Schizophrenia research
January 1, 2014
Louis A Sass
216 citations
The ipseity-disturbance or self-disorder hypothesis proposes that a disruption of minimal or core self-experience is central to schizophrenia. This paper reviews and refines that model, recommending research into what is distinctive about the schizophrenia spectrum, the internal structure of self-disturbance, and testable pathways for pathogenesis and therapy. Exploratory comparisons of self-anomalies in mania, psychotic depression, depersonalization disorder, and intense introspection found similarities—such as alienation of thoughts and bodily experiences, fading of self and world—but also key differences: outside schizophrenia, severe erosion of minimal self-experience or confusion of self and other was absent. These findings support and refine the model. Future work should treat self-experience as an independent variable to study its links with cognition, affect, expression, and neural functioning.
Schizophrenia research
January 1, 2014
Ji-Won Hur, Jun Soo Kwon, Tae Young Lee et al.
165 citations
People with schizophrenia experience significant disturbances in the minimal self, particularly in the sense of body ownership and sense of agency. A meta-analysis of 25 studies (690 patients, 979 controls) found a moderate overall effect (Hedge's g = 0.51) indicating basic self-disturbance. Body ownership showed a large effect (0.91), agency a moderate effect (0.49), and self-reported subjective experiences a moderate effect (0.57). The disturbed sense of agency suggests exaggerated self-consciousness rather than a diminished sense of self. Results remained significant after correcting for publication bias.
Schizophrenia research
September 1, 2023
Angelica M Silva, Roberto Limongi, Michael Mackinley et al.
49 citations
Syntactic complexity, specifically the number of nominal subjects per clause in spoken language, declines in the six months following a first episode of psychosis among individuals who later receive a schizophrenia diagnosis. In a cohort of 26 first-episode psychosis patients and 12 healthy controls, automated analysis of speech samples from the Thought and Language Index interview showed that a 50% decrease in mean nominal subjects per clause after six months was explained by the presence of first-episode psychosis with 95.4% probability. Among those with psychosis, a 30% decrease predicted a schizophrenia diagnosis with 95% probability. This longitudinal decline distinguishes schizophrenia from other psychotic disorders.
Schizophrenia research
April 1, 2020
Karl Erik Sandsten, Julie Nordgaard, Troels Wesenberg Kjaer et al.
45 citations
Patients with schizophrenia often report not recognizing themselves in the mirror, a form of self-alienation. Using the Enfacement Illusion, a multisensory paradigm that manipulates self-other facial recognition through visuo-tactile stimulation, this study compared 35 patients with schizophrenia and 35 healthy matched controls. At baseline, patients showed a significant skew toward perceiving another person's face as their own. After both synchronous and asynchronous visuo-tactile stimulation, patients' self-recognition was significantly altered compared to baseline. In contrast, healthy controls only showed altered self-recognition after synchronous stimulation, consistent with prior research. The findings suggest that temporal factors in multisensory integration may contribute to altered self-recognition in schizophrenia.
Schizophrenia research
December 1, 2015
Louis A Sass, Juan P Borda
44 citations
Schizophrenia involves a core disturbance in the sense of self (disturbed ipseity), which can be traced to a primary disruption in how the brain integrates perceptions from different senses (perceptual dys-integration). This article describes secondary phenomenological alterations that arise either as downstream consequences of that primary disruption or as defensive compensations. These include heightened self-consciousness (hyperreflexivity), a diminished sense of self-presence, and a weakened grip on one's field of awareness. These secondary experiences vary greatly between individuals and over time, and they become more pronounced in adolescence due to developing prefrontal lobe capacities. This variability may explain much of the clinical diversity in schizophrenia while still pointing to a common underlying disturbance.
