'An experience of meaning': A 20-year prospective analysis of delusional realities in schizophrenia and affective psychoses.

Delusions are transdiagnostic and heterogeneous phenomena with varying degrees of intensity, stability, and dimensional attributes where the boundaries between everyday beliefs and delusional beliefs can be experienced as clearly demarcated, fuzzy, or indistinguishable. This highlights the difficulty in defining delusional realities. All individuals in the current study were evaluated at index and at least one of six subsequential follow-ups over 20 years in the Chicago Longitudinal Study. We assessed 16 distinct delusions categorized as thought or thematic delusions. We also examined the probability of recurrence and the relationships between delusions and hallucinations, depression, anxiety, and negative symptoms. The sample consisted of 262 individuals with schizophrenia vs. affective psychosis. Thought delusions were significantly different between groups at all follow-up evaluations except the 20-year timepoint. Thematic delusions were more common than thought delusions and show a significant decreasing pattern. In general, delusional content varied over time. Referential, persecutory, and thought dissemination delusions show the highest probability of recurrence. Hallucinations were the strongest indicator for thought, thematic, and overall delusions. The formation and maintenance of delusions were conceptualized as a multimodal construct consisting of sensory, perceptual, emotional, social, and somatic embodiment of an "experience of meanings". Given the significant associations between delusions and hallucinations, future work incorporating participatory research is needed to better define and align subjective and objective perspectives. Our research also points to the need for future clinical interventions that specifically evaluate and target the coexistence and entanglement of delusions and hallucinations.

'Are these my thoughts?': A 20-year prospective study of thought insertion, thought withdrawal, thought broadcasting, and their relationship to auditory verbal hallucinations.

The co-occurrence of delusions and other symptoms at the onset of psychosis is a challenge for theories about the aetiology of psychosis. This paper explores the relatedness of delusions about the experience of thinking (thought insertion, thought withdrawal, and thought broadcasting) and auditory verbal hallucinations by describing their trajectories over a 20-year period in individuals diagnosed with schizophrenia, affective and other psychosis, and unipolar depression nonpsychosis. The sample consisted of 407 participants who were recruited at index hospitalization and evaluated over six follow-ups over 20 years. The symptom structure associated with thought insertion included auditory verbal hallucinations, somatic hallucinations, other hallucinations, delusions of thought-dissemination, delusions of control, delusion of self-depreciation, depersonalization and anxiety. The symptom constellation of thought withdrawal included somatic hallucinations, other hallucinations, delusions of thought dissemination, delusions of control, sexual delusions, depersonalization, negative symptoms, depression, and anxiety. The symptom constellation of thought broadcasting included auditory verbal hallucinations, somatic hallucinations, delusions of thought-dissemination, delusion of self-depreciation, fantastic delusions, sexual delusions, and depersonalization. Auditory verbal hallucinations and delusions of self-depreciation were significantly associated with both thought insertion and thought broadcasting. Thought insertion and thought withdrawal were significantly associated with other hallucinations, delusions of control, and anxiety; thought withdrawal and thought broadcasting were significantly related to sexual delusions. We hypothesize that specific symptom constellations over time might be explained as the product of pseudo-coherent realities created to give meaning to the experience of the world and the self of individuals in psychosis based on both prior top-down and ongoing bottom-up elements.

Twenty-year effects of antipsychotics in schizophrenia and affective psychotic disorders.

BACKGROUND: Studies that examine course and outcome in psychosis have reported considerable heterogeneity in terms of recovery, remission, employment, symptom presentation, social outcomes, and antipsychotic medication effects. Even with demonstrated heterogeneity in course and outcome, prophylactic antipsychotic maintenance therapy remains the prominent practice, particularly in participants with schizophrenia. Lack of efficacy in maintenance antipsychotic treatment and concerns over health detriments gives cause to re-examine guidelines. METHODS: This study was conducted as part of the Chicago follow-up study designed as a naturalistic prospective longitudinal research study to investigate the course, outcome, symptomatology, and effects of antipsychotic medication on recovery and rehospitalization in participants with serious mental illness disorders. A total of 139 participants with 734 observations were included in the analysis. GEE logistic models were applied to adjust for confounding factors measured at index hospitalization and follow-ups. RESULTS: Our data show that the majority of participants with schizophrenia or affective psychosis experience future episodes of psychosis at some point during the 20-year follow-up. There was a significant diagnostic difference between groups showing an increase in the number of future episodes of psychosis in participants with schizophrenia. Participants with schizophrenia not on antipsychotics after the first 2 years have better outcomes than participants prescribed antipsychotics. The adjusted odds ratio of not on antipsychotic medication was 5.989 (95% CI 3.588-9.993) for recovery and 0.134 (95% CI 0.070-0.259) for rehospitalization. That is, regardless of diagnosis, after the second year, the absence of antipsychotics predicted a higher probability of recovery and lower probability of rehospitalization at subsequent follow-ups after adjusting for confounders. CONCLUSION: This study reports multiple findings that bring into question the use of continuous antipsychotic medications, regardless of diagnosis. Even when the confound by indication for prescribing antipsychotic medication is controlled for, participants with schizophrenia and affective psychosis do better than their medicated cohorts, strongly confirming the importance of exposing the role of aiDSP and antipsychotic drug resistance.

