- Email: [email protected]
P.2.c.028 Candidate genes expression profile associated with antidepressants response: baseline predictors and longitudinal targets
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P.2.c. Affective disorders and antidepressants − Antidepressants (clinical)
with different therapeutic effects depending on the dose [1]. Trazodone is mostly used at lower doses (75–150 mg) for its hypnotic properties and in combinations with other antidepressants. The aim of this study was to evaluate the treatment of patients with moderate to severe depressive disorder with the optimal antidepressant (300 mg) dose of trazodone. This dose allows to fully develop the antidepressant effect of trazodone and offers the clinical benefit from the proper therapy. Methods: A post-authorization, questionnaire-based safety study with antidepressant dose of trazodone (300 mg daily) was performed. The questionnaire focused on the efficacy and tolerability of trazodone in the out-patients suffering from moderate and severe depressive disorder. Efficacy and safety evaluations were done at baseline, after titration (week 2−3) and at final visit (week 8−9). The initial dose was 100 mg evening; the target dose was 300 mg. The primary endpoint of this 8-weeks study was the change in the MADRS and CGI-S total score and occurrence of adverse events. Further, quality of sleep, occurrence of anxiety and sexual dysfunction and changes in body mass index were evaluated separately. Results: The study was performed from April to December 2011 at 11 psychiatric centers in the Czech Republic. A total of 163 patients were included, 10 patients (6%) prematurely discontinued the study. During the study a significant decrease of the mean total MADRS and CGI-S scores was observed. Remission (defined by MADRS <10) was achieved in 84 (52%) of the patients. The treatment was relatively well tolerated. During the course of the study 86 patients (52.8%) reported at least one adverse event. The most common adverse events were headache, somnolence, dry mouth, dizziness, sedation and fatigue, however the severity was low. A significant improvement in all three qualities of sleep was observed. At the end of the study 126 patients (77.3%) reported having either excellent or good overall quality of sleep versus 7 patients at baseline (5.6%), 129 patients (79.1%) reported never or rarely trouble falling asleep versus 22 patients at baseline (13.5%) and 133 patients (81.6%) reported never or rarely awakening during the night versus 19 patients at baseline (11.7%). Simultaneously a significant reduction of hypnotic and anxiolytic co-medication was found. The incidence of sexual dysfunction in patients treated with trazodone dropped from 30% to 8.6%, anxiety from 73% to 11.7%. Average BMI minimally increased (from 25.12 to 25.21), weight gain was reported in 49 cases (30.0%), loss in 25 cases (15.3%). Conclusions: Trazodone modified release tablets at the daily dose of 300 mg appeared to be an appropriate monotherapy for the patients with moderate to severe depressive disorder in outpatient settings. It could be a treatment of choice in depressive patients with anxiety and sleep impairment. A great advantage is the minimal need for concomitant hypnotics and anxiolytics. The study (PASS study N. 53–2011) was initiated and supported by research grant from Medicom International Ltd. CR. References [1] Stahl, S.M., 2009. Multifunctional drugs: a novel concept for psychopharmacology. CNS Spectr 14, 71−3.
