The neurophenomenology of early psychosis: An integrative empirical study.

BACKGROUND: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model. METHODS: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience. RESULTS: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores. DISCUSSION: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant constructs such as temporal processing, intermodal/multisensory integration, and hierarchical predictive processing. The cross-sectional data reported here will be expanded with longitudinal analysis in subsequent reports. These data and other related recent research show an emerging picture of neuro-features of core phenomenological aspects of schizophrenia spectrum disorders beyond surface-level psychotic symptoms.

Can schizophrenia be predicted on the basis of a symptom? A psychopathological appraisal of early detection research in schizophrenia.

Predictive prospective studies of schizophrenia date back to the late 1950s. At the turn of the Millennium, an Australian research group initiated programs of early detection of schizophrenia and early therapeutic intervention. The theoretical foundations of early schizophrenia detection usually remain unaddressed. In this paper, we focus on the issue of prediction of future schizophrenia in the general population on the basis of a symptomatic picture. Several notions used in this research program such as disease, symptom, and clinical staging derive from a medical model, which in our view is not entirely adequate for grasping the nature of schizophrenia. Schizophrenia is a spectrum of disorders with a shared core Gestalt comprising dis-order of selfhood and intersubjectivity. This core Gestalt has manifold manifestations, often predominantly in the existential or experiential domain. It is not feasible to apply medical concepts to this symptomatically poorly demarcated spectrum for which we do not know robust biological validators. Moreover, there is increasing evidence that the current DSM and ICD criteria of schizophrenia distort the original concept of schizophrenia and are formulated on a very high severity level. This often results in incorrect diagnoses of young help-seeking patients. In sum, it seems more appropriate to detect psychosis among already help-seeking patients than to implement detection programs in the general population. We discuss a reorientation of psychiatry towards more refined psychopathological knowledge and assessment that are needed in order to optimize the treatment of young help-seeking patients.

Exploring social cognition in schizophrenia.

The aim of the study was to compare social cognition between groups of patients diagnosed with schizophrenia and healthy controls and to replicate two previous studies using tests of social cognition that may be particularly sensitive to social cognitive deficits in schizophrenia. Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 11 "imaginary conversation (i.e., theory of mind)" items, 10 "psychological understanding" items, and 10 "practical understanding" items. Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence and neuropsychological test performance. Healthy controls performed better than patients on all types of social cognitive tests, particularly on "psychological understanding." However, after adjusting for intelligence and neuropsychological test performance, all group differences became nonsignificant. When intelligence and global cognitive functioning is taken into account, schizophrenia patients and healthy controls perform similarly on social cognitive tests.

Temporal persistence of anomalous self-experience: A 5years follow-up.

BACKGROUND: The concept of self-disorders in schizophrenia has gained substantial interest and it has now been established empirically that self-disorders aggregate in schizophrenia-spectrum disorders but not in other mental disorders or in healthy controls. Yet, the issue of temporal persistence has not been addressed. AIM: The aim of this study is to examine the temporal persistence of self-disorders. METHODS: 96 first admission patients were thoroughly assessed for psychopathology including SD at baseline and again 5years later. We created a 25-item self-disorder scale which was used both at baseline and follow-up to assess self-disorders. The scale was a pre-cursor of the later published EASE-scale. Additionally, we examined the development of positive and negative syndromes and of the Global Assessment of Functioning (GAF). RESULTS: There was a high correlation between self-disorders at baseline and at follow-up, and the majority of the items in self-disorders scale showed equal proportions between baseline and follow-up. CONCLUSION: Self-disturbances showed a high level of persistence at 5-year follow-up.

The phenomenology of emotion experience in first-episode psychosis.

