Psychobiological states: the traumatised patient s body Dr Nuri Gene-Cos PhD, MRCPsych, LMS (MD) Traumatic Stress Service Clinical Treatment Centre Maudsley Hospital Denmark Hill London SE5 8AZ nuri.genecos@slam.nhs.uk Psychiatrist
Programme of the talk 1. Normal response to threat in humans. 2. Human brain: McLean brain Limbic system ANS (autonomic nervous system) Hormones acting on CNS (central nervous system) 3. PTSD Biological model: Cortisol system NE ( norepinephrine) 5HT (serotonin) - Physiological arousal model 4. PTSD Clinical symptoms
Group work 1- Do you think there is a connection between endocrine system and trauma? 2-what would be in your experience the difference between chronic and acute PTSD in relation to symptoms and body involvement? 3-what is in your opinion the connection between neuronal system and endocrine system in PTSD? 4-what do you think are the main differences between developmental traumas and adult PTSD? Groups in equal sizes: discussion 15 minutes then shared with the group. Psychiatrist 3
Normal response to threat in humans Increase of arousal (LC: NE) Increase in vigilance Cognitive assessment of the situation (threat and response to it) Increase autonomical activity (preparing body to fight/flight) (EP: SNS and adrenal medulla: epinephrine/sympathetic nervous system) Increase output of cortisol from adrenal cortex In animal and humans: learning in relation to threat, limbic system is implicated: in immediate threat, amygdala and in cases where the threat is perceived/assessed, the hippocampus may play a role (Ledoux 1995) Psychiatrist 4
THREAT CORTISOL Psychiatrist 5
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AMYGDALA S A ventromedial frontal cortex E M planning and decision making N Y hippocampus S G basal ganglia memory and attention O D basal forebrain R A homeostasis Y L hypothalamus visceral A neuroendocrine output 11/11/2010 Psychiatrist 7
HUMAN BRAIN In the course of evolution, the human brain has developed 3 interdependent parts: 1-brainstem and hypothalamus (primarily associated with the regulation of internal homeostasis (e.g. regulation of hormones) 2-limbic system, in charge with maintaining the balance between the internal world and the external reality (oral and genital function; parental care; audio vocal behaviour and play) 3-neocortex, responsible for analysing and interacting the external world. (primarily oriented to the external world; reasoning strategies to attain personal goals, making decisions, weighing a range of options and predicting outcomes of our own actions; also deciding which stimuli is useful and which is not) Psychiatrist 8
HUMAN BRAIN Together the 3 systems control a range of regulatory functions: 1-internal vegetative functions, rhytms of life-rest/sleep and activity;feeding,reproductive cycles, etc 2-control relationships with the outside world, assessing novelty, danger, gratifying.novelty needs to be analysed against the previously stored knowledge. The use what is needed and discard what is not relevant. 3-in addition, the organism needs to be able to engage in routine tasks without being distracted by irrelevant stimuli able to learn from experience 4-social function of the brain allows to engage in complex social systems. Psychiatrist 9
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LIMBIC SYSTEM (LS) Has centers responding to: Reward and punishment behaviour Pain Anger Rage Fear Vigilance Somnolence. Some of the parts of the LS: Hypothalamus Thalamus Amygdala Hippocampus Basal Ganglia Psychiatrist 11
AUTONOMIC NERVOUS SYSTEM: ANS It regulates visceral organs in the body, helping to regulate: sweat, temperature, urinary elimination, blood pressure, amongst others. The hypothalamus is the organ that regulates this system. It is made up of 2 subsystems: the sympathetic (SNS) (born from the Medulla) the parasympathetic (PSS) (80% plus from Vagal nerves) Often they have opposite effects in the body: SNS (accelerator) dilates pupils, heart rate increases, stimulates metabolism (increased use of glucose by the liver, glucose in blood increases, increased mental activity), increased blood pressure, increased blood in muscles and different tissues. PSNS ( brakes) constricts pupils, heart rate decreases. Psychiatrist 12
HORMONES ACTING IN THE CENTRAL NERVOUS SYSTEM Hormones interact with neurons by 2 different types of processes: binding to receptors on membranes binding on receptors that can attach to DNA Steroid hormones are able to use both types of mechanisms: able to play a role medium and long term responses to environmental stimuli in adulthood, but also in the development of the CNS (Beato 1989). previous STRESS somatic experience stress HIPPOCAMPUS NE system (LC) BRAIN-STEM Hypothalamus (CRF) Pituitary (ACTH) Adrenal cortex (cortisol) Psychiatrist 13
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PTSD: Biological model Many neurotransmitters have been implicated in PTSD. Intense stress is accompanied by the release of neurohormones such as: Cortisol Epinephrine (adrenaline) Norepinephrenie (NE) Vasopressin Oxytocin Endogenous opioids. These hormones help the organism to mobilise the required energy to deal with the stress. In a healthy organism these hormonal changes responding to stress, return rapidly to baseline after the threat has passed. Chronic and catastrophic stress has been shown to inhibit the effectiveness of the stress response and to induce desensitisation (Axelrod J 1984). Most studies of neurohormone function in PTSD show responses that are in the opposite direction from those of the ordinary stress response. Psychiatrist 15