P.2.c.028 Candidate genes expression profile associated with antidepressants response: baseline predictors and longitudinal targets A. Cattaneo1 ° , M. Gennarelli2 , U. Rudolf3 , G. Breen3 , A. Farmer3 , K.J. Aitchison3 , C. Anacker4 , P.A. Zunsztain4 , P. McGuffin3 , C.M. Pariante4 1 University of Brescia, Biomedical Sciences and Biotechnology, Brescia, Italy; 2 University of Brescia/ IRCCS San Giovanni di Dio, Biomedical Sciences and Biotechnology, Brescia, Italy; 3 King’s College London Institute of Psychiatry, MRC Social Genetic and Developmental Psychiatry, London, United Kingdom; 4 King’s College London Institute of Psychiatry, Department of Psychological Medicine, London, United Kingdom Despite the increasing variety of antidepressants currently available, only a third of patients respond adequately to treatment, and up to half of them relapse within one year. Unfortunately, we still cannot predict the likelihood of response of an individual patient to a specific drug [1]. Therefore, there is a pressing need to identify biomarkers that, assessed before starting treatment, predict future response, as well as biomarkers that are targeted by antidepressants and change longitudinally during antidepressant treatment. To reach this aim, we have analyzed in the leukocytes of controls (n = 34) and depressed patients (n = 74) prior to and after 8 weeks of AD treatment with escitalopram or nortryptiline (GENDEP study) by Real Time PCR the expression levels of genes belonging to HPA axis functionality (GR, FKBP5, FKBP4), inflammation (TNF-a, IL-6, MIF, IL-7, IL-10, IL-1b, IL1-a, IL-4, IL-8) and neuroplasticity (BDNF, VGF, p11) [2]. We found that depressed patients, as compared to controls, had higher FKBP-5 (+27%, p < 0.0001) and lower GR mRNA levels (−18%, p < 0.0001). Moreover, they had higher mRNA levels of IL-1b, (+48%, p < 0.0001), IL-6 (+24%, p < 0.0001), MIF (+32%, p < 0.0001), and TNF-a (+58%, p < 0.0001), and lower levels of IL-4 (−9%, p = 0.02). Finally, depressed patients had lower mRNA levels of BDNF (−24%, p < 0.0001), p11 (−16%, p = 0.001) and VGF (−36%, F = 37.3, p < 0.0001). When we compared the baseline levels of these genes in patients who responded versus patients who didn’t respond to the treatment, we found that non-responders had higher mRNA levels of IL-1b (+33%, p < 0.0001), MIF (+48%, p < 0.0001) and TNF-a (+39%, p < 0.0001). Indeed the expression levels of MIF, IL-1b and TNF-a at baseline were all strongly and negatively correlated with the treatment outcome (IL-1b, r = −0.56; MIF, r = −0.62; and TNF-a, r = −0.44; all p < 0.0001). Antidepressant treatment reduced FKBP5 (−11%, p < 0.0001) and increased VGF levels (+20%, p < 0.0001) only in patients who responded to the treatment, whereas no effect was observed in non-responders (p = 0.45 for FKBP-5 and p = 0.97 for VGF). IL-6 was regulated by antidepressant treatment in a drug- and response-specific way. Namely, IL-6 levels decreased significantly in responders (−9%, p < 0.0001), and this was present for both responders to escitalopram (−12%, p = 0.001) and to nortryptiline (−6%, p = 0.02). In non-responders there was no overall effect (p = 0.5) but, when the two drugs were analysed separately, IL-6 did not change in the non-responders to escitalopram (−2%, p = 0.5) but increased in the non-responders to nortryptiline (+7%, p = 0.037). Finally, four genes were regulated by antidepressant treatment, irrespective of the antidepressant used or of treatment response. Specifically, antidepressant treatment significantly increased GR
P.2.c. Affective disorders and antidepressants − Antidepressants (clinical) mRNA levels (+5%, p = 0.009) and p11 levels (+8%, p = 0.005), and reduced the expression levels of IL-1b (−6%, p = 0.006) and MIF (−24%, p < 0.0001). These results demonstrate that three inflammation-related genes, IL-1b, MIF and TNF-a, predict lack of response to antidepressants, but successful antidepressant response is not associated with reduction in the levels of these genes. This suggests that persistence of inflammation is not a factor preventing treatment response, as the levels of these cytokines tend to normalize in both responder and non responders. References [1] Uher R (2011). Genes, environments and individual differences in response to treatment. Harvard Review of Psychiatry 19: 109–124. [2] Chopra K, Kumar B, Kuhad A. (2011). Pathobiological targets of depression. Expert Opin Ther Targets 15: 379–400. Review.