A word is worth a thousand pictures: A 20-year comparative analysis of aberrant abstraction in schizophrenia, affective psychosis, and non-psychotic depression.

thinking is a cognitive process that involves the assimilation of concepts reduced from diffuse sensory input, organized, and interpreted in a manner beyond the obvious. There are multiple facets by which abstraction is measured that include semantic, visual-spatial and social comprehension. This study examined the prevalence and course of abstract and concrete responses to semantic proverbs and aberrant abstraction (composite score of semantic, visual-spatial, and social comprehension) over 20 years in 352 participants diagnosed with schizophrenia, affective psychosis, and unipolar non-psychotic depression. We utilized linear models, two-way ANOVA and contrasts to compare groups and change over time. Linear models with Generalized Estimation Equation (GEE) to determine association. Our findings show that regardless of diagnosis, semantic proverb interpretation improves over time. Participants with schizophrenia give more concrete responses to proverbs when compared to affective psychosis and unipolar depressed without psychosis. We also show that the underlying structure of concretism encompasses increased conceptual overinclusion at index hospitalization and idiosyncratic associations at follow-up; whereas, abstract thinking overtime encompasses increased visual-spatial abstraction at index and rich associations with increased social comprehension scores at follow-up. Regardless of diagnosis, premorbid functioning, descriptive characteristics, and IQ were not associated with aberrant abstraction. Delusions are highly and positively related to aberrant abstraction scores, while hallucinations are mildly and positively related to this score. Lastly, our data point to the importance of examining the underlying interconnected structures of 'established' constructs vis-à-vis mixed methods to provide a description of the rich interior world that may not always map onto current quantitative measures.

Clarifying the direction of impact of negative symptoms and neurocognition on prospective work functioning in psychosis: A 20-year longitudinal study.

Both neurocognition and negative symptoms have demonstrated strong links to functional outcomes, such as work functioning, among those with severe mental illness (SMI). Prior models have suggested that reduced neurocognition 1) precedes or predicts greater negative symptoms and 2) indirectly influences functional outcomes via its impact on negative symptoms. The current study sought to also test a divergent model: whether greater negative symptoms predict reduced neurocognition and indirectly influence work functioning through their impact on neurocognition. Both models were tested using cross-sectional and prospective data spanning 20-years in a sample of 277 people with a SMI with psychotic features. Results showed that both models were supported in cross-sectional analyses. However, in prospective models predicting work functioning, only the models examining the indirect influence of negative symptoms on work functioning (7.5 to up to 20-years later) through neurocognition demonstrated significant mediation (i.e., a significant indirect effect); further, higher negative symptoms significantly predicted lower prospective neurocognition, while lower neurocognition did not significantly predict greater prospective negative symptoms. Although cross-sectional data were consistent with prior models, our prospective models offered greater support for a putative causal pathway running from negative symptoms to neurocognition-rather than the reverse-to work functioning. Findings have implications for mechanisms contributing to longitudinal work functioning and suggest that targeting negative symptoms prior to neurocognition could be more beneficial for long-term work outcomes.

A 20-Year multi-followup longitudinal study assessing whether antipsychotic medications contribute to work functioning in schizophrenia.

To assess the long-term effectiveness of antipsychotic medications in facilitating work functioning in patients with schizophrenia we conducted longitudinal multifollowup research on 139 initially psychotic patients. The 70 patients with schizophrenia and 69 initially psychotic mood disordered control patients were followed up 6 times over 20 years. We compared the influence on work functioning of patients with schizophrenia continuously prescribed antipsychotics with patients with schizophrenia not prescribed antipsychotics, using statistical controls for inter-subject differences. While antipsychotics reduce or eliminate flagrant psychosis for most patients with schizophrenia at acute hospitalizations, four years later and continually until the 20 year followups, patients with schizophrenia not prescribed antipsychotics had significantly better work functioning. The work performance of the patients who were continuously prescribed antipsychotics was at a low rate and did not improve over time. Multiple other factors also interfere with work functioning. The data suggest that some patients with schizophrenia not prescribed antipsychotics for prolonged periods can function relatively well. Multiple other factors are associated with poor post-hospital work performance. The longitudinal data raise questions about prolonged treatment of schizophrenia with antipsychotic medications.

Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery?

Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. However, evidence on long-term (10 or more years) efficacy of antipsychotics is mixed. Double-blind discontinuation studies indicate significantly more relapses in unmedicated schizophrenia patients in the first 6-10 months, but also present some potentially paradoxical features. These issues are discussed.

A randomized controlled trial of a feedback method for improving empathic accuracy in psychotherapy.

OBJECTIVES: To develop and evaluate a feedback method for reducing empathic errors in psychotherapy. DESIGN: Randomized controlled trial conducted in a university-affiliated out-patient psychiatric clinic. METHODS: Sixteen non-psychotic patients treated for Axis I disorders by 12 psychiatry residents were randomly assigned to intervention and control conditions. In both conditions, at the end of each session, patients rated their own functioning on the Global Assessment of Functioning scale, and therapists predicted patients' ratings. Patients predicted their therapist's accuracy and therapists rated their confidence in their own predictions. In the intervention condition, therapists and patients reviewed their respective ratings from the previous session together. In the control condition, ratings were given directly to the investigator without being reviewed by either patients or therapists. RESULTS: Therapists in the intervention condition showed greater overall accuracy than controls as well as evidence of increasing empathy later in therapy on the Barrett-Lennard empathy subscale. Patients in the control group perceived their therapists as significantly more or less accurate than was warranted according to the accuracy measure (over-/under-idealization). Therapists in the control group were more likely than those in the intervention group to overestimate their own accuracy (overconfidence). Affective responses to the instrument were positive overall and did not differ by condition. CONCLUSION: An intervention such as the one tested in this study may be a practical and useful method for improving accuracy of understanding in a variety of training and clinical settings.

Principled versus statistical thinking in diagnosis and treatment of stroke.

Medical science is now synonymous with probability-based statistics. Statistics deals with a group; it does not need probability theory. Probability theory is consistent with the worldview that the universe is infinite, bounded, random, and governed by chance. Its logic is binary, its geometry is Cartesian, its rules offer a scientific method by which hypotheses may be tested. Clinical trials and even hypothesis testing at the bedside have nestled into the probability foundation. As a result, scientific "evidence" now appears only through the lens of probability theory. Because there is no definitive truth in the worldview of probability theory, the truth of evidence lies in probabilities only. The probabilistic view of science has a firm impact on the practice of medicine and implications for medical-legal decisions.

How frequent is chronic multiyear delusional activity and recovery in schizophrenia: a 20-year multi-follow-up.

To determine how frequent chronic multiyear delusional activity is in modern-day schizophrenia, we studied 200 patients over a 20-year period. We also studied the relation of delusions to hallucinations and thought disorder-disorganization, to work disability, and to later periods of global recovery and assessed several protective factors against delusional activity. The sample was assessed 6 times over 20 years and includes 43 patients with schizophrenia. Participants were evaluated at each follow-up for delusions, hallucinations, thought disorder-disorganization, work disability, and global recovery. Possible protective factors were assessed prospectively at index hospitalization. Twenty-six percent of the patients with schizophrenia were delusional at all follow-ups over the 20 years. Overall, 57% had frequently recurring or persistent delusions. A subgroup of over 25% of the schizophrenia patients had no delusional activity at any of the 6 follow-ups over 20 years. Schizophrenia patients with posthospital delusional activity had increased work disability (P < .05). Delusions that persisted after the acute phase in schizophrenia patients predicted a lower likelihood of future global recovery (P < .01). In conclusion, slightly over half of modern-day schizophrenia patients are vulnerable to frequent or "chronic" delusional activity after the acute phase. Schizophreniform patients and other types of psychotic disorders are vulnerable to posthospital delusional activity, but less frequently, less severely, and more episodically. Delusional activity is associated with work disability. Internal factors such as good premorbid developmental achievements and favorable prognostic factors are protective factors that reduce the probability of chronic multiyear, delusional activity in schizophrenia (P < .01).

Measurable prediction for the single patient and the results of large double blind controlled randomized trials.

