Severe Hallucinations Research Articles

Anxiety symptoms in schizophrenia spectrum disorders: associations with social function, positive and negative symptoms, hope and trauma history

Anxiety is commonly observed in schizophrenia, but its relationship with other features of illness is unclear. We examined correlations between measures of anxiety, positive and negative symptoms, hope, psychosocial function and trauma history among 128 participants with schizophrenia or schizoaffective disorder. Cluster analyses were conducted to determine whether we could detect a subgroup with severe anxiety. Higher levels of anxiety were associated with greater hallucinations, withdrawal, depression, hopelessness, better insight and poorer function. Cluster analyses produced three groups according to anxiety level: subclinical anxiety (n = 37), moderate anxiety (n = 55) and severe anxiety (n = 36). anova revealed that the severe anxiety group had more severe hallucinations, poorer psychosocial function and less hope than either of the other two groups. Self-report of sexual trauma predicted higher levels of anxiety overall. A subgroup of persons with severe anxiety may be identifiable in schizophrenia with a unique clinical profile.

ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease

To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson disease (YOPD). We studied 46 patients, mostly from Italy or Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA. A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia. Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state. We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.

Gender Differences in Young Adults With First-Episode Schizophrenia Spectrum Disorders at Baseline in the Danish OPUS Study

Gender differences in age at first onset, duration of untreated psychosis, psychopathology, social functioning, and self-esteem were investigated in a group of 578 young adults with a first-episode schizophrenia spectrum disorder. The mean age at first-onset of symptoms, age at first contact, and duration of untreated psychosis were similar for men and women. Men had more severe negative symptoms, poorer premorbid functioning, and poorer social networks, whereas women had more severe hallucinations. More men than women were substance abusers, were unemployed, and lived alone. Women had poorer self-esteem than men, in spite of better scores in functioning. Premorbid social adjustment was significantly related to the level of negative symptoms and number of friends. Conclusion is that men and women with first-episode psychosis showed different psychopathological characteristics and different social functioning, which cannot be explained by older age of onset for women. Women make more suicide attempts and experience lower self-esteem in spite of better social functioning.

Using striatal dopamine transporter single photon emission computed tomography imaging to rule out Dementia with Lewy Bodies in elderly patients with antipsychotic‐induced parkinsonism

The persistence of antipsychotic-induced parkinsonism (AIP) after antipsychotic withdrawal in elderly patients requires particular attention. A Dementia with Lewy bodies (DLB) could underlie this phenomenon, since DLB is the second most common type of dementia and severe extra-pyramidal reactions are shown in 53% of DLB patients treated with antipsychotics.1 Moreover, the early detection of DLB is important for therapeutic and prognostic management.2 The authors report the use of striatal dopamine transporter (DAT) with single photon emission computed tomography (SPECT) in ruling out DLB in an elderly patient with severe AIP, hallucinations and cognitive symptoms. DAT are dopamine re-uptake proteins located on the presynaptic terminals of dopaminergic neurons, which can be evaluated in vivo by using DAT transported molecules such as [123I]-FP-CIT, that is, iodine I123 radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropan and SPECT.3 A significant reduction in striatal uptake of [123I]-FP-CIT has been found in DLB, therefore, showing the degeneration of nigrostriatal dopaminergic presynaptic neurons.4 Striatal uptake of [123I]-FP-CIT remains normal in AIP because antipsychotics have a postsynaptic mechanism of action.5 A 75-year-old woman with progressive cognitive decline during the past several months was hospitalized for a major depressive episode with auditory hallucinations. No parkinsonism was detected at the time of admission. She received venlafaxine (150 mg/d) and haloperidol (5 mg/d). On day 8 after the initiation of treatment, she developed severe parkinsonism, which remained unchanged despite central anticholinergic treatment (tropatepine 20 mg/d) and haloperidol discontinuation on day 19. On day 60, depressive symptoms improved markedly, but parkinsonism persisted with a Mini Mental State score of 21. A positive history of severe antipsychotic sensitivity is strongly suggestive of DLB. This suggestive feature is considered sufficient to warrant a diagnosis of possible DLB.6 However, DAT SPECT showed normal uptake and absence of an underlying dopamine deficit, therefore, arguing against the diagnosis of DLB and establishing the diagnosis of AIP. A 2-year clinical follow up further confirmed the diagnosis. [123I]-FP-CIT DAT SPECT is recommended for early detection of dementia with Lewy bodies in elderly patients with severe AIP, hallucinations and cognitive symptoms.