BACKGROUND: Although it has been suggested that disturbances in emotion experience and regulation play a central role in the aetiology and psychopathology of schizophrenia spectrum disorders, the phenomenology of emotion experience in schizophrenia remains under-researched. SAMPLING AND METHODS: In-depth interviews were conducted twice with each of the 20 participants (firstly at admission and secondly 6 months later). Data collection and analysis were guided by the principles of phenomenological study of lived experience. RESULTS: The emotion experiences described by our participants vary greatly in both quality and intensity, but appear to have a common phenomenology. Anxiety is reported as the basic emotion which buffers, transforms and sometimes supplants all others. Emotions in general are experienced as foreign, unstable and perturbing, thereby contributing greatly to feelings of ambivalence, perplexity and an unstable sense of self in general. CONCLUSIONS: The findings of this study have important therapeutic and theoretical implications because they suggest that emotion experiences in schizophrenia spectrum disorders may underlie a wide range of psychopathological phenomena in both the cognitive and social functioning domains. Due to the relatively small sample size and its selection from psychotherapeutic units, the results may not be generalizable to all schizophrenia patients.

Cognitive-behavioral therapy for schizophrenia: a critical evaluation of its theoretical framework from a clinical-phenomenological perspective.

BACKGROUND: Cognitive-behavioral therapy (CBT) has played an increasingly important role in psychotherapy for schizophrenia since the 1990s, but it has also encountered many theoretical and practical limitations. For example, methodologically rigorous meta-analyses have recently found only modest overall effect sizes of CBT treatment, and therefore questions have emerged about forwhat and for whom it actually works. METHOD: The focus of the present paper is to elucidate the theoretical assumptions underlying CBT for schizophrenia and to examine their consistency with abnormalities of experience and self-awareness frequently reported by schizophrenia patients and systematically studied in phenomenological psychopathology from the beginning of the 20th century. RESULTS: We argue that a strong theoretical emphasis on cognitive appraisals with only subsidiary attention devoted to affective and behavioral processes - as is characteristic of many forms of CBT - cannot satisfactorily account for the complex subjective experiences of schizophrenia patients. We further argue that certain theoretical strategies widely employed in CBT to explore and explain mental disorders, which involve atomization and, at times, a reification of mental phenomena, can be problematic and may result in a loss of explanatory potential. Finally, we provide a detailed account of how negative symptoms and delusions are conceptualized in CBT and consider the question of how these concepts fit the actual phenomenology of schizophrenia. CONCLUSION: We suggest that further advancement of CBT theory and practice can benefit from a dialogue with phenomenological psychiatry in the search for effective psychotherapeutic strategies for schizophrenia patients.

Disturbances of basic self and prodromal symptoms among non-psychotic help-seeking adolescents.

BACKGROUND: The goal of this study was to explore the notion that anomalies of self-experience (ASE) are a core, 'not-yet-psychotic' clinical phenotype of emerging schizophrenia and its spectrum. Method To accomplish this goal, we examined the relationship between ASE and commonly accepted risk markers in a sample of 87 help-seeking, non-psychotic adolescents (aged 14-18 years). ASE were assessed with the Examination of Anomalous Self-Experience (EASE), subclinical psychotic symptoms were assessed with the Prodromal Questionnaire and the Structured Interview for Prodromal Syndromes, deterioration in psychosocial functioning was assessed with the Social and Role Functioning Scales, and level of distress with the Mood and Anxiety Symptoms Questionnaire. RESULTS: About 82 participants completed the entire EASE interview. The number of participants who reported ASE at a clinically meaningful level (n = 18, 22%) was smaller than that who met diagnostic criteria for a prodromal syndrome (n = 28, 34%). The degree of overlap between the two conditions was moderate but statistically significant (χ2 (1) = 7.01, p = 0.008). An exploratory factor analysis revealed that ASE load on a different factor than prodromal symptoms and deterioration in functioning, but that there is a moderate correlation between the three factors. CONCLUSIONS: These results suggest that ASE are prevalent among non-psychotic help-seeking adolescents, yet at a considerably lower rate than prodromal symptoms. In addition, they suggest that ASE and prodromal symptoms constitute distinct but moderately related dimensions of potential risk. Taken together, they provide preliminary support for the clinical usefulness of supplementing and refining the methods of early detection of risk with assessment of ASE.

Intellectual functioning and the long-term course of schizophrenia-spectrum illness.

