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PubMed2002

Donepezil in the treatment of hallucinations and delusions in Parkinson's disease.

As cholinergic mechanisms may be at least partially responsible for hallucinations and delusions in Parkinson's disease (PD), we conducted an open study in 8 PD patients to assess the efficacy and tolerability of the cholinesterase inhibitor donepezil, 5 mg at bedtime for two months, in the treatment of these complications. Hallucinations and delusions improved significantly in all patients. Donezepil was overall well tolerated, but a deterioration in motor disability was noted in 2 out of 8 patients.

Aged↗
PubMed2005

Hallucinations in children and adolescents.

Clinicians need to consider a wide range of differential diagnoses when children and adolescents present with hallucinations. This includes considering whether it is a developmentally normal phenomenon or if there is a psychiatric, medical, or neurologic diagnosis. Nonpsychotic children with hallucinations can be differentiated from psychotic children. Nonpsychotic children who are at risk (or prodromal) for future psychosis can be differentiated from nonprodromal healthier children. We examine the epidemiology, prognosis, and neurobiological research. Lastly, we discuss treatment approaches, including medication and cognitive behavioral therapy.

Adolescent↗
PubMed1985

Association between amino acid alterations and hallucinations in alcoholic patients.

Because available evidence suggests that alterations in the serotonergic as well as dopaminergic tones underlie hallucinatory activity, we decided to investigate whether serotonin and dopamine pathways are modified in alcoholics with a history of hallucinosis. Brain serotonin has been shown to depend on the plasma ratio of its precursor tryptophan over other amino acids competing with it for brain entry. Similarly, brain dopamine depends on the plasma ratio of its precursors phenylalanine and dopamine over their competitors. Amino acid abnormalities are common in alcoholics. For this reason, we assessed whether alcoholics who had experienced hallucinations have alterations in amino acids believed to be associated with neurotransmitter modifications. Patients with a history of hallucinations were found to have a tryptophan ratio significantly lower than that of patients without such a history, and a tyrosine + phenylalanine ratio significantly higher. These data suggest that amino acid abnormalities believed to result in decreased brain serotonin and in increased brain dopamine render certain individuals more vulnerable to hallucinatory experiences.

Adult↗
PubMed1996

A computational model of visual hallucinations in migraine.

Cortical spreading depression is a wave of electrical and biochemical changes that spreads across the cerebral cortex. It has been hypothesized to be an important underlying cause of the visual disturbances occurring during the migraine aura, but this is difficult to test in animals or humans. We created a computational model of cortical spreading depression and found that during the wave of biochemical changes the spatial pattern of neural activity broke up into irregular patterns of lines and small patches of highly activated elements. The corresponding visual disturbances that would be produced by these patterns of neural activity resemble the hallucinations reported during the migraine aura, providing strong support for the cortical spreading depression hypothesis of migraine. The model also makes the testable prediction that these hallucinations move at an exponentially increasing speed across the visual field.

Animals↗
PubMed1994

Geniculocalcarine hyperintensities on brain magnetic resonance imaging associated with visual hallucinations in the elderly.

Magnetic resonance scans of five geriatric patients presenting with formed visual hallucinations in the absence of other psychopathology were compared with those of 12 healthy elderly subjects for the presence and extent of subcortical and periventricular signal hyperintensity. While the number of discrete brain lesions did not differ between groups, scans from the patient group contained a higher incidence (100% vs. 50%) and greater mean size (11.1 vs. 2.9 mm) of periventricular signal hyperintensity in the posterior region. Peripheral visual acuity was impaired in all of the patients, but cerebrovascular risk factors were not elevated in this group. The authors suggest that structural abnormalities in the area of the primary visual pathway may predispose some older individuals, particularly those with poor peripheral visual acuity, to develop the symptom of visual hallucination.

Aged↗
PubMed1985

The anatomy and chemistry of hallucinations and a rational surgical approach to the treatment of some schizophrenic syndromes.

The hallucinations of schizophrenia and delirium tremens are suggested to be caused by the intrusion of the chemistry of rapid eye movement (REM) sleep into the wake period. Hippocampal and temporal lobe sites seem to contain the substrate for hallucinations. Elimination of the sympathetic nerve supply to the pineal gland could be curative in some schizophrenic syndromes.

Alcohol Withdrawal Delirium↗
PubMed2006

Visual hallucinations after intravitreal injection of bevacizumab in vascular age-related macular degeneration.