P.2.c.029 Repetitive transcranial magnetic stimulation and pharmacological treatment in patients with major depressive disorder F. Magnano1 ° , C. Concerto1 , D. Cannav`o1 , G. Lanza2 , M. Pennisi2 , E. Aguglia1 1 A.O.U. Policlinico-Vittorio Emanuele, U.O.P.I. of Psychiatry, Catania, Italy; 2 A.O.U. Policlinico-Vittorio Emanuele, Department of Neuroscience, Catania, Italy Introduction: Major depression is one of the leading causes of disease burden worldwide. Its impact on society with renard to human suffering and economic charge is enormous and is even projected to increase in upcoming decades. The World Health Organization (WHO) estimates that they will be the second most important cause of disability by the year 2020. Current approaches to the treatment of major depression, while effective, are nevertheless associated with substantial percentages of nonresponders or partial responders. Approximately 30% of depressed patients do not show sufficient improvements after the first course of adequate antidepressant treatment and a further 20% discontinue due to tolerability problems. Half of patients who do not respond adequately to a first course also fail to respond to a second antidepressant treatment trial. If several antidepressant treatment trials have been inefficient, even lower response rates after switching to other drugs may be observed. Because of relapses and recurrences, major depression tends to be a chronic illness. Given the pervasive nature of depression and the need for more effective, safer and more socially acceptable therapeutic strategies, alternative approaches are being investigated, such as repetitive Transcranial Magnetic Stimulation (rTMS). Several Clinical Trials on Repetitive Transcranial Magnetic Stimulation (rTMS) have shown its effectiveness in the treatment of depression proposing rTMS as an augmentation strategy [1,2]. Objectives: Object of this study was to compare the effectiveness of rTMS associated with pharmacotherapy and single drug treatment in pharmacotherapy-resistant major depressive patients. Methods: A sample of 20 outpatients was randomly assigned to one of two treatment groups. Inclusion criteria: age between 45 and 65; diagnosis of major depressive disorder (according to the criteria of DSM-IV-TR); score 20 at the 21-item HDRS score 25 or the MADRS; drug resistance to at least three adequate courses of at least 2 different classes of antidepressants; serious neurological evaluation was excluded performing CT or MRI. Group I was treated with drugs and high-frequency rTMS over the left dorso-lateral-prefrontal-cortex. Group II was treated only
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with drugs. Effectiveness data was gathered at baseline and at week 4. Clinician-rating of depressive symptoms included the Hamilton Depression Rating Scale and the Montgomery Asberg Depression Rating Scale. All patients underwent an evaluation of neuropsychological battery for the evaluation of different frontal lobe abilities, both before and after rTMS, including the Frontal Assessment Battery and the Stroop Color Word Test interference. Results: Comparison of the two group treatment revealed statistically significant mood improvements in the first group as indexed by a reduction of more than 40% on the Hamilton Rating Scale for Depression and on Montgomery Asberg Depression Rating Scale. Conclusion: Left prefrontal rTMS as combined therapy with drugs produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than single drug treatment [3]. References [1] Kim D.R., 2009. Transcranial Magnetic Stimulation in the Treatment of Psychiatric Disorders, Current Psychiatry Reports 11: 447–452. [2] O’Reardon J.P., 2007. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 62: 1208–1216. [3] Berlim M.T., 2011. High frequency repetitive transcranial magnetic stimulation as an augmenting strategy in severe treatment-resistant major depression: A prospective 4-week naturalistic trial. Journal of Affective Disorders130(1−2): 312−7.
