In the news round-up this week, mild behavioural impairment was found to be significantly associated with progress to dementia at 5 years, a pathway for tau deposition in healthy ageing and dementia was identified in another study, 22 core ‘facts’ for use in modelling schizophrenia have been proposed, chronic insomnia was associated with hypertension, naltrexone was found to be useful in kleptomania and a robotic scientist has successfully designed and completed an experiment on yeast genes.
Research in Dementia
A retrospective case series of 17 people who developed Frontotemporal Dementia identified prior diagnoses of bipolar disease and schizophrenia in 5 of the people. A supplementation of the case series with a literature review provided additional evidence of a potential relationship between a small number of cases of adult-onset psychosis and later Frontotemporal Dementia. However large prospective cohort studies would be beneficial to test this relationship (Velakoulis et al, 2009)(STT5). A cotton seed extract with potential antidepressant effects was found to hippocampal neurogenesis effects (Zhang et al, 2009)(STT5). A virtual reality spatial navigation task was found to effectively discriminate between young adults and older adults with Alzheimer’s Disease suggesting the utility of this paradigm (Zakzanis et al, 2009)(STT5). 99 people with early-onset AD were compared with 192 people with late-onset AD and the younger-onset group were found to have a more rapid decline particularly if they were APOE4 negative (van der Vlies et al, 2009)(STT3). Distinguishing between frontal function (using a frontal assessment battery) and posterior function (using a perceptual assessment battery) was effective in distinguishing between early-onset dementias and late-onset dementias in this small pilot study which looked at 23 people with dementia and 20 controls (Mendez et al, 2009)(STT3). In a 5 year follow up of 239 people over the age of 65 with Mild Cognitive Impairment and 119 people with Mild Behavioural Impairment, the latter group were found to convert to dementia in 70% of cases, the most common being Frontotemporal dementia. 34% of the Mild Cognitive Impairment group converted (Taragano et al, 2009)(STT3). Incidence of dementia was not found to be increased among 2286 atomic bomb survivors compared to a control group (Yamada et al, 2009). Tau deposition in an ageing sample (from the Medical Research Council Cognitive Function and Ageing Study) was found to proceed along a pathway which included the entorhinal cortex, CA1 and dentate (Lace et al, 2009)(STT4). Ibuprofen was associated with a reduction in the increasing rate of delta rhythms with time in people with mild Alzheimer’s Disease in this small placebo controlled study and the authors recommend further studies (Babiloni et al, 2009)(STT4). People with early-onset Alzheimer’s Disease and AD associated with higher education were found to have thinner cortical thickness in a number of areas compared to a control group without cognitive impairment (Seo et al, 2009)(STT4).
Research in Psychosis
People with schizoaffective disorder and related affective disorders were significantly more likely to carry the val66Met polymorphism of BDNF than people with schizophrenia in this study of 381 people with schizophrenia, affective disorders or schizoaffective disorder and 222 controls (Lencz et al, 2009)(STT4). A comparison of women with and without childhood abuse found that the former group were significantly more likely to develop psychosis in adulthood in this case-control study (cases n=181, controls n=246). The same finding was not identified in men. However further prospective cohort studies would could explore causality (Fisher et al, 2009)(STT5). Anandamide which binds to cannabinoid receptors was found to be elevated in 27 people with the prodromal state of psychosis compared to 81 controls and the authors suggest that Adandamide may be protective in the prodromal phase (Koethe et al, 2009)(STT4). The authors of a review of 85 studies looking at coping mechanisms for psychosis conclude that multiple coping mechanisms most likely represent an optimal strategy (Phillips et al, 2009)(STT3). A post-hoc analysis of 5 double-blind RCT’s comparing olanzapine, quetiapine, ziprasidone, aripiprazole and risperidone concluded that olanzapine did not differ from aripiprazole but did show a lower loss of response than the other 3 antipsychotics at 24 and 28 weeks of treatment. Nevertheless it would be interesting to see the results for longer periods of treatment (Stauffer et al, 2009)(STT4). A small pilot study showed some benefit for a weight-reduction program in people taking second-generation antipsychotics compared to a control group. Larger replication studies would be beneficial (Blouin et al, 2009)(STT5). A