Synch Before You Speak: Auditory Hallucinations in Schizophrenia

Objective: Synchronization of neural activity preceding self-generated actions may reflect the operation of the forward model, which acts to dampen sensations resulting from those actions. If this is true, pre-action synchrony should be related to subsequent sensory suppression. Deficits in this mechanism may be characteristic of schizophrenia and related to positive symptoms, such as auditory hallucinations. If so, schizophrenia patients should have reduced neural synchrony preceding movements, especially patients with severe hallucinations. Method: In 24 patients with schizophrenia or schizoaffective disorder and 25 healthy comparison subjects, the authors related prespeech neural synchrony to subsequent auditory cortical responsiveness to the spoken sound, compared prespeech neural synchrony in schizophrenia patients and healthy comparison subjects, and related prespeech neural synchrony to auditory hallucination severity in patients. To assess neural synchrony, phase coherence of single-trial EEG preceding talking was calculated at a single site across repeated trials. To assess auditory cortical suppression, the N1 event-related brain potentials to speech sound onset during talking and listening were compared. Results: In healthy comparison subjects, prespeech neural synchrony was related to subsequent suppression of responsiveness to the spoken sound, as reflected in reduction of N1 during talking relative to listening. There was greater prespeech synchrony in comparison subjects than in patients, especially those with severe auditory hallucinations. Conclusions: These data suggest that EEG synchrony preceding speech reflects the action of a forward model system, which dampens auditory responsiveness to self-generated speech and is deficient in patients who hallucinate.

Synch Before You Speak: Auditory Hallucinations in Schizophrenia

Synchronization of neural activity preceding self-generated actions may reflect the operation of the forward model, which acts to dampen sensations resulting from those actions. If this is true, pre-action synchrony should be related to subsequent sensory suppression. Deficits in this mechanism may be characteristic of schizophrenia and related to positive symptoms, such as auditory hallucinations. If so, schizophrenia patients should have reduced neural synchrony preceding movements, especially patients with severe hallucinations. In 24 patients with schizophrenia or schizoaffective disorder and 25 healthy comparison subjects, the authors related prespeech neural synchrony to subsequent auditory cortical responsiveness to the spoken sound, compared prespeech neural synchrony in schizophrenia patients and healthy comparison subjects, and related prespeech neural synchrony to auditory hallucination severity in patients. To assess neural synchrony, phase coherence of single-trial EEG preceding talking was calculated at a single site across repeated trials. To assess auditory cortical suppression, the N1 event-related brain potentials to speech sound onset during talking and listening were compared. In healthy comparison subjects, prespeech neural synchrony was related to subsequent suppression of responsiveness to the spoken sound, as reflected in reduction of N1 during talking relative to listening. There was greater prespeech synchrony in comparison subjects than in patients, especially those with severe auditory hallucinations. These data suggest that EEG synchrony preceding speech reflects the action of a forward model system, which dampens auditory responsiveness to self-generated speech and is deficient in patients who hallucinate.

Association of Auditory Hallucinations and Anticonvulsant Hypersensitivity Syndrome with Carbamazepine Treatment

Carbamazepine is effective in the treatment of acute mania and in the prevention of episodes in bipolar disorder, and it may also be useful in depression, impulse-control disorder and withdrawal from alcohol and benzodiazepine dependence. A potentially life-threatening side effect is the anticonvulsant hypersensitivity syndrome. Here, we describe a patient who developed severe auditory hallucinations followed by a distinct hypersensitivity syndrome most likely induced by carbamazepine treatment.

When mitigation evidence makes a difference: effects of psychological mitigating evidence on sentencing decisions in capital trials.

Little empirical research has addressed the effects of psychological or psychosocial evidence on sentencing decisions. The present study found that death-qualified mock jurors were more likely to sentence a defendant to death without mitigating evidence than in a case with mitigating evidence present. Mock jurors were less likely to assign a death sentence in cases that contained one of the following types of mitigating evidence: The defendant was (i) diagnosed with schizophrenia, not medicated, and suffered from severe delusions and hallucinations, (ii) drug addicted and high at the time of the murder, (iii) diagnosed as borderline mentally retarded during childhood, or (iv) severely physically and verbally abused by his parents during childhood.

