A novel way to quantify schizophrenia symptoms in clinical trials.

BACKGROUND: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. MATERIALS AND METHODS: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24-week period during a multi-site clinical trial of N-Acetylcysteine as an add-on to maintenance medication for the treatment of chronic schizophrenia. RESULTS: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77-0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long-lasting change following a treatment, while subscales of the five-factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%-50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. CONCLUSIONS: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.

Tobacco smoking in schizophrenia: investigating the role of incentive salience.

BACKGROUND: Smoking is highly prevalent in people diagnosed with schizophrenia, but the reason for this co-morbidity is currently unclear. One possible explanation is that a common abnormality underpins the development of psychosis and independently enhances the incentive motivational properties of drugs and their associated cues. This study aimed to investigate whether incentive salience attribution towards smoking cues, as assessed by attentional bias, is heightened in schizophrenia and associated with delusions and hallucinations. METHOD: Twenty-two smokers diagnosed with schizophrenia and 23 control smokers were assessed for smoking-related attentional bias using a modified Stroop task. Craving, nicotine dependence, smoking behaviour and positive and negative symptoms of schizophrenia were also recorded. RESULTS: Both groups showed similar craving scores and smoking behaviour according to self-report and expired carbon monoxide (CO), although the patient group had higher nicotine dependence scores. Attentional bias, as evidenced by significant interference from smoking-related words on the modified Stroop task, was similar in both groups and correlated with CO levels. Attentional bias was positively related to severity of delusions but not hallucinations or other symptoms in the schizophrenia group. CONCLUSIONS: This study supports the hypothesis that the development of delusions and the incentive motivational aspects of smoking may share a common biological substrate. These findings may offer some explanation for the elevated rates of smoking and other drug use in people with psychotic illness.

Subthalamic nucleus stimulation for Parkinson disease with severe medication-induced hallucinations or delusions.

OBJECT: Subthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson disease (PD) and reduces antiparkinsonian medication. Therefore, STN DBS seems to be well indicated for patients suffering from medication-induced psychotic symptoms. However, there are few available data dealing with the effect of STN DBS in this kind of patient. The authors studied the effect of STN DBS in patients with PD and severe medication-induced hallucinations or delusions. METHODS: The authors retrospectively reviewed the clinical course of 10 patients who suffered from severe medication-induced hallucinations or delusions and underwent bilateral STN DBS. Patients whose preoperative thought disorder score (Unified Parkinson's Disease Rating Scale Part I, item 2) was 3 or more were enrolled in this study. All patients underwent cognitive function examination and brain perfusion SPECT preoperatively to exclude dementia with Lewy bodies. RESULTS: Subthalamic nucleus DBS yielded significant improvement of motor function in all patients. In 8 patients, psychotic symptoms completely disappeared with significant reduction of dopaminergic medication. In 2 patients, hallucinations and delusions deteriorated immediately after surgery despite complete withdrawal of antiparkinsonian medication. However, these psychotic symptoms completely disappeared after a few months with administration of antipsychotics, and no recurrence was observed afterward in either patient. CONCLUSIONS: Subthalamic nucleus DBS is a good treatment option for patients with PD who are suffering severe medication-induced hallucinations or delusion. However, vigilance is needed, because temporary deterioration of psychotic symptoms may occur after surgery.

Comprehensive model of how reality distortion and symptoms occur in schizophrenia: could impairment in learning-dependent predictive perception account for the manifestations of schizophrenia?

Conventional wisdom has not laid out a clear and uniform profile of schizophrenia as a unitary entity. One of the key first steps in elucidating the neurobiology of this entity would be to characterize the essential and common elements in the group of entities called schizophrenia. Kraepelin in his introduction notes 'the conviction seems to be more and more gaining ground that dementia praecox on the whole represents, a well characterized form of disease, and that we are justified in regarding the majority of the clinical pictures which are brought together here as the expression of a single morbid process, though outwardly they often diverge very far from one another'. But what is that single morbid process? We suggest that just as the uniform defect in all types of cancer is impaired regulation of cell proliferation, the primary defect in the group of entities called schizophrenia is persistent defective hierarchical temporal processing. This manifests in the form of chronic memory-prediction errors or deficits in learning-dependent predictive perception. These deficits account for the symptoms that present as reality distortion (delusions, thought disorder and hallucinations). This constellation of symptoms corresponds with the profile of most patients currently diagnosed as suffering from schizophrenia. In this paper we describe how these deficits can lead to the various symptoms of schizophrenia.

Neurophysiological characteristics of cognitive functions in patients with first episodes of endogenous psychosis.

