In February 2008, there were a number of neuropsychiatry articles reviewed on Alzheimer’s Disease and also on the Insular Cortex, the latter being by A. Craig – and some of the ideas from this paper will be incorporated into the internet model of the Insular Cortex being developed on the blog. A number of clinically relevant and psychologically oriented papers were reviewed on subjects including the therapeutic alliance. Social psychiatry articles reviewed included Department of Health documents and an editorial in Nature on how the research community should engage with the blogosphere! In the books section, two works by Freud were reviewed including the classic ‘Interpretation of Dreams’ and Fromm’s ‘The Art of Being’. A number of science podcasts were reviewed as well as episodes from John Betts series on Analytical Psychology. There were a number of blogs reviewed including the Dream Journal which allows users to upload their dreams for analysis! Finally in the news section there were a number of studies covered including one looking at an association between diabetes and dementia, plaques in Alzheimer’s Disease being more likely to form in a region referred to as the cortical hub, the finding that individual neurons can hold information for up to a minute, a possible role for allopurinol in the treatment of psychosis, improvement in a number of cognitive domains in people with schizophrenia who were taught and played chess, a correlation between scores on an emotional intelligence test and negative symptoms in people with schizophrenia, a small study showing benefits of Mirtazapine augmentation on PANSS scores in people with schizophrenia, an association between baseline Young Mania rating scores and treatment emergent mania and 2-week response of an antidepressant as a predictor of treatment outcome.
Medical Articles Reviewed
Psychology/Psychotherapy Articles Reviewed
Social Psychiatry Articles
February 2009 News Round-Up
Research in Dementia and Related Areas
Alan Johnson, Health Secretary, unveiled a national dementia strategy to Parliament. There was a case-control study finding in 13693 twins (65 years or older), that the risk of dementia was associated with a 2-fold increase in (people with) diabetes. This is an interesting finding as there may be modifiable risk factors and also there is a relatively obscure hypothesis about potential CNS actions of insulin. However the obvious confounders in such an argument are the cardiovascular risk factors but this must at least begin a theoretical debate in this area (STT3). One of the difficulties that can occur in research in dementia is when the potential subject does not have the capacity to consent although there is appropriate guidance in this area. In a recent survey of 538 people over the age of 65, 92% of people were found to be willing to give blood and 75% to give blood and undergo lumbar punctures as part of a research study at a future point if they no longer had capacity, even if the research didn’t benefit them directly. An emerging theory with supporting data is that there are cortical hubs in the brain, areas which are well connected in which ABeta plaques are more likely to form (using PIB-PET). In a study of people with probable Alzheimer’s Disease, 140 were prescribed memantine and a cholinesterase inhibitor, 387 a cholinesterase inhibitor only and 416 were prescribed neither. Although there was no significant effect on time to death, ChEI’s significantly delayed time to nursing home admission compared to without ChEI’s and the addition of memantine significantly delayed admission compared to the ChEI alone group (STT2).
The consultation document is here (STT1). A slightly abstract piece of research is one at the cellular level, but i’ve included it here as it has important implications for memory. Thus in Nature Neuroscience, Cooper and colleagues have used a patch-clamp recording technique on layer V Pyramidal cells in the Prefrontal Cortex and found that the cell’s depolarisation on receiving input from another cell continues for up to a minute even when the other synapsing neuron is no longer firing. As cocaine has an influence on working memory and also eliminated the depolarisation, the authors conclude that this cell was retaining a memory (STT4). A study in healthy elderly (average age 60 years) volunteers showed an improvement in verbal memory with calorific restriction together with a reduction in C-Reactive Protein and Insulin levels. The results will need further replication but fit with a body of evidence emerging in the area of calorie-restriction. However, such approaches have potential to compromise the immune system and the Department of Health has given advice about not reducing calories during the winter months when infections are more prevalent. Larger and longer term studies will be required before any recommendations can be safely made (STT4).
