVA, Valencia, Spain b Department of Psychiatry, Hospital Peset, Av. de Gaspar Aguilar, 90, 46017 Valencia, Spain c Department of Radiology, Quirón Hospital, Avda. Blasco Ibáñez, 14, 46010 Valencia, Spain d Biomedical Imaging Research Group (GIBI2^30), Hospital Universitari i Politècnic La Fe, Avda. Fernando Abril Martorell 106, Torre A, 46026, Valencia, Spain e Bipolar Disorder Unit, Hospital Clinic of Barcelona, University of Barcelona, Spain f Department of Medicine and Psychiatry, Hospital Clinico, University of Zaragoza, Zaragoza, Spain g Instituto de Investigación Sanitaria Aragón (IIS Aragon) y Universidad de Zaragoza, Spain h Dept. of Child and Adolescent Psychiatry and Psychology, SGR-489, Institute Clinic of Neurosciences, Hospital Clinic of Barcelona, Spain i Department of Psychiatry, Hospital Universitario de Álava (Sede Santiago), EHU/University of the Basque Country, Vitoria, Spain j Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona, Spain k Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPS, Barcelona, Spain l Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañon, School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain m Barcelona Clinic Schizophrenia Unit, Neurosciences Institute, Hospital Clinic, Barcelona, Spain n Faculty of Medicine, Universitat de València, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain o Ciber del Área de Salud Mental (CIBERSAM), Spain article info abstract Article history: Background: Auditory hallucinations (AH) are a core symptom of psychosis. The brain abnormalities responsible Received 12 July 2018 for AH remain controversial due to inconsistent and conflicting findings across studies, with substantial con- Received in revised form 5 February 2019 founding factors, such as chronicity. Few studies have examined the pathological changes that occur in the Accepted 1 May 2019 gray matter (GM) of patients with first-episode psychosis (FEP) and AH. The present study aims to validate Available online 18 May 2019 the presence and characteristics of these structural abnormalities in relation to the intensity of psychotic symp- toms and AH in a larger homogeneous sample than those of previous studies. Methods: A magnetic resonance voxel-based morphometric analysis was applied to a group of 215 patients with FEP (93 patients with AH and 122 patients without AH) and 177 healthy controls. The patients were evaluated using the PANSS scale. Results: Patients with FEP exhibited greater reductions in GM concentrations in the tem- poral, frontal, cingulate and insular areas than the healthy controls did. No specific differences were found between the patients with FEP and AH and the patients without AH. In addition, total scores on the PANSS were negatively correlated with GM reductions in the FEP group. No correlations were found between the sever- ity of the AH and the GM volumes. Conclusions: As in previous studies, reductions in the GM concentrations in patients with FEP suggest that alter- ations are present in the early stages of psychosis, and these alterations are correlated with the severity of the ill- ness. The GM reductions were not found to be related to the presence or severity of AH. © 2019 Elsevier B.V. All rights reserved. 1. Introduction Hallucinations are considered a fundamental symptom within psy- chiatry (Waters et al., 2012). Specifically, auditory hallucinations (AH) are the most common psychotic symptom, affecting approximately ⁎ Corresponding author at: Centro de Investigación Biomédica en Red de Salud Mental 60–80% of patients with schizophrenia (Andreasen and Flaum, 1991). (CIBERSAM), ISC III, Avda. Blasco Ibáñez 15, Valencia 46010, Spain. E-mail addresses: [email protected], [email protected] (M.J. Escarti). Currently, the mechanism and pathophysiology of AH are still 1 These authors have contributed equally to this work. largely unknown. Neuroimaging studies of AH, have improved the https://doi.org/10.1016/j.schres.2019.05.001 0920-9964/© 2019 Elsevier B.V. All rights reserved. M.J. Escarti et al. / Schizophrenia Research 209 (2019) 148–155 149 Table 1 Clinical and demographic variables. FEP patients with auditory FEP patients without auditory Control ANOVA (F; p value; hallucinations hallucinations subjects degrees-of-freedom) or χ2 (N = 93) (N = 122) (N = 177) Age in years: mean (SD) 22.85 (6.25) 23.39 (6.22) 24.58 (6.70) F = 2.534; p = 0.810; df = 389 Sex: no. (%) χ2 = 2.26; p = 0.324 Male 58 (62.4) 85 (67.9) 109 (61.6) Female 35 (37.6) 37 (30.3) 