Language lateralization in schizophrenia, an fMRI study

Anatomical studies have shown that cerebral asymmetry is reduced in schizophrenia. Functional asymmetry appears to be reduced also, as was shown with dichotic listening studies. These studies, however, have not revealed whether reduced lateralization is the result of decreased language activity of the left hemisphere or whether it is the consequence of increased language-related activity in the right hemisphere. To elucidate this, we examined hemispheric dominance for language processing by means of functional MRI. Twelve schizophrenic patients and twelve healthy controls were scanned while they were engaged in a verb-generation and a semantic decision task. Activation was measured bilaterally in the frontal, temporal and temporo-parietal language areas, and a laterality index was derived from activity in these regions of interest in the left and the right hemispheres. Clinical symptoms were rated at the time of scanning. The results indicate that language processing is less lateralized in patients than in controls (a mean laterality index of 0.35 versus 0.63, respectively, difference p<0.01). Analysis of variance of the extent of activity, i.e. numbers of active voxels, revealed a significant hemisphere by group interaction ( F(1,22)=11.2, p<0.001), which was due to increased activation in the right hemisphere of the patients (post hoc t-test p<0.05). We found no evidence of reduced activity in the left hemisphere. Further analysis of clinical symptoms rated prior to scanning revealed that decreased language lateralization was associated with more severe hallucinations ( r=−0.54, p<0.05). We postulate that decreased language lateralization in schizophrenia may result from failure to inhibit the right hemisphere.

IM olanzapine in the treatment of agitation and aggression

Agitation or aggressive behaviors are frequently associated with an acute psychotic episode. Patients experiencing severe auditory hallucinations, paranoia or acute mania are particularly prone to agitation. In the elderly, agitation and aggression are often associated with delirium, dementia or various medical illnesses. Agitated patients urgently require rapid control of symptoms. Traditionally, treatment has included administration of iv. or im. benzodiazepines or neuroleptics. However, each of these is associated with adverse effects that may be serious in nature. An injectable formulation of a novel antipsychotic may effectively treat agitation and aggression while placing the patient at a lower risk for more serious side effects frequently associated with parenteral neuroleptics.

A five-year followup study of deficit and nondeficit schizophrenia

Previous studies have suggested that deficit schizophrenia is a stable subtype of schizophrenia, and that patients with the deficit schizophrenia have different course of illness from other people with schizophrenia. We tested the ability of the deficit/nondeficit categorization to predict clinical features at five years' followup in a group of chronically ill outpatients. Outpatients categorized into deficit ( N=46) and nondeficit ( N=174) schizophrenia were assessed at an average of five years after the categorization was made. Raters making the followup assessments were blind to the initial categorization. At followup, the deficit patients had poorer quality of life, poorer social and occupational function, and more severe negative symptoms. Despite these differences, deficit patients were less distressed (as measured by depressive mood, anxiety, and guilt), and they did not have more severe hallucinations, delusions, thought disorder. These differences could not be attributed to demographic differences. The group differences in quality of life and level of psychosocial function remained significant after accounting for the severity of baseline negative symptoms. These findings confirm that patients with the deficit schizophrenia have a set of relatively stable clinical features that are associated with poor outcome.

Prevalence and clinical correlates of psychotic symptoms in Parkinson disease: a community-based study.

Hallucinations and delusions are frequent in patients with Parkinson disease (PD) and may have severe clinical consequences for those patients and their caregivers. However, the prevalence and clinical features of these symptoms have not been studied in a representative sample. To study the prevalence and clinical correlates of psychosis in a population-based sample of patients with PD. Total ascertainment of patients with PD in a defined geographical area in Norway was attempted through a detailed community study. Clinical evaluation consisted of a neurologic examination and assessments of depression and cognition. Psychosis was assessed with the thought disorder subscale of the Unified Parkinson's Disease Rating Scale. A total of 245 patients with PD were identified, 235 (95.9%) of whom participated in this study. Twenty-three patients (9.8%) had hallucinations with insight retained, and another 14 patients (6.0%) had more severe hallucinations or delusions. Psychotic symptoms were associated with age, stage and diagnostic subgroup of PD, severity of depression, and cognitive impairment. Type, duration, and dose of antiparkinson drug therapy did not differ between those patients with PD who had or did not have psychosis. In a polychotomous logistic regression analysis, severity of depression, cognitive impairment, and impairment of activities of daily living were the only significant concomitants of psychosis. Hallucinations and delusions are common in patients with PD. More advanced and widespread brain changes seem to increase the risk for developing psychosis in patients with PD receiving levodopa therapy.