A group from Oxford have presented the results of a novel approach to diagnosing Parkinson’s Disease. They hypothesise that the distribution of metal ions in neurons in Parkinson’s Disease is affected by the disease process and that it can be used in identifying the disease at an early stage. They argue that the method of preparing tissue before analysis has the potential to influence the iron content of cells and they have developed and are using a method that they state does not alter the iron composition of cells. They then used the UK National Synchrotron which can focus beams in a small area of the tissue to characterise the form in which the iron is stored very precisely using a technique referred to as Microfocus Spectroscopy. They are due to formally announce their findings at the AAAS in which they have identified an altered distribution of iron in cells in Parkinson’s Disease. The next stage is to use this information to interpret MRI studies. While this novel approach is encouraging it will be interesting to see the published research and to see the results of MRI interpretations (STT5).
An intriguing study looked at the possibility that Rivastigmine could act partly through the induction of heat shock proteins for which there is evidence of a neuroprotective role (Zhou et al, 2009)(STT5). The authors of a recent meta-analysis on MCI concluded that the risk of progression to dementia may be reduced by anticholinesterase inhibitors. This is a complex area and no doubt this debate will continue (Diniz et al, 2009)(STT3). The authors of an interesting study looking at lacunar infarcts concluded that memory was more likely to be affected if the thalamus, putamen and pallidus were affected rather than the internal capsule and caudate nucleus (Benisty et al, 2009)(STT3).
Research in Psychosis
In a small study with 13 subjects with schizophrenia and formal thought disorder and 13 controls there was found to be a correlation between perfusion of left fronto/temporoparietal language areas and severity of formal thought disorder and between reduced temporoparietal grey matter volume and severity of formal thought disorder (STT5). In a longitudinal study there was found to be an association between length of untreated psychosis and functional outcome at 12 months with the authors suggesting that treatment options can be developed at earlier (i.e. prodromal) phases of the illness (STT3).
A recent meta-analysis of blinded studies of head-to-head 2nd generation antipsychotics found that there were differences in efficacy. The authors utilised metaregression and sensitivity analyses to examine bias for factors such as industry sponsorship and concluded that the differences remained.In a Janssen-Cilag sponsored 3-year longitudinal study involving 211 people taking Risperidone Long-Acting injections looked at discontinuation. The discontinuation rate at 3 years was 84% and factors associated with discontinuation included age (younger) and duration of illness (longer). The authors conclude that outcome could be improved by targetting treatment and also comment on dosage (Taylor et al, 2009)(STT3). There was some evidence of a benefit in early psychosis for augmentation with allopurinol and it would be interesting to see how this develops (Dickerson et al, 2009). A meta-analysis of studies looking at Theory of Mind in schizophrenia identified heterogeneity secondary to state and also differences in tasks but concluded that there was evidence of a trait from the persistence after remission (Bora et al, 2008) (STT4). In another study, 10 hours of chess tuition and playing was found to improve performance on the Stroop and Tower of London tests in people with schizophrenia relative to a treatment as usual group. The authors suggest this represents an improvement in planning abilities due to playing chess which fits with other studies of chess players although it will be interesting to see the results of further research in this area (Demily et al, 2009)(STT4). Another intriguing study looked at emotional intelligence in people with schizophrenia using a validated test – the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). The researchers found that in 50 people with schizophrenia and 39 non-psychiatric controls, the people with schizophrenia scored significantly worse on the total MSCEIT and that their scores also correlated with negative symptoms, disorganised symptoms and community functioning (Kee et al, 2009)(STT4). A small RCT (n=39) in people with schizophrenia showed a significant and clinically relevant improvement in PANSS scores with the addition of Mirtazapine to a first-generation antipsychotic compared to FGA-plus placebo (Joffe et al, 2009)(STT3). A meta-analysis found a trend towards higher schizotypal traits in people with non-right handedness compared to strong right handers (the non-right handed group consisted of left handers and mixed handedness) although there wasn’t a significant difference between strong right and left handers. The authors argue that these results support a model in which bilateral language organisation may relate to loosening of associations (Somers et al, 2009)(STT4).
