Pakko- oireiden aivomekanismit. Hasse Karlsson Integra5ivisen neuro5eteen ja psykiatrian professori Turun yliopisto Ylilääkäri, VSSHP/Psykiatria

Transkriptio

1 Pakko- oireiden aivomekanismit Hasse Karlsson Integra5ivisen neuro5eteen ja psykiatrian professori Turun yliopisto Ylilääkäri, VSSHP/Psykiatria

2 Pakko- oireinen häiriö (OCD) nuorilla Elinikäinen prevalenssi n. 2 % Pisteprevalenssi n. 1 % Noin 50 % tapauksista alku lapsuus- tai nuoruusiässä Sukupuolijakauma nuoruusiässä 1:1

3 Kliininen kuva Obsessiot ovat toistuvia, hellisämäsömiä ajatuksia, impulsseja ja mielikuvia, jotka koetaan tunkeileviksi ja sopimasomiksi ja jotka aiheusavat merkisävää ahdistuneisuusa

4 Kliininen kuva Kompulsiot ovat toistuvia käysäytymisiä (käsien pesu, tavaroiden järjestely, tarkistaminen) tai mentaalisia toimia (rukoileminen, laskeminen, sanojen toistaminen mielessä), joita po5laan pitää toteusaa vasteena obsessioille tai säännöille, joita pitää noudasaa jäykäs5

5 Pauls et al. 2014

6 Aivot 86 miljardia hermosolua Jokainen on yhteydessä noin 1000 muuhun hermosoluun Kehityksen huippukohdassa syntyy noin hermosolua joka minuuy Suurta plas5suusa kehityksen aikana

7 Pauls et al. 2014

8 Ensimmäinen aivojen kuvantamistutkimus (FDG- PET) Baxter et al. 1987

9 SSRI- lääkityksen ja käysäytymisterapian vaikutus Baxter et al. 1992

10 Junnila & Karlsson 1998

11 Miksi nucleus caudatus? Taustalla ajatus, esä n.caudatus ei kykene riisäväs5 suodasamaan frontaalikorteksilta generoituvaa huolestuneisuusa Mallin mukaan n. caudatuksen liiallinen ak5ivisuus johtaa muiden basaaliganglioiden inhibi5oon, joka puolestaan johtaa thalamuksen ak5vaa5oon ja sitä kausa frontaalikorteksin ak5vaa5oon synnysäen näin noidankehän

12 Kor5ko- striato- talamo- kor5kaalinen hermoverkosto Pauls et al. 2014

13 Ahmari & Dougherty 2015

14 Cortex 2015

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16 Cerebral white ma-er volume changes in pa6ents with obsessive compulsive disorder: Voxel- based morphometry Psychiatry and Clinical Neurosciences Volume 69, Issue 11, pages , 26 JUN 2015 DOI: /pcn hsp://onlinelibrary.wiley.com/doi/ /pcn.12317/full#pcn fig- 0001

17 Cerebral white ma-er volume changes in pa6ents with obsessive compulsive disorder: Voxel- based morphometry Psychiatry and Clinical Neurosciences Volume 69, Issue 11, pages , 26 JUN 2015 DOI: /pcn hsp://onlinelibrary.wiley.com/doi/ /pcn.12317/full#pcn fig- 0002

18 Figure 2. Significant increase in glucose metabolism in the right frontal middle gyrus (Brodmann's area 10) in Off-Stimulation obsessive-compulsive disorder patients compared with healthy control subjects (p <.005). Coronal views projected onto brain slice... Florence Le Jeune, Marc Vérin, Karim N'Diaye, Dominique Drapier, Emmanuelle Leray, Sophie Tezenas Du Montcel, Nicolas Baup, Antoine Pelissolo, Mircea Polosan, Luc Mallet, Jérome Yelnik, Bertrand Devaux, Denys Fontaine, Isabelle Chereau, Aurélie Bourguignon, Julie Peron, Paul Sauleau, Sylvie Raoul, Etienne Garin, Marie-Odile Krebs, Nematollah Jaafari, Bruno Millet Decrease of Prefrontal Metabolism After Subthalamic Stimulation in Obsessive-Compulsive Disorder: A Positron Emission Tomography Study Biological Psychiatry, Volume 68, Issue 11, 2010,

19 Figure 4. Correlation between metabolic change induced by stimulation and concomitant clinical improvement. Whole-brain analysis shows a significant cluster of correlation in the ventromedial prefrontal cortex with the decrease in the Yale Brown Obsessive Comp... Florence Le Jeune, Marc Vérin, Karim N'Diaye, Dominique Drapier, Emmanuelle Leray, Sophie Tezenas Du Montcel, Nicolas Baup, Antoine Pelissolo, Mircea Polosan, Luc Mallet, Jérome Yelnik, Bertrand Devaux, Denys Fontaine, Isabelle Chereau, Aurélie Bourguignon, Julie Peron, Paul Sauleau, Sylvie Raoul, Etienne Garin, Marie-Odile Krebs, Nematollah Jaafari, Bruno Millet Decrease of Prefrontal Metabolism After Subthalamic Stimulation in Obsessive-Compulsive Disorder: A Positron Emission Tomography Study Biological Psychiatry, Volume 68, Issue 11, 2010,