BACKGROUND: Recent neurodevelopmental models of schizophrenia, together with substantial evidence of neurocognitive dysfunction among people with schizophrenia, have led to a widespread view that general cognitive deficits are a central aspect of schizophrenic pathology. However, the temporal relationships between intellectual functioning and schizophrenia-spectrum illness remain unclear. METHOD: Longitudinal data from the Copenhagen High-Risk Project (CHRP) were used to evaluate the importance of intellectual functioning in the prediction of diagnostic and functional outcomes associated with the schizophrenia spectrum. The effect of spectrum illness on intellectual and educational performance was also evaluated. The sample consisted of 311 Danish participants: 99 at low risk, 155 at high risk, and 57 at super-high risk for schizophrenia. Participants were given intellectual [Weschler's Intelligence Scale for Children (WISC)/Weschler's Adult Intelligence Scale (WAIS)] assessments at mean ages of 15 and 24 years, and diagnostic and functional assessments at mean ages 24 and 42 years. RESULTS: Intellectual functioning was found to have no predictive relationship to later psychosis or spectrum personality, and minimal to no direct relationship to later measures of work/independent living, psychiatric treatment, and overall severity. No decline in intellectual functioning was associated with either psychosis or spectrum personality. CONCLUSIONS: These largely negative findings are discussed in the light of strong predictive relationships existing between genetic risk, diagnosis and functional outcomes. The pattern of predictive relationships suggests that overall cognitive functioning may play less of a role in schizophrenia-spectrum pathology than is widely believed, at least among populations with an evident family history of schizophrenia.

What is bizarre in bizarre delusions? A critical review.

Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) treats the presence of bizarre delusions (BD) as the heaviest-weighted clinical criterion of schizophrenia. Although BD play a major role in contemporary diagnostic systems, only a few empirical studies explore this issue. These studies provide highly heterogenous results because they are based on different experimental paradigms, in terms of definition, clinical sample, and number of raters. Here, we first discuss the psychopathological sources of the concept of BD, which were initially described as either nonsensical or incomprehensible. Then, we provide a critical review of contemporary studies on the reliability of BD and their methodological and conceptual limitations. Current approaches have focused intensely on BD's reliability and have defined BD strictly in terms of delusional content--mainly in terms of the physical impossibility or the cultural or historical incomprehensibility of the delusional claims. These approaches have neglected formal features of experience that underlie BD and the crucial issue of the nature and validity of BD. In the discussion, we argue that clinical diagnosis of BD cannot be limited to delusional contents alone and requires taking into account the subjective side of BD (how altered experience manifests itself) as well as the conditions of intersubjective encounter (how BD are expressed to and experienced by the clinician). The notion of "bizarreness" in schizophrenia is not purely theoretical; it has practical relevance for the therapeutic encounter and implications on further empirical research and on diagnostic approaches.

Pre-morbid IQ in mental disorders: a Danish draft-board study of 7486 psychiatric patients.

BACKGROUND: Longitudinal studies indicate that future schizophrenia patients exhibit lower IQ than healthy controls. Recent studies suggest that future patients with other mental illnesses obtain lower pre-morbid IQ. The aims of this study were to compare pre-morbid IQ among five diagnostic categories and normal controls, to examine the distribution of pre-morbid IQ, and to investigate the relationship between pre-morbid IQ and risk of mental illness. METHOD: A total of 7486 individuals hospitalized with psychiatric disease and 20 531 controls. IQ was measured at the draft board and hospital diagnoses [schizophrenia (Sz), non-schizophrenic, non-affective psychoses (NSAP), affective (AD), personality (PD) and neurotic/stress disorders (ND)] were followed up to ages 43-54 years. Individuals hospitalized < or = 1 year after appearing before the draft board were excluded. RESULTS: All future patients obtained significantly lower pre-morbid IQ than controls (3-7 IQ points), AD had the highest IQ and PD the lowest. In each diagnostic category, decreasing IQ was associated with an increasing risk of becoming a patient [odds ratios (ORs) 0.5-2.5 over the full IQ spectrum]. IQ distributions was nearly normal and uni-modal. CONCLUSIONS: IQ deficits in each diagnostic category may reflect different functional patterns and temporal vicissitudes of the specific pathogenetic processes involved in different mental disorders.

Diagnostic agreement of schizophrenia spectrum disorders among chronic patients with functional psychoses.

