Running Head: AMYGDALA SWITCH
The Amygdala Switch: A Neurobiological and Evolutionary Theory of Stress-induced Antisocial Disorders
Nicholas J. Albertini
Senior Capstone Project Paper
The author reviews current neurobiological data on Capgras Syndrome and Williams Syndrome in comparison with post-traumatic stress disorder (PTSD), borderline personality disorder (BPD) and psychopathy, which are taken to have a common neurobiological etiology. It is theorized that extreme stress or lack of social stimulus is responsible for this proposed spectrum of stress-induced antisocial disorders (SIAD). Different combinations and amounts of stress and social under-stimulation are proposed for PTSD, BPD and psychopathy. Stress induced degeneration or under-stimulation induced subnormal growth of a specifically proposed in-group recognition circuit (IRC) in the lateral amygdala with input connections from the fusiform face area (FFA) and auditory association cortex is conjectured as the underlying root of these social disorders.
The Amygdala Switch: A Neurobiological and Evolutionary Theory of Stress-induced Antisocial Disorders
The amygdale store emotionally related memories and control our emotional responses to stimuli. Bilateral removal of the amygdale in humans does not produce the same extreme symptoms as is reported for monkeys (Aggleton and Young, 2000), partial Klüver-Bucy Syndrome. Limited bilateral destruction of the amygdale in humans produces only a very subtle shift in behavior, making the subject apparently less excitable. Interspecies differences in amygdala nuclei and cortex volume, as well as white matter connectivity must explain this difference. The Amygdala on the whole is an excitatory body of circuitry, since removal in both humans and monkeys produces docility and lowered excitability. This does not mean that all circuits in the amygdaloid complex are excitatory. The particular circuit that I describe in this paper, whose lowered complexity I propose as the cause of a set of three related stress-induced antisocial disorders (SIAD), must be mostly inhibitory. The particular circuit, which I have termed the in-group recognition circuit (IRC), has been previously proposed to reside in the amygdale of primates (Emery and Amaral, 2000). Though the role of facial expression of affect recognition has been implicated in antisocial disorders such as psychopathy before (Kosson et al., 2002; Blair et al. 2004; Book, Quinsey & Langford, 2007), in-group recognition seems not to have been widely discussed as a causal mechanism. In this paper, I will attempt to outline a theory of SIAD in which progressive reduced functional complexity of this IRC might produce the symptoms seen in Posttraumatic Stress Disorder (PTSD), Borderline Personality Disorder (BPD) and psychopathy. These disorders are proposed to occur at stages of functional IRC complexity from reduced complexity of recognition in PTSD, through minimal functional complexity consisting of a simple switching mechanism in BPD, to complete non-functionality in psychopathy.
The lateral amygdala is connected to areas of the cortex which are activated by particular faces or particular voices (Ramachandran, 1998). The portion of the visual association cortex in the temporal lobe that deals with recognizing faces is called the fusiform face area (FFA). The FFA connects both to the amygdala and the orbitofrontal (OFC) cortex. The connections between the FFA and frontal and anterior temporal cortexes tells us who’s face we are looking at, if we recognize it. We can say, “That is Joe.” The connection between the FFA and the amygdala tells us what to feel in response to that face. The locus of activation in the FFA corresponds to specific memory traces for emotional response in the amygdala, responses built up over consistent pairings of that face with other pleasant or unpleasant stimuli in a process of classical conditioning.
When the connections between the FFA and amygdala are severed, a patient will experience what is called Capgras Syndrome. In Capgras, the patient has no emotional response to identified faces. When the patient looks upon a loved one, there is no warm and fuzzy feeling, which they had used to experience. This is disturbing and the Capgras patient rationalizes that their loved one has been replaced by a doppelganger, a fraudulent duplicate that looks identical but is not, in fact, their loved one. This rationalization is a secondary process as can be demonstrated by the fact that a capgras patient can recognize their loved one’s voice and feel that warmth and fuzziness when speaking with them over the telephone. In humans this in-group recognition appears to occur by face recognition and voice recognition via this pathway. The second and third pathways to the frontal and temporal cortexes are irrelevant for emotional response. Even though the capgras patient knows that he is looking at a face that looks identical to his mother’s face (because it is), he doesn’t feel like it is his mother. To him, the woman just looks exactly like his mother. Removal of the dominant (visual) stimulus allows Capgras patients with an intact auditory connection to the amygdala to experience that warm and fuzzy feeling, such as talking to Mom on the telephone. So, in Capgras, it is just the connection to some emotional in-group recognition circuit that is severed, and only the one from the visual system. I will propose that, in psychopaths, this process of in-group recognition is completely non-functional.
There is a group of people with a genetic disorder called Williams Syndrome, caused by a micro-deletion on human chromosome 7, who are the opposite of psychopaths in the sense that they inherently possess no concept of an out-group. People with this syndrome have no fear of strangers and are generally highly socially amenable. This behavior has been traced to an alteration in the amygdala (Santos, Meyer-Lindenberg & Deruelle, 2010). Further, this same study found that individuals with Williams syndrome, matched to controls on gender and mental age, also do not show any prejudice toward other races, while control subjects show strong bias, as is quite normal. These researchers found, however that both groups showed gender bias. These experimenters hypothesize that social fear is at the root of racial bias, and apparently all out-group bias, while they suggest that it is not for gender. Perhaps a look at research on the brain abnormalities in Williams Syndrome can be enlightening with regard to other disorders marked by problems with in-group recognition. If some portion of the brain that would logically be implicated in in-group recognition is enlarged in Williams Syndrome patients and reduced in PTSD, BPD and psychopathic individuals, this would strongly suggest the existence of such a specific circuit, help identify its potential role in SIAD, and help pinpoint its’ location. Interestingly, genes involved in autism, another disorder marked by problems with empathy and sociality (Decety, & Moriguchi, 2007), have been found on human chromosome 7 (Scherer et al., 2003, Holt et al., 2010).