20 Fig. 1. Areas of reduced [11C]DASB binding potential (BPND) in patients with OCD relative to healthy controls. SPM2 projections superimposed on representative transaxial, sagittal, and coronal magnetic resonance images (threshold for display: p < 0.001, unc... Ryohei Matsumoto, Masanori Ichise, Hiroshi Ito, Tomomichi Ando, Hidehiko Takahashi, Yoko Ikoma, Jun Kosaka, Ryosuke Arakawa, Yota Fujimura, Miho Ota, Akihiro Takano, Kenji Fukui, Kazuhiko Nakayama, Tetsuya Suhara Reduced serotonin transporter binding in the insular cortex in patients with obsessive compulsive disorder: A [11C]DASB PET study NeuroImage, Volume 49, Issue 1, 2010,

21 Fig. 2. Scatter plot of [11C]DASB binding potential (BPND) in the insular cortex and orbitofrontal cortex. Region-of-interest (ROI) analysis revealed significant group differences in the BPND values of the insular cortex and orbitofrontal cortex within the Ryohei Matsumoto, Masanori Ichise, Hiroshi Ito, Tomomichi Ando, Hidehiko Takahashi, Yoko Ikoma, Jun Kosaka, Ryosuke Arakawa, Yota Fujimura, Miho Ota, Akihiro Takano, Kenji Fukui, Kazuhiko Nakayama, Tetsuya Suhara Reduced serotonin transporter binding in the insular cortex in patients with obsessive compulsive disorder: A [11C]DASB PET study NeuroImage, Volume 49, Issue 1, 2010,

22 Both structural and func5onal imaging studies provide evidence that orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, and anterior thalamus are involved in OCD pathophysiology. A) A circuit linking medial OFC (mofc), ventral striatum (vstr), ventral pallidum (VP), and thalamus is thought to be involved in OCD pathology. This circuit has classically been associated with asribu5on of value to the outcome of par5cular ac5ons to facilitate reward learning. Links between this circuit and amygdala provide opportuni5es for regula5on of ac5vity by affect. Dopaminergic projec5ons from substan5a nigra/ ventral tegmental area (SN/VTA) provide cri5cal modulatory input. B) Though the role of ACC in OCD symptomatology is unclear, a circuit linking dorsal ACC (dacc), dorsal striatum (dstr), VP (ventral pallidum), and thalamus is cri5cal for ac5on selec5on. Abnormali5es in this loop could therefore contribute to persevera5ve behaviors in OCD. Ahmari & Dougherty 2015

23 The loop runs from the orbital frontal cortex to the cingulate gyrus, striatum (caudate nucleus and putamen), globus pallidus, thalamus and back to the frontal cortex Organic insult to these regions can produce obsessive and compulsive symptoms Surgical interrup5on of this loop by means of cingulotomy, anterior capsulotomy or subcaudate tractotomy brings about symptoma5c improvement in a large propor5on of pa5ents unresponsive to all other treatments. Cingulotomy interrupts this loop at the anterior cingulate cortex, thereby disrup5ng frontal cor5cal input into the Papez circuit and limbic system, which are believed to mediate anxiety and other emo5onal symptoms Anterior capsulotomy (lesions within the anterior limb of the internal capsules) and subcaudate tractotomy (lesions in the substan5a innominata, just under the head of the caudate nucleus) interrupt fronto- thalamic fibers, which may mediate the obsessive and compulsive components of OCD.

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25 Brody et al. 1998

26 Psychiatr Res Neuroimag 2015

27 A form of behavior therapy exposure and ritual preven5on is thought to enhance emo5onal learning by altering connec5ons in a brain circuit (yellow arrows) involving the orbital frontal cortex (OFC), striatum and thalamus. This circuit s responses to emo5onal s5muli (red arrows), mediated by the amygdala, are suspected of being dysregulated in OCD. An5depressant and an5psycho5c medica5ons target ac5vity of regula5ng neurotransmisers from lower brain structures (raphe, LC, VTA).

28 Transverse section through human brain, showing the two capsulotomy lesions (crosshatched areas). David Christmas et al. APT 2004;10: by The Royal College of Psychiatrists

29 Sagittal section through human brain, showing a cingulotomy lesion (cross-hatched area). David Christmas et al. APT 2004;10: by The Royal College of Psychiatrists

30 DBS Figee et al. 2014

31 Figee et al. 2014

32 PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infec5ons) Presence of OCD or 5c disorder, prepubertal symptom onset, abrupt onset or exacerba5on of symptoms with an episodic course, temporal associa5on between presence of symptoms and infec5on with GABHS, and associated neurological abnormali5es such as choreiform movements

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34 Taudin syynä on arveltu olevan A- ryhmän streptokokki - infek5o, joka johtaa autoimmuunireak5oon basaaliganglioissa Hoitoina an5bioo5t ja immunomodulatoriset lääkkeet Murphy & Pichichero 2002, Williams & Swedo 2915

35 Williams & Swedo 2015