population-based case-control study looked at side-effects of psychotropic medication in people over the age of 67 and found an association between SSRI’s, Olanzapine and Amitripytlline and increased risk of hypertensions at 6-months after the medication was prescribed as well as a significant association between Olanzapine and Diabetes at 6-months while conventional antipsychotics were associated with a reduction in the incidence of hypertension (Kisely et al, 2009)(STT3). A placebo-controlled trial of Mirtazapine as an adjunct to atypical antipsychotics for schizophrenia found no evidence of benefit in a small 6-week study with 40 participants – 20 in each arm (Berk et al, 2009)(STT4). A change in prolactin levels was association with olanzapine treatment response in an open label study (Chen et al, 2009)(STT4). People with non-affective psychosis and difficulties in social recovery were found to benefit from CBT when compared to treatment as usual although the authors recommend further larger replication studies (Fowler et al, 2009)(STT4). In an interesting development, two authors have proposed a group of 22 ‘facts’ that can be used in constructing models of schizophrenia (MacDonald and Schulz, 2009)(STT5). Significantly greater weight gain for Risperidone and Olanzapine compared to placebo were identified from a database analysis of 21 placebo-controlled RCT’s (Parsons et al, 2009)(STT3). A case of torsade de pointes occurring after haloperidol administration in a person with complete heart block was identified in this paper (Ginwalla et al, 2009)(STT5). Elevated antibodies to helicobacter pylori were found in the CSF of people with Alzheimer’s Disease (n=27) compared to age-matched controls (n=27)(Kountouras et al, 2009)(STT5).
Research in Affective Disorders
Migraine with aura was found to be significantly higher in people with depression than in controls with an odds ratio of 5.6 (Samaan et al, 2009)(STT3). In a study of 45 inpatients with treatment resistant depression, cortisol response was found to be reduced relative to 46 controls and the authors concluded that the HPA axis is set a higher level (i.e. higher cortisol levels)(Juruena et al, 2009)(STT4).
News in Brief
There is evidence that Amyloid Plaques in Alzheimer’s Disease may produce synaptic damage by a mechanism which involves free radical production and the mitochondrial protein DRP1. Maintaining a focus on the external environment improved posture in Parkinson’s Disease in one study. A proposal has been made to create a map of mammalian brain circuitry. Naltrexone has been found to benefit people with kleptomania in one study. There is evidence that neurons use proteins to fix the cell body to the extracellular matrix and then send out dendrites to target cells during development. A study of the offspring of centenerians (who would be expected to have similar longevity) were found to have low neuroticism and high extraversion. Acceptance and Commitment Therapy was found to be better than control conditions but not superior to other treatments in a meta-analysis of 18 studies. In fruit flies, sleep deprivation was associated with a build up of a synaptic protein known as Bruchpilot (BRP) and this might well generalise to humans although further research will be needed. A protein Nurr1 was found to be involved in modulating the inflammatory response of microglia through a specific pathway and this response might be important in neurodegenerative processes. In the moderate stages of semantic dementia, a recent study provided evidence that autobiographical memory is impaired regardless of recency. Sleeping less than 5 hours a day was associated with a 500% increase in the risk of hypertension compared to those who slept more than six hours. A single intensive treatment for phobias which can last up to three hours was found to be effective in 55% of children in one study. An abnormal response to a glucose challenge was found in 16% of people with schizophrenia or related psychoses compared to none in the control group in a Spanish study. There is indirect evidence that Indoleamine 2, 3 dioxygenase may play an important role in the onset of depressive symptoms in chronic inflammation. Relationships formed in an online music community on the basis of shared musical tastes were found to be ‘fragile’ in one recent study. A computer-robotic system has constructed and completed an experiment in Yeast genes paving the way for a new generation of automated scientists to work alongside humans. A lack of a morning rise in cortisol in children with Asperger Syndrome is suggested as a potential contributor to their clinical presentation. 5 single nucleotide polymorphisms of transthyretin (which inhibits amyloid beta protein production) were associated with significant hippocampal atrophy (Cuenco et al, 2009).
