Development Of Hallucinations Research Articles

Hallucinations and Brain Morphology Across Early Adolescence: A Longitudinal Neuroimaging Study

BackgroundPsychotic disorders have been widely associated with structural brain abnormalities. However, it is unclear whether brain structure predicts psychotic experiences in youth from the general population, owing to an overall paucity of studies and predominantly cross-sectional designs. Here, the authors investigated longitudinal associations between brain morphology and hallucinations from childhood to early adolescence. MethodsThis study was embedded in the population-based Generation R Study. Children underwent structural neuroimaging at age 10 years (N = 2042); a subsample received a second scan at age 14 years (n = 964). Hallucinations were assessed at ages 10 and 14 years and studied as a binary variable. Cross-lagged panel models and generalized linear mixed-effects models were fitted to examine longitudinal associations between brain morphology and hallucinations. ResultsSmaller total gray and white matter volumes and total cortical surface area at baseline were associated with a higher occurrence of hallucinations between ages 10 and 14 years. The regions associated with hallucinations were widespread, including the frontal, parietal, temporal, and occipital lobes, as well as the insula and cingulate cortex. Analyses of subcortical structures revealed that smaller baseline hippocampal volumes were longitudinally associated with hallucinations, although this association was no longer significant following adjustment for intracranial volume. No evidence for reverse temporality was observed (i.e., hallucinations predicting brain differences). ConclusionsThe findings from this longitudinal study suggest that global structural brain differences are associated with the development of hallucinations. These results extend findings from clinical populations and provide evidence for a neurodevelopmental vulnerability across the psychosis continuum.

Delirium in neurological practice

Delirium is an acute, usually reversible, fluctuating impairment of the level of consciousness, attention, and cognitive activity resulted from impaired brain metabolism due to a wide range of various neurological and non-neurological diseases, the effects of drugs and other substances. The main manifestations of delirium are acute changes in consciousness, disturbance of attention, perception, often with the development of hallucinations, emotion, sleep-wake cycle, psychomotor and autonomic activity. Delirium is divided into hypoactive and hyperactive subtypes depending on the severity of psychomotor and emotional disturbances. Patients with acute stroke are also often susceptible to episodes of delirium at the risk factors such as age, pre-existing cognitive impairment, pneumonia, urinary tract infections, and right hemispheric stroke. The pathophysiology of delirium has been less known, but there is evidence of the role of cholinergic deficiency. Delirium is a transient condition, but it needs treatment to prevent the development of complications since it is usually associated with poor functional outcomes, longer hospitalization and higher mortality. The strategy for the treatment of patients with delirium should be directed to early identification of its symptoms, elimination of modifiable risk factors and metabolic causes. In patients with severe symptoms of agitation and hallucinations, short-term prescription of antipsychotics for their relief is possible.

Associations between Trauma, Dissociation, Adult Attachment and Proneness to Hallucinations.

Childhood adversity, dissociation and adult attachment have all been implicated in the development of hallucinations or 'voice-hearing'. Testing psychological models in relation to subclinical phenomena, such as proneness to hallucinations in non-clinical samples, provides a convenient methodology to develop understanding of the processes and mechanisms underlying clinical symptoms. This paper investigates the relative contribution of childhood adversity, dissociation and adult attachment in explaining hallucination proneness in a non-clinical sample. Students and staff with no previous contact with secondary care at the University of Manchester were recruited. Participants completed a series of self-report measures: the Launay‒Slade Hallucination Scale (LSHS), the Relationship Scale Questionnaire (RSQ), the Childhood Trauma Questionnaire (CTQ), the Dissociative Experiences Schedule (DES II) and the Positive and Negative Affect Schedule (PANAS). As hypothesized, insecure attachment, childhood adversity and dissociative symptoms were correlated with hallucination proneness. Multiple regression analysis, controlling for confounds of age and negative affect, indicated that the RSQ, CTQ and DES II predicted hallucination proneness. Only DES II and RSQ avoidant attachment were significant independent predictors in the final model. This study provides further evidence to support the idea that attachment and dissociation are important psychological mechanisms involved in voice-hearing proneness. Further testing is required with a clinical population.

