Connectome-based predictive modeling predicts paranoid ideation in young men with paranoid personality disorder: a resting-state functional magnetic resonance imaging study.

Paranoid personality disorder (PPD), a mental disorder that affects interpersonal relationships and work, is frequently neglected during diagnosis and evaluation at the individual-level. This preliminary study aimed to investigate whether connectome-based predictive modeling (CPM) can predict paranoia scores of young men with PPD using whole-brain resting-state functional connectivity (rs-FC). College students with paranoid tendencies were screened using paranoia scores ≥60 derived from the Minnesota Multiphasic Personality Inventory; 18 participants were ultimately diagnosed with PPD according to the Diagnostic and Statistical Manual of Mental Disorders and subsequently underwent resting-state functional magnetic resonance imaging. Whole-brain rs-FC was constructed, and the ability of this rs-FC to predict paranoia scores was evaluated using CPM. The significance of the models was assessed using permutation tests. The model constructed based on the negative prediction network involving the limbic system-temporal lobe was observed to have significant predictive ability for paranoia scores, whereas the model constructed using the positive and combined prediction network had no significant predictive ability. In conclusion, using CPM, whole-brain rs-FC predicted the paranoia score of patients with PPD. The limbic system-temporal lobe FC pattern is expected to become an important neurological marker for evaluating paranoid ideation.

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia.

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

Amygdala hyperconnectivity in the paranoid state: A transdiagnostic study.

BACKGROUND: Paranoia significantly contributes to social impairments across clinical diagnoses, and amygdala dysfunction has been identified as a neurobiological marker of paranoia among individuals with schizophrenia. Therefore, we aimed to investigate amygdala functional connectivity (FC) in paranoia across diagnoses. METHODS: Forty-five patients with recent history of clinically significant paranoid ideation and a current DSM-5 diagnosis of any disorder underwent resting-state functional magnetic resonance imaging either in a paranoid (N = 23) or non-paranoid (N = 22) state. Amygdala FC were compared between paranoid and non-paranoid patients. Supplemental correlation analyses between amygdala FC and paranoia score were performed separately in patients and a non-equivalent healthy control (HC; N = 60) group. RESULTS: Increased FC was found between right amygdala and the prefrontal cortex (PFC) [bilateral medial superior frontal gyrus, anterior cingulate, medial frontal gyrus, the triangular part and the opercular part of the inferior frontal gyrus (IFG); right orbital part of IFG], the frontal cortex (bilateral median cingulate, left precentral gyrus), and subcortical areas (right insula) in the paranoid group compared with the non-paranoid group. No significant between-group differences were observed in left amygdala FC. FC between right amygdala and PFC and frontal cortex was positively correlated with paranoia in patient and HC groups. CONCLUSION: Paranoia is associated with right amygdala hyperconnectivity with PFC, frontal cortex, and insula. This hyperconnectivity was evident regardless of diagnosis and therefore identify a likely transdiagnostic neural mechanism, which may help to identify treatment targets that could potentially improve the social functioning of individuals with clinical diagnoses.

Increased structural connectivity of the medial forebrain bundle in schizophrenia spectrum disorders is associated with delusions of paranoid threat and grandiosity.

In many cases delusions in schizophrenia spectrum disorders (SSD) are driven by strong emotions such as feelings of paranoia or grandiosity. We refer to these extreme emotional experiences as psychotic affectivity. We hypothesized that increased structural connectivity of the supero-lateral medial forebrain bundle (slMFB), a major tract of the reward system, is associated with delusional psychotic affectivity. Forty-six patients with SSD and 44 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. The slMFB and a comparison tract (corticospinal tract) were reconstructed using diffusion tensor imaging (DTI)-based tractography. Fractional anisotropy (FA) was sampled across the tracts. We used a mixed-model analyses of variance controlling for age and gender to compare FA of bilateral slMFB between SSD-patients and HC. Correlations of FA of bilateral slMFB and the PANSS-positive item delusions were calculated. In addition, FA was compared between three clinically homogeneous SSD-subgroups in terms of psychotic affectivity (severe, mild and no PA, sPA, mPA, nPA) and HC. FA of the slMFB did not differ between all SSD-patients and HC. In SSD-patients there was a positive correlation between delusions and FA in bilateral slMFB. Likewise, SSD-subgroups of psychotic affectivity and HC differed significantly in FA of the slMFB. Results were driven by higher FA in the right slMFB in sPA as compared to nPA and to HC. There was no significant effect for the comparison tract. In conclusion, increased structural connectivity of the slMFB may underlie delusional experiences of paranoia and grandiosity in SSD.