It turns out that the people with Williams Syndrome (WS) have been demonstrated to possess “grossly increased volumes” in their amygdale and several other relevant brain areas (Reiss et al., 2004). This brain-mapping study with 43 WS patients and 40 controls found a highly (p < 0.001) significant 10% increase in amygdale grey matter in the WS group versus controls. This is confounded, for our purposes here, by the finding that they also had a 30% increase in the orbital prefrontal cortex, both compared to an 11% overall decreased brain volume and with similar significance. The OFC is responsible for aiding in conscious in-group recognition via a direct connection to the FFA in the temporal lobe and feeds back to the amygdala to modulate emotional response. Problems with impulse control by the OFC has been linked to violence in antisocial disorders and the severity of impulse-related symptoms in these disorders (Beauchaine et al., 2009). As will be elaborated on in the next paragraph, I believe that increased neural complexity in areas of the WS cortex tends to compensate for decreased functional complexity per unit volume due to developmental organizational issues that result from the genetic micro-deletion. In the case of the OFC in WS, this idea is supported by the prevalence of mild to moderate intellectual handicap among these individuals and a apparent lack of superhuman self-control.
The FFA is twice as large by area as determined by functional magnetic resonance imaging (FMRI) in WS patients (Golarai et al., 2010), but they show no greater ability than controls for facial recognition on the Benton Facial Recognition Test (BFRT). Another study with 42 WS subjects and 40 controls showed significant (p < 0.002) increased cortical thickness at the right FFA by 10% but no significant difference in the left FFA. This is interesting due to the well known right hemispheric dominance of emotional processing. This produces a bit of a confound for the current purpose. Perhaps the normal functioning with the BFRT in the Golarai (2010) study and the increased emotional response to faces in WS, including the lack of out-group recognition, reflects bilateral asymmetry regarding language and emotional processing in the cortex. But this bilateral asymmetry was not found for the increase in surface area. While an increase in 10% cortical thickness was significant in terms of neurological complexity, which was correlated to thickness ; it is clearly a tiny volumetric, and therefore complexity, difference when compared to a doubling of surface area. The associated increase in cortical thickness found in this study for language processing areas in the WS group would suggest a better performance on language related tests or conscious recognition tests such as the BFRT which are associated to left hemispheric function. It serves well to remember also that increased neural complexity of a system does not necessarily translate into increased functional complexity or better processing. Such functional complexity requires both neural complexity and connectivity that optimizes information processing. In a group that is differentiated from normal by a chromosomal deletion, it would be bad to assume that increased neural complexity necessarily translates to increased functional complexity, since that increase in neural complexity has not been operated on by natural selective forces, as normal genetic variations resulting in such population disparities have. In this case, involving the FFA in WS, it seems that increased neural complexity is compensating for a decrease in functional complexity per unit volume, likely due to developmental organizational issues, resulting in a similar ability for conscious facial recognition, which has been reflected in histological differences from normal in the WS cortex.
Stress-induced antisocial disorders.
Psychological trauma can produce a similar dulling or elimination of this warm and fuzzy emotional reaction to loved ones as is found in Capgras Syndrome. Etiological factors and symptoms of PTSD which are important for this analysis include: the experience of terror or horror (DSM-IV-TR, APA, 2000) (all, unless specifically cited as from another source), detachment from other people or restricted ability to feel warm social emotions like love, outbursts of anger, hypervigilance or always being on guard and ready for a fearful situation (ready to fight or flee), memory loss (commonly memory of or related to the terrifying or horrifying incidents, traumatic events, and sometimes other memories), anhedonia or inability to feel pleasure in response to normally pleasurable stimuli, exaggerated startle response (Pole, 2007), and flashbacks or uncontrollable and intrusive memories of traumatic events. (see figure 1)
Compare these point by point to some key etiological factors and symptoms of secondary psychopathy, which are not from the DSM but in line with Hare’s (2006) model: the experience of childhood abuse, relationships that are exploitative and not loving, a lack of social emotion or not feeling that warmth and fuzziness ever in reaction to any other, reactive aggression or outbursts of anger or aggression in reaction to perceived threat either physical or not, interpersonal paranoia (sort of a social hypervigilance), reduced memory capacity (Dolam & Fullam, 2005), anhedonia or psychopathic boredom, inhibited startle response (Herpertz et al., 2001; Vanman et al., 2003; Pastors et al., 2003). The similarities should be fairly striking. They are to me. Secondary psychopathy seems like a greatly exaggerated form of PTSD with some key differences in terms of symptoms. (see figure 1)
Now let’s take a similar look at etiological factors and symptoms of BPD (DSM-IV-TR, APA, 2000) (all, unless otherwise cited): Experienced early abuse or neglect (Kernberg, 1975; Linehan, 1993), unstable relationships (particularly with close family and other loved ones – that is, volatile relationships with many breakups and feuds), labile affect or greatly fluctuating mood and emotions (at times seemingly emotionless or psychopathic while at others highly emotional, see: Linehan and Kernberg), reactive aggression (Newhil, Eack and Mulvey, 2009), non-delusional paranoia, reduced non-verbal memory (Burgess, 1992; O’Leary, Brouwers, Gardner, & Cowdry, 1991), anhedonia, exaggerated startle response (Pole, 2007), and transient perceptual distortions that are described as short psychosis-like events and similar to some of the effects of lysergic acid diethylamide (LSD) (Tuinier et al., 1997) but lasting seconds to minutes only. (see figure 1)
Kroll (1993) suggests that PTSD and BPD are very similar and that BPD appears to be a more pathologically serious and developmental version of PTSD or may be a form of PTSD. Professor Gerald Metalsky (in a Clinical Field Experience class which I took from him) suggested on a number of occasions that BPD and secondary psychopathy are identical or nearly identical, clinically. I believe that he was referring more to Cleckley’s (1941) description rather than Hare’s (2006) model, or more to an underlying borderline personality organization (BPO) (Kernberg, 1975) rather than strict DSM BPD criteria classification, from the context. This, in fact, is what prompted me toward this line of study regarding these disorders. Hare’s concept of secondary psychopathy is completely in line with Kernberg’s ( Clarkin et al., 2007) theory of BPO, in my opinion. But, there is more to it than just BPO, as Hare’s model makes clear. Psychopaths do not love. In terms of the present theory, they do not have any emotionally experienced concept of an in-group. Like the Capgras patient, they are missing that warm and fuzzy feeling; except they are missing it completely. In the borderline individual, this feeling is transient or labile, meaning it can be fleeting or it can appear and disappear instantaneously even after longer periods (Millon et al., 2004). It is there at times in an extreme sense and then just gone at others. It is as if the borderline personality is either completely on or off, in terms of social emotion. Both borderlines and psychopaths do experience emotion.