BACKGROUND: It has been shown that the clinical state of one patient can be represented by known measured variables of interest, each of which then form the element of a fuzzy set as point in the unit hypercube. We hypothesized that precise comparison of a single patient with the average patient of a large double blind controlled randomized study is possible using fuzzy theory. METHODS/PRINCIPLE FINDINGS: The sets as points unit hypercube geometry allows fuzzy subsethood to define in measures of fuzzy cardinality different conditions, similarity and comparison between fuzzy sets. A fuzzy measure of prediction is defined from fuzzy measures of similarity and comparison. It is a measure of the degree to which fuzzy set A is similar to fuzzy set B when different conditions are taken into account and removed from the comparison. When represented as a fuzzy set as point in the unit hypercube, a clinical patient can be compared to an average patient of a large group study in a precise manner. This comparison is expressed by the fuzzy prediction measure. This measure in itself is not a probability. Once thus precisely matched to the average patient of a large group study, risk reduction is calculated by multiplying the measured similarity of the clinical patient to the risk of the average trial patient. CONCLUSION/SIGNIFICANCE: Otherwise not precisely translatable to the single case, the result of group statistics can be applied to the single case through the use of fuzzy subsethood and measured in fuzzy cardinality. This measure is an alternative to a Bayesian or other probability based statistical approach.

Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multifollow-up study.

This prospective longitudinal 15-year multifollow-up research studied whether unmedicated patients with schizophrenia can function as well as schizophrenia patients on antipsychotic medications. If so, can differences in premorbid characteristics and personality factors account for this? One hundred and forty-five patients, including 64 with schizophrenia, were evaluated on premorbid variables, assessed prospectively at index hospitalization, and then followed up 5 times over 15 years. At each follow-up, patients were compared on symptoms and global outcome. A larger percent of schizophrenia patients not on antipsychotics showed periods of recovery and better global functioning (p < .001). The longitudinal data identify a subgroup of schizophrenia patients who do not immediately relapse while off antipsychotics and experience intervals of recovery. Their more favorable outcome is associated with internal characteristics of the patients, including better premorbid developmental achievements, favorable personality and attitudinal approaches, less vulnerability, greater resilience, and favorable prognostic factors. The current longitudinal data suggest not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives.

A fuzzy theory of cortical computation: neuropoietic engrams, fuzzy hypercubes, and the nature of consciousness.

We apply fuzzy logic to a theory of memory representation and computation in the human cerebral cortex. The theory termed neuropoiesis is based on the hypothetical transfer of mRNA polyribosomes from the post-synaptic dendritic spine of cortical pyramidal neurons to the presynaptic boutons of connecting axons through a hypothetical process termed retroduction. The net effect of this process is a vast increase in predicted memory storage. The fuzzification of memory engrams permits this expansion in memory capacity and requires multiplex signaling which, in turn, requires the formation of a spike packet whose length is determined by the EEG frequencies generated by the thalamo-cortical rhythm generators. The role of the EEG frequencies is to provide a wavelet-like transform of the multiplex signal which in turn determines the degree of data compression that is required for memory recruitment at a given level of vigilance during cortical computation. In this conceptual model cortical computation is hypothesized to be a form of cluster analysis that can be represented by a fuzzy hypercube in which each dimension of the unit hypercube represents an apical dendrite of a layer 5 pyramidal cell in a cortical fascicle. The tuftal area of the apical dendrite in cortical layer one corresponds to the MIN or zero point of the hypercube's dimension and the cell body in layer 5 corresponds to the MAX or one point of that dimension in the unit hypercube. The neuroanatomical location of synapses on the apical dendrites in the fascicle is mapped onto the fuzzy hypercube. These synapses form clusters composed of both bottom-up and top-down signals represented as metasynaptic fuzzy sets-as-points in the hypercube. Soft winner-take-all gating by inhibitory neurons is proposed to supply the only non-linear operation needed for cortical computation. Feed-forward inhibition is envisioned to play the decisive role of spicing or de-fuzzifying the output signal. Proper transmission of the multiplex signal that carries the fuzzy engram requires synchrony of neuronal firing. For this fuzzy cortical model, synchrony of firing, multiplex signaling, winner-take-all gating, and the known spectrum of EEG frequencies are all derivable from the fundamental mechanism termed synaptopoiesis as described in the theory of neuropoiesis. Finally, this theory predicts that the neural correlate of consciousness must include inhibitory subcortical connections and that its function is largely that of limiting coherence to a narrow range of cortical engrams.

From fuzzy logic toward plurimonism: the science of active and empathic observation.