Wandering behaviour in community-residing persons with dementia.

To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. Cross-sectional, case-control investigation. University-affiliated outpatient neuropsychiatric assessment center. Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.

Independent frontal-system deficits in schizophrenia: cognitive, clinical, and adaptive implications

This study examined whether frontal-system impairments in schizophrenia occur independently of one another and whether they have distinct implications for information processing, symptom severity, and adaptive functioning. We assessed 26 medication-free schizophrenic outpatients and 18 normal control subjects on eight frontally mediated tasks, semantic information processing, IQ, the BPRS, and long-term psychosocial adaptation. Schizophrenic subjects showed three types of deficits, which were uncorrelated with one another: (1) Executive dysfunction (inflexible problem solving) was related to decreased use of expectancy during controlled semantic priming, lower intelligence, more severe negative symptoms and stereotyped mannerisms. (2) Disinhibition of responses (to irrelevant stimuli) was associated with increased automatic priming, a trend for more severe hallucinations, and was unrelated to intelligence. (3) Motor dyscoordination (inaccurate, dysfluent motor sequencing) was not related to semantic processing, intelligence, or symptoms. Furthermore, all three impairments were unrelated to generalized slowness, age, sex, illness length, or pre-washout neuroleptic dose. Two deficits accounted for aspects of long-term psychosocial adaptation, even after statistical correction for IQ: Executive dysfunction was associated with younger illness onset, poor purposefulness and planning, impaired social relations, and lower global functioning. Motor dyscoordination was associated with poor treatment outcome and restricted educational advancement. Furthermore, executive and motor deficits interacted significantly; subjects who had both deficits showed the least favorable treatment outcome. These findings are neither consistent with generalized impairment nor with a unitary `frontal syndrome' in schizophrenia. They provide preliminary evidence for at least three frontal-system deficits (dorsolateral, orbital, and premotor), which are dissociable from one another, can occur without general intellectual impairment, and have distinct implications for long-term adaptive functioning.

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Neuropsychology of schizophrenia, what are the implications of intellectual and experiential abnormalities for the neurobiology of schizophrenia?

The diagnosis of schizophrenia is largely based on reports of bizarre experiences such as having alien thoughts inserted into one's mind. Many patients with this diagnosis show a marked intellectual decline and particular problems with tasks involving certain kinds of memory or requiring mental flexibility. Similar patterns of performance can be seen in patients with damage in the prefrontal cortex. However, patients with schizophrenia show a very varied pattern of impairments relating to their current mental state. Chronic patients with negative features, such as poverty of speech, are most likely to show poor test performance, while the presence of severe hallucinations and delusions need not be associated with any impairment. A cognitive approach suggests that hallucinations and delusions result from the patient attributing his own actions to an external agency. This error is due to an inability to distinguish between external events and perceptual changes caused by his own actions. The basis of this failure could be a functional disconnection between frontal brain areas concerned with action and posterior areas concerned with perception.

Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.

The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

Datura poisoning—The Angel’s Trumpet

A group of seven ate flowers of Datura arborea ("The Angel's Trumpet" or "Trumpet Lilies") and suffered severe hallucinations. One member of the group drowned in shallow water while suffering from these effects. Although poisoning with related species is common, poisoning with this plant is rare, perhaps due to its terrifying rather than pleasurable hallucinogenic effect.

Jimsonweed intoxication in adolescents and young adults.

Seventy-three jimsonweed exposures reported to a regional poison center over a five-year period were reviewed. The ingestors' mean age was 17.3 years (range, 11 to 28 years). The most common route of exposure was oral, and the circumstance was drug abuse or experimentation in the majority of the cases. Although 11 callers remained at home, 59 required medical care in an emergency department or were admitted to the hospital. Treatment consisted of gastrointestinal decontamination, supportive care, and physostigmine salicylate administration. Almost 40% of the medically treated patients received physostigmine for severe hallucinations. One of the 59 medically treated patients had seizures develop. Calls to the poison center regarding jimsonweed differed from other calls in several respects. Jimsonweed abuse is a potentially serious form of substance abuse in adolescents and young adults.

Immunoglobulin levels in psychiatric patients

In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.