All of these disorders can facilitate addiction (Mills et al., 2004; Clark et al.,2001; Sansone, Whitecar, & Wiederman, 2008; Cohen et al. 2008). In my opinion, this reflects a lack of social reinforcement which leads to self-reinforcement. The organism requires some level of reinforcement. For social personalities, I conjecture that most of this need is fulfilled by social reinforcement. Those with SIAD have problems with social emotion and therefore with social reinforcement and punishment. Recognition of some in-group, full of others that can be trusted to be supportive, and the fear of withdrawal of that support, is what is just plain lacking in BPD and psychopathy. This also seems to be what is eroded in PTSD to a lesser degree. Whatever circuitry in the brain is responsible for this trusting and social reinforcing behavior is what should be implicated in these disorders. I will attempt to show that depersonalization and other symptoms of these disorders are secondary symptoms to this underlying lack of in-group recognition and directly related to the neurological functional complexity of such an in-group recognition circuit (IRC) in the brain.
The in-group recognition circuit.
Comparisons between Capgras and WS patients’ anatomies leave the nuclei of the amygdale as candidates for localizing this IRC. The lateral nucleus of the amygdala receives input from the visual and auditory cortexes. Particularly of interest at present are the inputs from the FFA and auditory association cortexes (AAC) which project to the lateral amygdala. In Capgras Syndrome, the connection between the FFA and lateral amygdala is severed while a second connection between the FFA and the OFC is preserved. Thus, the Capgras patient can identify a familiar face but does not experience a familiar paired emotion in response. Since the connection from the AAC to the amygdala is usually preserved, the patient does experience the associated emotion in response to voice-only stimuli of that person, as by telephone (Ramachandran, 1998).
Since humans lack a functioning vomeronasal organ (VNO), the current role of olfaction with regard to this IRC is unclear, but dubious. Evolutionarily however, it would make sense for such a circuit to have originally developed to respond to olfactory input, possibly from a VNO, prior to the evolution of the neocortex, and later adapted to support input from the complex pattern recognition systems of the neocortex: the FFA and AAC. From the example of Capgras, we can be pretty sure that visual stimulus from the FFA is primary to this circuit, while auditory input appears to be secondary. Since the Capgras patient does not smell his loved ones and gain reassurance of their true identity, we can also be quite sure that vision must at least trump olfaction for in-group emotional recognition in humans. Since smells do directly influence emotion in humans, however; perhaps it really is the old connection from the now vestigial (if even existent in humans) VNO which can help us pinpoint this circuit with the most accuracy. If some humans can be identified with vestigial VNOs, and one could trace the efferent tracts from around that area to the amygdala, this may help give a better idea as to where the IRC may be precisely located.
The IRC most likely lies within the lateral nucleus of the amygdala (LA), since there are non-feedback projections from the LA to other amygdaloid nuclei which process and send different information to different regions of the cortex. All of these separate outputs appear to be responsible for symptoms found in the various disorders of PTSD, BPD and secondary psychopathy, and appear to be a direct result of reduced in-group recognition. The LA projects to the central nucleus, which processes information resulting in global regulation of most important neurotransmitters in relation to the cortex and emotional arousal, such as Dopamine (DA), Norepinephrine (NE), Serotonin (5-HT), and Acetylcholine (Ach) (see figure 2). The LA also projects to the basal nucleus, which processes information resulting in instrumental behavior via projection to the OFC and other structures. These represent streams of information flow that do not feed back to the LA. Cortical feedback to the amygdala does occur at later stages of processing representing a “two-pathway architecture” (Rudrauf et al., 2008). These later stages are insufficient for emotional recognition by visual stimulus in Capgras and, therefore, must lie after the IRC in processing. That is, the IRC lies on only one of these pathways into the amygdala. Since the basal nucleus also has projections to these other important nuclei, there is a possibility that the IRC may be located there. I believe this to be unlikely due to the above proposed evolutionary development of the IRC and its distance from the afferent tracts coming from the sensory cortexes and olfactory system. In a review of literature on the role of the amygdala in primate sociality, Emery and Amaral (2000) conclude that the basal nucleus, with the OFC, is involved in putting social sensory information into context. This stage of processing should necessarily follow identification of in-group status in the LA. These writers also suggest that differentiation of in-group and out-group may occur within this circuitry. In the same book, Aggleton and Young (2000) cite a study (Stephan et al., 1987, as cited in) which demonstrates that lateral, basal and central nuclei are increased in size in humans relative to lower primates and suggest that this is most notable in the LA due to increased connections from sensory association cortexes. They suggest that this increase should be associated with increased group size between species. These writers also note that cells responding to specific faces have been found in the accessory basal nucleus in monkeys, which receives much input from the LA and contains many projections from the temporal pole. This may also implicate this area in the strange perceptual disturbances in borderlines which will be discussed later, if it is indeed the location of the IRC.