SU32. Impact of Catechol-O-Methyl Transferase Polymorrphism on Cognition and Information Processing in Schizophrenia Using Novel MBIAL Computerized Battery—A Case-Control Study

Abstract Background: Frontal executive dysfunction have been robustly demonstrated in schizophrenia. Several fundamental information processing deficits were reported in schizophrenia underlying the various symptom dimensions. Results of previous studies of neuropsychological functioning in schizophrenia were inconsistent. Association between COMT allele type and cognition was not confirmed in all studies. This study attempted to assess the neuropsychological performance on a hypothesis-driven MBIAL-computerized neuropsychological battery in a sample of schizophrenia subjects and matched healthy comparison subjects and its relationship with the gene polymorphism. Methods: Total 34 patients and 30 matched healthy controls were recruited after obtaining informed consent. An HMSE was applied to exclude those with scores <23. The matrix reasoning module of WAIS-III was applied to obtain an estimate of their perceptual organization index as a reflection of their intellectual abilities, independent of verbal abilities. A novel MBIAL Computerized neuropsychological battery consisting of 6 tests was applied on all the subjects. Later, both the groups were assessed for symptom severity using PANSS. All Neuropsychological tests and PANSS Interviews using SCI-PANSS were Video and Audio recorded. Genotyping for COMTval158met polymorphism was accomplished by PCR-RFLP method. Genotype frequencies across groups were noted using chi-square test and later were compared using ANCOVA as we had WAIS III and HMSE as covariates. Results: Schizophrenia patients performed significantly poorly on most of the neuropsychological tests as compared with healthy matched controls. Negative symptom severity was associated with significant impairment in neuropsychological deficits as compared to positive symptoms. Separate analysis of association of gene polymorphism on these cognitive tests done on patients and controls did not reveal much results. But on pooled data, we found Val-Carriers performed poorly on most of the Neuropsychological and Information processing tasks and have high threat perception compared to Non-Val Carriers. Conclusion: Hypothesis-driven neuropsychological battery was used in schizophrenia that incorporated tests for frontal executive functioning; rostral prefrontal functioning; threat perception (aberration of which is postulated to underlie delusion formation); and cross-modal sensory integration (aberration of which is postulated to underlie development of hallucinations). The MBIAL battery is sensitive in detecting differences between patients and controls in the adult population. We suggest here that Val158Met polymorphism rather exerts a modifying influence on brain activation in general than impacts directly on performance of the particular neuropsychological task.

Current Understanding of Psychosis in Parkinson's Disease.

Psychosis in Parkinson's disease (PD) is one of the greatest determinants of nursing home placement and caregiver stress. Traditionally associated with medications with dopaminergic effect, it has now been linked to other medications and other stressors e.g. systemic illnesses. The development of hallucinations in a PD patient can herald the onset of dementia and usually predicts increased mortality risk. Medication reduction in PD psychosis usually reduces the symptoms; however, this comes at the cost of worsening motor function. If gradually decreasing the patient's medications does not resolve the psychosis, the treatment of choice is an atypical antipychotic. Though only clozapine has level A recommendation for this indication, other atypicals like quetiapine continue to get used for this purpose on account of the logistics involved with clozapine use. Cholinesterase inhibitors are also increasingly being used for PD psychosis on account of the association with dementia. The treatment of PD psychosis is an unmet need in PD management and search for suitable agents constitutes an active area of research in PD.

Surviving 10 years with deep brain stimulation for Parkinson's disease--a follow-up of 79 patients.

Deep brain stimulation (DBS) for severe Parkinson's disease (PD) outperforms the best medical treatment in controlling motor symptoms and improving quality of life. Nevertheless disease progression cannot be controlled, and the development of dementia over time is nearly inevitable, often resulting in nursing home placement. Ten-year survival, development of hallucinations, dementia and nursing home placement were examined and adverse events were assessed. Patient files were scrutinized from baseline up to 10 years of treatment or death on all 79 PD patients treated with DBS of the subthalamic nucleus from 1998 to 2003 at Aarhus University Hospital. Twenty-four patients died during the follow-up period of 10 years. Age above 60 years at surgery increased mortality 2.3-fold (P = 0.04). Of the 55 surviving patients 29 (53%) were demented and 19 (35%) were in nursing homes. Average time from operation to dementia was 5.6 ± 2.9 years. Hallucinations and nursing home placement were associated with increased mortality. Survival of 70% after a mean of 25 years of PD including 10 years with DBS illustrates that this is a selected group of PD patients. The prevalence of dementia steadily increased after surgery as expected from disease progression and can be an early event. Compared with the few similar long-term studies, the present study presents a larger cohort followed at the same DBS center for a longer period of time and none was lost to follow-up, making conclusions more valid. The present findings are of significant prognostic help for the patient, caregiver and physician when treatment with DBS has to be decided.