BACKGROUND: To investigate whether diagnostic agreement across different diagnostic systems improves in a sample of chronic patients suffering from functional psychosis compared to first-admitted patients. SAMPLING AND METHODS: Among 353 patients with a history of functional psychosis, a subset of 100 individuals (35 women and 65 men) were randomly sampled and assessed using the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT). Based on the OPCRIT diagnoses the subjects suffering from schizophrenia and schizophrenia spectrum disorders according to seven diagnostic systems were identified. Diagnostic agreement was assessed using unweighted kappa-statistics and pairwise concordance rates (CR). RESULTS: High diagnostic agreement of schizophrenia was observed across the ICD-10 and DSM systems (CR >0.70, kappa >0.70), which all had a significantly lower concordance to the St. Louis Criteria (SLC), research diagnostic criteria and Schneider's first rank symptoms (FRS) (0.32< CR <0.66; -0.10< kappa <0.51). Agreement on schizophrenia across all systems was observed for one fourth of the subjects. Elimination of the diagnostic impact of 'co-occurrence of psychotic and affective symptoms' excluded FRS standalone individuals from the sample, increased overall homogeneity and resulted in a dichotomized sample according to SLC (46 positive vs. 47 negative). SLC status could be predicted in 78% of cases by four items relating to family history and psychosocial function previous to the onset of illness. Similarly high pairwise CR were observed for schizophrenia spectrum disorders across all diagnostic systems. CONCLUSIONS: This study demonstrates that diagnostic agreement is higher among chronic patients than that observed in subjects with a recent onset of psychosis, although considerable discordance is also observed in this chronic sample. However, the discordance among chronic patients with functional psychosis largely derives from the different emphasis that diagnostic systems place on co-occurrence of psychotic and affective symptoms. This may have serious epistemological consequences, thus underlining the conventional nature of the present schizophrenia diagnoses and the need for biologically founded diagnostic criteria.

Schizoaffective disorder-- the reliability of its clinical diagnostic use.

OBJECTIVE: Patients with psychoses often suffer from affective symptoms. The originally broad concept of schizoaffective disorder (SAD) has been significantly narrowed, transformed into a convoluted set of criteria both in the ICD-10 and DSM-IV. We examined the reliability of the clinical use of this diagnosis in university settings. METHOD: All patients discharged from two university hospitals in Copenhagen in year 2002 with a diagnosis of ICD-10 SAD (n = 59) were re-evaluated using the Operational Criteria (OPCRIT) checklist expanded by additional items and applied to hospital chart material. Diagnoses were allocated by OPCRIT algorithm and by consensus of two psychiatrists. RESULTS: No patients fulfilled the SAD lifetime diagnosis according to DSM-IV criteria and the raters diagnosed only six patients as possible ICD-10 SAD. CONCLUSION: A moratorium on the clinical use of the SAD diagnosis is suggested.

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia.

Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, genetic variation in the ApoD is associated with long-term clinical outcome to antipsychotic treatment. We genotyped two single-nucleotide polymorphisms in the ApoD gene in 343 chronic patients with schizophrenia spectrum disorders (ICD-10) and 346 control subjects of Danish origin. We did not find ApoD alleles, genotypes or haplotypes to be associated with disease. However, we did find that long-term clinical outcome was associated with the ApoD polymorphism rs7659 (P = 0.041) following adjustment for lifetime clinical global impression, age at first admission and gender.

COMT haplotypes suggest P2 promoter region relevance for schizophrenia.

