Aberrant salience network functional connectivity in auditory verbal hallucinations: a first episode psychosis sample

BackgroundIn dimensional understanding of psychosis, auditory verbal hallucinations (AVH) are unitary phenomena present on a continuum from non-clinical voice hearing to severe mental illness. There is mixed evidence for this approach and a relative absence of research into subjective experience of AVH in early psychosis.AimsTo conduct primary research into the nature of subjective experience of AVH in first-episode psychosis.MethodA phenomenological study using diary and photo-elicitation qualitative techniques investigating the subjective experience of AVH in 25 young people with first-episode psychosis.ResultsAVH are characterised by: (a) entity, as though from a living being with complex social interchange; and (b) control, exerting authority with ability to influence. AVH are also received with passivity, often accompanied by sensation in other modalities.ConclusionsA modern detailed phenomenological investigation, without presupposition, gives results that echo known descriptive psychopathology. However, novel findings also emerge that may be features of AVH in psychosis not currently captured with standardised measures.

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Longitudinal Changes in Functional Connectivity in Antipsychotic-treated and Antipsychotic-naive Patients with First Episode Psychosis

10.1101/2021.04.13.21255375 ◽

2021 ◽

Author(s):

Sidhant Chopra ◽

Shona M. Francey ◽

Brian O’Donoghue ◽

Kristina Sabaroedin ◽

Aurina Arnatkeviciute ◽

...

Keyword(s):

Functional Connectivity ◽

First Episode Psychosis ◽

Common Finding ◽

First Episode ◽

Control Group ◽

Antipsychotic Treatment ◽

Long Term Effects ◽

Limbic Systems ◽

Episode Psychosis ◽

The Brain

AbstractBackgroundAltered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.MethodsSixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.ResultsAt baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.Conclusions and RelevanceAntipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

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Neurochemical and brain functional changes in the ventromedial prefrontal cortex of first-episode psychosis patients: A combined functional magnetic resonance imaging—proton magnetic resonance spectroscopy study

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419898520 ◽

2020 ◽

Vol 54 (5) ◽

pp. 519-527 ◽

Cited By ~ 1

Author(s):

Haixin Cen ◽

Jiale Xu ◽

Zhilei Yang ◽

Li Mei ◽

Tianyi Chen ◽

...

Keyword(s):

Prefrontal Cortex ◽

Magnetic Resonance ◽

Functional Connectivity ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

First Episode Psychosis ◽

Ventromedial Prefrontal Cortex ◽

First Episode ◽

Gaba Level ◽

Episode Psychosis

Objective: Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. Methods: In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. Results: In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. Conclusion: Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

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Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419885452 ◽

2019 ◽

Vol 54 (5) ◽

pp. 509-518 ◽

Cited By ~ 1

Author(s):

Sanghoon Oh ◽

Minah Kim ◽

Taekwan Kim ◽

Tae Young Lee ◽

Jun Soo Kwon

Keyword(s):

Functional Connectivity ◽

Anterior Cingulate Cortex ◽

Negative Symptoms ◽

Primary Motor Cortex ◽

Cingulate Cortex ◽

First Episode Psychosis ◽

Anterior Cingulate ◽

First Episode ◽

Healthy Controls ◽

Episode Psychosis

Objective: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Methods: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. Results: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate–left primary motor cortex/right dorsal rostral putamen–anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen–anterior cingulate cortex functional connectivity predicted improvement in general functioning. Conclusion: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.

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30.1 RELATIONSHIP BETWEEN CORTICAL EXCITATION AND INHIBITION, TASK-INDUCED BOLD RESPONSE AND FUNCTIONAL CONNECTIVITY: A COMBINED MR SPECTROSCOPY AND FUNCTIONAL MRI STUDY AT 7T IN FIRST EPISODE PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbz022.122 ◽

2019 ◽

Vol 45 (Supplement_2) ◽

pp. S138-S138

Author(s):

Adrienne Lahti ◽

Gregory Overbeek ◽

Timothy Gawne ◽

Nina Kraguljac ◽

Meredith Reid

Keyword(s):

Functional Connectivity ◽

Functional Mri ◽

Mr Spectroscopy ◽

First Episode Psychosis ◽

First Episode ◽

Bold Response ◽

Episode Psychosis ◽

Cortical Excitation ◽

Mri Study

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Anterior Hippocampal–Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment

Schizophrenia Bulletin ◽

10.1093/schbul/sbz076 ◽

2019 ◽

Vol 46 (3) ◽

pp. 680-689 ◽

Cited By ~ 3

Author(s):

Esther M Blessing ◽

Vishnu P Murty ◽

Botao Zeng ◽

Jijun Wang ◽

Lila Davachi ◽

...

Keyword(s):

Functional Connectivity ◽

Random Forest ◽

Treatment Response ◽

Second Generation ◽

First Episode Psychosis ◽

First Episode ◽

Antipsychotic Treatment ◽

Episode Psychosis ◽

Second Generation Antipsychotic ◽

Cortical Regions

Abstract Background Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. Methods We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal–whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. Results Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular–opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). Conclusions Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.

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