Clinical Implication of REM Sleep Behavior Disorder in Parkinson's Disease

REM sleep behavior disorder (RBD) appears to have a predilection for some neurodegenerative disorders, especially synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. The frequency of RBD in PD has been reported to variably range from 20 to 72%. RBD may precede or follow onset of parkinsonism. Idiopathic RBD may foreshadow neurodegenerative diseases, and RBD in patients with PD has several associated clinical factors although their causal or temporal relationships are not known. RBD may be associated with the development of hallucinations and dementia in PD. It has been reported that the male gender, old age, a non-tremor motor subtype, a more severe parkinsonism, fall, longer disease duration, autonomic dysfunction, and higher levodopa doses are factors associated with RBD in PD. This review will address the clinical implications of RBD as a preclinical marker of neurodegenerative diseases and PD phenotypes associated with RBD.

Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: A prospective study

One of the most devastating nonmotor manifestations of PD is dementia. There are few established predictors of dementia in PD. In numerous cross-sectional studies, patients with rapid eye movement (REM) sleep behavior disorder (RBD) have increased cognitive impairment on neuropsychological testing, but no prospective studies have assessed whether RBD can predict Parkinson's dementia. PD patients who were free of dementia were enrolled in a prospective follow-up of a previously published cross-sectional study. All patients had a polysomnogram at baseline. Over a mean 4-year follow-up, the incidence of dementia was assessed in those with or without RBD at baseline using regression analysis, adjusting for age, sex, disease duration, and follow-up duration. Of 61 eligible patients, 45 (74%) were assessed and 42 were included in a full analysis. Twenty-seven patients had baseline RBD, and 15 did not. Four years after the initial evaluation, 48% with RBD developed dementia, compared to 0% of those without (P-adjusted = 0.014). All 13 patients who developed dementia had mild cognitive impairment on baseline examination. Baseline REM sleep atonia loss predicted development of dementia (% tonic REM = 73.2 ± 26.7 with dementia, 40.8 ± 34.5 without; P = 0.029). RBD at baseline also predicted the new development of hallucinations and cognitive fluctuations. In this prospective study, RBD was associated with increased risk of dementia. This indicates that RBD may be a marker of a relatively diffuse, complex subtype of PD.