PURPOSE: To describe transient structured visual hallucinations in a patient with vascular age-related macular degeneration (AMD), following an intravitreal Avastin-injection. DESIGN: Interventional case reports. METHODS: A fully alert 83-year-old woman with disciform scar right eye (OD) and occult choroidal neovascularization (CNV) left eye (OS) experienced a progressive visual loss to 20/800 OD and 20/400 OS. A coherent 84-year-old woman with occult CNV both eyes (OU) experienced decreased vision of 20/800 OU. After both patients gave informed consent, an uneventful intravitreal injection of 1.25 mg Avastin was performed in the left eyes. RESULTS: One day and three days after an uneventful intravitreal injection both patients experienced structured hallucinations including trees, faces, and water for approximately 15 to 30 minutes. CONCLUSIONS: We report a typical symptoms of Charles-Bonnet syndrome (CBS) in patients with severe AMD after intravitreal Avastin-injections. The reduced retinal edema and realignment of the photoreceptors may promote the release phenomenon and trigger hallucinatory episodes.

Aged, 80 and over↗
PubMed2007

Coping with hallucinated voices in schizophrenia: a review of self-initiated strategies and therapeutic interventions.

This article reviews the state of knowledge about strategies used by people with a diagnosis of schizophrenia to cope with hallucinated voices, and considers the role of coping in psychological treatments for persisting symptoms. The use of self-initiated ('natural') coping strategies appears almost universal amongst voice-hearers. These strategies are similar across cultures, and include diverse behaviours, only a minority of which is specific to hallucinations. Most strategies are reported by at least some users to be effective, but more sophisticated outcome studies are lacking. Some evidence for the efficacy of certain behavioural techniques of coping, for the manipulation of auditory input, and for strategies involving subvocalisation, is available from experimental studies. Therapeutic enhancement of natural coping strategies for persisting symptoms has demonstrated some efficacy, but its benefit for voices is unknown. Despite this, it has become an established part of some CBT interventions for psychosis. Further advances in knowledge and practice may come from utilisation of coping models in research, longitudinal and ideographic methods of study and a movement away from descriptive coping lists to investigations of coping styles, mechanisms of action, and the process of coping.

Adaptation, Psychological↗
PubMed2004

A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia.

Recent studies have suggested that DNA variations in the CCK-AR gene might predispose individuals to schizophrenia and particularly to auditory hallucinations (AH). The aim of this study is to assess the association between AH, using a specific scale for AH in schizophrenia (PSYRATS), and the CCK-AR polymorphism at 779 in a Spanish sample. A total of 105 DSM-IV schizophrenic patients with AH and 93 unrelated controls were studied. Twenty-two patients were considered as persistent auditory hallucinators, which showed similar clinical and demographic characteristic than patients with episodic AH, but with the exception of the PSYRATS values. The persistent AH group showed an excess of the A1 allele when was compared with episodic or control groups. Our data support the possible role of the CCK-AR gene in the development of persistent AH in schizophrenic patients.

Adult↗
PubMed2005

Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations?

Failure of corollary discharge, a mechanism for distinguishing self-generated from externally generated percepts, has been posited to underlie certain positive symptoms of schizophrenia, including auditory hallucinations. Although originally described in the visual system, corollary discharge may exist in the auditory system, whereby signals from motor speech commands prepare auditory cortex for self-generated speech. While associated with sensorimotor systems, it might also apply to inner speech or thought, regarded as our most complex motor act. In this paper, we describe the results of a series of studies in which we have shown that: (1) event-related brain potentials (ERPs) can be used to demonstrate the corollary discharge phenomenon during talking, (2) corollary discharge is abnormal in patients with schizophrenia, (3) EEG gamma band coherence between frontal and temporal lobes is greater during talking than listening and is disrupted by distorted feedback during talking in normals, and (4) patients with schizophrenia do not show this pattern for EEG gamma coherence. While these studies have identified ERPs and EEG gamma coherence indices of the efference copy/corollary discharge system and documented abnormalities in these systems in patients with schizophrenia, we have so far had limited success in establishing a relationship between these neurobiologic indicators of corollary discharge abnormality and reports of hallucinations in patients.

Auditory Cortex↗
PubMed2006

Sensory gating deficits, pattern completion, and disturbed fronto-limbic balance, a model for description of hallucinations and delusions in schizophrenia.