Research in Mood Disorders
In an analysis from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) of 1380 people who met criteria for Bipolar I or II, 2/3 of people with bipolar depression were found to have concurrent manic symptoms and a number of associations with this group were found including earlier age at onset, rapid cycling in past year and bipolar I (STT2). In a 10-week trial of 176 adults with bipolar disorder, treatment emergent mania was associated with significantly higher baseline scores on the Young Mania Rating Scale (STT1). There was a study looking at complex pharmacology in Bipolar Disorder. 4035 Subjects were recruited from the STAR*D study (just before commencing participation). A receiver operating characteristic analysis was performed (a method which is designed to discriminate between signal and noise). The researchers found that factors such as a high income, taking an atypical antipsychotic , and more than 6 episodes of depression but not age of onset, previous psychosis or hospitalisation were associated with prescription of 4 or more medications (Lithium, anticonvulsant, antidepressant, antipsychotic) (Goldberg et al, 2009)(STT3). In another STAR*D study a family history of depression didn’t alter remission or response rates but was associated with earlier age of onset of major depressive disorder, longer length of illness and comorbid anxiety (Husain et al, 2009)(STT4). A potentially important meta-analysis looked at trials of Mirtazapine with comparators/placebo in major depressive disorder and the findings suggested that response in the first two weeks is associated with treatment outcome and in this particular analysis there was a high sensitivity (Szegedi et al, 2009)(STT3). A longitudinal study looked at 115 people with Bipolar Disorder and examined the relationship between onset of depression and concurrent alcohol use. The researchers concluded that number of days of alcohol use predicted depression when controlling for concurrent substance misuse and current depression (Jaffee et al, 2009)(STT3). The Maudsley Staging Method for treatment resistant depression has been described in a recent paper where the authors found evidence of face and predictive validity (Fedadu et al, 2009) (STT2). Using data from the Consortium for Research on Electroconvulsive Therapy (CORE), researchers found that relapse after continuation ECT occurred in 9.8% of people not having had at least 1 antidepressant trial before ECT compared to 34.6% of people who had received at least 1 trial of an antidepressant (Rasmussen et al, 2009)(STT3). Mirtazapine improved performance on a simulated driving test at 16 and 30 days on measures of road position and crashes (in the simulation) in people with major depressive disorder (28 people with MDD, half of whom received Mirtazapine and the other half were untreated) (Shen et al, 2009)(STT3).
Research in Liaison Psychiatry
Childhood adversity and anxiety or depression were independently associated with adult-onset headaches in a study which pooled data from cross-sectional surveys in several continents (n=18303). The results of longitudinal studies in this area will be interesting to see (STT4). In another study there was found to be a similar prevalence of Chronic Fatigue Syndrome in Brazil and Britain although it was underdiagnosed in comparison in Brazil. The authors conclude that cultural factors may contribute to recognition of the illness by doctors (STT3).
Research in Anxiety, PTSD and Related Disorders
A recent study looking at the effect of Beta-Blockers on emotionally disturbing memories in Nature Neuroscience is discussed in more detail here.
At the AAAS meeting, a study of children in 50 familes was presented in which gesturing at age 14/12 was associated with a larger vocabulary at age 4.5 years. Further examination of an association between gesturing and vocabulary is of potential relevance to conditions where gesturing is reduced (STT5). There is a commentary in the American Journal of Psychiatry about publication bias and the effectiveness of antidepressants partially in response to the Kirsch study and following another editorial in the British Journal of Psychiatry. A recent study looking at dreams is discussed here in more detail. The study looked at cultural differences in dreams and the researchers also found that people were more likely to think the dreams related to their life if it was consistent with their beliefs. A recently extinct species, the Pyrenean Ibex has been cloned (using DNA from skin samples) after the eggs were introduced into a goat. Unfortunately the infant died soon after birth. This will surely trigger an ethical debate while at the same time offering an option unthinkable to conservationalists even a decade ago as well as having ramifications across the life sciences.