Schizophrenia research
December 19, 1997
J Ciprian-Ollivier, M G Cetkovich-Bakmas
34 citations
The transmethylation hypothesis of schizophrenia proposes that an inborn error of metabolism causes serotonin or tryptamine to gain extra methyl groups, forming hallucinogenic methylated indolealkyalamines (MIAs) such as bufotenin and DMT. Studies examining MIA excretion in psychotic patients and controls have yielded contradictory results: some show elevated levels in patients with schizophrenia, others do not. The hallucinogenic brew ayahuasca may model how such compounds produce psychotic symptoms. Certain perceptual disturbances in schizophrenia could contribute to deterioration and negative symptoms. Further research into MIA neurophysiology and their role in psychoses is needed.
Schizophrenia research
February 1, 2019
Alexandre Andrade Loch, Elder Lanzani Freitas, Lucas Hortêncio et al.
31 citations
Organizational religious activity—such as attending churches or temples—is positively linked to perceptual abnormalities and hallucinations in individuals at ultra-high risk for psychosis, and also to lower ideational richness. Intrinsic religious activity is negatively correlated with suspiciousness, while non-organizational religious activity is associated with higher ideational richness. These findings come from 79 ultra-high-risk and 110 control individuals in Brazil, where religious syncretism and Spiritism may normalize hallucinatory experiences. The results suggest that subclinical psychosis may lead people to use religious organizations to cope with hallucinations, and highlight the need to assess religion and cultural context when studying psychosis risk.
Schizophrenia research
March 1, 2024
Josef Parnas, Janne-Elin Yttri, Annick Urfer-Parnas
28 citations
Auditory verbal hallucinations in schizophrenia differ from ordinary perception in several ways, and only a minority of patients experience them as localized externally. The official definition of hallucinations as a perception without object does not fit the lived experience of these voices. Auditory verbal hallucinations are associated with anomalies of subjective experience known as self-disorders, and they should be understood as a product of self-fragmentation. This has implications for how hallucinations are defined, how clinical interviews are conducted, how psychotic states are conceptualized, and what targets are pursued in pathogenetic research.
Schizophrenia research
December 1, 2018
Minji Bang, Hae-Jeong Park, Chongwon Pae et al.
23 citations
Minimal self-disturbance, a core feature of schizophrenia, is linked to altered connectivity between the cerebellum and the brain's default mode network. In a resting-state fMRI study, individuals at ultra-high risk for psychosis and first-episode schizophrenia patients showed reduced cerebellar functional connectivity with the presupplementary motor area, anterior prefrontal cortex, and precuneus compared to healthy controls. Ultra-high-risk individuals exhibited intermediate reductions. Minimal self-disturbance severity, similar in both clinical groups, correlated with these connectivity patterns, though the associations differed between groups. Aberrant cerebro-cerebellar connectivity may offer insights into schizophrenia's core pathology and help predict psychosis in at-risk individuals.
Schizophrenia research
July 1, 2024
Vittorio Gallese, Martina Ardizzi, Francesca Ferroni
18 citations
Schizophrenia is often explained by neurotransmitter or genetic abnormalities, but an alternative view sees it as a disorder of the self, marked by anomalous self-experience and awareness. This perspective can guide empirical research into the bodily and neurobiological changes underlying the condition. Recent evidence on the bodily self—a minimal sense of self rooted in the body and its motor potentialities—is reviewed. Findings show that anomalies in brain-body functions, particularly multisensory integration and the differential processing of self- versus other-related bodily information, may disrupt self-experience and blur the self-other distinction in schizophrenia. These disruptions likely underlie the self-disorders characteristic of the syndrome.
Schizophrenia research
September 1, 2019
Luis Madeira, Elizabeth Pienkos, Teresa Filipe et al.
18 citations
People with first-episode psychosis often experience profound changes in how they perceive the world around them—including alterations in space, time, and other people—alongside disturbances in their sense of self. In a study comparing 24 outpatients with first-episode psychosis to 24 healthy controls, those with psychosis scored significantly higher on both the Examination of Anomalous World Experience (EAWE) and the Examination of Anomalous Self Experience (EASE). Scores on the two measures were strongly correlated, even after accounting for overlapping items. The types of world-experience anomalies varied widely among patients. These findings suggest that anomalous world experiences are a relevant feature of first-episode psychosis and may be linked to the self-disturbances thought to underlie schizophrenia spectrum disorders.