Studies have shown amygdala abnormality in all three of the disorders: PTSD, BPD, and psychopathy which I am lumping under the heading of SIAD. Shin, Rauch, and Pitman (2006) review research showing amygdala hyperactivity in PTSD patients directly correlated to symptom severity. Weniger et al. (2008) demonstrate reduced amygdala volume in PTSD subjects versus controls and patients with Dissociative Identity Disorder or dissociative amnesia. In a meta analysis including over a hundred BPD patients, Nunes et al. (2009) conclude that there is reduced amygdala gray matter in borderlines. Schmahl et al. (2003) found a 21.9% reduction in amygdala grey matter in BPD subjects versus healthy controls. Amygdala hyperactivity has also been demonstrated in BPD (Donegan et al., 2003). I will propose that this extreme hyperactivity can produce psychogenic temporolimbic seizure-type episodes that account for the strange perceptual distortions experienced by borderlines similar to temporal lobe epilepsy (TLE). Yang et al. (2009) demonstrate damage to the LA in psychopathic studies with reduced bilateral amygdale volume of about 17-19% with significant correlation between reduced volume and symptom scores, particularly for affective and interpersonal aspects. They also found reduction in other nuclei: basolateral, cortical and central; suggesting that the IRC may not be located in the accessory basal nucleus since it was not among these, but rather in the LA. In the next section, I will address stress-induced excitotoxicity and its potential role in doing the damage that is seen in these studies. There are both forward and feedback routes that might cause toxic effects in the amygdala. Jones et al. (2009) show hyporeactivity of the amygdala in psychopathy, as opposed to the hyperreactivity seen in both PTSD and to a greater extent BPD. Something changes drastically in psychopathy. Amygdala function decreases below normal. How can this be with similar reductions in amygdaloid grey matter?
Etiological Theory of SIAD.
The answer may have to do with the precise location of reduction in complexity. I propose that extreme stress causes excitotoxic effects throughout the limbic system (Bellis, 2004). Millon et al. (2004, p. 506), for instance, suggests two developmental pathways of BPD: “In the first, the personality develops a significant level of integration but breaks down under conditions of persistent environmental stress. In the second, no significant level of integration develops.” It is clear that appropriate social contact is the key factor in this integration. In the first case, abuse destroys what has already been built up by appropriate socialization. In the second a combination of neglect and/or abuse never allows this development to occur. Lacking social interaction during development or extreme stress at any stage can cause these problems. Eluvathingal et al. (2006) found direct evidence of neurotoxicity of early stress in white matter tracts that connect to the amygdala or surrounding regions, particularly reduced functional anisotropy in the uncinate faciculus, which connects the amygdala as well as other limbic structures with the anterior temporal lobe. A possible mechanism by which this might occur is the reversal of the direction of information flow in these areas: the IRC and other parts of the lateral amygdala, the FFA and possibly the AAC. A study by Mohanty et al. (2009) demonstrated that, during a spatial search for a stimulus (faces), if the subject is primed to search for a threatening stimulus (angry face), they searched faster, while FMRI showed “limbic guidance of spatial attention”, whereby the limbic system took over the search. One aspect of this was activation of the fusiform gyrus by the amygdala. Perhaps this reversal of information flow can be disruptive to information flow in the other direction or cause neurotoxicity or other developmental problems if chronic.
The symptoms surrounding these stress-induced antisocial disorders primarily revolve around in-group recognition complexity and its psychological consequences. With limited exposure to extreme stressors, PTSD develops. There is some damage to the IRC and the rest of the limbic system. This results in lowered social affect and heightened fear response as well as proper function of the amygdala with regard to conditioned response. Flashbacks and trauma reminder avoidance reflect relatively healthy conditioning responses to fearful stimuli in my opinion. Far from being disordered, I suggest that these reactions are quite healthy evolutionary responses to have; though for modern clinical purposes they are pathological due to their debilitating effects on modern life. Prehistorically, one ought to have been very afraid of the lion that tried to eat one yesterday and his territory.
Chronic or early extreme stressors, on the other hand, will tend to produce more and more lasting damage to the limbic system resulting in BPD or psychopathy. I hypothesize that the difference between these two disorders lies almost completely in the IRC. In psychopathy, I propose that the IRC is completely non-functional, similar to Capgras for visual stimuli, except for any stimulus. That is, psychopaths are incapable of emotionally recognizing an in-group. This is pretty straight forward. They just can’t feel a warm emotional response to any social stimulus, face, voice etc. They still get frustrated, and with cascading damage to the rest of the limbic system, potentially including the OFC, may or may not be more violent. If there are functioning invisible psychopaths, this cannot ever be explained by damage to the OFC or other impulse regulating circuitry. It is only the criminals that tend to have such frontal deregulation and this is a primary reason that psychopathy research has survived separate from research on Antisocial Personality Disorder (ASPD). There may be many more psychopaths than identifiable by the DSM criteria for ASPD.
BPD, or even more generally borderline personality organization (Kernberg, 1975), would appear to lie between PTSD and psychopathy with regard to the function of the IRC. I propose that the IRC in borderlines is similar to that which we are all born with, a simple switching mechanism. With an IRC that functions as a switch, the simplest possible neural circuit, a human object is recognized as totally in-group, or equivalent to self (projective identification), or totally out-group (psychopathic reaction), a thing to be destroyed or entirely avoided (with this fight or flight decision made in the hypothalamus, post IRC). This might be the initial or a connected mechanism of any number of other mechanisms of introjection and self-relevance decisions regarding objects in the environment which are associated to those human objects. This assumes that self-relevance of objects recognized by the association cortexes is emotional in nature. This is not a great assumption. If we are born with a simplistic IRC, adequate and appropriate social stimulation, originally via parenting and then more general socialization involving peer interaction, works to increase the complexity of the circuit.
In many people considered social and normal humans, this goes so far as allowing the loving tenderness of close and community-integrated intimate relationships to live in relative harmony with the absolute hatred and destruction of out-group members. Don’t most societies consider their warriors to be normal and good social individuals? Don’t most warriors function normally in society even when expected to and engaged in the killing of out-group members as required by their societies? Is it really violence that marks the antisocial personality, or to whom that violence is directed? Research that studies violence or aggression and claims that these are the same as antisociality ignores the reality of culture. Violence toward the out-group is accepted and praised in most cultures and the perpetrators of that intergroup violence are usually what most psychologists would consider normal. Thus it is the distinction between in-group and out-group that seems to differentiate the social tolerability of violence and aggression among humans. Being that there is clearly no ethical reason that killing an out-group member for some purpose that would not be acceptable for killing an in-group member should be logically any different than killing an in-group member for that same purpose, the basis of this behavior in humans is very likely emotional. Humans do not have the same emotional reaction to the death of an out-group member and this makes it easier to rationalize their killing. Xenophobia is another impetus that pushes human groups to accept this unethical and illogical behavior, despite what should produce by its very illogic, a strong cognitive dissonance reaction. Thus, differentiation between in-group and out-group is the key to our definition of unacceptable violence and part of our definition of psychopathy as a personality disorder.