There were a number of recent studies with findings relating to the Insular Cortex. In one study, regional cerebral blood flow in the right Insular Cortex decreased at 30 minutes after exercise and the authors argue for an association with exercise induced decreases in blood pressure (Williamson et al, 2009)(STT4). In a post-mortem stereological study at the end of last year, involving 15 people with schizophrenia, 15 with unipolar depression and 15 with bipolar disorder as well as 15 controls there was found to be a significant decrease in neuronal volume in layer 2 of the Insular Cortex in schizophrenia. The authors recommend further work to expand upon these findings in schizophrenia (STT4)(Pennington et al, 2008). A longitudinal (4 years) MRI study in 23 people with first episode psychosis, 11 people with chronic schizophrenia and 26 controls showed that significant grey matter reduction in the insular cortex of the people with first-episode psychosis relative to controls (1 year v 4 years). Furthermore there was a correlation between loss of grey matter volume in the left insular cortex and positive and negative symptoms. Both people with first-episode psychosis and schizophrenia had a significant reduction in grey matter volume in the anterior insular cortex (Takahshi et al, 2009)(STT4).
There were also a few Neanderthal studies recently. These are of increasing importance because the Neadnethal genome is being sequenced and the differences between the human and Neanderthal genome may give clues to the genes that are involved in human intelligence. The first is that a study of the genome obtained from Neanderthal specimens from Croatia reveal that a specific gene – Microcephalin 1 suggests that they did not interbreed with Homo Sapiens. The group however are examining possible speech capabilities given that they share the FOX-1 gene that is one of many genes associated with speech. . The other piece of research looks at climate changes in the Iberian Peninsula (using marine core samples which allow determination of sea level) where it was found that there was a drop in sea level coinciding with the presumed extinction date of Neanderthals in that area (in the absence of evidence to the contrary). The hypothesis is that Neanderthals in that area would have been exposed to a drought which led to their extinction rather than competition with Homo Sapiens who did not arrive in that region until much later.
Benisty S, Gouw A, Porcher R, Madureira S, Hernandez K, Poggesi A, Van der Flier W M, Van Straaten E C W, Verdelho A, Ferro J, Pantoni L, Inzitari, D, Barkhof F, Fazekas F and Chabriat H. Location of lacunar infarcts correlates with cognition in a sample of non disabled subjects with age-related white matter changes: the LADIS study. Journal of Neurology, Neurosurgery and Psychiatry. 11 Feb 2009. Online.
Bora E, Yucel M and Pantelis C. Theory of mind impairment in schizophrenia: Meta-analysis. 2009. Feb 3. (Epub ahead of print).
Demily C, Cavezian C, Desmurget M, Berquand-Merle M, Chambon V and Franck N. The game of chess enhances cognitive abilities in schizophrenia. Letter to the Editor. January 2009. Vol 107. Issue 1. 112-113.
Dickerson F.B, Stallings C.R, Origoni A.E, Sullens A, Kushalani S, Sandson N and Yolken R.H. A double-blind trial of adjunctive allopurinol for schizophrenia. Schizophrenia Research. 2009. Feb 3 (Epub).
Diniz B S, Pinto J A, Gonzaga M L C, Guimaraes F M, Gattaz W F and Forlenza O V. To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer’s Disease. European Archives of Psychiatry and Clinical Neuroscience. Feb 18. 2009.
Fedadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, Poon L and Cleare A. A Multidimensional tool to quantify treatment resistance in depression: The Maudsley Staging Method. J Clin Psychiatry 2009;70(2):177-184. Online Ahead of Print January 27, 2009.
Goldberg JF, Brooks JO, Kurita K, Hoblyn JC, Ghaemi SN, Perlis RH, Miklowitz DJ, Ketter TA, Sachs GS, Thase ME. Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: Findings from the STEP-BD. J Clin Psychiatry. 2009 Feb 10. pii: [Epub ahead of print].