Schizophrenia research
August 1, 2024
Josef Parnas, Karl Erik Sandsten
17 citations
Schizophrenia's resistance to understanding its causes may stem from neglecting its characteristic overall pattern (Gestalt) of psychopathological structure. Disorders of selfhood play a crucial role in forming this Gestalt. A phenomenological account of the self is presented, followed by basic complaints in schizophrenia that reflect a disordered selfhood, often dating back to childhood. Characteristic features of schizophrenic psychosis include "double bookkeeping," where hallucinations, delusions, and double bookkeeping are all linked to instability of the self. Self-disorders play an important diagnostic role in encounters with patients. The article emphasizes the role of phenomenology in psychiatric research.
Schizophrenia research
October 1, 2024
Michele Poletti, Andrea Raballo
10 citations
A two-stage phenomenological-developmental model explains how early deficits in multisensory integration disrupt the formation of the Minimal Self in the first years of life, creating a schizotaxic vulnerability that later manifests as basic self-disorders and subjective anomalies characteristic of schizophrenia spectrum disorders. Self-disorders capture the experiential aspects of vulnerability to these disorders, emerge before major diagnostic symptoms, and are detectable in populations with familial risk.
Schizophrenia research
February 1, 2024
Andreas Rosén Rasmussen
8 citations
Disturbances of imagination were once discussed in schizophrenia research but have largely disappeared from mainstream psychopathology. Recent work suggests these phenomena may aid differential diagnosis and early psychosis detection. This paper reviews 20th-century psychopathological literature and recent neurocognitive studies on imagination disturbances and their role in symptom formation. It discusses empirical investigations of subjective anomalies of imagination in schizophrenia-spectrum disorders, proposing a clinical-phenomenological account linking these anomalies to basic self-disturbance. Patients' descriptions indicate that increased spatial articulation and instability of first-personal imaginative experience can contribute to delusions and hallucinations. A potential link between these subjective anomalies and source monitoring deficits is also explored.
Schizophrenia research
September 1, 2024
Ana Teresa Caliman-Fontes, Flávia Vieira, Gustavo C Leal et al.
7 citations
Catatonia, a condition recognized since the 1800s, remains difficult to diagnose and treat. A systematic review of 20 studies involving 25 patients who received ketamine or esketamine for catatonia found that 80% of patients responded to treatment and 44% achieved remission, with no worsening of catatonic or psychotic symptoms. Only one patient stopped treatment due to intolerable dissociative effects. Most patients were female (61.9%), with an average age of 44.4 years, and had underlying mood disorders. The evidence suggests ketamine may be effective for catatonia, even in patients with psychotic disorders, where it has traditionally been considered contraindicated. The authors advocate reevaluating this contraindication, noting potentially greater benefits for those with mood disorders.
Schizophrenia research
June 1, 2026
L Palaniyappan, V S Sreeraj, G Venkatasubramanian et al.
5 citations
Formal Thought Disorder (FTD) is strongly linked to poor outcomes and genetic risk in psychosis, yet it remains poorly defined and rarely measured in clinical practice. A systematic review of 50 years of assessment tools (16 rating scales, 32 factor analyses) reveals that research has treated FTD as a natural kind—a latent entity causing observable signs—but empirical evidence contradicts this. Construct definitions are radically heterogeneous, factor structures do not replicate at the item level, and no essential properties are universal. The authors propose measuring FTD as a Constituted Practical Entity: a probabilistic cluster of linguistic-cognitive features whose interaction produces communication failure, with no single feature necessary or sufficient. This framework reconciles FTD's multidimensional nature with measurement and recommends establishing consensus constituents, measuring their interactions, and developing computational tools.
Schizophrenia research
July 1, 2025
Antonia Meinhart, Annika Schmueser, Steffen Moritz et al.