If the IRC in the borderline remains a mere switching mechanism long after infancy, a human object may appear to them to be in-group at one moment in time and out-group in the next. This would lead to variable psychopathic behavior in which the borderline personality, unlike the psychopath, is capable of feeling loving and tender emotions toward perceived in-group members at some times, but incapable of feeling those same emotions toward them at other times. Clearly the operation of this circuit, like other neural circuits in the brain is dependent upon some level of excitatory input from other areas. It must be fed by neurotransmitters originating in cell bodies located in the raphe nuclei, ventral tegmental area and other activation nuclei which project to the amygdaloid complex. One mechanism by which a switching mechanism at the IRC might be ‘flipped’, switched from the on state to the off state or vice versa, would be a change in its activation by these arousal pathways. Another might involve more complex feedback mechanisms involving general mood or sympathetic and parasympathetic nervous system activation plus cognitive interpretation, which would, of course, alter the arousal pathways just mentioned. Changes in the intensity or informational content of the stimuli which feed into the IRC might also have a similar switch flipping effect in borderlines. Perhaps a simple change in volume of auditory input might be enough to alter the information coming into the IRC from the AAC. Many experiments with such changes could be attempted to try to pin down just what stimulus changes might trigger such switch flipping events in the IRC.
Finally, to sum up: I propose that PTSD results from normal development that disrupted after the fact. That is, in PTSD I propose that normal development has caused an increase in IRC complexity that is reduced by excitotoxic effects of acute and post-developmental extreme stress and results in lowered social functioning. I propose that BPD results either from a lack of social stimulus causing a lack of growth of the IRC beyond the simple switching mechanism present at birth or a reduction to this level of complexity of the IRC after some amount of normal social development has occurred. This scenario would likely have a better prognosis due to the development of other associated brain regions during the initial period of social development. I propose that psychopathy results from either a birth defect causing a person not to possess a functioning IRC (primary psychopathy), or due to chronic extreme stress or developmental trauma which destroys all function in the IRC. For psychopathy, I conjecture that the presence of some grey matter at the location of the IRC, though non-functional, would mediate any potential recovery of IRC function, and therefore prognosis.
Strange perceptual experiences and transient psychotic events. Just as certain changes in the activity of general arousal pathways, such as the mesolimbic dopamine pathway, which supplies the amygdaloid complex with dopamine - for example - ought to have a potential flipping effect on an IRC that is reduced to a simplistic switching operation in the borderline; so too should this operation have a feedback effect on them. (see figure 2) The output from the amygdala effects the entire brain’s arousal via the central nucleus. The central nucleus is downstream of the proposed IRC location, in terms of processing. Strong arousal of excitatory amygdaloid nuclei at or upstream of the central nucleus can produce strong arousal in many parts of the brain. As is well known in psychopharmacology, the brain will adapt to a change in arousal via a change in some arousal pathway. Since this takes time, the rapidity of onset of a drug, for instance, changes its reinforcement and addiction profile, as well as the subjective effect.
In a normally functioning amygdala of some human older than infancy, the IRC is proposed here to be complex, and so would not often tend to produce massive changes in amygdala output, unless as an adaptive reaction to environmental stimuli. Since this proposed circuit would be so integral to the functioning of other circuits that may exist within the limbic system, a zero to one hundred percent shift, or one hundred to zero percent shift, in output from this location (‘flipping’ the switch) would cause a rapid and potentially massive change in arousal pathways, possibly including those feeding serotonin to the cortex. If these pathways were to, all of a sudden, dump a massive amount of serotonin onto the anterior temporal cortex, the effect might be similar to a short lived LSD trip (Tuinier et al., 1997) due to the massive and rapid activation of 5-HT2A receptors there. This is just what is described with regard to borderlines’ strange perceptual experiences.
A major white matter tract called the uncinate faciculus feeds directly from the area of the amygdaloid complex to the lateral and anterior temporal lobe. This might explain the previously cited findings of Eluvanthingal et al. (2010), in which socially deprived children from poorly run orphanages showed reduced functional anisotropy in this tract. If these children were borderline due to lack of social stimulation causing a lack of increase in functional complexity of the IRC, repeated abrupt changes in the activity of this tract might cause the detected problems. At one moment, the tract would be underactive, and at the next greatly overactive. Could this cause such white matter pathology?
Similarities of BPD to temporal lobe seizure disorders.
Neurologists, not psychologists, tend to deal with a group of people with seizure disorders in the temporal lobe or limbic system. They will first look for an electroencephalograph (EEG) signature of epileptic firing. Epilepsy in the limbic system is hard to diagnose in this way since EEG devices tend only to be capable of looking at the surface cortex and not deeper brain structures. If repeated EEGs do not find an epileptic signal, patients may be sent away to a psychiatrist. No one knows just how many of these might have some form of deep brain epilepsy. Regardless of the location of the epileptic focus, if it induces abnormal firing in the temporal cortex, particularly the anterior portion of the lateral temporal lobe, it can produce a perceptual disturbance that some patients equate with “seeing God” (Ramachandran, 1998, 174-198). Others perceive less splendiferous distortions in their perception similar to what is described in borderlines. Some of these patients become obsessively religious and also claim that the world appears “more real” after such an event. As Ramachandran suggests in this chapter, this may be due to a kindling effect, or the strengthening of neural pathways due to hyper-activation. They also tend to develop narcissistic tendencies, literally believing themselves to be ‘God’s gift’. Could the mechanism expounded for borderline perceptual distortions similarly result in a kindling effect in the temporal lobe which could lead to narcissism?