This report presents studies of the neurophysiological correlates of the characteristics of cognitive disorders in patients with first psychotic episodes of endogenous psychosis at juvenile age. Three groups of patients were studied: those with a predominance of catatonic symptomatology (22 patients), those with a predominance of hallucinatory-delusional symptomatology (22 patients), and those with a predominance of affective-delusional symptomatology (24 patients), along with a group of psychologically healthy subjects (15 subjects). Parameters of auditory evoked potentials were analyzed using the oddball paradigm. The group with a predominance of catatonic disorders showed the greatest differences in the latent periods (LP) of the N200 and P300 components as compared with the other groups; patients with a predominance of hallucinatory-delusional symptomatology showed the most localized anomalies in the latent period of the P300 component; the group of patients dominated by affective-delusional symptomatology showed almost no increase in the latent period of the N200 component, though the extents of anomalies in the N100 component in responses to non-target signals and deviations in the P300 component were more marked than in the other groups. These characteristics of the neurophysiological correlates of cognitive functions in each group of patients supported the significance of evaluating the psychopathological structure of manifest psychotic episodes for determining the clinical typology.

A vanishing lesion in the temporal lobe associated with schizophrenialike psychosis and catatonia.

OBJECTIVE: To present the case of a patient with hallucinations and psychotic symptoms that co-occurs with a temporary lesion in the left posterior temporal lobe. BACKGROUND: Psychosis and auditory hallucinations are characteristic features of schizophrenia, but may also complicate many somatic diseases. Current functional imaging studies suggest a role of the temporal lobes. METHOD: We describe a patient who initially presented with schizophrenialike psychotic symptoms at an age of 23. She did not respond to antipsychotic medication and developed severe medication-resistant catatonia. RESULTS: Magnetic resonance imaging studies revealed an opaque left temporal lesion that could not be diagnosed otherwise. Electroconvulsive therapy led to remission of her catatonic and psychotic symptoms. After clinical remission, the temporal lesion had vanished. CONCLUSIONS: The longitudinal association between the lesion and the occurrence and disappearance of psychosis supports current theories on the role of the left temporal lobe in psychosis.

Relationship between delusions and regional cerebral blood flow in Alzheimer's disease.

UNLABELLED: To investigate the association between delusions and cerebral functional deficits in Alzheimer's disease (AD), we evaluated probable AD patients with and without delusions. METHODS: Functional brain imaging was performed by single photon emission computed tomography with technetium-99m-labeled ethyl cysteinate dimer (99mTc-ECD) in 64 AD patients and 76 age-matched normal healthy volunteers. SPECT data were analyzed by statistical parametric mapping. RESULTS: In AD patients, no differences were found in age and cognitive activities between those with (n = 25) and without (n = 39) delusions. Compared with normal healthy volunteers, AD patients had significantly decreased perfusion in the posterior cingulate gyri, precunei, and parietal association cortex. Moreover, in the patients with delusions, perfusion was significantly decreased in the frontal lobe with right side dominance. In the comparison between the patients with and without delusions, the patients with delusions had significantly decreased perfusion in the prefrontal cortex, anterior cingulate gyri, inferior to middle temporal cortices, and parietal cortex of the right hemisphere (p < 0.01). CONCLUSION: The functional deficits in the right hemisphere may be the cause of delusions in AD.

Frontal lobe psychopathology: mania, depression, confabulation, catatonia, perseveration, obsessive compulsions, and schizophrenia.

The frontal lobes can be subdivided into major functional neuroanatomical domains, which, when injured, surgically destroyed, or reduced in activity or volume, give rise to signature pathological and psychiatric symptomology. A review of case reports and over 50 years of research, including magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography scans, indicates that apathy, "blunted" schizophrenia, major depression, and aphasic-perseverative disturbance of speech and thought are associated with left lateral as well as bilateral frontal (and striatal) abnormalities. Impulsiveness, confabulatory verbosity, grandiosity, increased sexuality, and mania are associated with right frontal (as well as bilateral) disturbances. Gegenhalten, catatonia, and disturbances of "will" are indicative of medial frontal injuries. Disinhibitory states and obsessive-compulsive perseverative abnormalities are more frequently observed with orbital frontal lobe dysfunction, including frontal-striatal disturbances. These associations, however, are not always clear-cut as patients with the same diagnosis may demonstrate different symptoms that may be due to an additional abnormality in a different region of the brain. Moreover, as the frontal subdivisions are richly interconnected, and as frontal lobe abnormalities are not always discrete or well localized, a wide array of seemingly divergent waxing and waning symptoms may be manifest, sometimes simultaneously, including manic depression and what has been referred to as the "frontal lobe personality."

Aura phenomena during syncope.