68 (38.4) Ethnicity: no. (%) χ2 = 21.10; p = 0.099 Caucasian 75 (80.6) 110 (90.2) 158 (89.3) Other 18 (19.4) 12 (9.8) 19 (10.7) Highest degree attained: no. (%) χ2 = 80.23; p b 0.001 Some graduate-level degree 31 (33.3) 26 (21.3) 13 (7.3) High school diploma 39 (41.9) 46 (37.7) 37 (20.9) Bachelor's or associate's degree 12 (12.9) 30 (24.6) 38 (21.5) Master's degree 11(11.8) 20 (16.4) 89 (50.3) Antipsychotic medication (mg) Total cumulative dose: mean (SD) 44,069.45 (51,829.94) 41,361.93 (74,012.17) – F = 0.080; p = 0.778; df = 389 Total intracranial volume (TIV) in milliliters: 1410.83 (143.55) 1420.12 (147.08) 1438.86 F = 1.379; p = 0.253; df = 389 mean (SD) (135.22) PANSS score at baseline evaluation: mean (SD) ⁎⁎ Total 90.43 (23.49) 62.01 (19.57) – F = 93.50; p b 0.001 ; df = 389 ⁎⁎ Positive 24.33 (6.55) 13.71 (6.08) – F = 150.22; p b 0.001 ; df = 389 ⁎⁎ Negative 21.75 (8.75) 16.41 (7.95) – F = 21.82; p b 0.001 ; df = 389 ⁎⁎ General 44.34 (13.75) 31.89 (10.02) – F = 59.03; p b 0.001 ; df = 389 ⁎⁎ p b 0.0005. understanding of the brain regions and networks involved in this symp- 2015). However, the study of first-episode schizophrenia seems impor- tom. The temporal and frontal lobe brain areas have been implicated in tant for elucidating the core pathophysiology of this illness (Whitford AH in repeated functional and structural imaging studies, reporting al- et al., 2005). GM volume reductions in the right temporal, left anterior terations in sensory regions, mainly in the superior temporal gyrus cingulate and cerebellar and insular regions may underlie the onset of (STG) and the middle temporal gyrus (MTG), and these findings have psychosis. GM reductions in the temporal regions have been shown to been confirmed by two meta-analyses (Jardri et al., 2011; Modinos be inversely correlated with the severity of psychotic symptoms et al., 2013). Volumetric and functional changes in nonsensory regions (Fusar-Poli et al., 2012). have also been reported. As described above, it seems that imaging studies with FEP patients Structural Magnetic Resonance imaging (MRI) studies have tried to using voxel-based morphometry (VBM) may be one of the best ways correlate volumetric changes with AH in patients with schizophrenia to shed light on certain aspects of the pathophysiology of AH that re- (Modinos et al., 2013). Most of them have found, specific relationships main unclear. Three studies have explored GM volume changes in FEP between gray matter (GM) volume reductions in the left STG and mar- with and without AH (Shin et al., 2005; Chen et al., 2015; Huang et al., ginally with the right STG and AH severity (Modinos et al., 2013). A re- 2015). Shin et al. (2005) measured the volumes of cerebral and cerebel- duction in the left Heschl's gyrus has also been found to be specifically lar regions in FEP patients with (n = 17) and without (n =8)AH.They related to AH (Sumich et al., 2005; Modinos et al., 2013). Our group pre- found that patients with AH showed larger frontal and temporal GM viously showed that GM reductions (bilateral insula, bilateral STG and volumes than patients without AH. Chen et al. (2015) applied a left amygdala) were correlated specifically with the severity of AH in a surface-based analysis approach in a sample of 49 patients with FEP highly homogeneous group of chronic patients with persistent halluci- and 50 matched controls. They found that a subgroup of 18 patients suf- nations (García-Martí et al., 2008). In addition, specific relationships be- fering from persistent AH showed lower cortical thickness in the right tween the left inferior frontal and right postcentral gyri reductions and Heschl's gyrus. This reduction was correlated with AH severity. Huang the severity of AH were observed. et al. (2015) conducted a VBM analysis in 36 drug naïve patients (18 Although morphometric studies have demonstrated evidence of ce- with AH) and 18 controls and found that patients with and without rebral deficits in patients with schizophrenia and AH, these studies have AH exhibited reduced GM volumes relative to the controls in the left mainly been performed with chronic hallucination patients. Confounds STG and the frontal, cerebellar, caudate and thalamic regions, showing associated with illness chronicity and prolonged exposure to antipsy- also correlation with the severity of the illness. No significant differences chotic medications may have, therefore, influenced the results. Com- were found between patients with and without AH.