Husain M.M, Rush J, Wisniekwski S.R, McClintock S.M, Fava M, Nierenberg A.A, Davis L, Balasubramani G.K, Young E, Albala A.A and Trivedi M.H. Family history of depression and therapeutic outcome: Findings from STAR*D. J Clin Psychiatry. 2009. 70(2). 185-195. J Clin Psychiatry. 2009. 70(2). 196-200.
Jaffee W.B, Griffin M.L, Gallop R, Meade C.S, Graff F, Bender R.E and Weiss R.D. Depression precipitated by alcohol use in patients with co-occurring Bipolar and Substance Use Disorders. J Clin Psychiatry. 2009. 70(2). 171-176. (EPub 30.12.2008).
Joffe G, Terevnikov V, Joffe M, Stenberg J.H, Burkin M and Tihonen J. Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: A double-blind, randomized, placebo-controlled trial. pp245-251. Vol 108. Issues 1-3.
Kee K.S, Horan W.P, Salovey P, Kern R.S, Sergi M.J, Fiske A.P, Lee J, Subotnik K.L, Nuechterlein K, Sugar C.A and Green M.F. Emotional intelligence in schizophrenia. Vol 107. Issue 1. Pages 1-114. January 2009.
Pennington K, Dicker P, Hudson L and Cotter D.R. Evidence for reduced neuronal somal size within the insular cortex in schizophrenia, but not in affective disorders. Schizophrenia Research. Vol 106. Issues 203. Dec 2008. 164-171.
Rasmussen K, Mueller M, Rummans T, Husain M, Petrides G, Knapp R, Fink M, Sampson S, Bailine S and Kellner C. J Clin Psychiatry. 2009. 70(2). 232-237.
Salvatore P, Baldessarini R.J, Tohen M, Khalsa H-M K, Sanchez-Toledo J.P, Zarate C, Vieta E and Maggini C. McLean-Harvard International First-Episode Project: Two-Year stability of DSM-IV diagnoses in 500 First-Episode psychotic disorder patients. J Clin Psychiatry. 2008. Dec 30. e1-e9. pii.
Shen J, Moller H.J, Wang X, Chung S.A, Shapiro G.K, Li X and Shapiro C. Mirtazapine, a sedating antidepressant and improved driving safety in patients with major depressive disorder: A prospective, randomized trial of 28 patients. J Clin Psychiatry. Jan 13. 2009. e1-e8. pii.
Somers M, Sommer I.E, Boks M.P and Kahn R.S. Hand-preference and population schizotypy: A meta-analysis. Vol 108. Schizophrenia Research. Issues 1-3. March 2009. pp25-32.
Szegedi A, Jansen W.T, van Willigenburg A P, Van der Meulen E, Stasses H.H and Thase M.E. Early improvement
in the first 2 weeks as a predictor of treatment outcome in patient swith major depressive disorder: A Meta-analysis including 6562 patients. J Clin Psychiatry February 24, 2009: e1-e10; pii.
Takahashi T, Wood S, Soulsby B, McGorry P.D, Tanino R, Suzuki M, Velakoulis D and Pantelis C. Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Vol 108. Issues 1-3. March 2009. 49-56.
Taylor D.M, Fischetti C, Sparshatt A, Thomas A, Bishara D and Cornelius V. Risperidone Long-Acting Injection: A Prospective 3-Year analysis of its use in clinical practice. J Clin Psychiatry. 2008. Nov 18. pii. Epub ahead of print.
Williamson JW, Querry R, McColl R, Mathews D.Are decreases in insular regional cerebral blood flow sustained during postexercise hypotension? Med Sci Sports Exerc. 2009 Mar;41(3):574-80.
Zhou X, Patel A.R, Perez F and Jurivich D.A. Acetylcholinesterase inhibitor rivastigmine enhances cellular defenses in neuronal and macrophage-like cell lines. Translational Research. Vol 153. Issue 3. March 2009. pp132-141.
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