Experimental And Clinical Study Of Low Frequency Repetitive Transcranial Magnetic Stimulation On Therapy Of Depression

PART Ⅰ: The establishment of chronic unpredictable mild stress depression model and effect of low frequency repetitive transcranial magnetic stimulation on behavior of rats being exposed to chronic unpredictable mild stressObjective: To study effect of chronic unpredictable mild stress (CUMS) on behavior of rats, establish depression model of rats. And study the effect of low frequency repetitive transcranial magnetic stimulation on behavior of rats being exposed to chronic unpredictable mild stress.Methods: Depression model group: Male Sprague-Dawley rats were exposed to an unpredictable sequence of mild stress for 21 days. rTMS interfere group: The rats were treated with low frequency rTMS combined with chronic unpredictable mild stress, each side of the prefrontal lobe of rats was applied with 30 stimulations each day. The stimulation intensity is 60% of the maximum intensity, and frequency 0.5 Hz. The low frequency rTMS treatment lasted for 21 consecutive days.Control group: The rats were not exposed to any stress and rTMS. Before and after stress, we evaluated Open-field test, consumption of sucrose solution and forced swimming test.Results: After an unpredictable sequence of mild stress, rats of depression model group and rTMS interfere group showed a reduction in level and vertical movements of Open-field test,consumption of sucrose solution and an increase in immobility time of forced swimming test, with significant difference VS pre-stress and the control group (p<0.01). Control group showed no significant difference(P>0.05)in level and vertical movements of Open-field, consumption of sucrose solution, immobility time of forced swimming test compared with before stress.There were no significant difference(P>0.05)in level and vertical movements of Open-field test, consumption of sucrose solution, immobility time of forced swimming test between depression model group and rTMS interfere group.Conclusion: The decreased locomotion , loss of interest, anhedonia and easy to despair in CUMS rats depression model may represent the core symptoms in the patients of depression. It is an ideal rat model for depression.Low frequency repetitive transcranial magnetic stimulation combined with chronic unpredictable mild stress can not change the effect of chronic unpredictable mild stress on behavior of rats. PART Ⅱ: Effects of low frequency repetitive transcranial magnetic stimulation on the behavior and cerebral monoamine and amino acids neurotransmitter in the rat model of depressive chronic stressObjective: To observe effects of low frequency repetitive transcranial magnetic stimulation on the behavior and monoamine and amino acids neurotransmitter in different cerebral area in the rats model of depressive chronic stress.And to study the therapeutic effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on depression and the mechanism of therapy.Methods: Male Sprague-Dawley rats were exposed to an unpredictable sequence of mild stress to establish depression model of rats. Rats of depression model were randomly allocated two groups: depression model group, rTMS group. Rats of rTMS group were treated with low frequency rTMS, each side of the prefrontal lobe was applied with 30 stimulations each day. The stimulation intensity is 60% of the maximum intensity, and frequency 0.5 Hz. The low frequency rTMS treatment lasted for 10 consecutive days. Rats of depression model group and control group were not treated with low frequency rTMS. Before and after the rTMS treatment, we evaluated Open-field test, consumption of sucrose solution, forced swimming test. Rats were killed 24 hour after the last rTMS. The concentration of monoamine neurotransmitter in different cerebral area and amino acids in hippocampus were determined by HPLC.Results: After rTMS, rats of rTMS group showed an increase in level and vertical movements, consumption of sucrose solution and a reduction in immobility time of forced swimming test compared with before rTMS treatment. Rats of depression model group and control group showed no significant difference( P>0.05)in level and vertical movements , consumption of sucrose solution, immobility time of forced swimming test compared with before rTMS .Rats of rTMS group showed an increase in level and vertical movements, consumption of sucrose solution and a reduction in immobile time of forced swimming test compared with depression model group. Rats of rTMS group showed no significant difference(P>0.05)in level and vertical movements, consumption of sucrose solution, immobility time of forced swimming test compared with control group. Rats of depression model group showed a reduction in level and vertical movements of Open-field test,consumption of sucrose solution and an increase in immobility time of forced swimming test, with significant difference VS the control group (p<0.01).The level of 5-HT in frontal brain regions, 5-HT and DA in hippocampus, DA in corpus striatum, 5-HT in hypothalamus in depression model group was lower than that in the control group(p<0.01). The level of 5-HT in frontal brain regions, 5-HT and DA in hippocampus, DA in corpus striatum, 5-HT in hypothalamus in rTMS group was higher than that in depression model group(p<0.01). There were no significant difference (P>0.05) in level of 5-HT and DA between rTMS group and the control group.The level of glutamate (Glu) in hippocampus in depression model group was lower than that in the control group (P<0.05). The level of glutamate in hippocampus in rTMS group was higher than that in depression model group (P<0.05). There were no significant difference (P>0.05) in level of glutamate in hippocampus between rTMS group and the control group. There were no significant difference( P>0.05) in level of Asp , Gly, GABA among three groups.Conclusion: Low frequency repetitive transcranial magnetic stimulation can change the behavior of rats of depression model. The rats of depression model showed a reduction in level of 5-HT, DA in different cerebral area and glutamate in hippocampus, it may be one of mechanism of depression. Low frequency repetitive transcranial magnetic stimulation can regulate the level of 5-HT, DA in different cerebral area and glutamate in hippocampus, it may be one of the antidepressive mechanism of low frequency rTMS. PART Ⅲ: Low frequency repetitive transcranial magnetic stimulation as a treatment in depressionObjective: To study the therapeutic effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on patients with depression.Methods: Twenty depression patients were treated with low frequency rTMS, each side of the prefrontal lobe was applied with 30 stimulations each day. The stimulation intensity is 60% of the maximum intensity, and frequency 0.5 Hz. The low frequency rTMS treatment lasted for 7 consecutive days. Before and after the rTMS treatment, we evaluated the patients by use of Hamilton Depression Scale (HAMD).Results: After the treatment of low frequency rTMS, the mean HAMD score was 13.8±7.8, prior to the rTMS treatment the mean HAMD score was 26.6±6.0. Score on the HAMD decreased significantly (p<0.01) after the treatment. The total efficient rate of low frequency rTMS on depression was 85% (17/20).Conclusion: Low frequency rTMS is an effective and safe treatment alternative for patients with depression. PART Ⅳ: Low frequency repetitive transcranial magnetic stimulation as rehabilitative treatment in poststroke depressionObjective : To study the rehabilitative therapeutic effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on patients with poststroke depression (PSD).Methods: Sixteen patients of poststroke depression were treated with low frequency rTMS combined with conventional treatment. Each side of the prefrontal lobe was applied with 30 stimulations each day. The stimulation intensity is 60% of the maximum intensity, and frequency 0.5 Hz. The low frequency rTMS treatment lasted for 7 consecutive days. The patients of control group were only received the conventional treatment. Before and after the rTMS treatment, we evaluated the patients of two groups by use of Hamilton Depression Scale (HAMD) and the clinical neurological function impairment score (MSSS).Results: After the treatment of low frequency rTMS, the mean HAMD score of rTMS group dropped obviously from 25.9 ± 5.2 to 15.4 ± 6.7,with significant difference VS pre-treatment and the control group (p<0.01). The total efficient rate of low frequency rTMS on PSD was 87.5% (14/16), there was significant differences (p<0.01) in total efficient rate between rTMS group and control group. The MSSS score of rTMS group dropped from 18.3 ± 4.8 to 12.6 ± 4.6 ,with significant difference VS pre-treatment (p<0.01) and the control group (p<0.05).Conclusion: Low frequency rTMS may be an effective and safe treatment for patients with poststroke depression.