różności cz1

23.06.09, 14:34
2009 Apr 30
Cortico-limbic response to personally challenging emotional
stimuli after complete recovery from depression.


Hooley JM, Gruber SA, Parker HA, Guillaumot J, Rogowska J, Yurgelun-
Todd DA.

Department of Psychology, Harvard University, Cambridge, MA 02138,
USA.

People vulnerable to depression are at increased risk of relapse if
they live in highly critical family environments. To explore this
link, we used neuroimaging methods to examine cortico-limbic
responding to personal criticisms in healthy participants and
participants with known vulnerability to major depression. Healthy
controls and fully recovered participants with a past history of
major depression were scanned while they heard praising, critical,
and neutral comments from their own mothers. Prior to scanning, the
formerly depressed and the control participants were
indistinguishable with respect to self-reported positive, negative,
or anxious mood. They also reported similar mood changes after being
praised or criticized. However, formerly depressed participants
responded to criticism with greater activation in the amygdala and
less activation in the dorsolateral prefrontal cortex (DLPFC) and
anterior cingulate cortex (ACC) than did controls. During praise and
neutral commentary, amygdala activation was comparable in both
groups, although lower levels of activation in the DLPFC and ACC
still characterized formerly depressed participants. Vulnerability
to depression may be associated with abnormalities in cortico-limbic
activation that are independent of mood state and that remain even
after full recovery. Criticism may be a risk factor for relapse
because it activates the amygdala and perturbs the affective
circuitry that underlies depression.
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Uderzające podobieństwo do najswizszego badania nt. anhedonii w
depresji.
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Predictors of nonresponse to cognitive behavioural therapy or
venlafaxine using glucose metabolism in major depressive disorder.


Konarski JZ, Kennedy SH, Segal ZV, Lau MA, Bieling PJ, McIntyre RS,
Mayberg HS.

University Health Network, Toronto General Hospital, 200 Elizabeth
St., Eaton North Wing 8-222, Toronto ON M5G2C4.

BACKGROUND: Longitudinal neuroimaging investigations of
antidepressant treatment offer the opportunity to identify potential
baseline biomarkers associated with poor outcome. METHODS: To
explore the neural correlates of nonresponse to cognitive
behavioural therapy (CBT) or venlafaxine (VEN), we compared
pretreatment (18)F-fluoro-2-deoxy-d-glucose positron emission
tomography scans of participants with major depressive disorder
responding to either 16 weeks of CBT (n = 7) or VEN treatment (n =
9) with treatment nonresponders (n = 8). RESULTS: Nonresponders to
CBT or VEN, in contrast to responders, exhibited pretreatment
hypermetabolism at the interface of the pregenual and subgenual
cingulate cortices. LIMITATIONS: Limitations of our study include
the small sample sizes and the absence of both arterial sampling to
determine absolute glucose metabolism and high-resolution structural
magnetic resonance imaging coregistration for region-of-interest
analyses. CONCLUSION: Our current findings are consistent with those
reported in previous studies of relative hyperactivity in the
ventral anterior cingulate cortex in treatment-resistant populations.

Cóż jak nie działa vanlafaksyna lub terapia cognitywno behawioralna,
to dlatego, że dolno (brzuszno) przednia zakręt obręczy jest
hiperaktywny. Chociaż autorzy zaznaczaja pewne ograniczenia tego
badania to mimo tego wyniki są zgodne z poprzednimi badaniami.


The influence of 5-HTTLPR and STin2 polymorphisms in the
serotonin transporter gene on treatment effect of selective
serotonin reuptake inhibitors in depressive patients.


Smits KM, Smits LJ, Peeters FP, Schouten JS, Janssen RG, Smeets HJ,
van Os J, Prins MH.