4 citations
A systematic meta-review of 18 meta-analyses (up to 2572 participants) examined mindfulness- and acceptance-based interventions for people with schizophrenia spectrum disorders. At the end of treatment, significant small-to-large effects were found for overall symptoms, positive symptoms, negative symptoms, affective symptoms, social functioning, mindfulness, and acceptance. For example, 100% of mindfulness-based intervention meta-analyses reported significant improvement in overall symptoms (effect size g = -0.7), while 25% of acceptance-based intervention meta-analyses did. All meta-analyses were rated low or critically low in quality. The largest effects came from studies with mostly Chinese samples. The authors conclude that these interventions show promise but caution that methodological limitations and cultural factors need further study.
Schizophrenia research
June 2, 2025
Maria Chiara Piani, Martin Jandl, Thomas Koenig et al.
3 citations
Self-disorders, which disrupt the basic sense of being a conscious subject, are central to schizophrenia spectrum disorders. Using 7 Tesla fMRI, 27 patients and 32 healthy controls performed a trait-judgment task probing pre-reflective and reflective self-experience. Greater severity of self-disorders correlated with reduced activity in the rostral posterior cingulate cortex during the pre-reflective component. During reflective self-experience, healthy controls showed bilateral frontopolar cortex activation, while patients engaged the left caudate, right frontopolar cortex, and left language area, suggesting patients rely more on analytical networks and deeper brain structures rather than the interoceptive processes typical of healthy controls.
Schizophrenia research
April 1, 2025
Sofia de Almeida Queiroz, Linério Ribeiro de Novais Junior, Anita Beatriz Pacheco de Carvalho et al.
2 citations
In a rat model of schizophrenia induced by ketamine, cannabidiol (CBD) restored rearing behavior (a measure of exploratory activity) without causing anhedonia-like behavior, whereas risperidone further reduced rearing and induced anhedonia-like effects in control rats. CBD reversed ketamine-induced increases in myeloperoxidase activity in the prefrontal cortex and striatum and protein carbonyls in the hippocampus, while risperidone reduced protein carbonyls in the prefrontal cortex and lowered the nitrite/nitrate ratio in the hypothalamus. Both compounds reduced oxidative stress and neuroinflammation in the striatum, hippocampus, and prefrontal cortex, but CBD did so more broadly and without the side effects seen with risperidone. These findings suggest CBD's antipsychotic effects may stem from its antioxidant and anti-inflammatory properties.
Schizophrenia research
June 16, 2026
David Olivares-Berjaga, Natàlia Rodríguez, Albert Martínez-pinteño et al.
In a mouse model of schizophrenia induced by postnatal ketamine exposure, the mitochondrial protein VDAC1 was elevated in the prefrontal cortex, and this increase was partially reversed by treatment with JNJ-46356479, a modulator of metabotropic glutamate receptors. Higher VDAC1 levels correlated with a greater Bax/Bcl-2 ratio—indicating apoptotic imbalance—and with worse performance on tests of memory and social behavior. VDAC1 may serve as a marker of apoptotic dysfunction in schizophrenia, and glutamatergic modulation could represent a therapeutic strategy targeting mitochondrial pathology.
Schizophrenia research
May 1, 2022
Andreas Rosén Rasmussen, Josef Parnas
Obsessive-compulsive symptoms are common in schizophrenia-spectrum disorders and can complicate diagnosis, especially in first-contact patients. Classic psychopathology defines true obsessions in obsessive-compulsive disorder (OCD) as intrusions with intact resistance and insight, while in schizophrenia, pseudo-obsessive-compulsive phenomena lack resistance and align with thought disorder or catatonia. Current diagnostic systems use broader, vaguer definitions, causing overlap with delusions and other anomalies. The authors examine links between obsessive-compulsive phenomena and disturbances of basic experience in schizophrenia-spectrum disorders, suggesting these experiential alterations aid differential diagnosis and early detection.