Schizophrenia, if not the most difficult, is one of the most difficult mysterious puzzles for psychiatrists, psychologists, and neuroscientists to solve. In this paper, based on the previously known pathologies of schizophrenia, a new model is proposed for explanation of the formation of positive psychotic symptoms of hallucinations and delusions. This model can be used for understanding psychotic or psychotic-like positive symptoms of bipolar mood disorder, posttraumatic stress disorder, obsessive compulsive, and amphetamine and drug-induced psychotic disorders. Based on the postulated model, a spectral view on these disorders with psychotic features is also proposed. These pathologies include auditory sensory gating deficits in hippocampus, abnormal emotional coding in amygdala, pattern completion in thalamic and cortical areas, and disturbed fronto-limbic balance. This model includes anatomical and neurotransmitter defects of hippocampus, amygdala, thalamus, cingula, and prefrontal cortex and their interconnections. A role for hippocampal sensory gating deficits in the pathogenesis of positive psychotic symptoms and interrelation between amygdala and its dopamine level with hippocampus is speculated. This model also hires the interesting function of pattern completion in thalamus and cortical areas for a better explanation of the pathogenesis of hallucinations and delusional psychotic symptoms. Furthermore, there is also explanation for the polygenic etiology of the schizophrenic and psychotic disorders and relation between schizophrenia and bipolar mood disorder in anatomy and neural systems involved. A spectral view is proposed that explains the absence of clear cut border between different psychotic or psychotic-like disorders in their form and severity based on the involved genes and brain functional systems. Including excessive prefrontal pruning, there is also explanation for the appearance of positive psychotic symptoms in early adulthood. An explanation for the high dopamine level of amygdala despite its decreased size and abnormal anatomy is also suggested as a compensatory function which might explain the decline in positive psychotic symptoms when schizophrenics age according to amygdala burn out. Based on this model, speculations are provided for: late onset of the effects of antipsychotics on positive psychotic symptoms, mechanism for the therapeutic effect of serotonin type 2A receptor blockers and GABAergic medications in psychosis, role of smoking in diminution of psychotic symptoms, and relationship between biological and psychological issues in the formation of psychotic symptoms. Finally, based on this model, a new role for nicotinic cholinergic drugs (such as galantamine) for treatment of schizophrenia and other psychotic or psychotic-like disorders is proposed.

Amygdala↗
PubMed2004

A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations.

The aim of this study was to evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on the left and right temporoparietal cortex compared with sham stimulation in schizophrenic patients with treatment-refractory auditory hallucinations (AH). Thirty-nine patients with schizophrenia with treatment-refractory AH were allocated randomly to one of three groups: daily left, right, and sham rTMS groups. rTMS was applied to the TP3 or 4 regions with the aid of the electroencephalography 10-20 international system at 1 Hz for 20 min per day for 10 treatment days. Symptoms were evaluated using the Auditory Hallucination Rating Scale (AHRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression--Severity (CGI-S), and Clinical Global Impression--Improvement (CGI-I) scale. For the time effect (within-subject comparison), there were significant changes in the frequency of AHs, positive symptoms of PANSS, and CGI-I. A between-group comparison revealed significant differences in the positive symptoms of PANSS, and CGI-I scores. Post hoc analysis revealed that both the right- and left-side rTMS treatment groups exhibited better CGI-I scores compared to the sham-stimulated group. This study suggests that 10 days of low-frequency rTMS applied daily for 20 min to either temporoparietal cortex significantly reduces the symptoms in patients with schizophrenia who are having refractory AH, but the left sided rTMS is not superior to right or sham rTMS.

Adolescent↗
PubMed2006

Temporal context discrimination in patients with schizophrenia: associations with auditory hallucinations and negative symptoms.

BACKGROUND: A deficit in remembering the temporal context of events (a type of source memory) has been observed in schizophrenia, and suggested to be associated with positive symptoms. METHODS: In order to investigate memory for temporal context, we administered a list discrimination task to a sample of schizophrenia patients and a sample of healthy controls. Participants were required to learn two lists of mixed high- and low-frequency words separated by 10 min, then to remember whether each word had been presented in the first or in the second list. RESULTS: The number of misattributions to the wrong list was significantly higher in patients than in healthy controls. However, the group difference was eliminated when recall efficiency was covaried. The number of list misattributions was higher in patients with auditory hallucinations than in the other patients, independently of verbal recall efficiency. By contrast, affective flattening and anhedonia were associated with fewer list misattributions of the high-frequency words. CONCLUSIONS: It is suggested that auditory hallucinations are associated with deficit in processing or remembering the temporal context. Conversely, certain negative symptoms are associated with reduced temporal context errors. The possible neural mechanisms involved in temporal context deficit as well as in these specific clinical symptoms are discussed.