Plurimonism is a new philosophy and method of science. It holds that the revolution in computer science and artificial intelligence has reached the point that all the sciences in general can now account for the complex relations of an irreducible plurality of unique observers engaged in describing the same event. Plurimonism seeks to describe the conscious and unconscious relations of the scientific observer during the act of observation of a given event while preserving the historical uniqueness and indivisible identity of each such observer. Using the framework of plurimonism, we mathematically formulate the problem of empathy. This self-reflective mathematical model entails four components of the empathic process involving two observers. They are: 1) the self; 2) the self's-other; 3) the other; and 4) the other's-self. It measures the degree of accuracy of the therapist-observer's empathy, as well as conscious and unconscious processes involved in the patient-observer's idealization and the therapist-observer's confidence in clinical psychotherapy. Ratings are obtained from both patient and therapist from four different points of view. The plural views of the patient's global assessment of functioning (GAF) are from: 1) the therapist's view (TGAF); 2) the patient's view (PGAF); 3) the therapist empathic view (TEGAF), which represents the therapist's estimate of PGAF; and 4) the patient's empathic estimate of the TGAF. The GAF scale is the standard dimensional 100-point-scale measure used in psychiatry for recording a patient's functioning. The patient's estimate of the therapist's degree of accuracy as well as the therapist's confidence in his or her empathic accuracy is also represented. Three formulae are presented that describe the degree of the therapist's empathic accuracy, the patient's over-idealization/under-idealization, and the therapist's over-confidence/under-confidence. The concept of empathy is here restricted to mean the degree to which one observer can take the point of view of another observer when both are observing the same thing.

Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up study.

Contrary to older views, with modern treatment some or many patients with schizophrenia may show intervals of recovery. The current 15-year prospectively designed follow-up research comparing schizophrenia patients with other types of psychotic and nonpsychotic patients studied how many schizophrenia patients ever show intervals of recovery. Two hundred seventy-four early young psychiatric patients from the Chicago Followup Study, including 64 schizophrenia patients, 12 schizophreniform patients, 81 other psychotic patients, and 117 nonpsychotic patients, were assessed as inpatients and then reassessed 5 times over 15 years. Patients were evaluated for recovery for 1 or more years using an operational definition of recovery. Cumulatively, over the 15-year period slightly over 40% of patients with schizophrenia showed 1 or more periods of recovery. However, schizophrenia is still a relatively poor outcome disorder, showing poorer courses than other types of psychotic and nonpsychotic disorders (p < .001). Most schizophrenia patients did not show the severe social isolation often described prior to the modern treatment era. Schizophreniform patients tended to show more favorable outcomes than schizophrenia patients. Over 50% of the schizophrenia patients did not have a disorder that was chronic and continuous. Rather, their disorder was episodic, although for many more vulnerable and less resilient schizophrenia patients the episodes were more frequent and severe, with slower recovery.

Fuzzy logic and continuous cellular automata in warfarin dosing of stroke patients.

"Evidence-based" recommendations for warfarin prescription in patients with history of ischemic stroke limit its use to prevention of stroke due to atrial fibrillation. Warfarin is also prescribed by the authors to prevent thrombosis in stroke patients with thrombophilia and potential cardiac or arterial source for thromboembolism. These potential conditions, in the face of thrombophilia, include, but may not be limited to, dilated cardiomyopathy, decreased left ventricular function, atrial septal aneurysm with or without patent foramen ovale (PFO), PFO with evidence of pelvic or lower extremity deep venous thrombosis or with clear thrombophilia, spontaneous echocardiographic contrast, intracardiac or intra-arterial thrombus, intra-aortic arch thrombus, high degree of stenosis of large- and medium-sized cerebrovascular arteries, and arterial dissection. Commonly diagnosed thrombophilic states in our population currently include protein S or C deficiency, antiphospholipid antibodies, and less commonly ATIII deficiency, factor V Leiden mutation, G20210A PT mutation, and plasminogen activator inhibitor-1 mutation. Thrombophilic states often occur in combination. The occurrence of combined arterial, cardiac, and thrombophilic sources of thromboembolism poignantly describes the complexity of causation of ischemic stroke in any one patient. Our practice of treating the complex interaction of thromboembolic sources is based on scientific evidence, which is not arbitrarily limited to probability-based statistics. Warfarin is well known in the clinical setting to interact with many different contextual factors of the individual patient, making its dosing and response unique to that patient. We have shown why the indications for warfarin use and its dosing cannot be directly extrapolated to the individual patient from the results of large, double-blind, randomized trials. In practice, the unique patient and his or her context must be considered by the expert physician who makes the therapeutic decision. The context includes, but is not limited to, known pathologies that contribute to thrombus formation according to the accepted pathophysiologic model of thrombosis based on Virchow's triad of altered flow, endothelium, and blood components.