Due to the integral link between the lateral temporal lobe and the limbic system, including the amygdala and the proposed IRC, mainly via the uncinate faciculus; these patients also can develop other issues. Neurologists have noted that those with temporal lobe epilepsy (TLE) tend to have similar personality traits that include: “affective dysregulation, irritability and impulsive aggression, anxiety and obsessive-compulsive symptoms, paranoia, abnormal patterns of social interaction, schizophrenic like symptoms and dissociative states” (Aycicegi-Dinn, Dinn, & Caldwell-Herris, 2008). A study by Tebartz van Elst et al. (2000), showed that, of a group of 25 patients in their study with TLE and intermittent explosive disorder (IED), 48% had severe amygdala atrophy (mostly associated with encephalitis) or lesions to the amygdala or pariamygdaloid areas. This suggests that damage to these areas can cause temporal lobe epilepsy and borderline-like symptoms indicative of hyperarousal.
BPD and psychogenic pseudoseizure. There is also a strong link between borderline personality disorder (and cluster B in general) and what are called psychogenic non-epileptic seizure (PNES) disorders, in which the patient appears to be having a seizure but no epileptic signal can be found by EEG (Lacey, Cook, & Salzberg, 2007). Reuber (2008, pp. 264-265) reviews many studies linking PNES and borderline personality traits.
Perhaps some borderline patients experience neurological arousal due to mechanisms mentioned earlier that cause this seizure-like activity without epileptic signal. That is, perhaps the change in arousal pathway from low excretion of neurotransmitter on the cortex to very high levels causes disruption in the motor cortex that mimics seizure. This may be similar to a dissociative or transient psychotic state except with activity in the motor cortex rather than focused on the anterior temporal lobe. It would be interesting to determine whether these patients show a different white matter structure to borderlines, but similar reduced amygdala volume. Maybe this is just a different localization of the same activity found in the more common transient psychotic state or strange perceptual experience reported by borderline patients. Discovery of the precise neurological differences between borderlines with that more common altered consciousness state and these psychogenic seizure patients with borderline symptoms might lead to a better understanding of how and via what pathways some switching effect in the IRC or other amygdala circuits could cause such transient altered brain activities.
Symptomology of SIAD
PTSD. In PTSD, with reduced functional complexity of the IRC, patients may have trouble identifying in-group members. This might present as reduced capacity to feel social emotions of love or tenderness toward loved ones and others. The perceived size of the patient’s in-group might be expected to decrease. Strangers or acquaintances might be expected to be viewed with greater suspicion and the general sense of security might be diminished. If a social organism views his group to be less powerful a protector relative to a previous time, this might be expected to produce general anxiety. Reduced in-group recognition might be expected to produce greater general anxiety even when the individual is within the group, manifesting behaviorally as hypervigilance. Memory disruptions may take other pathways than the IRC. However, the formation of new memories that are social-emotional in nature may be disrupted via the IRC. Generally, social perception should be the primary disruption in PTSD associated with reduction in IRC functionality. Angry outbursts can be seen as a protective measure in response to perceived insecurity within the social group and the change of social perception likely in a lowered dominance direction. Since much pleasure in normal social humans is derived from socialization, equivalent to grooming in lower simians, lowered function of the IRC might produce a social anhedonia resulting from lack of social emotional reaction. Combined with increased anxiety, this lowered arousal might decrease sensitivity to pleasurable stimuli in general. Anxiety produced by reduced sociality and the strength of traumatic associations might give rise to flashbacks, especially in response to stimuli resembling trauma. That is, the combination between social dysfunction via the IRC, the resultant hypervigilance and strong memory associations elsewhere in the amygdala would seem to be likely to induce strong trauma related memories.
BPD. In BPD, with a simplistic switching mechanism at the IRC, patients flip between attachment and hostile responses. Possibly depending upon cognitive associations, these can be specific to individuals or possibly even global at times. Within specific individual human objects, the patient may respond highly socially at one time and be very hostile at another. This must occur in all borderlines according to this theory. Global splitting, where the patient might view himself as completely unloved by and unloving of anyone at one time and be highly social at another, may be seen as potentially more severe and might, therefore, be associated more with strange perceptual experiences and more excitotoxic damage to downstream circuits. That is, simple switching per individual is not the same as simple switching globally. Per individual represents a higher functional complexity, as it requires differentiation of individuals for complete inclusion in or complete exclusion from the in-group. Global social switching would suggest an even lower IRC complexity that is incapable of this distinction; or it may be the case that this distinction is mostly cognitive in the borderline and that this differentiation in severity is not associated with the IRC.
The extreme variability in output from the IRC in borderlines might cause damage to downstream circuits and pathways. As was discussed in a previous section, this extreme variability in output may be responsible for the strange perceptual experiences reported by borderline patients. It may also produce the more generalized memory issues found in both borderlines and psychopaths, via downstream excitotoxicity. Exaggerated startle response suggests that other amygdala function is still generally higher than in psychopaths, and may result from similar mechanisms as in PTSD. Outbursts of anger ought to be more extreme, on average, in BPD patients, due to unpredictable and split in-group recognition as well as increased affective labiality caused by extreme swings in amygdala output. Cortical disruption due to this rapid and extreme change in output may result either in an excitotoxic effect or kindling effect, and may do so differentially across cortexes. A kindling effect in the anterior temporal lobe may result in narcissism and one may expect to find a correlation between perceptual disturbance and extremes of narcissism in BPD patients, possibly alternating with extreme self-devaluation as mediated by the IRC. The power of the feeling of in-group affiliation should not be discounted with regard to depressive symptoms in these patients. Depressive symptoms may turn on and off with the same rapidity and frequency as perceived in-group belonging with activation or deactivation of the simple switching IRC. Imagine suddenly feeling completely alone in the universe for no reason. Flipping off the IRC ought to have such an effect. How could such an experience not result in non-delusional paranoia? If conscious perception is disturbed at the same time, even delusional paranoia might be expected, at least transiently. More severe globally splitting IRC borderlines may lapse into longer psychopathic states in which the IRC is completely non-functional for some long period of time. The key difference between these and truly psychopathic individuals may be transient perceptual disturbances or periods of extreme emotional arousal or attachment seeking. These categories might blend into each other. BPD is highly comorbid with psychopathy in clinical studies but, for instance shows gender differences in manifestation (Kendall, S. J., 2006), suggesting cognitive or brain structure other than the IRC influences clinical presentation. It would be interesting to see if borderlines have significantly different psychopathy scores on standard measures at different times, when presenting with different moods, relative to non-comorbid psychopaths.