Progressive paranoid psychosis in a 20-year-old with central congenital hypoventilation syndrome.

A 20-year-old man with a history of congenital central hypoventilation syndrome presented with recent-onset psychosis, catatonia, and a diagnosis of schizophrenia. Psychiatric symptoms were resistant to conventional treatment. A fluorodeoxyglucose positron emission tomography scan of the brain obtained during the hospitalization revealed a hypometabolism distribution more consistent with hypoperfusion than with primary central nervous system disease. Increased mechanical ventilation was successfully used to treat the psychiatric symptoms.

Neuropathological and neuroradiological correlates of paranoid symptoms in organic mental disease.

This paper reviews paranoid symptoms in older patients with organic mental disease. We have taken a dual approach to this topic, examining patients with dementia in whom paranoid symptoms are present and also assessing the presence of organic brain changes in patients diagnosed as having late-onset schizophrenia, paraphrenia or delusional disorder. (For the sake of continuity and not wishing to pre-empt any discussion of the nosological categorisation of late-onset psychoses, we refer to late-onset persecutory state as paraphrenia.) Firstly, there is a description of the various paranoid symptoms which have been described in patients with dementia. Secondly, brain imaging studies are discussed which have highlighted changes in patients with paraphrenia and particular associations between psychotic phenomenology and brain changes in patients with dementia. Thirdly, neuropathological and neurochemical changes in the brains of patients with dementia in whom paranoid symptoms have been present are presented. We intersperse all three sections with data from work carried out by the authors at the Institute of Psychiatry in London from 1986 and 1992. For other reviews, see Allen and Burns (1995), Burns and Förstl (1996), Eisiri (1996) and Howard (1996).

Organic factors and the clinical features of late paranoid psychosis: a comparison with Alzheimer's disease and normal ageing.

The diagnostic allocation and aetiological basis of paranoid psychoses with late onset is controversial. We examined the clinical features of patients with a diagnosis of paranoid psychosis and we compared their cranial computed tomography (CT) scans and electroencephalographic (EEG) recordings with findings from matched samples of patients with Alzheimer's disease and non-demented elderly controls. During a 5-year period, 81 patients (15 men and 66 women) with a diagnosis of paranoid psychosis and onset after age 50 were referred to our Institute. They represent 5.4% of the patients older than 50 admitted during the same period. More than half of these patients had first-rank symptoms. The ventricles, anterior and sylvian fissures of the paranoid group were larger than in non-demented controls but smaller than in Alzheimer's disease. The posterior dominant alpha EEG rhythm was slower than in normal aging and faster than in Alzheimer's dementia. If paranoid patients with first-rank symptoms were distinguished from the ones without, the former had less severe brain atrophy and faster posterior dominant rhythm, although they received higher doses of neuroleptics. This could be explained by the existence of at least 2 subgroups of late paranoid psychosis: late-onset schizophrenia and organic paranoid syndrome, the former characterized by first-rank symptoms and less severe brain atrophy, the latter by more severe EEG and CT scan changes with a closer resemblance to degenerative brain disease.

A cerebral computed tomography study of patients with drug-induced psychoses.

Twelve male patients with chronic drug consumption including cannabis (ICD = 304.3) and morphine (ICD = 304.7), who required inpatient treatment for drug-induced paranoid hallucinatory states (ICD = 292.1) were investigated using computed tomography for macroscopic structural changes in the brain. The findings were compared with those in a control group of schizophrenic patients who did not consume drugs. The brain scans were measured and not show any significant morphological differences between the two groups.