Publishing trends in the field of psychiatry in Finland 2019

Peer reviewe

Functional network connectivity and topology during naturalistic stimulus is altered in first-episode psychosis

Background: Psychotic disorders have been suggested to derive from dysfunctional integration of signaling between brain regions. Earlier studies have found several changes in functional network synchronization as well as altered network topology in patients with psychotic disorders. However, studies have used mainly resting-state that makes it more difficult to link functional alterations to any specific stimulus or experience. We set out to examine functional connectivity as well as graph (topological) measures and their association to symptoms in first-episode psychosis patients during movie viewing. Our goal was to understand whole-brain functional dynamics of complex naturalistic information processing in psychosis and changes in brain functional organization related to symptoms. Methods: 71 first-episode psychosis patients and 57 control subjects watched scenes from the movie Alice in Wonderland during 3 T fMRI. We compared functional connectivity and graph measures indicating integration, segregation and centrality between groups, and examined the association between topology and symptom scores in the patient group. Results: We identified a subnetwork with predominantly decreased links of functional connectivity in firstepisode psychosis patients. The subnetwork was mainly comprised of nodes of and links between the cinguloopercular, sensorimotor and default-mode networks. In topological measures, we observed between-group differences in properties of centrality. Conclusions: Functional brain networks are affected during naturalistic information processing already in the early stages of psychosis, concentrated in salience- and cognitive control-related hubs and subnetworks. Understanding these aberrant dynamics could add to better targeted cognitive and behavioral interventions in the early stages of psychotic disorders.Peer reviewe

State-like changes in the salience network correlate with delusion severity in first-episode psychosis patients

Background and hypothesis: Delusions are characteristic of psychotic disorders; however, the brain correlates of delusions remain poorly known. Imaging studies on delusions typically compare images across individuals. Related confounding of inter-individual differences beyond delusions may be avoided by comparing delusional and non-delusional states within individuals. Study design: We studied correlations of delusions using intra-subject correlation (intra-SC) and inter-subject correlation of functional magnetic resonance imaging (fMRI) signal time series, obtained during a movie stim-ulus at baseline and follow-up. We included 27 control subjects and 24 first-episode psychosis patients, who were free of delusions at follow-up, to calculate intra-SC between fMRI signals obtained during the two time points. In addition, we studied changes in functional connectivity at baseline and during the one-year follow-up using regions where delusion severity correlated with intra-SC as seeds. Results: The intra-SC correlated negatively with the baseline delusion severity in the bilateral anterior insula. In addition, we observed a subthreshold cluster in the anterior cingulate. These three regions constitute the cortical salience network (SN). Functional connectivity between the bilateral insula and the precuneus was weaker in the patients at baseline than in patients at follow-up or in control subjects at any time point. Conclusions: The results suggest that intra-SC is a powerful tool to study brain correlates of symptoms and highlight the role of the SN and internetwork dysconnectivity between the SN and the default mode network in delusions.Peer reviewe

Anti-neuronal anti-bodies in patients with early psychosis

It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n = 70) or a clinical high-risk for psychosis (n = 6) and controls (n = 34). We investigated the serum prevalence of 24 antineuronal autoantibodies: IgG antibodies for anti-N-methyl-D-aspartate-type glutamate receptor (anti-NMDAR), glutamate and gamma-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner. Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence. Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram.Peer reviewe

Activation of the motivation-related ventral striatum during delusional experience

Delusion is the most characteristic symptom of psychosis, occurring in almost all first-episode psychosis patients. The motivational salience hypothesis suggests delusion to originate from the experience of abnormal motivational salience. Whether the motivation-related brain circuitries are activated during the actual delusional experience remains, however, unknown. We used a forced-choice answering tree at random intervals during functional magnetic resonance imaging to capture delusional and non-delusional spontaneous experiences in patients with first-episode psychosis (n = 31) or clinical high-risk state (n = 7). The motivation-related brain regions were identified by an automated meta-analysis of 149 studies. Thirteen first-episode patients reported both delusional and non-delusional spontaneous experiences. In these patients, delusional experiences were related to stronger activation of the ventral striatum in both hemispheres. This activation overlapped with the most strongly motivation-related brain regions. These findings provide an empirical link between the actual delusional experience and the motivational salience hypothesis. Further use and development of the present methods in localizing the neurobiological basis of the most characteristic symptoms may be useful in the search for etiopathogenic pathways that result in psychotic disorders.Peer reviewe

Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder

Background: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. Methods: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. Results: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. Limitations: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. Conclusion: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.Peer reviewe

Aberrant Cortical Integration in First-Episode Psychosis During Natural Audiovisual Processing

BACKGROUND: Functional magnetic resonance imaging studies of psychotic disorders have reported both hypoactivity and hyperactivity in numerous brain regions. In line with the dysconnection hypothesis, these regions include cortical integrative hub regions. However, most earlier studies focused on a single cognitive function at a time, assessed by delivering artificial stimuli to patients with chronic psychosis. Thus, it remains unresolved whether these findings are present already in early psychosis and whether they translate to real-life-like conditions that require multisensory processing and integration. METHODS: Scenes from the movie Alice in Wonderland (2010) were shown to 51 patients with first-episode psychosis (16 women) and 32 community-based control subjects (17 women) during 3T functional magnetic resonance imaging. We compared intersubject correlation, a measure of similarity of brain signal time courses in each voxel, between the groups. We also quantified the hubness as the number of connections each region has. RESULTS: Intersubject correlation was significantly lower in patients with first-episode psychosis than in control subjects in the medial and lateral prefrontal, cingulate, precuneal, and parietotemporal regions, including the default mode network. Regional magnitude of between-group difference in intersubject correlation was associated with the hubness. CONCLUSIONS: Our findings provide novel evidence for the dysconnection hypothesis by showing that during complex real-life-like stimulation, the most prominent functional alterations in psychotic disorders relate to integrative brain functions. Presence of such abnormalities in first-episode psychosis rules out long-term effects of illness or medication. These methods can be used in further studies to map widespread hub alterations in a single functional magnetic resonance imaging session and link them to potential downstream and upstream pathways.Peer reviewe

Is It Possible to Predict the Future in First-Episode Psychosis?

The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features-like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis-are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognosticmarkers in FEP. Combination of differentmarkers inMLmodels with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.Peer reviewe