Department of Epidemiology, Maastricht University, Maastricht, The
Netherlands. kim.smits@epid.unimaas.nl

BACKGROUND: Serotonin transporter gene (SLC6A4) variations have been
proposed as an explanation for interindividual differences in
selective serotonin reuptake inhibitors (SSRIs) effects.
Quantitative assessment of genetic influences is necessary to
evaluate whether genetic testing before antidepressant prescription
would lead to earlier treatment effects. This study evaluates the
influence of two polymorphisms (5-HTTLPR and STin2) on SSRI
treatment outcome in depression. METHODS: We included 50 SSRI
nonresponders (cases) and 164 referents meeting Diagnostic and
Statistical Manual Of Mental Disorder-IV criteria for major
depression and using an SSRI for at least 6 weeks. Blood samples or
buccal swabs were gathered to determine 5-HTTLPR (N=48 for cases and
161 for referents) and STin2 (N=50 for cases and 162 for referents)
genotypes. The association between genotype and SSRI response was
assessed by use of logistic regression. RESULTS: Patients with the 5-
HTTLPR s-allele had a nonsignificantly increased risk of SSRI
nonresponse; odds ratio (OR) 1.60, 95% confidence interval (CI) 0.66-
3.89. 5-HTTLPR effects were strongest in female patients (OR 3.54,
95% CI 1.05-11.92), and for male patients 5-HTTLPR seemed to have no
effect (OR 0.29, 95% CI 0.04-2.34). An age-dependent effect of 5-
HTTLPR was observed; patients under 44 years of age had an increased
nonresponse risk (OR 9.34, 95% CI 1.41-61.98). STin2 genotype had no
clear influence on treatment outcome. CONCLUSION: Our findings
indicate that women with the 5-HTTLPR s-allele have a less favorable
response to SSRI treatment. To our knowledge, this is the first time
that a gender-dependent influence of 5-HTTLPR is reported. More
research is needed, particularly in subgroups of patients, before
implementation of genetic testing can be recommended.
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Czyli kobiety z wariantem genu SLC6A4 5-HTTLPR mają mniejsze szansę
na odpowiedz kliniczną przy stosowaniu leków SSRI.
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    • neuroleptyk Re: różności cz2 23.06.09, 14:56

      Jeszcze o wariantach genów i ich znaczeniu w efektywności leczania
      antydepresantami

      [5-HT1A gene polymorphisms contributed to antidepressant response
      in major depression]


      Kato M, Fukuda T, Wakeno M, Okugawa G, Takekita Y, Serretti A, Azuma
      J, Kinoshita T.

      Department of Neuropsychiatry, Kansai Medical University, 10-15
      Fumizonocho, Moriguchi 570-8506, Japan. katom@takii.kmu.ac.jp

      Variability in antidepressant response is due to genetic and
      environmental factors. Among genetic factors, the ones controlling
      for availability of the drug at the target site are interesting
      candidates. Rs6295C/G SNP in the 5-HT1A gene (HTR1A) has been found
      to affect the expression and function of HTR1A. In fact rs6295C/G is
      in strong linkage disequilibrium with other polymorphisms of HTR1A
      suggesting that those functional effects could be associated with
      polymorphisms other than or together with the synonymous rs6295C/G.
      In the present study we examined the possible association of a panel
      of markers in strong linkage disequilibrium of HTR1A with SSRI/SNRI
      response in 137 Japanese major depression subjects followed for 6
      weeks. We observed a significant association of better response to
      antidepressant in rs10042486C/C (P < 0.0001), rs6295G/G (P < 0.0001)
      and rs1364043T/T (P = 0.018) genotype carriers, independently from
      clinical variables. Furthermore minor allele homozygous carriers in
      all these 3 SNPs were associated with treatment response by various
      assessments such as HAM-D score change over time (P = 0.001), week 2
      (P < 0.0001), 4 (P = 0.007), and 6 (P = 0.048) as well as response
      rate (P = 0.0005) and remission rate (P = 0.004). We also pointed
      out the genotyping mis-definition of rs6295C/G in the previous four
      papers.