We studied the frequency and clinical characteristics of aura phenomena in 60 patients with cardiac and 40 subjects with vasovagal syncopes. The majority (93%) of all syncope patients recalled having experienced an aura. Aura phenomena were similar in both groups and were mostly compound auras comprising epigastric, vertiginous, visual, or somatosensory experiences, but were more detailed in the noncardiac group. The localizing significance of auras preceding a syncope was generally poor. Although hard to distinguish from epileptic auras from their structure and shape, syncope-related auras lacked symptoms that are commonly reported after epileptic seizures such as tastes, smells, déjà vu phenomena, scenic visual perceptions, and speech impairments. A detailed anamnestic exploration of auras seems worthwhile in unexplained disorders of consciousness.

Síndromes delirantes de falso reconhecimento: curiosidade ou chave para um novo conhecimento psiquiátrico? / Misidentification syndromes: curiosity or a key for a new psychiatric knowledge?

Objetivos: Partindo das definiçoes das Síndromes Delirantes de Falso Reconhecimento, tendo como principais modelos as Síndromes de Capgras e Frégoli, os autores fizeram uma revisao dos aspectos psicopatológicos envolvidos nesses quadros. Métodos: Foi realizado um levantamento da Literatura fenomenológica clássica e posterior adaptaçao de um modelo neuropsicológico que aprofunde o entendimento desses quadros, geralmente negligenciados pela literatura ou tratados como extravagências de psicopatólogos antigos. Conclusoes: O entendimento das Síndromes Delirantes de Falso Reconhecimento, no entender dos autores, pode ser de grande valia para formar novos conceitos no estudo dos quadros psiquiátricos delirante-alucinatórios maiores, principalmente das correlaçoes entre Sensaçao, Percepçao e Atribuiçao de Significado.

Post-ictal psychosis after right temporal lobectomy.

Of 298 patients who had temporal lobectomies for intractable epilepsy, 4 (1.3%) developed post-ictal psychosis for the first time after surgery. All were males of normal intelligence with no pre-operative psychiatric disorder. Psychosis followed both complex partial and generalised seizures. The psychotic symptoms showed polymorphic features. Right temporal lobectomy may increase the susceptibility to post-ictal psychosis in patients who are not seizure free after surgery, particularly in the first post-operative year.

Delusions of parasitosis.

The fixed belief that one is infested with living organisms, in the absence of any objective evidence that such infestation exists, is termed "delusions of parasitosis." For most patients, this is a "monosymptomatic" disorder because there is no evidence of psychotic ideation in other areas of their lives. This overall normality of thought processes, together with exceptional strength of conviction regarding infestation, makes confirmation of a suspected diagnosis difficult. We want, and need, to be certain that a true infestation is not missed. This requires careful history taking, thorough examination of the skin, microscopic review of the material brought in by the patient and, occasionally, biopsy of lesions identified by the patient as "bite" sites. Establishment of a diagnosis is difficult enough, but it is even more difficult (usually impossible) to convince the patient that there are no "bugs" present. Attempts to have the patient visit a psychiatrist are virtually always rebuffed, leaving the clinician no choice but to begin therapy. Pimozide, a blocker of dopamine receptors, represents the pharmacological treatment of choice. The use of this drug is usually quite helpful, but relapse frequently occurs when treatment is stopped. For patients who will not take the drug, and for those who fail treatment, the best that can generally be achieved is the provision of a supportive environment. In such a setting, many of these patients eventually shift to a less troublesome chronic phase of their disease during which the delusion partially or even completely slips into the subconsciousness thus allowing for more normal daily functioning.

Case report: acquired antisocial personality disorder associated with unilateral left orbital frontal lobe damage.

We report on our analysis of a patient who developed personality changes which strongly resembled an antisocial personality disorder after surgical resection of a pituitary tumor. Despite behavioral changes that were obvious to friends, family and health care professionals, formal neuropsychological and personality testing revealed no specific cognitive deficits or psychopathology. We hypothesize that damage to a circumscribed region of the left orbitofrontal cortex, illustrated by magnetic resonance imaging, underlies these personality alterations. In contrast to previous reports, which ascribe such personality changes to bilateral frontal lobe injury, we suggest that unilateral frontal lobe damage alone may have resulted in the development of this syndrome.

[Progressiveness of schizophrenia. II. The progressiveness of continuously proceeding forms of schizophrenia]. / K probleme progredientnosti shizofrenii. Soobshcheniee II. K probleme progredientnosti nepreryvno tekushchikh form shizofrenii.

The study involved a clinical examination of 568 patients with continious forms of schizophrenia and different degrees of progression (from mild sluggish to malignant forms). The following stages of the diseases are differentiated: an initial one, a stage of the highest process activity, a stage of stabilization, reduction of the psychosis and formation of the terminal state. A thorough analysis of the cases demonstrated that even in a continuous development of schizophrenia, the progression of the process is limited in time. It was found that the more polymorphic and severe are the signs of the process in active phase, the less is the time taken by this phase. In compliance with varying duration of the active stages of the disease the age periods during which there ensue a stabilization of the malignant, sluggish and paranoid forms of schizophrenia are very diverse.