Multimodal prediction of the need of clozapine in treatment resistant schizophrenia; a pilot study in first-episode psychosis.

As many as one third of the patients diagnosed with schizophrenia do not respond to first-line antipsychotic medication. This group may benefit from the atypical antipsychotic medication clozapine, but initiation of treatment is often delayed, which may worsen prognosis. Predicting which patients do not respond to traditional antipsychotic medication at the onset of symptoms would provide fast-tracked treatment for this group of patients.

FreeSurfer 7 quality control: Key problem areas and importance of manual corrections.

We have studied the effects of manual quality control of brain Magnetic Resonance Imaging (MRI) images processed with Freesurfer. T1 images of first episode psychosis patients (N = 60) and healthy controls (N = 41) were inspected for gray matter boundary errors. The errors were fixed, and the effects of error correction on brain volume, thickness, and surface area were measured.

Hippocampus-Centered Network Is Associated With Positive Symptom Alleviation in Patients With First-Episode Psychosis.

Background: Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non-stimulus-related) neural processes.

Depression core network-based individualized targeting for transcranial magnetic stimulation.

Background: Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for major depressive disorder (MDD). Recent attempts to improve TMS efficacy by individually targeting DLPFC subregions that are functionally connected to the subgenual anterior cingulate cortex (sgACC) appear promising. However, sgACC covers only a small subset of core MDD-related areas.

Connectivity alterations of mesostriatal pathways in first episode psychosis.

Background And Hypothesis: Pathogenic understanding of the psychotic disorders converges on regulation of dopaminergic signaling in mesostriatocortical pathways. Functional connectivity of the mesostriatal pathways may inform us of the neuronal networks involved.

Study Design: This longitudinal study of first episode psychosis (FEP) (49 patients, 43 controls) employed seed-based functional connectivity analyses of fMRI data collected during a naturalistic movie stimulus.

Associations between acceptance of the implausible bias, theory of mind and delusions in first-episode psychosis patients; A longitudinal study.

Multiple different cognitive biases, among them the liberal acceptance (LA) bias, have been suggested to contribute to reality distortion in psychotic disorders. Earlier studies have been cross-sectional and considered a limited set of cognitive correlates of psychosis, thus the relationship between LA bias and psychosis remains poorly known. We studied a similar bias (acceptance of the implausible (AOI)) in 62 first-episode psychosis (FEP) patients and 62 control subjects, who watched movie scenes with varying degrees of realism and were asked to evaluate the probability of these events occurring in real life.

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.

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.

Delineating insight-processing-related functional activations in the precuneus in first-episode psychosis patients.

Poor insight is a central characteristic of psychotic disorders, and it has been suggested to result from a general dysfunction in self-reflection. However, brain processing of clinical insight and more general self-reflection has not been directly compared. We compared tasks on (1) self-reflection on psychosis-related mental functioning (clinical insight, in patients only), (2) self-reflection on mental functioning unrelated to psychosis (general metacognition), and (3) semantic control during blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging with 19 first-episode psychosis patients and 24 control participants.

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.

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.

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.

Immunomodulatory effects of antipsychotic treatment on gene expression in first-episode psychosis.

Previous studies suggest immunological alterations in patients with first-episode psychosis (FEP). Some studies show that antipsychotic compounds may cause immunomodulatory effects. To evaluate the immunological changes and the possible immunomodulatory effects in FEP, we recruited patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, from the catchment area of the Helsinki University Hospital and the City of Helsinki, Finland.

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.

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.

Connectivity of the precuneus-posterior cingulate cortex with the anterior cingulate cortex-medial prefrontal cortex differs consistently between control subjects and first-episode psychosis patients during a movie stimulus.

Background: Functional connectivity is altered in psychotic disorders. Multiple findings concentrate on the default mode network, anchored on the precuneus-posterior cingulate cortex (PC-PCC). However, the nature of the alterations varies between studies and connectivity alterations have not been studied during an ecologically valid natural stimulus.

Single dose of mirtazapine modulates whole-brain functional connectivity during emotional narrative processing.

The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI).

The interaction of emotion and pain in the insula and secondary somatosensory cortex.

Pain is processed in a large neural network that partially overlaps structures involved in emotion processing. Despite the fact that pain and emotion are known to share neural regions and interact in numerous clinical conditions, relatively little is known about the interaction of pain and emotion at the neural level. This study on healthy adults aimed to investigate the interaction between negative and positive emotional stimuli and experimental pain in an essential pain processing network.

A single dose of mirtazapine attenuates neural responses to self-referential processing.

Increased self-focus is a core factor in the psychopathology of depression. Cortical midline structures (CMS) are implicated in the neurobiology of self, depression and antidepressant treatment response. Mirtazapine, an antidepressant that increases serotonin and norepinephrine release, enhances processing of positive and attenuates processing of negative emotional information in healthy volunteers after a single dose.

Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie.

Altered activation of innate immunity associates with white matter volume and diffusion in first-episode psychosis.

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later.

Supernatural believers attribute more intentions to random movement than skeptics: an fMRI study.

A host of research has attempted to explain why some believe in the supernatural and some do not. One suggested explanation for commonly held supernatural beliefs is that they are a by-product of theory of mind (ToM) processing. However, this does not explain why skeptics with intact ToM processes do not believe.

Association of stigma resistance with emotion regulation - functional magnetic resonance imaging and neuropsychological findings.

Background: [corrected] Personal characteristics contribute to whether negative attitudes in society are internalized as deteriorating self-stigma. Studies in healthy subjects suggest that resilience is associated with the regulation of amygdala activation by the medial prefrontal cortex (mPFC), but little is known about the factors that contribute to individual stigma resistance in psychiatric patients.

Methods: We assessed stigma (by measuring association strengths between social inferiority and schizophrenia by an implicit association test) in 20 patients with schizophrenia and in 16 age- and sex-matched healthy control subjects.

Is it just a brick wall or a sign from the universe? An fMRI study of supernatural believers and skeptics.

We examined with functional magnetic resonance imaging the brain activity of 12 supernatural believers and 11 skeptics who first imagined themselves in critical life situations (e.g. problems in intimate relationships) and then watched emotionally charged pictures of lifeless objects and scenery (e.

Association of poor insight in schizophrenia with structure and function of cortical midline structures and frontopolar cortex.

Background: Poor insight is a central characteristic of psychosis and schizophrenia. Accumulating evidence indicates that cortical midline structures (CMS) and frontopolar cortex (FPC), both of which are associated with insight-related processing in healthy subjects, are among the most affected brain structures in schizophrenia. However, the hypothesis that direct associations between function of these brain regions and poor insight in schizophrenia exist has not been tested previously.