Prevalence, types and associations of medically unexplained symptoms and signs. A cross-sectional study of 1023 adults with intellectual disabilities

Medically unexplained symptoms and signs are common in the general population and can respond to appropriate managements. We aimed to quantify the types and prevalence of unexplained symptoms and signs experienced by adults with ID and to determine the associated factors. In a population-based study, 1023 adults with ID aged 16 and over had a detailed health assessment, which systematically considered symptoms and signs. Descriptive data were generated on their symptoms and signs. Backwards stepwise logistic modelling was undertaken to determine the factors independently associated with the unexplained symptoms. Medically unexplained symptoms and signs were present in 664 (64.9%), 3.8 times higher than in the general population, and 470 (45.9%) had multiple unexplained symptoms or signs. Some were similar to those reported in the general population, such as dyspnoea, dyspepsia, headache, nausea and dizziness. However, others are not commonly reported in the general population, including dysphagia, ataxia, polyuria, oedema and skin rash. Having unexplained symptoms and signs was independently associated with older age, female gender, not having Down syndrome, extent of ID and more GP visits in the last 12 months. It was not associated with living in deprived areas, type of living/support arrangements, number of hospital visit in the last 12 months, smoking, autism, problem behaviours or mental disorders. People with ID have substantial additional unexplained symptoms and signs, some of which are painful or disabling. These findings should inform the content of health checks undertaken for adults with intellectual disabilities, which should not just focus on management of their long-term conditions and health promotion

Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness

Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist. Using simultaneous PET-MRI in healthy volunteers, we find strong evidence that patterns of striatal dopamine signaling and cortical blood flow (an index of local neural activity) contain shared information. This shared information links amphetamine-induced changes in gradients of striatal dopamine receptor availability to changes in brain-wide blood flow and is informed by spatial patterns of gene expression enriched for genes implicated in schizophrenia, bipolar disorder, and autism spectrum disorder. These results advance our knowledge of the relationship between cortical function and striatal dopamine, with relevance for understanding pathophysiology and treatment of diseases in which simultaneous aberrations of these systems exist

The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations

Synaptic terminal density early in the course of schizophrenia: an in vivo UCB-J positron emission tomographic imaging study of synaptic vesicle glycoprotein 2A (SV2a).

BACKGROUND: The synaptic hypothesis is an influential theory of the pathoaetiology of schizophrenia. Supporting this, there is lower uptake of the synaptic terminal density marker UCB-J in patients with chronic schizophrenia compared to controls. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [11C]UCB-J volume of distribution (VT) in antipsychotic-naïve/free patients with schizophrenia (SCZ) recruited from first-episode services compared to healthy volunteers (HV). METHODS: Forty-two volunteers (SCZ n = 21, HV n = 21) underwent [11C]UCB-J positron emission tomography to index [11C]UCB-J VT and distribution volume ratio (DVR) in the anterior cingulate, frontal, and dorsolateral prefrontal cortices, temporal, parietal and occipital lobes, hippocampus, thalamus and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale (PANSS). RESULTS: We found no significant effects of group on [11C]UCB-J VT or DVR in most regions of interest (effect sizes from d=0.0 to 0.7, p>0.05), other than lower DVR in the temporal lobe (d=0.7, uncorrected p<0.05) and lower VT/fp in the anterior cingulate cortex in patients (d=0.7, uncorrected p<0.05). PANSS total score was negatively associated with [11C]UCB-J VT in the hippocampus in the SCZ group (r =-0.48, p=0.03). CONCLUSIONS: These findings indicate that large differences in synaptic terminal density are not present early in schizophrenia, although there may be more subtle effects. When taken with prior evidence of lower [11C]UCB-J VT in patients with chronic illness, this may indicate synaptic density changes during the course of schizophrenia

Non-pharmacological interventions for adults with intellectual disabilities and depression

Background: Although high rates of depression symptoms are reported in adults with intellectual disabilities (IDs), there is a lack of knowledge about non-pharmacological treatment options for depression in this population. The first research question of this paper is: Which non-pharmacological interventions have been studied in adults with ID and depression? The second research question is: What were the results of these non-pharmacological interventions?. Method: Systematic review of the literature with an electronic search in six databases has been completed with hand searches. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines have been followed. Selected studies met predefined inclusion criteria. Results: Literature search resulted in 4267 papers of which 15 met the inclusion criteria. Five different types of non-pharmacological interventions have been studied: cognitive behavioural therapy, behavioural therapy, exercise intervention, social problem-solving skills programme and bright light therapy. Conclusion: There are only a few studies of good quality evaluating non-pharmacological interventions for adults with ID and depression. Some of these studies, especially studies on cognitive behavioural therapy, show good results in decreasing depressive symptoms. High-quality randomised controlled trials evaluating non-pharmacological

Treating negative symptoms of schizophrenia: current approaches and future perspectives

: Negative symptoms are core symptoms of schizophrenia which are common throughout the course of the illness. We outline their functional impact, before reviewing the latest research and guidelines on their assessment and treatment. Finally, we discuss conceptual issues related to measurement of negative symptoms and approaches to address these

Interventions for adults with mild intellectual disabilities and mental ill-health: a systematic review

Background: People with intellectual disabilities have very high rates of mental ill health. Standard psychosocial interventions designed for the general population may not be accessible for people with mild intellectual disabilities, and drug usage tends to be modified – ‘start low and go slow’. This systematic review aims to synthesise the evidence on psychological, pharmacological and electroconvulsive therapy (ECT) interventions for adults with mild intellectual disabilities and mental ill health. Method: PRISMA guidelines were followed. Medline, Embase, PsycINFO and CINAHL were searched, as was grey literature and reference lists of selected papers. Papers were selected based on pre-defined inclusion and exclusion criteria. A proportion of papers were double reviewed. Data was extracted using a structured table. Study registration: PROSPERO 2015:CRD42015015218. Results: Initially, 18 949 records were identified. Sixteen studies were finally selected for inclusion; seven on psychological therapies, two on group exercise, five on antipsychotics and two on antidepressants. They do not provide definitive evidence for effectiveness of psychosocial interventions, nor address whether starting low and going slow is wise, or causes sub-optimum therapy. Conclusions: There are few evidence-based interventions for people with mild intellectual disabilities and mental ill-health; existing literature is limited in quantity and quality. Group cognitive-behavioural therapies have some supporting evidence – however, further randomised control trials are required, with longer-term follow-up, and larger sample sizes