      Lepsza odpowiedź na leczenie SSRI/SNRI jeśli się jest posiadaczem
      form genu 5HT1A rs10042486C/C, rs6295G/G rs1364043T/T

      Effects of the serotonin type 2A, 3A and 3B receptor and the
      serotonin transporter genes on paroxetine and fluvoxamine efficacy
      and adverse drug reactions in depressed Japanese patients.


      Kato M, Fukuda T, Wakeno M, Fukuda K, Okugawa G, Ikenaga Y,
      Yamashita M, Takekita Y, Nobuhara K, Azuma J, Kinoshita T.

      Department of Neuropsychiatry, Kansai Medical University, Moriguchi,
      Japan. pangaea1975@yahoo.co.jp

      In this study, we tested the influence of the serotonin type 2A, 3A
      and 3B receptor genes (HTR2A, HTR3A, HTR3B) in addition to a
      polymorphism in the promoter region of the serotonin transporter
      (SERTPR), and investigated the different characteristics of clinical
      responses to paroxetine and fluvoxamine. A total of 100 Japanese
      patients affected by major recurrent depression were enrolled in a
      randomized 6-week study. The clinical response was evaluated using
      the Hamilton Rating Scale for Depression (HAM-D), and adverse drug
      reactions were assessed at each visit. Patients with the l allele of
      SERTPR showed a better response to SSRIs than s/s genotype carriers
      (p = 0.015-0.042), more significantly to fluvoxamine. The -1438G/G
      genotype of HTR2A was associated with a good response to SSRIs (p =
      0.010-0.039), especially to fluvoxamine, and significantly with
      severe nausea in paroxetine-treated patients (p = 0.013). The 178C/C
      genotype of the HTR3A was associated with an antidepressant response
      (p = 0.022-0.042), and more significantly in paroxetine-treated
      patients (p = 0.002-0.042). These effects were independent of one
      another. We replicated the finding that the SERPTR polymorphism was
      associated with a response to SSRIs. We additionally found that
      HTR2A and HTR3A polymorphisms are associated with the efficacy, and
      the HTR2A polymorphism is also associated with adverse drug
      reactions. Furthermore, the effects of these polymorphisms varied
      from one SSRI to another and thus may depend on the characteristics
      of each SSRI.

      Further evidence of a combined effect of SERTPR and TPH on SSRIs
      response in mood disorders.


      Serretti A, Cusin C, Rossini D, Artioli P, Dotoli D, Zanardi R.

      Department of Psychiatry, Vita-Salute University, San Raffaele
      Institute, Milan, Italy. serretti.alessandro@hsr.it

      We reported an independent association of the short variant of the
      serotonin transporter gene-linked polymorphic region (SERTPR) and
      tryptophan hydroxylase (TPH) genes with antidepressant response to
      selective serotonin reuptake inhibitors (SSRIs). The aim of the
      present study was to confirm the effect of the SERTPR and TPH gene
      variants on the SSRIs antidepressant activity in a new sample of
      major and bipolar depressives. Two hundred and twenty one inpatients
      (major depressives = 128, bipolar disorder = 93) were treated with
      SSRIs (fluvoxamine or paroxetine) for 6 weeks; the severity of
      depressive symptoms was weekly assessed with the Hamilton Rating
      Scale for Depression (HAMD). SERTPR and TPH variants were determined
      using PCR-based techniques, 220 subjects genotyped for SERTPR and
      221 for TPH that were never included in previous studies. SERTPR*s/s
      variant association with a poor response to SSRI treatment was
      confirmed, even if with less significant P values (P = 0.034),
      independently from clinical variables; pooling the present sample
      with previous ones we observed a highly significant effect (P <
      0.000001). TPH*A/A variants showed higher HAMD scores throughout the
      trial but with only a trend in the same direction of our previous
      study in terms of a worse response of A/A genotypes. Thus, the
      previous positive association was not fully replicated for TPH. The
      present independent replication confirms SERTPR variants as a
      liability factor for antidepressant efficacy while the TPH effect is
      not unequivocal. Copyright 2004 Wiley-Liss, Inc.
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