P.2.c.030 Volumetric changes in amygdala and hippocampus after three months of paroxetine treatment for major depressive disorder H.G. Ruhe1 ° , E. Miedema2 , J. Booij3 , M.W.A. Caan4 , D.J. Veltman5 , A.H. Schene2 1 University Medical Center Groningen, Program for Affective Disorders University Center for Psychiatry, Groningen, The Netherlands; 2 Academic Medical Center, Program for Mood Disorders Dept. of Psychiatry, Amsterdam, The Netherlands; 3 Academic Medical Center, Dept. of Nuclear Medicine, Amsterdam, The Netherlands; 4 Academic Medical Center, Dept. of Radiology, Amsterdam, The Netherlands; 5 VU Medical Center, Dept. of Psychiatry, Amsterdam, The Netherlands Background: Amygdala and hippocampal volumes are reduced in patients with major depressive disorder (MDD) relative to healthy controls (HC) [1,2]. A meta-analysis of cross-sectional studies of amygdala-volumes revealed that antidepressants might increase these volumes [1], which is unclear for the hippocampus [2]. Furthermore, by the cross-sectional nature of the studies underlying these meta-analyses, it cannot be excluded that patients who need antidepressant treatment represent a selected population with different amygdala and hippocampus structure. To our knowledge, this association was not yet investigated prospectively. Aim: To prospectively measure volumetric changes of amygdala and hippocampus after 12 weeks of paroxetine-treatment in MDD-patients. Methods: We compared 3T structural MRI-scans of 22 drug free MDD-patients (25−55yrs, Hamilton (HDRS)-score>18; 64% drug-naive) and 22 gender and age matched HC (free of lifetime psychiatric disorders and no psychiatric disorders in first degree relatives). Thereafter, we treated patients with paroxetine (20−50 mg/day) and obtained repeated scans at 6 and 12 weeks (n = 19). After segmentation we used DARTEL in SPM8 to obtain
P.2.c. Affective disorders and antidepressants − Antidepressants (clinical)
with different therapeutic effects depending on the dose [1]. Trazodone is mostly used at lower doses (75–150 mg) for its hypnotic properties and in combinations with other antidepressants. The aim of this study was to evaluate the treatment of patients with moderate to severe depressive disorder with the optimal antidepressant (300 mg) dose of trazodone. This dose allows to fully develop the antidepressant effect of trazodone and offers the clinical benefit from the proper therapy. Methods: A post-authorization, questionnaire-based safety study with antidepressant dose of trazodone (300 mg daily) was performed. The questionnaire focused on the efficacy and tolerability of trazodone in the out-patients suffering from moderate and severe depressive disorder. Efficacy and safety evaluations were done at baseline, after titration (week 2−3) and at final visit (week 8−9). The initial dose was 100 mg evening; the target dose was 300 mg. The primary endpoint of this 8-weeks study was the change in the MADRS and CGI-S total score and occurrence of adverse events. Further, quality of sleep, occurrence of anxiety and sexual dysfunction and changes in body mass index were evaluated separately. Results: The study was performed from April to December 2011 at 11 psychiatric centers in the Czech Republic. A total of 163 patients were included, 10 patients (6%) prematurely discontinued the study. During the study a significant decrease of the mean total MADRS and CGI-S scores was observed. Remission (defined by MADRS <10) was achieved in 84 (52%) of the patients. The treatment was relatively well tolerated. During the course of the study 86 patients (52.8%) reported at least one adverse event. The most common adverse events were headache, somnolence, dry mouth, dizziness, sedation and fatigue, however the severity was low. A significant improvement in all three qualities of sleep was observed. At the end of the study 126 patients (77.3%) reported having either excellent or good overall quality of sleep versus 7 patients at baseline (5.6%), 129 patients (79.1%) reported never or rarely trouble falling asleep versus 22 patients at baseline (13.5%) and 133 patients (81.6%) reported never or rarely awakening during the night versus 19 patients at baseline (11.7%). Simultaneously a significant reduction of hypnotic and anxiolytic co-medication was found. The incidence of sexual dysfunction in patients treated with trazodone dropped from 30% to 8.6%, anxiety from 73% to 11.7%. Average BMI minimally increased (from 25.12 to 25.21), weight gain was reported in 49 cases (30.0%), loss in 25 cases (15.3%). Conclusions: Trazodone modified release tablets at the daily dose of 300 mg appeared to be an appropriate monotherapy for the patients with moderate to severe depressive disorder in outpatient settings. It could be a treatment of choice in depressive patients with anxiety and sleep impairment. A great advantage is the minimal need for concomitant hypnotics and anxiolytics. The study (PASS study N. 53–2011) was initiated and supported by research grant from Medicom International Ltd. CR. References [1] Stahl, S.M., 2009. Multifunctional drugs: a novel concept for psychopharmacology. CNS Spectr 14, 71−3.