Psychopathy. Not only is the IRC likely completely non-functional in psychopaths according to this theory, but I suspect that excitotoxicity has destroyed other excitatory circuits in the amygdala in many psychopaths. A non-functional IRC no longer inhibits any downstream circuit which it is usually supposed to inhibit, possibly causing excitotoxicity downstream of the IRC. Also, excitation strong enough to completely destroy functionality at the IRC may be strong enough to damage other normally less susceptible circuits via other pathways. Since such damage to other circuits could be variable in a psychopathic patient, the complete and constant non-functionality of the IRC itself should define the disorder. The more extreme the damage to other areas of the limbic system, the more extreme the manifestation of the disorder, particularly with regard to excitability. Herpertz et al. (2001), for example, demonstrate a significant difference between psychopaths and borderlines with regard to electrodermal startle reactivity, psychopaths being less reactive, but not with regard to facial reactivity to disturbing imagery. The very extreme form of anhedonia in psychopaths, called psychopathic boredom, and resulting sensation seeking behavior ought to be considered possible results of this destruction of excitatory circuits.
Without ever experiencing in-group recognition, psychopathic patients would not view any other human being as someone to care about emotionally, which may make it impossible to perceive the care of others. That is, showing tenderness to a psychopath ought to be much like sending a letter to a person who cannot read. The psychopath himself may not even recognize that there is anything amiss. If he is clever and not too sensation seeking or retains more of that downstream circuitry, no one else may either; since, unlike the borderline, he is not at the mercy of extreme changes amygdaloid complex output. A psychopath that is not threatened may be calm or depressed. It may partially be the lack of a perceived in-group which can propel the psychopathic person to extremes of violence, especially when threatened. He may feel completely alone with no reason to believe that anyone will come to his aid. Without loving bonds in social interaction, all such interaction becomes cognitively motivated. This might result in a plethora of exchange or exploitative relationships. We must not confuse general amorality and psychopathy (Glenn et al., 2009). There are likely a large number of non-criminal psychopaths out there, and definitely many non-psychopathic criminals. However, in psychopaths with severely disrupted downstream circuitry, the lack of fear response would make predatory behavior more possible and therefore, for some, more probable.
The brain of homo sapiens sapiens evolved from earlier models. At some point our ancestors were not social animals. We evolved social circuits once in our limbic system and then evolved a second, augmented, form of sociality as we developed our neocortex and its resultant language and consciousness. Integration of the lower and higher brain systems needed to balance emotional and cognitive reactions to environment in such a way as to favor survival. Clearly it is a combination of these two systems in the proper balance of their interaction which has allowed humans to flourish. However, the brain is an adaptable structure with a basic genetic blueprint that only provides the necessary basis for self-organization that is adaptive to the environment of its development. This developmental self-organizational property has potentially greater survival assets. Humans can apparently learn to live in just about any environment.
But, what if environmental demands directly conflict with what most might consider innate human nature? We are indeed social animals, but what of our survival in non-social environments? A key to human sociality is the sharing of resources. When sharing becomes deadly due to scarcity or lack of reciprocity, normal human society can break down. When this happens, those who continue to act in accordance with the rules of society may die off, while those who do not share resources that will not be returned in time for survival, and who take those scarce resources from the weaker animals, survive to procreate. The suddenness with which such changes can occur necessitates a rapid response. Excitotoxicity is a means to destroy entire neurological circuits quickly. A single circuit that must exist in humans for the survival of the species in general, but must be easily destroyed if the environment requires, would be this in-group recognition circuit. The destruction of all of the other complex neurological machinery that goes into our sociality would be very detrimental to many other functions of the brain, by interfering with other processes that overlap those circuits.
A linchpin in the entire system of sociality would be the recognition of other in-group members for a targeted social response relative to a default fearful-aggressive response to out-group members of the species. I propose that this circuit is normally weak in humans due to selective pressure and that it is easily destroyed by stress-induced excitotoxicity, allowing us to rapidly adapt to a suddenly antisocial environment. Within-individual reversal of this adaptive pathology for the socialization of the next generation after such a calamity may be aided by the elegant solution of a single weak circuit. It is much easier to tear down a complex system than it is to provide for a means to rebuild it after sensitive periods have come and gone. However, it may be the preservation of other systems by the weakness of a single circuit which might allow us to heal after such traumatic events. If a single circuit is at the center of these disorders, healing afflicted individuals becomes that much easier.
Posttraumatic Stress Disorder
• Experienced terror
• Detachment from other people
• Restricted range of affect
• Outbursts of anger
• Traumatic memory loss
• Exaggerated startle response
Borderline Personality Disorder
• Experienced early abuse or neglect
• Unstable relationships
• Unstable affect (restricted or labile)
• Reactive aggression
• Non-delusional paranoia
• Reduced memory capacity
• Exaggerated startle response
• Transient perceptual distortions
• Experienced abuse
• Exploitative relationships
• No social affect
• Reactive aggression
• Interpersonal paranoia
• Reduced memory capacity
• Inhibited startle response
American Psychiatric Association, & American Psychiatric Association. Task Force on DSM-IV. (2000). Diagnostic and statistical manual of mental disorders : DSM-IV-TR (4th , text revision ed.). Washington, DC: American Psychiatric Association.
Aggleton, J. P., & Young, A. W. (2000). The enigma of the amygdala: On its contribution to human emotion. In R. D. Lane, & L. Nadel (Eds.), Cognitive neuroscience of emotion. (pp. 106-128). New York, NY, US: Oxford University Press.
