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Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study.
BACKGROUND: Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. METHOD: We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. RESULTS: Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06-1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03-1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution. CONCLUSIONS: IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.
Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up.
BACKGROUND: Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure. AIMS: To examine lifetime blood pressure as a predictor of brain structure in old age. METHOD: A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985-2013). In 2012-2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities. RESULTS: Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy. CONCLUSIONS: Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose-response pattern.
Resilience and MRI correlates of cognitive impairment in community-dwelling elders.
BACKGROUND: The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of 'normal for age' minor brain abnormalities. METHOD: Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes. RESULTS: Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy. CONCLUSIONS: Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.
Establishing the cause of memory loss in older people.
Common causes of memory loss in older people are mild cognitive impairment, the various types of dementia, and psychiatric illness, mainly depression. Around 10% of patients with mild cognitive impairment progress to dementia each year. Alzheimer's disease accounts for 60-80% of cases. Other common types of dementia are vascular, fronto-temporal, Lewy body, Parkinson's, and mixed type dementia. There is evidence to suggest that dementia pathology is established before the onset of symptoms, and thus mild cognitive impairment can be considered as a predementia stage. NICE guidance suggests examination of: attention, concentration, short- and long-term memory, praxis, language and executive function. Particular attention should be paid to any signs of neglect, state of dress, agitation or poor attention. Dysphasia and difficulty in naming objects is often present. Mood symptoms (including suicidal ideation) may be primary or comorbid. Abnormal thoughts and perceptions should be probed for, as psychotic symptoms are common. Primary care options for cognitive testing include the General Practitioner Assessment of Cognition or the Abbreviated Mental Test Score. Physical examination should include observation of gait, inspection for tremor; examination for rigidity, bradykinesia, frontal release signs, upper motor neurone lesions, pulse and BP. Structural brain imaging can improve diagnostic accuracy, exclude other pathologies and act as a prognostic marker of dementia progression but the overlap in structural changes between the dementias makes imaging alone insufficient for diagnostic purposes. NICE guidelines recommend referral to a memory clinic for patients with mild cognitive impairment, those at high risk of dementia, such as patients with learning disabilities, Parkinson's disease, or patients who have had several strokes.
Considering the senses in the diagnosis and management of dementia.
Associations between dementia and impairments in hearing, vision, olfaction and (to a lesser degree) taste have been identified. Hearing impairment has been shown to precede cognitive decline, but it is not clear if the hearing loss is an early marker of dementia or a modifiable risk factor. Olfactory impairment is seen in many neurodegenerative conditions, but it has been shown that those with dementia have particular difficulties with the recognition and identification of odours rather than the detection, suggesting a link to impairment of higher cognitive function. Olfactory impairment has been shown to be predictive of conversion from mild cognitive impairment to Alzheimer's disease with 85.2% sensitivity. As cognitive function deteriorates, the world is experienced at a sensory level, with reduced ability to integrate the sensory experiences to understand the context. Thus, people with dementia are very sensitive to sensory experiences and their environment needs to be managed carefully to make it understandable, comfortable, and (if possible) therapeutic. Light can be used to stabilise the circadian rhythm, which may be disturbed in dementia. Music therapy, aromatherapy, massage and multisensory stimulation are recommended by NICE for the management of behavioural and psychological symptoms of dementia (BPSD), although the mechanisms behind such interventions are poorly understood and evidence is limited. Sensory considerations are likely to play a greater role in dementia care in the future, with the development of purpose-built dementia care facilities and the focus on non-pharmacological management strategies for BPSD.
Hypomania
Hypomania is characterized by elevated mood in addition to behavior change including increased energy, increased confidence, increased activity, impulsivity, irritability, disinhibition and a reduced need for sleep. Some of these symptoms present practical difficulties for neuroimaging research, for example, consent to receiving radioactive substances during research requires a sound judgment of risks that may be absent in patients with manic symptoms. Nevertheless, there is cross-modal consensus that active manic symptoms are associated with fronto-limbic imbalance, affecting functional and structural connectivity. Specific symptom of mania can be mapped onto neural networks.
Aging and Psychological Stress
The conceptual link between aging and psychological stress is the construct ‘allostatic load’ – i.e. the notion that a repeated and cumulative disturbance of homeostasis may lead to certain syndromes that are triggered by a dysregulation of the chronic stress response. We summarize the markers of this hypothetical process at primary, secondary and tertiary stages, with particular attention on brain mechanisms that are in this pathway or are even instrumental to such dysregulation and its pathological consequences. As cumulative stress and allostasis are highly correlated with chronological age, we present an example for the statistical isolation of such mechanisms from the generic effect of age.