Babiloni C et al. Ibuprofen treatment modifies cortical sources of EEG rhythms in mild Alzheimer’s Disease. Clin Neurophysiol. 2009. Epub.
Berk M et al. Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: a double-blind, randomised placebo-controlled clinical trial. Hum Psychopharmacol. 2009. 24(3). Epub.
Blouin M et al. Improvement of metabolic risk profile under second-generation antipsychotics: A pilot intervention study. Can J Psychiatry. 2009. 54(4). 275-279.
Chen Y et al. Prolactin levels in Olanzapine treatment correlate with positive symptoms of schizophrenia: Results from an open-label, flexible-dose study. Prim Care Companion. J Clin Psychiatry. 2009. 11(1). 16-20.
Cuenco K et al. Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families. Neurobiol Aging. 2009. Epub.
Fisher H et al. Gender differences in the association between childhood abuse and psychosis. The British Journal of Psychiatry. 2009. 194. 319-325.
Fowler D et al. Cognitive behaviour therapy for improving social recovery in psychosis: a report from the ISREP MRC Trial Platform study (improving social recovery in early psychosis). Psychol Med. 2009. 1-10. Epub
Ginwalla et al. Torsade de pointes following intravenous haloperidol administration in a patient with complete heart block. WMJ. 2009. 108. 1. 48-50.
Juruena M et al. Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance. The British Journal of Psychiatry. 194. 342-349. 2009.
Kisely S et al. An epidemiologic study of psychotropic medication and obesity-related chronic illnesses in older psychiatric patients. Can J Psychiatry. 2009. 54(4). 269-74.
Koethe D et al. Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Short Report. 2009. 194.
Kountouras J et al. Increased cerebrospinal fluid helicobacter pylori antibody in Alzheimer’s Disease. Int J Neurosci. 2009. 119(6). 765-77.
Lace G et al. Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study. Brain. 2009. Epub.
Lencz T et al. Molecular differentiation of schizoaffective disorder from schizophrenia using BDNF haplotypes. The British Journal of Psychiatry. 2009. 194. 313-318.
MacDonald A and Schulz S. What we know: Findings that every theory of schizophrenia should explain. Schizophrenia Bulletin. 2009. Epub.
Mendez M et al. Frontal-executive versus posterior-perceptual mental status deficits in early-onset dementias. Am J Alzheimers Dis Other Dement. 2009. Epub.
Parsons B et al. Weight effects associated with antipsychotics: A comprehensive database analysis. Schizophrenia Research. 2009. Epub.
Phillips L. Strategies used by psychotic individuals to cope with life stress and symptoms of illness: a systematic review. Anxiety Stress Coping. 2009. 1-40. Epub.
Samaan Z et al. Migraine in recurrent depression: case-control study. The British Journal of Psychiatry. 2009. 194. 350-354.
Seo S et al. Effects of demographic factors on cortical thickness in Alzheimer’s Disease. Neurobiol Aging. 2009. Epub.
Stauffer V et al. Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: A post-hoc analysis of 5 double-blind, randomised, clinical trials. BMC Psychiatry. 2009. 9(1). Epub.
Taragano F et al. Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. J Clin Psychiatry. 2009. Epub.
Van der Vlies A et al. Most rapid cognitive decline in APOE epsilon4 negative Alzheimer’s Disease with early onset. Psychol Med. 2009. 1-5. Epub.
Velakoulis D, Walterfang M, Mocellin R, Pantelis C and McLean C. Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases. British Journal of Psychiatry. 2009. 194. 298-305.
Yamada M et al. Incidence of dementia among atomic-bomb survivors – Radiation Effects Research Foundation Adult Health Study. J Neurol Sci. 2009. Epub.
Zakzanis K et al. Age and dementia related differences in spatial navigation within an immersive virtual environment. Med Sci Monit. 2009. 15(4). CR140-50.
Zhang L et al. CTN-986, a compound extracted from cottonseeds, increases cell proliferation in hippocampus in vivo and in cultured neural progenitor cells in vitro. Eur J Pharmacol. 2009. 607(1-3). 110-3.
Steps To Treatment (STT)
STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.
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