A recent study found, in a large sample of Ashkenazi Jews, a highly significant association between schizophrenia and a particular haplotype of three polymorphic sites in the catechol-O-methyl transferase, COMT, gene: an IVS 1 SNP (dbSNP rs737865), the exon 4 functional SNP (Val158Met, dbSNP rs165688), and a downstream SNP (dbSNP rs165599). Subsequently, this haplotype was shown to be associated with lower levels of COMT cDNA derived from normal cortical brain tissue, most likely due to cis-acting element(s). As a first step toward evaluating whether this haplotype may be relevant to schizophrenia in populations other than Ashkenazi Jews, we have studied this haplotype in 38 populations representing all major regions of the world. Adding to our previous data on four polymorphic sites in the COMT gene, including the Val158Met polymorphism, we have typed the IVS 1 rs737865 and 3' rs615599 sites and also included a novel IVS 1 indel polymorphism, yielding seven-site haplotype frequencies for normal individuals in the 38 globally distributed populations, including a sample of Ashkenazi Jews. We report that the schizophrenia-associated haplotype is significantly heterogeneous in populations worldwide. The three-site, schizophrenia-associated haplotype frequencies range from 0% in South America to 37.1% in Southwest Asia, despite the fact that schizophrenia occurs at roughly equal frequency around the world. Assuming that the published associations found between the exon 4 Val158Met SNP and schizophrenia are due to linkage disequilibrium, these new haplotype data support the hypothesis of a relevant cis variant linked to the rs737865 site, possibly just upstream in the P2 promoter driving transcription of the predominant form of COMT in the brain. The previously described HindIII restriction site polymorphism, located within the P2 promoter, varies within all populations and may provide essential information in future studies of schizophrenia.

Anomalies of subjective experience in schizophrenia and psychotic bipolar illness.

OBJECTIVE: Contemporary psychopathology, as a result of behaviourally dominated epistemological stance, downplays anomalies of the patient's subjectivity. This neglect has probably deleterious consequences for research in the causes and the boundaries of the schizophrenia spectrum conditions. The purpose of this study is to explore frequency of qualitative, not-yet-psychotic, anomalies of subjective experience in patients with residual schizophrenia and psychotic bipolar illness in remission. METHOD: The patients were examined with the Danish version of the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Anomalies of experience were condensed into rational scales with good internal consistencies. RESULTS: Diagnosis of schizophrenia was associated with elevated scores on the scales measuring perplexity (loss of immediate meaning), disorders of perception, disorders of self-awareness, and marginally so, disorders of cognition. CONCLUSION: These findings, in conjunction with those from other, methodologically similar studies, suggest that certain anomalies of subjective experience aggregate significantly in schizophrenia. These experiential anomalies appear to be relevant for early differential diagnosis and therefore potentially useful in the preonset detection of the schizophrenia spectrum illness.

Schizophrenia, neurodevelopment and corpus callosum.

The Zeitgeist favors an interpretation of schizophrenia as a condition of abnormal connectivity of cortical neurons, particularly in the prefrontal and temporal cortex. The available evidence points to reduced connectivity, a possible consequence of excessive synaptic pruning in development. A decreased thalamic input to the cerebral cortex appears likely, and developmental studies predict that this decrease should entail a secondary loss of both long- and short-range cortico-cortical connections, including connections between the hemispheres. Indeed, morphological, electrophysiological and neuropsychological studies over the last two decades suggest that the callosal connections are altered in schizophrenics. However, the alterations are subtle and sometimes inconsistent across studies, and need to be investigated further with new methodologies.

Visual binding abilities in the initial and advanced stages of schizophrenia.

OBJECTIVE: The study tests the hypothesis that intramodal visual binding is disturbed in schizophrenia and should be detectable in all illness stages as a stable trait marker. METHOD: Three groups of patients (rehospitalized chronic schizophrenic, first admitted schizophrenic and schizotypal patients believed to be suffering from a pre-schizophrenic prodrome) and a group of normal control subjects were tested on three tasks targeting visual 'binding' abilities (Muller-Lyer's illusion and two figure detection tasks) in addition to control parameters such as reaction time, visual selective attention, Raven's test and two conventional cortical tasks of spatial working memory (SWM) and a global local test. RESULTS: Chronic patients had a decreased performance on the binding tests. Unexpectedly, the prodromal group exhibited an enhanced Gestalt extraction on these tests compared both to schizophrenic patients and to healthy subjects. Furthermore, chronic schizophrenia was associated with a poor performance on cortical tests of SWM, global local and on Raven. This association appears to be mediated by or linked to the chronicity of the illness. CONCLUSION: The study confirms a variety of neurocognitive deficits in schizophrenia which, however, in this sample seem to be linked to chronicity of illness. However, certain aspects of visual processing concerned with Gestalt extraction deserve attention as potential vulnerability- or prodrome- indicators. The initial hypothesis of the study is rejected.