The striatum acts in conjunction with the cortex to control and execute functions that are impaired by abnormal dopamine neurotransmission in disorders such as Parkinson's and schizophrenia. To date, ...in vivo quantification of striatal dopamine has been restricted to structure-based striatal subdivisions. Here, we present a multimodal imaging approach that quantifies the endogenous dopamine release following the administration of d-amphetamine in the functional subdivisions of the striatum of healthy humans with (11)CPHNO and (11)CRaclopride positron emission tomography ligands. Using connectivity-based (CB) parcellation, we subdivided the striatum into functional subregions based on striato-cortical anatomical connectivity information derived from diffusion magnetic resonance imaging (MRI) and probabilistic tractography. Our parcellation showed that the functional organization of the striatum was spatially coherent across individuals, congruent with primate data and previous diffusion MRI studies, with distinctive and overlapping networks. d-amphetamine induced the highest dopamine release in the limbic followed by the sensory, motor, and executive areas. The data suggest that the relative regional proportions of D2-like receptors are unlikely to be responsible for this regional dopamine release pattern. Notably, the homogeneity of dopamine release was significantly higher within the CB functional subdivisions in comparison with the structural subdivisions. These results support an association between local levels of dopamine release and cortical connectivity fingerprints.
Some patients admitted to acute stroke units are diagnosed as stroke mimics. A minority have a functional neurological disorder ('functional mimics').
To determine the incidence of functional stroke ...mimics admitted to a hyperacute stroke unit (HASU); to compare their clinical characteristics with medical mimics and stroke cases and obtain information about outcomes.
Patients admitted to the King's College Hospital HASU between 2011 and 2012 were analysed. Data were obtained from the Stroke Improvement National Audit Programme (SINAP) database. Expert consensus diagnosis was used to classify functional mimics. Follow-up information was obtained from a retrospective case series in primary care over the year following discharge.
1165 patients were admitted to the HASU; 904 patients with stroke (77.6%), 163 medical mimics (14%) and 98 functional mimics (8.4%). Functional mimics were significantly more likely to be female (63.3%) versus 49.7% medical mimics and 45.5% stroke, and younger (mean age (SD)) 49.1 (18.8) than medical mimic (63.5 years (16.7)) and stroke cases (71 years (15.5)). Weakness and slurred speech were the commonest presentations of functional mimics and diagnostic MRI was used more often. Clinician recorded visual and speech symptoms and neglect were significantly more frequent in patients with stroke than either mimic group. Of the 68 functional mimics on whom follow-up information was obtained, 40 (59%) were referred to another service most often for a psychologically-based intervention.
Functional stroke mimics are an important subgroup admitted to acute stroke services and have a distinct demographic and clinical profile. Their outcomes are poorly monitored. Services should be developed to better diagnose and manage these patients.
BackgroundPeople with functional/dissociative seizures (FDS) are at elevated suicidality risk.ObjectiveTo identify risk factors for suicidality in FDS or epilepsy.MethodsRetrospective cohort study ...from the UK’s largest tertiary mental healthcare provider, with linked national admission data from the Hospital Episode Statistics. Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01 January 2007 and 18 June 2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (International Classification of Diseases, version 10: X60–X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models.FindingsIn both groups, ethnic minorities had significantly reduced odds of hospitalisation following suicide attempt (OR: 0.45–0.49). Disorder-specific risk factors were gender, age and comorbidity profile. In FDS, both genders had similar suicidality risk; younger age was a risk factor for both outcomes (OR: 0.16–1.91). A diagnosis of depression or personality disorders was associated with higher odds of suicidal ideation (OR: 1.91–3.01). In epilepsy, females had higher odds of suicide attempt-related hospitalisation (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88–1.06). A substance abuse disorder was associated with higher suicidal ideation (OR: 2.67). Developmental disorders lowered the risk (OR: 0.16–0.24).ConclusionsThis is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.Clinical implicationsRisk factors identified will help identify higher-risk groups in clinical settings.
11CPHNO is a D2/D3 agonist positron emission tomography radiotracer, with higher in vivo affinity for D3 than for D2 receptors. As 11C-( + )-PHNO is an agonist, its in vivo binding is expected to be ...more affected by acute fluctuations in synaptic dopamine than that of antagonist radiotracers such as 11Craclopride. In this study, the authors compared the effects of an oral dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of 11C-( + )-PHNO and 11Craclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D3 receptors is negligible and both tracers predominantly bind to D2 receptors, the reduction of 11C-( + )-PHNO binding potential (BPND) was 1.5 times larger than that of 11Craclopride. The gain in sensitivity associated with the agonist 11C-( + )-PHNO implies that ~65% of D2 receptors are in the high-affinity state in vivo. In extrastriatal regions, where 11C-( + )-PHNO predominantly binds to D3 receptors, the amphetamine effect on 11C-( + )-PHNO BPND was even larger, consistent with the higher affinity of dopamine for D3. This study indicates that 11C- ( + )-PHNO is superior to 11Craclopride for studying acute fluctuations in synaptic dopamine in the human striatum. 11C-( + )-PHNO also enables measurement of synaptic dopamine in D3 regions.
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Psychosis (delusions and/or hallucinations) is a well-recognized complication of treatment of Parkinson's disease (PD). Quetiapine is a currently favored treatment, but data on its efficacy are ...equivocal. This trial aimed to provide further evidence on the efficacy of quetiapine in PD psychosis.
We conducted a 12 week double blind randomized placebo-controlled trial. Time to dropout due to lack of improvement of psychosis was the primary outcome measure. Other important secondary outcomes were evaluated using standard rating scales for PD and psychiatric symptoms.
