ECT VERKNINGSMEKANISMER

Transcription

1 ECT VERKNINGSMEKANISMER

2 LEVEL OF ORGANISATION - LEVEL OF STUDY transcendence/ existence interactions complex behaviour patterns of reaction and behaviour cognition, affect and emotion brain functional systems neuronal networks neuron intraneuronal function DNA code and expression

3 THE EPILEPTIC SEIZURE

4 ORIGINAL BILATERAL ELECTRODE PLACEMENT (BL) + -

5 d ELIA UNILATERAL ELECTRODE PLACEMENT (RUL) + RIGHT HEMISPHERE -

6 TRESHOLD STIMULATION (TS) - bilateral motor seizure ORIGINAL BILATERAL ELECTRODE PLACEMENT (BL) RIGHT UNILATERAL ELECTRODE PLACEMENT (RUL) BL 2 x TS RUL 5 x TS

7 EFFEKTER AV ECT (EPILEPTISK AKTIVITET) (level: brain functional systems and neuronal networks) Viktiga centra involverade i känsloreglering finns djupt i hjärnans centrala delar. För ECT effekten är det avgörande att den epileptiska aktiviteten även omfatter dessa centra (och inte bara den motoriska hjårnbarken). Hjärnstamspåverkan: Pulsstegring BT-stegring Flushing

8 REGULATION OF EMOTIONS AND AFFECTS CINGULUM STRIATUM SEPTAL NUCLEI ACCUMBENS THALAMUS FRONTAL CORTEX FORNIX HYPOTHALAMUS ORBITO- FRONTAL CORTEX AMYGDALA HIPPOCAMPUS MESENCEPHLON CEREBELLUM

9 EFFEKTER AV ECT (EPILEPTISK AKTIVITET) (level: brain functional systems and neuronal networks)

10 EFFEKTER AV ECT på receptor/ transmittor system (level: brain functional systems and neuronal networks) Serotonin-, och dopaminreceptorerna blir känsligare medan noradrenalinreceptorerna normaliseras i sin känslighet. Det är samma signalsubstanser som påverkas av antidepressiva mediciner, men effekten kommer snabbare och är kraftfullare vid ECT. Aktivering av hämmande neurotransmittorer (GABA systemet) (textböcker: exempelvis Ottosson, Psykiatri 2004)

11 Sensitization of MONOAMIN RECEPTORS 5-HT1A (Serotonin 1A) DA (Dopamin D1, D3?) Activation of INHIBITORY NEUROTRANSMITTERS Increased GABA activity serum GABA (Esel 2008) Lower Glutamate/GABA ratio ECS in rats (Sartorius 2007) GABA receptors present in more than 75% of all NEURONS

12 METABOLIC EFFECTS of ECT (level: brain functional systems and neuronal networks) BLOD FLOW (SPECT) ECT decrease BF in Prefrontal regions (Segawa et al, 2004) ECT increase BF in Prefrontal regions (Awata et al, 2002) ACC Anterior Cingulate Cortex

13 DEPRESSION : too high activity in ACC? too low activity in ACC? Time frame (metabolic activity): Depression Immediate ECT Acute ECT Late ECT effects

14 ENDOCRINOLOGICAL EFFECTS of ECT (level: brain functional systems and neuronal networks) Severe depression/ Melancholia: High cortisol Low circadian variation Dexamethasone non-suppression HPA AXIS dexamethasone ECT: HPA-axis normalisation Normalised circadian cortisole variation Normalised Respons to Dexamethasone

15 LEVEL OF ORGANISATION - LEVEL OF STUDY transcendence/ existence interactions complex behaviour patterns of reaction and behaviour cognition, affect and emotion brain functional systems neuronal networks neuron intraneuronal function DNA code and expression

16 NEUROTROFISKA EFFEKTER (level: neuronal- and intraneuronal function. DNA code and expression)

17 NEUROGENESIS Cheng et al 2009: ECS increase total number of synapses in adult rat Hippocampus Perera et al 2007: ECS induced neurogenesis in the Hippocampus of adult primates Madsen et al 2005 Electroconvulsive Seizure Treatment Increases (glia) Cell Proliferation in Rat Frontal Cortex ECS: Electro Convulsive Stimulation (animal experiments)

18 Hippocampal Volume and Depression: A Meta-Analysis of MRI Studies Videbech, Ravnkilde Am J Psychiatry 2004 A meta-analysis of the 12 studies of unipolar depression LEFT HIPPOCAMPUS

19 Untreated Depression and Hippocampal Volume Loss Sheline et al Am J Psychiatry 2003; 38 female outpatients,

20 Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression A Volumetric Magnetic Resonance Imaging Study Pia Nordanskog et al 12 patients with depression MRI within 1 week before and after the ECT BEFORE 27 year old woman AFTER

21 EFFECTS ON GENE EXPRESSION (Altar et al 2004) ECS increase or decrease Gene Expression for at least 120 different genes (rats)

22 FROZEN NEURONAL NETWORK

23 LEVEL OF ORGANISATION - LEVEL OF STUDY transcendence/ existence interactions complex behaviour patterns of reaction and behaviour cognition, affect and emotion brain functional systems neuronal networks neuron intraneuronal function DNA code and expression

24 Electroconvulsive Therapy A Theory for the Mechanism of Action Anthony T. Frais, MA Journal of ECT & Volume 26, Number 1, March 2010 In cases of severe depression, it is as if patients have lost access to the memories that define who they are the very spirit of their existence and their personal identity. Schechtman (2005): super autobiographical memory = the fundamental nature of the self-awareness that constitutes us as persons. It may be argued that a theory explaining the mechanisms of successful ECT treatment in restoring a patient s memory system that is the link to his or her character and personal identity may be somewhat removed from what is presently thought to be true of ECT.

25 Cognitive effects of Depression and ECT Mood General pattern valid for most Cognitive functions

26 The functional neuroanatomy of autobiographical memory: A meta-analysis Eva Svoboda, Margaret C. McKinnona, Brian Levine Neuropsychologia 44 (2006) fmri studies

27 CORE AUTOBIOGRAPHICAL MEMORY NETWORK Temporoparietal junc cerebellum ventrolateral PFC retrosplenial cingulum medial PFC MTL

28 BRAIN REGION BRODMANN LEFT RIGHT MID TOTAL VL PFC 45, 44, Med. PFC 9, Retrospl./post-cing. 29, 30, 23, Temporoparietal junc MTL HC, 34, 27, 28, 35, 36, Mid. lateral temporal Cerebellum (junc.) junction; (Med.) medial; (Mid.) middle; (MTL) medial temporal lobe; (PFC) prefrontal cortex; (Retrospl./post-cing.) retrosplenial/posterior cingulate (VL) ventrolateral.

29 AUTOBIOGRAPHICAL MEMORY RETRIEVAL Semantic memory Episodic memory Emotional memory Executive function left right