Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases

Seeing Voices: Potential Neuroscience Contributions to a Reconstruction of Legal Insanity

Part I of this Article explains the insanity defense in the United States. Next, Part II discusses some of the brain-based research about mental illness, focusing on schizophrenia research. Then, Part III looks at traumatic brain injury and the relationship among injury, cognition, and behavior. Finally, Part IV explains how a new neuroscience-informed standard might better inform our moral decision making about legal insanity

Is there a Degenerative Process Going on in the Brain of People with Schizophrenia?†

Schizophrenia is a biological and behavioural disorder which manifests itself in neurocognitive dysfunctions. The question of whether these key characteristics of the disorder are due to schizophrenia being a degenerative disorder has been discussed for more than 100 years. Neuropsychological data indicate that neurocognitive functions are relatively stable over time after illness onset. Several studies show that there is a decline in neurocognitive functioning prior to and in connection with onset of illness. There is no convincing evidence, however, that there is a progressive neurodegenerative process after onset of illness. Morphological data, on the other hand, indicate a degenerative process. Several novel longitudinal studies indicate a rapid reduction of vital brain tissues after onset of illness. In this paper some ideas about compensatory reactions and Cognitive Reserve Theory is outlined as possible explanations of the recent magnetic resonance imaging studies that show structural changes in the brain after the onset of schizophrenia, at the same time as cognitive functioning does not become more impaired. Determining whether schizophrenia is a neurodegenerative illness with progressive structural changes in the brain after debut of the illness, or a neurodevelopmental disorder starting in early life, is of significant importance for understanding the pathophysiology of the illness and its treatments

Frontal lobe changes occur early in the course of affective disorders in young people

<p>Abstract</p> <p>Background</p> <p>More severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately.</p> <p>Results</p> <p>The patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups.</p> <p>Conclusions</p> <p>This study suggests that, in terms of frontal grey matter changes, a major transition point may occur in the course of affective illness between early attenuated syndromes and later discrete illness stages.</p

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis

Background: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. Method: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. Results: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p<0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. Conclusions: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences

Grey matters: Mapping the transition to psychosis

Despite many neuroimaging studies on schizophrenia showing brain abnormalities the exact time course of their occurrence is unknown. Studies of gray matter are a powerful tool in biological psychiatry and provide an unprecedented opportunity for brain structure investigations. Here we compared cross-sectional and longitudinal structural neuroimaging studies distinguishing high-risk subjects developing psychosis from those who did not. These investigations on gray matter volumes in the prodromal phase potentially identify core structural markers of impending psychoses and clarify dynamic changes underlying the transition. Subjects at high risk of psychosis show qualitatively similar albeit less severe gray matter abnormalities as patients with psychosis

Structural and functional MRI study in mentally ill persons considered socially dangerous with diminished penal responsibility