A Case of Ropinirole-Induced Psychosis

To the Editor: Ropinirole, a dopamine receptor agonist, has a high affinity for dopamine D2 receptors and shows highest affinity for the D3 receptor subtype.1 Studies indicate that ropinirole also has antidepressant properties in Parkinson's disease and treatment-resistant depression.2 However, some case reports have documented that ropinirole can induce mania3 and psychosis.4 In a recently published study5 of 95 subjects treated with ropinirole for Parkinson's disease or restless legs syndrome, 13 developed psychotic features that required therapeutic intervention with either the use of an antipsychotic or dose adjustment of ropinirole. Although ropinirole has been available in India for some time now, there is no report of psychiatric symptoms associated with its use. We present a case of a patient with bipolar disorder who developed psychotic symptoms without accompanying affective symptoms while receiving ropinirole, which resolved with stoppage of ropinirole. Case report. Ms A, a 62-year-old woman, was diagnosed with bipolar affective disorder (per DSM-IV-TR) for the previous 18 years and was on lithium carbonate treatment for the same, with breakthrough relapses that were managed with increase in dose of lithium and addition of antipsychotics for short durations. A year prior to presentation to us in December 2009, while on lithium treatment, she had developed loose motion, coarse tremors of both hands, slowness of movement, stooped posture, increased salivation, and pill-rolling movement of hands. Initially, she was seen by a neurologist, was diagnosed to have parkinsonism, and was started on tablet ropinirole 5 mg/d. Later, investigations found high serum lithium levels, following which, lithium was stopped and sodium valproate was started and increased to 1,500 mg/d. With the stoppage of lithium, tremors of hands decreased, and there was marked improvement in the patient's posture. While on valproate 1,500 mg/d and ropinirole 5 mg/d, Ms A developed delusion of persecution, elementary auditory hallucination, and decreased sleep, without accompanying symptoms of mania or depression. After her symptoms continued for about 2 weeks, she was seen by a psychiatrist, who added quetiapine up to 100 mg/d, but her symptoms kept on worsening and continued for a period of 2 months. When she was brought to our center in December 2009, she was receiving valproate 1,500 mg/d, quetiapine 75 mg/d, and ropinirole 5 mg/d. On mental status examination, she was ill kempt, was speaking irrelevantly, and had blunted affect, persecutory delusions, and elementary delusions with preserved cognitive functions. In view of the temporal correlation of starting ropinirole and psychotic symptoms in the absence of core manic or depressive features, ropinirole-induced psychosis was suspected and ropinirole was stopped. Within 2 weeks of stopping ropinirole, all of the above symptoms subsided without any change in the dose of valproate 1,500 mg/d and with increase in the dose of tablet quetiapine to 100 mg/d. The patient has been euthymic for the last 2 months. Ropinirole, a nonergot D2/D3 dopamine agonist, has greatest affinity for the D3 receptors. Theoretically it is considered that, because of greater affinity for the D3 receptor, use of ropinirole may not lead to excessive stimulation of D2 receptors in the mesolimbic area and hence would not lead to psychosis. Studies have reported an incidence of 5% to 17% for development of hallucinations in subjects receiving ropinirole for Parkinson's disease.5–7 In the index case, the patient developed psychotic symptoms without associated affective symptoms while on treatment with ropinirole and valproate, symptoms that had not responded to quetiapine 100 mg/d in the past, but responded to stoppage of ropinirole. This suggests that the psychosis was related to ropinirole. In the index patient, the psychotic symptoms included paranoid features, a finding that is in line with the previous reports in the literature of psychotic symptoms with ropinirole. Our patient's score on the Naranjo Adverse Reaction Scale8 was 6, indicating a probable association between psychosis and ropinirole. Our case adds to the scant literature about the association of ropinirole and psychosis and highlights the fact that, like all other dopaminergic agents, ropinirole should be used with caution in patients with affective and psychotic symptoms.

Risk factors for somnolence, edema, and hallucinations in early Parkinson disease

The CALM-PD trial evaluated the development of motor complications in subjects with early Parkinson disease (PD) randomized to initial treatment with either pramipexole or levodopa. A secondary finding of the trial was a higher than anticipated development or worsening of somnolence and edema and development of hallucinations. To investigate risk factors for somnolence, edema, and hallucinations in patients with early PD initiating dopaminergic therapy. This was a secondary analysis of data from the CALM-PD trial. Baseline patient characteristics were evaluated for their associations with the development or worsening of somnolence and edema and the development of hallucinations using Cox proportional hazards regression models. Kaplan-Meier estimates of the 4-year incidence of the development or worsening of somnolence and edema and the development of hallucinations were 35%, 45%, and 17%. Initial pramipexole treatment (hazard ratio [HR] 2.22, 95% CI 1.41, 3.50, p < 0.001), male gender (HR 1.79, 95% CI 1.09, 2.93, p = 0.02), and >5 systems with a comorbid illness (HR 1.62, 95% CI 1.04, 2.51, p = 0.03) were associated with somnolence. Initial pramipexole treatment (HR 3.18, 95% CI 1.95, 5.18, p < 0.0001), female gender (HR 1.46, 95% CI 0.94, 2.27, p = 0.09), and comorbid cardiac disease (HR 1.59, 95% CI 1.02, 2.47, p = 0.04) were associated with edema. Age > or =65 (HR 2.06, 95% CI 0.98, 4.32, p = 0.06), Mini-Mental State Examination score >28 (HR 0.42, 95% CI 0.19, 0.91, p = 0.03), and >5 systems with a comorbid illness (HR 3.42, 95% CI 1.59, 7.38, p = 0.002) were associated with hallucinations. Comorbid illnesses are important and overlooked risk factors for the development of somnolence, edema, and hallucinations. When initiating therapy with pramipexole, patients should be counseled about and monitored for somnolence and edema. Slight decrements in cognitive function and older age are associated with an increased risk of hallucinations.