Adult↗
PubMed2006

Mental representation of space: insights from an oblique distribution of hallucinations.

Three-dimensional spatial distributions of hypnagogic and hypnopompic hallucinations associated with sleep paralysis were used to investigate the internal representation of space. Left-right asymmetries in human preferences and abilities are well established. Parallel effects are also observed as lower-upper asymmetries. These parallels could reflect common underlying mechanisms or additive effects of independently evolved horizontal and vertical asymmetries. This study adds to the growing literature on multidimensional spatial biases in a context free from the influence of task-related factors. We present evidence of an oblique bias in the projection of both sensory and motor hallucinations toward lower-left and especially upper-right external space exceeding that accounted for by an additive model of separate horizontal and vertical biases. These observations are consistent with theories regarding a systematic functional relation of hemispheric with ventral and dorsal cerebral organization.

Adult↗
PubMed2006

Orbitofrontal seizures presenting with ictal visual hallucinations and interictal psychosis.

Hallucinations are commonly believed to reflect temporal lobe dysfunction. This report presents the clinical, electroencephalographic, and neuroimaging findings in an 8-year-old male who experienced the acute onset of ictal auditory and visual hallucinations associated with epileptic activation of the right orbitofrontal region. Right frontal lobe surgery resulted in seizure freedom and disappearance of his psychotic symptoms. Histologic tissue examination revealed non-balloon cell Taylor type cortical dysplasia.

Child↗
PubMed2006

Optimization of a multinomial model for investigating hallucinations and delusions with source monitoring.

Studies of source monitoring have played an important role in cognitive investigations of the inner/outer confusions that characterize hallucinations and delusions in schizophrenia, and multinomial modelling is a statistical/cognitive modelling technique that provides a powerful method for analyzing source monitoring data. The purpose of the current work is to describe how multinomial models can be optimized to answer direct questions about hallucinations and delusions in schizophrenia research. To demonstrate this, we present a reanalysis of previously published source monitoring data, comparing a group of patients with schneiderian first rank symptoms to a group without schneiderian first rank symptoms. The main findings of this analysis were (1) impaired recognition of self-generated items and (2) evidence that impaired source discrimination of perceived items is accompanied by an internalization bias in the target symptom group. Statistical and cognitive interpretations of the findings are discussed.

Cognition Disorders↗
PubMed2006

Emotion and psychosis: links between depression, self-esteem, negative schematic beliefs and delusions and hallucinations.

BACKGROUND: The role of emotion in psychosis is being increasingly recognised. Cognitive conceptualisations of psychosis (e.g. [Garety, P.A., Kuipers, E.K., Fowler, D., Freeman, D., Bebbington, P.E., 2001. A cognitive model of the positive symptoms of psychosis. Psychological Medicine, 31, 189-195]) emphasise a central, normal, direct and non-defensive role for negative emotion in the development and maintenance of psychosis. This study tests specific predictions made by Garety et al. [Garety, P.A., Kuipers, E.K., Fowler, D., Freeman, D., Bebbington, P.E., 2001. A cognitive model of the positive symptoms of psychosis. Psychological Medicine, 31, 189-195] about the role of emotion and negative evaluative beliefs in psychosis. METHODS: 100 participants who had suffered a recent relapse in psychosis were recruited at baseline for the Prevention of Relapse in Psychosis (PRP) trial. In a cross-sectional analysis, we examined the role of depression, self-esteem and negative evaluative beliefs in relation to specific positive symptoms (persecutory delusions, auditory hallucinations and grandiose delusions) and symptom dimensions (e.g. distress, negative content, pre-occupation and conviction). RESULTS: Analysis indicated that individuals with more depression and lower self-esteem had auditory hallucinations of greater severity and more intensely negative content, and were more distressed by them. In addition, individuals with more depression, lower self-esteem and more negative evaluations about themselves and others had persecutory delusions of greater severity and were more pre-occupied and distressed by them. The severity of grandiose delusions was related inversely to depression scores and negative evaluations about self, and directly to higher self-esteem. CONCLUSIONS: This study provides evidence for the role of emotion in schizophrenia spectrum-disorders. Mood, self-esteem and negative evaluative beliefs should be considered when conceptualising psychosis and designing interventions.

Adolescent↗