There were a number of interesting studies including a possible cellular mechanism by which anticholinesterase inhibitors might work, predicting treatment outcome with antidepressants and the potential benefits of playing chess!
Research in Mild Cognitive Impairment and Dementia
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 Mood Disorders
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 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.
Research in Psychosis
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 clinicall 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).
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).
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.
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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