La complessa relazione tra malattia mentale e criminalità rappresenta un tema di concreta rilevanza sociale, dibattuto da anni ma sempre di grande attualità. Secondo il codice penale, è considerato “socialmente pericoloso” il soggetto autore di reato, anche se non imputabile per vizio totale o parziale di mente, che abbia una elevata probabilità di recidiva del reato. Per questo motivo la prevenzione delle azioni socialmente pericolose riveste un ruolo di fondamentale importanza giuridica e sociale. In questo contesto la psichiatria forense si occupa delle questioni che sorgono all’interfaccia tra psichiatria e giurisprudenza, con l’obiettivo principale di evidenziare lo stato di salute mentale dei soggetti che commettono un reato attraverso una perizia psichiatrica. La disciplina neuroradiologica, grazie anche all’utilizzo di tecniche avanzate di analisi delle immagini, si pone oggi come strumento di valido ausilio nella valutazione clinica dei pazienti psichiatrici e può supportare gli sforzi congiunti di psichiatri e giuristi per studiare la relazione tra malattia mentale e criminalità. L’obiettivo di questo progetto di dottorato è stato quello di effettuare uno studio volumetrico della sostanza grigia cerebrale attraverso un esame di Risonanza Magnetica (RM) su un gruppo di soggetti autori di reato, considerati non imputabili al momento del fatto per vizio totale o parziale di mente, detenuti nella REMS dell’ASL Rm5 e considerati socialmente pericolosi. I risultati dell’analisi volumetrica sono stati confrontati con un gruppo di controllo, comparabile per età e sesso. E’stata inoltre effettuata un’analisi della connettività funzionale cerebrale a riposo (resting-state functional MRI) con l’intento di indagare i network cerebrali alla base del comportamento morale, dell’attribuzione della salienza e dei processi di ricompensa, confrontando sempre i risultati con un gruppo di controllo. Nel gruppo sperimentale sono stati inclusi 13 individui destrorsi (età media: 44 ± 7 anni) detenuti nella REMS dell’ASL Rm5 con disturbo dello spettro psicotico (schizofrenia, disturbo bipolare con caratteristiche psicotiche, disturbo schizo-affettivo, disturbi deliranti), che hanno commesso crimini violenti (omicidi, tentati omicidi, aggressioni e violenze domestiche) e che sono stati dichiarati socialmente pericolosi dall’autorità giudiziaria a causa dell’ alto rischio di recidiva criminale. I dati di RM sono stati acquisiti su un magnete 3 Tesla (Verio, Siemens) dotato di una bobina a 12 canali, utilizzando sequenze volumetriche T13D e sequenze BOLD eco-planari (EPI). Nello studio I abbiamo eseguito un’analisi della volumetria cerebrale con tecnica VBM (Voxel-based morphometry) utilizzando il Computational Anatomy Toolbox (CAT12) del software Statistical Parametric Mapping (SPM12). Abbiamo riscontrato come il volume della sostanza grigia cerebrale del gruppo sperimentale fosse significativamente ridotto, rispetto ai controlli, a livello della corteccia insulare bilaterale, nel giro temporale superiore (STG) dell’emisfero sinistro e nel giro fusiforme dell’emisfero destro. Abbiamo infine eseguito un’analisi di correlazione tra la gravità dei sintomi psichiatrici e le regioni con volume corticale ridotto. I cluster di volume a livello di STG e insula sinistra sono risultati essere significativamente correlati alla gravità dei sintomi espressa dalla scala di valutazione BPRS (Brief Psychiatric Rating Scale). Nello studio II abbiamo esaminato la connettività cerebrale a riposo nelle 19 regioni selezionate “a priori” sulla base della letteratura che risultassero coinvolte nella morale, nell’ attribuzione della salienza e nei processi di ricompensa. L’analisi è stata effettuata utilizzando il software CONN v. 18a, sulla piattaforma Matlab. Abbiamo documentato una ridotta connettività tra le regioni del sistema limbico, come il nucleo accumbens e l’amigdala, ed aumentata connettività nello striato dorsale, tra il nucleo accumbens e la corteccia cingolata posteriore, tra corteccia fronto-orbitale e gangli della base e tra corteccia cingolata anteriore e amigdala. Sulla base di questi risultati ipotizziamo che l’alterata connettività in queste specifiche aree possa rappresentare la modificazione del comportamento in senso maladattativo degli individui del gruppo sperimentale, in termini di alterata risposta emotiva circa le proprie violazioni morali o di mancanza di empatia verso gli altri al fine di ottenere vantaggi personali o riguardo al controllo dell’impulsività. Nonostante la bassa numerosità campionaria non consenta di approdare a conclusioni definitive, questo studio cerca di approfondire i correlati neurali degli individui autori di reato con ridotta responsabilità penale e socialmente pericolosi al fine di fornire un eventuale strumento di ausilio nella valutazione di questa particolare categoria di persone, con importanti risvolti giuridici ed etici oltre che nella pianificazione e nello sviluppo del trattamento di questi pazienti durante la loro permanenza nelle REMS.The relation between mental illness and criminality is a relevant social issue that has been debated over the years. Socially dangerous actions committed by mentally ill patients often have severe consequences, which is why much public attention is directed toward the prevention of these actions by these individuals. Modern neuroimaging investigations support the joint efforts of psychiatrists and lawyers to study the relationship between psychiatric illness and criminality. The overall aim of this PhD project was to investigate differences in cortical GM volumes of this population, compared to a control group of healthy non-offender participants, using a VBM analysis of structural MRI. We also decided to investigate brain networks underpinning moral behaviour, salience attribution and reward processes performing a functional MRI at resting-state. Experimental Group (EG) included 13 right-handed individuals (mean age: 44 ± 7 yrs) who committed violent crimes (homicides, attempted homicides, aggressions, and domestic violence), had a diagnosis included in the psychotic spectrum (schizophrenia, bipolar disorder with psychotic features, schizoaffective disorder, delusional disorders) and were declared socially dangerous by the judicial authority due to a high risk of criminal recidivism. All subjects of the EG were institutionalized in the REMS psychiatric unit of ASL RM5 (Rome, Italy) for no longer than two years. Thirteen healthy right-handed men, who had never received a psychiatric diagnosis, undergone any psychiatric treatment, or been convicted of any crime were included in the control group (CG) (mean age: 38 ± 11yrs). MRI data were acquired using a 3 Tesla Siemens imaging system (Siemens, Verio, Erlangen, Germany) equipped with a 12-channel head coil. Structural scans of the brain were acquired for each participant using a T1-weighted three dimensionals sagittal magnetization-prepared rapid gradient echo sequence. Resting state functional (rs-fMRI) data were collected while participants lay still and awake, with eyes closed using T2*-weighted gradient-echo echo-planar functional images (EPIs). In study I we performed a voxel-based morphometry (VBM) analyses on participants’ T1-weighted structural images using Computational Anatomy Toolbox (CAT12), which runs within SPM12. We found that total cerebral GM volume was significantly reduced in EG in specific regions within the bilateral insular cortex compared to controls. We also found a reduced GM volume in the superior temporal gyrus (STG) of left hemisphere and in the fusiform gyrus of the right hemisphere. We finally performed a correlation analyses between psychiatric symptoms and regions with reduced GM volume. The clusters in STG and insula of left hemisphere significantly correlated with the gravity of symptoms expressed by the BPRS (Brief Psychiatric Rating Scale). In study II, temporal correlations of the resting-state BOLD signal time series were examined between nineteen seed regions that we selected “a priori” among those known to be involved in moral judgment salience attribution and reward processes. Analysis was performed using the software CONN v. 18a, running in Matlab. Our results documented reduced connectivity in limbic regions like the nucleus accumbens and the amiygdala and augmented connectivity within the dorsal striatum, between nucleus accumbens and the posterior cingulate cortex, between fronto- orbitalis cortex and basal ganglia and anterior cingulate cortex and amygdala. We suggest that dysregulation in these areas reflects the maladaptive behavior of socially dangerous subjects in terms of an altered emotional response to their own moral violations and a lack of empathy for others when making personal desire-oriented decisions. While the small sample size does not allow definitive conclusions to be reached, the present study sheds some light on the neural correlates of this specific population, which deserves further attention due to their theoretical and clinical implications. A further understanding of the neural basis of risk evaluation in mentally ill persons with a history of violence who are judged not criminally responsible could aid in forensic assessment and treatment development