Psychiatry - Research Publications
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ItemNo Preview AvailableImpaired olfactory ability associated with larger left hippocampus and rectus volumes at earliest stages of schizophrenia: A sign of neuroinflammation?(ELSEVIER IRELAND LTD, 2020-07)Impaired olfactory identification has been reported as a first sign of schizophrenia during the earliest stages of illness, including before illness onset. The aim of this study was to examine the relationship between volumes of these regions (amygdala, hippocampus, gyrus rectus and orbitofrontal cortex) and olfactory ability in three groups of participants: healthy control participants (Ctls), patients with first-episode schizophrenia (FE-Scz) and chronic schizophrenia patients (Scz). Exploratory analyses were performed in a sample of individuals at ultra-high risk (UHR) for psychosis in a co-submission paper (Masaoka et al., 2020). The relationship to brain structural measures was not apparent prior to psychosis onset, but was only evident following illness onset, with a different pattern of relationships apparent across illness stages (FE-Scz vs Scz). Path analysis found that lower olfactory ability was related to larger volumes of the left hippocampus and gyrus rectus in the FE-Scz group. We speculate that larger hippocampus and rectus in early schizophrenia are indicative of swelling, potentially caused by an active neurochemical or immunological process, such as inflammation or neurotoxicity, which is associated with impaired olfactory ability. The volumetric decreases in the chronic stage of Scz may be due to degeneration resulting from an active immune process and its resolution.
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ItemS166. EFFECTIVE CONNECTIVITY OF FRONTOSTRIATAL SYSTEMS IN FIRST-EPISODE PSYCHOSIS(Oxford University Press (OUP), 2020-05-18)Abstract Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.
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ItemPsychosocial Intervention With or Without Antipsychotic Medication for First-Episode Psychosis: A Randomized Noninferiority Clinical Trial(Oxford University Press (OUP), 2020-01-01)Abstract This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).
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ItemDoes cortical brain morphology act as a mediator between childhood trauma and transition to psychosis in young individuals at ultra-high risk?(ELSEVIER, 2020-10)BACKGROUND: Childhood trauma, particularly sexual abuse, has been associated with transition to psychosis in individuals at "ultra-high risk" (UHR). This study investigated whether the effects of various forms of childhood trauma on transition to psychosis are mediated by cortical thickness and surface area abnormalities. METHODS: This prospective study used data from 62 UHR individuals from a previous (PACE 400) cohort study. At follow-up, 24 individuals had transitioned to psychosis (UHR-T) and 38 individuals had not transitioned (UHR-NT). Student-t/Mann-Whitney-U tests were performed to assess morphological differences in childhood trauma (low/high) and transition. Mediation analyses were conducted using regression and bootstrapping techniques. RESULTS: UHR individuals with high sexual trauma histories presented with decreased cortical thickness in bilateral middle temporal gyri and the left superior frontal gyrus compared to those with low sexual trauma. Participants with high physical abuse had increased cortical thickness in the right middle frontal gyrus compared to those with low physical abuse. No differences were found for emotional abuse or physical/emotional neglect. Reduced cortical thickness in the right middle temporal gyrus and increased surface area in the right cingulate were found in UHR-T compared to UHR-NT individuals. Sexual abuse had an indirect effect on transition to psychosis, where decreased cortical thickness in the right middle temporal gyrus was a mediator. CONCLUSIONS: Results suggest that childhood sexual abuse negatively impacted on cortical development of the right temporal gyrus, and this heightened the risk of transition to psychosis in our sample. Further longitudinal studies are needed to precisely understand this link.