P.2.c.028 Candidate genes expression profile associated with antidepressants response: baseline predictors and longitudinal targets A. Cattaneo1 ° , M. Gennarelli2 , U. Rudolf3 , G. Breen3 , A. Farmer3 , K.J. Aitchison3 , C. Anacker4 , P.A. Zunsztain4 , P. McGuffin3 , C.M. Pariante4 1 University of Brescia, Biomedical Sciences and Biotechnology, Brescia, Italy; 2 University of Brescia/ IRCCS San Giovanni di Dio, Biomedical Sciences and Biotechnology, Brescia, Italy; 3 King’s College London Institute of Psychiatry, MRC Social Genetic and Developmental Psychiatry, London, United Kingdom; 4 King’s College London Institute of Psychiatry, Department of Psychological Medicine, London, United Kingdom Despite the increasing variety of antidepressants currently available, only a third of patients respond adequately to treatment, and up to half of them relapse within one year. Unfortunately, we still cannot predict the likelihood of response of an individual patient to a specific drug [1]. Therefore, there is a pressing need to identify biomarkers that, assessed before starting treatment, predict future response, as well as biomarkers that are targeted by antidepressants and change longitudinally during antidepressant treatment. To reach this aim, we have analyzed in the leukocytes of controls (n = 34) and depressed patients (n = 74) prior to and after 8 weeks of AD treatment with escitalopram or nortryptiline (GENDEP study) by Real Time PCR the expression levels of genes belonging to HPA axis functionality (GR, FKBP5, FKBP4), inflammation (TNF-a, IL-6, MIF, IL-7, IL-10, IL-1b, IL1-a, IL-4, IL-8) and neuroplasticity (BDNF, VGF, p11) [2]. We found that depressed patients, as compared to controls, had higher FKBP-5 (+27%, p < 0.0001) and lower GR mRNA levels (−18%, p < 0.0001). Moreover, they had higher mRNA levels of IL-1b, (+48%, p < 0.0001), IL-6 (+24%, p < 0.0001), MIF (+32%, p < 0.0001), and TNF-a (+58%, p < 0.0001), and lower levels of IL-4 (−9%, p = 0.02). Finally, depressed patients had lower mRNA levels of BDNF (−24%, p < 0.0001), p11 (−16%, p = 0.001) and VGF (−36%, F = 37.3, p < 0.0001). When we compared the baseline levels of these genes in patients who responded versus patients who didn’t respond to the treatment, we found that non-responders had higher mRNA levels of IL-1b (+33%, p < 0.0001), MIF (+48%, p < 0.0001) and TNF-a (+39%, p < 0.0001). Indeed the expression levels of MIF, IL-1b and TNF-a at baseline were all strongly and negatively correlated with the treatment outcome (IL-1b, r = −0.56; MIF, r = −0.62; and TNF-a, r = −0.44; all p < 0.0001). Antidepressant treatment reduced FKBP5 (−11%, p < 0.0001) and increased VGF levels (+20%, p < 0.0001) only in patients who responded to the treatment, whereas no effect was observed in non-responders (p = 0.45 for FKBP-5 and p = 0.97 for VGF). IL-6 was regulated by antidepressant treatment in a drug- and response-specific way. Namely, IL-6 levels decreased significantly in responders (−9%, p < 0.0001), and this was present for both responders to escitalopram (−12%, p = 0.001) and to nortryptiline (−6%, p = 0.02). In non-responders there was no overall effect (p = 0.5) but, when the two drugs were analysed separately, IL-6 did not change in the non-responders to escitalopram (−2%, p = 0.5) but increased in the non-responders to nortryptiline (+7%, p = 0.037). Finally, four genes were regulated by antidepressant treatment, irrespective of the antidepressant used or of treatment response. Specifically, antidepressant treatment significantly increased GR
P.2.c. Affective disorders and antidepressants − Antidepressants (clinical) mRNA levels (+5%, p = 0.009) and p11 levels (+8%, p = 0.005), and reduced the expression levels of IL-1b (−6%, p = 0.006) and MIF (−24%, p < 0.0001). These results demonstrate that three inflammation-related genes, IL-1b, MIF and TNF-a, predict lack of response to antidepressants, but successful antidepressant response is not associated with reduction in the levels of these genes. This suggests that persistence of inflammation is not a factor preventing treatment response, as the levels of these cytokines tend to normalize in both responder and non responders. References [1] Uher R (2011). Genes, environments and individual differences in response to treatment. Harvard Review of Psychiatry 19: 109–124. [2] Chopra K, Kumar B, Kuhad A. (2011). Pathobiological targets of depression. Expert Opin Ther Targets 15: 379–400. Review.