CORTISOL SYSTEM Body responds to stress by increasing cortisol output. HPT (hypothalamus) plays a role via the HPA (Hypothalamus/Pituitary/Adrenal) axis. Hippocampus and amygdala are among the primary sites that drive the hypothalamus to promote cortisol release during stress. Both hippocampus and amygdala integrate information from external environment and from memory, about the situation. People with greatest cortisol elevation in response to stress situations exhibit the greatest impaired memory (declarative memory) (Lupien et al, 1997). Cortisol: antistress hormone, Released by the adrenal gland in response to stress. During stressful situations, the brain signals the pituitary gland to stimulate the release of cortisol from the adrenal gland. The role of cortisol in response to stress is to contain biological reactions that have been activated in response to the short-term demands of the stress. If cortisol did not facilitate the termination of these reactions, they would do long-term damage to the body. Psychiatrist 16
CORTISOL: STRESS RESPONSE Hippocampus STRESS Amygdala Hypothalamus Pituitary Adrenal cortex CORTISOL: decreases response to stress STRESS CORTISOL PTSD: reduce CORTISOL Increases use of glucose Decreases use of glucose Problems with energy/glucose Decreases tissue repair Increases tissue repair Decrease healing processes Decreases immune reaction Increases immune reaction More vulnerability to infections Psychiatrist 17
CORTISOL SYSTEM Trauma survivors with PTSD show a different cortisol response from that observed under conditions of acute and chronic stress and in disorders such as major depression. Patients with PTSD have lower cortisol levels that healthy controls and people with other psychiatric diagnoses (Yehuda R et al. 1990, Kellner M et al. 1997). Patients with PTSD respond to dexamethasone by suppressing their cortisol levels to a greater extent than healthy people do (Yehuda R et al. 1995, Stein MB 1997). The hypersuppression of cortisol in response to dexamethasone in these patients suggests that cortisol receptors are more sensitive (Yehuda R et al. 1995). This hypersuppression is opposite to the non-suppression seen in depressed patients (Carrol BJ. 1982). These suggest that, unlike depressed patients, PTSD patients may be extremely sensitive to external events and may hyper-respond, even to non-dangerous environmental stimuli (Yehuda R et al. 1996). Psychiatrist 18
CORTISOL SYSTEM Disregulation of corticotropin-releasing factor (CRF) may be the most important abnormality in PTSD. CRF is the hypothalamic hormone that releases ACHT from the pituitary, which then signals the adrenals to release glucocorticoids. The neurotransmitter in the final common pathway also activates the Locus Ceruleus (LC) and therefore the adrenergic system. CRF is also known to initiate the immunological response to stress (Friedman 1997). Resnick et al. (1995) measured cortisol levels within several hours after rape. Lower cortisol levels were observed in women who had histories of rape or assault compared with women who did not have this risk factor. It was the risk factor of prior trauma that was associated with a different neuroendocrine response to a subsequent traumatic event. This alteration observed is consistent with observations of individuals who have chronic PTSD. Psychiatrist 19
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NOREPINEPHRENIE (NE) NE is important for: Alerting the organism to deal with a threat, Initiating fight/flight behavior; It also has a role in memory consolidation. Vietnam veterans with PTSD studies: elevated 24-hour excretion of urinary NE and E, compared with other psychiatric patients (Kosten TR. 1987), proving a chronically increased sympathetic nervous system activity in PTSD. Van der Kolk et al. (1985): inescapable shock in animals. They focused on the LC, as the primary source of noradrenergic innervation of the limbic system, cerebral cortex, cerebellum and hypothalamus. LC also has control over the autonomic nervous system and is involved in stress responses. They concluded that most of the PTSD symptoms as due to chronic adrenergic hypersensitivity. Long term potentiation of LC pathways are seen as the possible cause of flashbacks and the eidetic quality of traumatic nightmares, as opposed to the oneiric (vague, disjointed) quality of the ordinary dreams and nightmares. Van der Kolk et al. (1985): link between LC and amygdala in rage reactions often found in PTSD. Suggesting, massive trauma causes vulnerability to response with excessive autonomic reactivity by altering LC activity. Psychiatrist 21
NOREPINEPHRINE stress Locus Ceruleus (LC): NE CORTEX CEREBELUM ANS HYPOTHALAMUS LIMBIC SYSTEM Psychiatrist 22