Be vigilant for perinatal mental health problems.
The postnatal period appears to be associated with higher rates of adjustment disorder, generalised anxiety disorder, and depression. Women who have a history of serious mental illness are at higher risk of developing a postpartum relapse, even if they have been well during pregnancy. Psychiatric causes of maternal death are more common than some direct causes of death. UK rates increased from 13/100,000 in 2006-2008 to 16/100,000 in 2010-2012, higher than, for example, mortality caused by haemorrhage or anaesthetic complications of childbirth. Postnatal depression is more severe than baby blues, follows a chronic course and may relapse outside the perinatal period. Although 13% of patients already have depression in pregnancy, the majority tend to be diagnosed after delivery; up to 19% from childbirth to three months postpartum. NICE recommends using the Two Question Depression Screen and the Generalized Anxiety Disorder scale from the booking visit through to one year postpartum. A positive response to depression or anxiety questions warrants a full assessment using either PHQ-9 or the Edinburgh Postnatal Depression Scale. Bipolar disorder may present as a first depressive episode in pregnancy or the postnatal period. In the postpartum period women have a high risk of severe relapse. Postpartum psychosis has a sudden and dramatic presentation with delusions, mania, severe depression, or mixed episodes with wide fluctuations of symptoms and severe mood swings.
Single photon emission computed tomography in a patient with unilateral auditory hallucinations
We report a patient with right unilateral auditory hallucinations in association with right-sided hearing loss and tinnitus, a degree of anxiety and depression leading to self-poisoning, and delusional elaboration of the sensory experiences. Poor performance in visuospatial neuropsychological tests sensitive to frontal lobe damage, and poor performance on a visuospatial recognition memory test at 12 s delay were associated with a relative reduction of regional cerebral tracer uptake in mainly right anterior cingulate and right posterior temporal cortex.
Calcium antagonists and multi‐infarct dementia: A trial involving sequential NMR and psychometric assessment
A double‐blind placebo‐controlled trial of the calcium antagonist Nimodipine in 10 patients with multi‐infarct dementia (MID) shows that there is no improvement when compared with 10 patients on placebo assessed by clinical ratings and sequential NMR imaging. The value of repeated NMR imaging in measuring changes in MID is described. Copyright © 1988 John Wiley & Sons, Ltd.
Realist approaches to psychopathology. A critique
A conceptual unity of science can be achieved either by universal methodological criteria (critical rationalism), or by the assumption of an homogenous reality from which models, hypotheses, and theories are naturally derived (realism). In this paper realist approaches to psychology and psychopathology are evaluated with particular reference to Jaspers' General Psychopathology. Realism is found to obscure real differences between causal analysis and the analysis of meaningful connections.
[Parkinson's disease and Alzheimer's disease--similarities in magnetic resonance imaging parameters and their possible explanation].
Eight demented and eight non-demented Parkinson patients are compared with ten controls and 22 Alzheimer patients. NMR images as well as NMR parameters (T1) show similarities within the demented and non-demented sub-groups. The neuropathological and physiological basis of this finding is discussed.
Personality associations with the uptake of the cerebral blood flow marker 99mTc-Exametazime estimated with single photon emission tomography
The associations between personality dimensions of the Eysenck Personality Questionnaire and individual differences in the regional uptake of 99mTc-Exametazime in brain were studied in 51 healthy volunteers. Extraversion was significantly correlated (r = 0.46, P <0.001) with tracer uptake in the anterior and posterior cingulate areas bilaterally, whereas no significant associations were found with neuroticism or psychoticism. The results are presented with reference to recent studies which have, on the one hand, interpreted extraversion differences in relation to theories of attention and, on the other, demonstrated the role of the cingulate area as a possible neuronal substrate for attentional processing mechanisms. © 1994.
The prediction of stress in carers: The role of behaviour, reported self care and dementia in patients with idiopathic Parkinson's disease
Stress scores were elicited from relatives living with Parkinsonian patients and correlated with various aspects of the patients' impairment. The (usually female) relatives looking after male patients reported higher levels of stress than husbands looking after their wives. In general, the best predictor of relatives' stress was the behavioural rating scale of the CAPE and a reported selfcare scale designed for the study. The relative contribution of Parkinsonian motor impairment and cognitive impairment to relatives' stress scores was examined. While motor impairment was still associated with relatives' stress after controlling for sex and cognitive deterioration, both dementia and cognitive impairment measured by the Mini‐Mental State Examination were not associated with relatives' stress if Parkinsonian disability was controlled for. Copyright © 1991 John Wiley & Sons, Ltd.