P.2.c.029 Repetitive transcranial magnetic stimulation and pharmacological treatment in patients with major depressive disorder F. Magnano1 ° , C. Concerto1 , D. Cannav`o1 , G. Lanza2 , M. Pennisi2 , E. Aguglia1 1 A.O.U. Policlinico-Vittorio Emanuele, U.O.P.I. of Psychiatry, Catania, Italy; 2 A.O.U. Policlinico-Vittorio Emanuele, Department of Neuroscience, Catania, Italy Introduction: Major depression is one of the leading causes of disease burden worldwide. Its impact on society with renard to human suffering and economic charge is enormous and is even projected to increase in upcoming decades. The World Health Organization (WHO) estimates that they will be the second most important cause of disability by the year 2020. Current approaches to the treatment of major depression, while effective, are nevertheless associated with substantial percentages of nonresponders or partial responders. Approximately 30% of depressed patients do not show sufficient improvements after the first course of adequate antidepressant treatment and a further 20% discontinue due to tolerability problems. Half of patients who do not respond adequately to a first course also fail to respond to a second antidepressant treatment trial. If several antidepressant treatment trials have been inefficient, even lower response rates after switching to other drugs may be observed. Because of relapses and recurrences, major depression tends to be a chronic illness. Given the pervasive nature of depression and the need for more effective, safer and more socially acceptable therapeutic strategies, alternative approaches are being investigated, such as repetitive Transcranial Magnetic Stimulation (rTMS). Several Clinical Trials on Repetitive Transcranial Magnetic Stimulation (rTMS) have shown its effectiveness in the treatment of depression proposing rTMS as an augmentation strategy [1,2]. Objectives: Object of this study was to compare the effectiveness of rTMS associated with pharmacotherapy and single drug treatment in pharmacotherapy-resistant major depressive patients. Methods: A sample of 20 outpatients was randomly assigned to one of two treatment groups. Inclusion criteria: age between 45 and 65; diagnosis of major depressive disorder (according to the criteria of DSM-IV-TR); score 20 at the 21-item HDRS score 25 or the MADRS; drug resistance to at least three adequate courses of at least 2 different classes of antidepressants; serious neurological evaluation was excluded performing CT or MRI. Group I was treated with drugs and high-frequency rTMS over the left dorso-lateral-prefrontal-cortex. Group II was treated only
S267
with drugs. Effectiveness data was gathered at baseline and at week 4. Clinician-rating of depressive symptoms included the Hamilton Depression Rating Scale and the Montgomery Asberg Depression Rating Scale. All patients underwent an evaluation of neuropsychological battery for the evaluation of different frontal lobe abilities, both before and after rTMS, including the Frontal Assessment Battery and the Stroop Color Word Test interference. Results: Comparison of the two group treatment revealed statistically significant mood improvements in the first group as indexed by a reduction of more than 40% on the Hamilton Rating Scale for Depression and on Montgomery Asberg Depression Rating Scale. Conclusion: Left prefrontal rTMS as combined therapy with drugs produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than single drug treatment [3]. References [1] Kim D.R., 2009. Transcranial Magnetic Stimulation in the Treatment of Psychiatric Disorders, Current Psychiatry Reports 11: 447–452. [2] O’Reardon J.P., 2007. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 62: 1208–1216. [3] Berlim M.T., 2011. High frequency repetitive transcranial magnetic stimulation as an augmenting strategy in severe treatment-resistant major depression: A prospective 4-week naturalistic trial. Journal of Affective Disorders130(1−2): 312−7.
P.2.c.030 Volumetric changes in amygdala and hippocampus after three months of paroxetine treatment for major depressive disorder H.G. Ruhe1 ° , E. Miedema2 , J. Booij3 , M.W.A. Caan4 , D.J. Veltman5 , A.H. Schene2 1 University Medical Center Groningen, Program for Affective Disorders University Center for Psychiatry, Groningen, The Netherlands; 2 Academic Medical Center, Program for Mood Disorders Dept. of Psychiatry, Amsterdam, The Netherlands; 3 Academic Medical Center, Dept. of Nuclear Medicine, Amsterdam, The Netherlands; 4 Academic Medical Center, Dept. of Radiology, Amsterdam, The Netherlands; 5 VU Medical Center, Dept. of Psychiatry, Amsterdam, The Netherlands Background: Amygdala and hippocampal volumes are reduced in patients with major depressive disorder (MDD) relative to healthy controls (HC) [1,2]. A meta-analysis of cross-sectional studies of amygdala-volumes revealed that antidepressants might increase these volumes [1], which is unclear for the hippocampus [2]. Furthermore, by the cross-sectional nature of the studies underlying these meta-analyses, it cannot be excluded that patients who need antidepressant treatment represent a selected population with different amygdala and hippocampus structure. To our knowledge, this association was not yet investigated prospectively. Aim: To prospectively measure volumetric changes of amygdala and hippocampus after 12 weeks of paroxetine-treatment in MDD-patients. Methods: We compared 3T structural MRI-scans of 22 drug free MDD-patients (25−55yrs, Hamilton (HDRS)-score>18; 64% drug-naive) and 22 gender and age matched HC (free of lifetime psychiatric disorders and no psychiatric disorders in first degree relatives). Thereafter, we treated patients with paroxetine (20−50 mg/day) and obtained repeated scans at 6 and 12 weeks (n = 19). After segmentation we used DARTEL in SPM8 to obtain