Twenty-four eligible subjects gave consent. The primary outcome, time to dropout, was examined using survival analysis. It was shown that patients in the quetiapine group dropped out earlier than those in the placebo group, but this difference was not significant (p = 0.68). No significant changes were found for any of the secondary outcome measures in either group.
In this study, quetiapine at doses of up to 150 mg/day failed to significantly improve psychosis compared to placebo, however the small sample size does not allow any conclusive interpretation of the results. Quetiapine did not appear to worsen PD motor functioning, but its use was limited by a faster drop out compared with placebo. Significant impediments were difficulty with recruitment and natural fluctuation in symptoms during the trial.
Functional neurological disorder (FND) is a common and disabling condition at the intersection of neurology and psychiatry. Despite remarkable progress over recent decades, the mechanisms of FND are ...still poorly understood and there are limited diagnostic tools and effective treatments. One potentially promising treatment modality for FND is virtual reality (VR), which has been increasingly applied to a broad range of conditions, including neuropsychiatric disorders. FND has unique features, many of which suggest the particular relevance for, and potential efficacy of, VR in both better understanding and managing the disorder. In this review, we describe how VR might be leveraged in the treatment and diagnosis of FND (with a primary focus on motor FND and persistent perceptual-postural dizziness given their prominence in the literature), as well as the elucidation of neurocognitive mechanisms and symptom phenomenology. First, we review what has been published to date on the applications of VR in FND and related neuropsychiatric disorders. We then discuss the hypothesised mechanism(s) underlying FND, focusing on the features that are most relevant to VR applications. Finally, we discuss the potential of VR in (1) advancing mechanistic understanding, focusing specifically on sense of agency, attention and suggestibility, (2) overcoming diagnostic challenges and (3) developing novel treatment modalities. This review aims to develop a theoretical foundation and research agenda for the use of VR in FND that might be applicable or adaptable to other related disorders.
Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson’s disease (PD). Use of the older ‘typical’ antipsychotic drugs led to worsening of motor symptoms. The ...introduction of ‘atypical’ antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.
•Deep brain stimulation is an effective treatment for obsessive-compulsive disorder.•Effects of deep brain stimulation on affective state are ambiguous.•Impact of deep brain stimulation on quality of ...life and cognition needs further investigation.•There is a need for clinical trials and standardisation of study methodology to address further questions.
Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive-compulsive disorder (trOCD). We conducted a systematic search to investigate the efficacy and safety of DBS for OCD. Primary outcomes included the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), adverse events (AE), and quality of life. We assessed affective state, global functioning, cognition, and tolerability as secondary outcomes. Eight studies comprising 80 patients with trOCD were analysed both individually and collectively. We found a pooled mean reduction in Y-BOCS of 38.68 %, indicating DBS could be considered an effective therapy for trOCD. Most AE were mild and transient, however there were five severe surgery-related AE: intracerebral haemorrhage in three patients and infection in two. Mood-related serious AE were one completed suicide, three suicide attempts in two patients, and suicidal thoughts and depression in four. Despite this, affective state improved following stimulation. Despite being limited by significant heterogeneity across studies, our review has shown DBS to be an effective treatment in otherwise trOCD. There is a need to standardise study methodology in future research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait ...impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and 11 Craclopride PET in 23 healthy volunteers. A partial correlational analysis showed a significant association between non-planning impulsiveness (lack of forethought or ‘futuring’) and limbic D2/3 receptor availability, which was only apparent after the exclusion of potential dissimulators (indexed by high scores on impression management). Our findings suggest that non-planning impulsiveness is associated with individual variation in limbic striatal D2/3 receptor availability and that different facets of impulsivity may have specific neurochemical correlates. Future studies that combine D2/3 receptor imaging with behavioral measures of impulsivity are required to further elucidate the precise relationship between individual components of trait impulsivity and brain dopaminergic function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Study in non-lesional epilepsy and Functional/Dissociative Seizures (FDS)•Correlation analyses between psychiatric and cognitive measures.•Results reveal distinct associations in FDS compared to ...epilepsy.•Neurocognitive processes might contribute to FDS generation or presentation.
To explore the relationship between cognitive functioning and psychopathological features in Functional/Dissociative Seizures (FDS), and test whether this differs from that observed in epilepsy.
We recruited a cross-sectional sample of adults (age > 18) with a diagnosis of non-lesional epilepsy or FDS between January 2021 and July 2022 (n = 73). Participants completed a series of psychiatric questionnaires and neuropsychological measures. Spearman’s Correlation Coefficient was computed between each of the psychiatric and cognitive measures in each group. Fisher’s Z test of significance for independent correlation coefficients then tested the significance of the difference between correlation coefficients for the two groups.
There were no group differences in neuropsychological test scores. However, people with FDS reported higher seizure severity, depression levels, number of medically unexplained somatic symptoms, and exposure to traumatic events compared to epilepsy. Results of the Fisher’s Z-test revealed significant differences in correlation coefficients between groups in two instances. First, in the association between the number of traumatic experiences and cognitive switching (z = 2.77, p = 0.006); the number of traumatic experiences were positively associated with cognitive switching in epilepsy but showed a non-significant negative trend in FDS. Secondly, in the association between vocabulary abilities and the number of medically unexplained symptoms (z = −2.71; p = 0.007); higher vocabulary ability was associated with fewer somatic symptoms in epilepsy, while no such correlation was observed in FDS.
This study provides preliminary evidence for the complex interplay between cognitive functioning and psychopathology in FDS and epilepsy. Neurocognitive functioning such as vocabulary abilities or attentional switching may play a role in the expression or maintenance of pathological features of FDS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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