SEROTONIN (5HT) In the brain it suppresses behaviour that is motivated by emergencies or by previous rewards (Depue RA, Spoont MR. 1986, Gray JF 1982, Soubrie P 1986). In animals, low serotonin levels are related to exaggerated startle response, increased arousal in response to novel stimuli (Gerson SC 1980). Decreased serotonin in humans has been correlated with impulsivity and aggression (Coccaro EF et al. 1989, Mann JD 1987); with hostility, impulsivity and self-aggression in patients with depression and with borderline personality disorder. Moreover, SSRIs have been found to be effective in the treatment of involuntary preoccupation with traumatic memories (van der Kolk et al. 1994). Other possible neurobiological systems known to be disregulated in PTSD include the thyroid, the endogenous opiod systems, the gammaaminobutyric acid (GABA)-benzodiazepine system; and the N-methyl-Daspartate (NMDA) or excitatory amino acid system. Possibly also involved in PTSD are neuropeptide Y (which inhibits CRF) and neurotensin, a dopamine antagoniser (Friedman 1997). Psychiatrist 23
Physiological arousal model PTSD follows the classic models of learning and conditioning, (initially described by Pavlov): fear conditioning, inability to habituate, inability to extinguish learned behaviour, inescapable stress and the fear-potentiated startle response, among others (Friedman 1997). Pittman et al. (1993) pointed out that the critical issue in PTSD is that the stimuli that caused people to over-react may not be conditional enough; therefore, a variety of triggers not directly related to the traumatic experience may precipitate extreme reactions. The presence of intrusive thoughts and images, by means of kindling, sets up a chronically disordered pattern of arousal, in which the patients reacts to a host of remainders with a physiological intensity appropriate to the original trauma. In an apparent attempt to compensate for their chronic hyperarousal, traumatised people, seem to shut down (avoiding stimuli that remind them of the trauma and becoming emotionally numb). Over time, people with chronic PTSD come to suffer from numbing of responsiveness to the environment, intermittent hyperarousal in response to emotionally arousing stimuli, and to neutral stimuli. This indicates that people with PTSD suffer from a loss of stimulus discrimination. Psychiatrist 24
Physiological arousal model Hyperarousal to intense but neutral stimuli and or loss of stimulus discrimination may be due to abnormalities in habituation to the acoustic startle response, as shown in several studies (Shalev et al. 1992, Ornitz & Pynoos 1989). The failure to habituate to acoustic startle suggests that traumatised people have difficulty evaluating sensory stimuli and mobilising appropriate levels of physiologic arousal (Shalev et al. 1992). These patients suffer from heightened physiologic arousal in response to sounds, images, and thoughts related to specific traumatic incidents, responding with increases in heart rates, skin conductance and blood pressure (Malloy et al. 1983, Pitman et al. 1987). Psychiatrist 25
PTSD Response to trauma is complex. PTSD is only one of the responses to trauma, not the only one. A patient is victimized by having memories of the event not by the event itself ( McFarlane 1988) Loss of emotions as signal: Chronic physiological arousal and the failure to regulate autonomic reactions to internal or external stimuli affects people s capacity to utilise emotions as signals They tend to react to things rather than process information to assess what is needed; often they overreact to stimuli and may become aggressive easily. Psychiatrist 26
PTSD The main clinical features of PTSD: Painful re-experiencing of the traumatic event Hyperarousal symptoms Frequently: Avoidance Emotional numbing Dissociative states Illusions and hallucinations Psychiatrist 27
PTSD Cognitive impairment (Golier & Yehuda (1998): memory-related impairment: memory loss: avoid conscious recollection of the trauma and the powerful feelings associated with it It can present as psychogenic amnesia (the inability to recall aspects of the trauma) excessive remembering :recollection or dreams of the trauma acting or feeling as if the trauma was happening physiologic reactivity to reminders of the trauma. These intrusive memories, and especially dissociative flashbacks, may be rich in perceptual detail including visual images, sounds and smells associated to the trauma. Additional memory-related impairments are present in the hyperarousal symptom cluster, including poor concentration and hypervigilance (hypervigilance as a way in which memory of having been traumatised continues to influence behaviour). Another common feature of PTSD is dissociation; 82% of individuals with PTSD and 52% of those with lifetime PTSD will have dissociative symptoms (Golier & Yehuda, 1998). Dissociation is more common in victims of childhood abuse than victims of any other type of trauma. In summary, the most important symptoms of PTSD are related to memory (intrusive memories or amnesia), autonomic hyperarousal, emotional numbing, conversion and dissociation. Psychiatrist 28
Autonomic Arousal Model [Ogden, Minton & Pain, 2006] Signs of Hyperarousal: overwhelm, panic, impulsivity, hypervigilance, defensiveness, feeling unsafe, reactive, racing thoughts, anger or rage Optimal Arousal Zone or Window of Tolerance:feelings and reactions are tolerable; we can think and feel simultaneously;our reactions adapt to fit the situation Signs of Hypoarousal: numb, dead, passive, no feelings, can t think, disconnected, shut down, not there, can t defend Psychiatrist 29
GUN she could feel the gun in her mouth -contracted- gut nausea, she could feel it -twice- asleep -sweat- -wakened- she could feel her lips against the tight teeth, walking down the street as she sat on her bed echoes -loud- heart, -frozenwhen she cooked. She could taste the blood -hot mouth- when she tried to talk. Psychiatrist 30