Aycicegi-Dinn, A., Dinn, W. M., & Caldwell-Harris, C. L. (2008). The Temporolimbic personality: a cross-national study. European Journal of Psychiatry, 22(4), 211-224.
Beauchaine, T. P., Klein, D. N., Crowell, S. E., Derbidge, C., & Gatzke-Kopp, L. (2009). Multifinality in the development of personality disorders: A biology x sex x environment interaction model of antisocial and borderline traits. Development and Psychopathology, 21(3), 735-770.
Bellis, M. D. D. (2004). Neurotoxic effects of childhood trauma: Magnetic resonance imaging studies of pediatric maltreatment-related posttraumatic stress disorder versus nontraumatized children with generalized anxiety disorder. In J. M. Gorman (Ed.), Fear and anxiety: The benefits of translational research. (pp. 151-170). Arlington, VA, US: American Psychiatric Publishing, Inc.
Blair, R. J. R., Mitchell, D. G. V., Peschardt, K. S., Colledge, E., Leonard, R. A., Shine, J. H., et al. (2004). Reduced sensitivity to others' fearful expressions in psychopathic individuals. Personality and Individual Differences, 37(6), 1111-1122.
Book, A. S., Quinsey, V. L., & Langford, D. (2007). Psychopathy and the perception of affect and vulnerability. Criminal Justice and Behavior, 34(4), 531-544.
Burgess, J. W. (1992). Neurocognitive impairment in dramatic personalities: Histrionic, narcissistic, borderline, and antisocial disorders. Psychiatry Research, 42(3), 283-290.
Clark, H. W., Masson, C. L., Delucchi, K. L., Hall, S. M., & Sees, K. L. (2001). Violent traumatic events and drug abuse severity. Journal of Substance Abuse Treatment, 20(2), 121-127.
Clarkin, J. F., Lenzenweger, M. F., Yeomans, F., Levy, K. N., & Kernberg, O. F. (2007). An object relations model of borderline pathology. Journal of Personality Disorders, 21(5), 474-499.
Cleckley, H. (1941). The mask of sanity; an attempt to reinterpret the so-called psychopathic personality. Oxford, England: Mosby.
Cohen, L. J., Grebchenko, Y. F., Steinfeld, M., Frenda, S. J., & Galynker, I. I. (2008). Comparison of personality traits in pedophiles, abstinent opiate addicts, and healthy controls: Considering pedophilia as an addictive behavior. Journal of Nervous and Mental Disease, 196(11), 829-837.
Decety, J., & Moriguchi, Y. (2007). The empathic brain and its dysfunction in psychiatric populations: Implications for intervention across different clinical conditions.
Dolan, M., & Fullam, R. (2005). Memory for emotional events in violent offenders with antisocial personality disorder. Personality and Individual Differences, 38(7), 1657-1667.
Emery, N. J., & Amaral, D. G. (2000). The role of the amygdala in primate social cognition. In R. D. Lane, & L. Nadel (Eds.), Cognitive neuroscience of emotion. (pp. 156-191). New York, NY, US: Oxford University Press.
Eluvathingal, T. J., Chugani, H. T., Behen, M. E., Juhasz, C., Muzik, O., Maqbool, M., Chugani, D. C., & Makki, M. (2006). Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study. Pediatrics, 117(6), 2093-2100.
Glenn, A. L., Iyer, R., Graham, J., Koleva, S., & Haidt, J. (2009). Are all types of morality compromised in psychopathy? Journal of Personality Disorders, 23(4), 384-398.
Golarai, G., Hong, S., Haas, B. W., Galaburda, A. M., Mills, D. L., Bellugi, U., et al. (2010). The fusiform face area is enlarged in williams syndrome. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 30(19), 6700-6712.
Hare, R. D., & Neumann, C. S. (2006). The PCL-R assessment of psychopathy: Development, structural properties, and new directions. In C. J. Patrick (Ed.), The handbook of psychopathy. (p. 58-88). New York, NY, US: Guilford Press.
Herpertz, S. C., Werth, U., Lucas, G., Qunaibi, M., Schuerkens, A., Kunert, H., et al. (2001). Emotion in criminal offenders with psychopathy and borderline personality disorders. Archives of General Psychiatry, 58(8), 737-745.
Holt, R., Barnby, G., Maestrini, E., Bacchelli, E., Brocklebank, D., Sousa, I., Mulder, E. J., Kantojärvi, K.,
Järvelä, I., Klauck, S. M., Poustka, F., Bailey, A. J., Monaco, A. P. (2010). Linkage and candidate gene studies of autism spectrum disorders in European populations. European Journal of Human Genetics, 2010.69
Jones, A. P., Laurens, K. R., Herba, C. M., Barker, G. J., & Viding, E. (2009). Amygdala hypoactivity to fearful faces in boys with conduct problems and callous-unemotional traits. The American Journal of Psychiatry, 166(1), 95-102.
Kendall, S. J. (2006). Borderline personality disorder and psychopathy in jail inmates: Gender differences in item functioning of the PAI borderline personality scales and the PCL-SV using rasch analysis. ProQuest Information & Learning). (Electronic; Print)
Kernberg, O. F. (1975). Transference and countertransference in the treatment of borderline patients. Journal of the National Association of Private Psychiatric Hospitals, 7(2), 14-24.
Kernberg, O. F. (1992). Psychopathic, paranoid and depressive transferences. The International Journal of Psychoanalysis, 73(1), 13-28.
Kosson, D. S., Suchy, Y., Mayer, A. R., & Libby, J. (2002). Facial affect recognition in criminal psychopaths. Emotion, 2(4), 398-411.
Kroll, J. (1993). PTSD/borderlines in therapy: Finding the balance. New York, NY, US: W W Norton & Co.
Lacey, C., Cook, M., & Salzberg, M. (2007). The neurologist, psychogenic nonepileptic seizures, and borderline personality disorder. Epilepsy & Behavior : E&B, 11(4), 492-498.
Linehan, M. M., & Kehrer, C. A. (1993). Borderline personality disorder. In D. H. Barlow (Ed.), Clinical handbook of psychological disorders: A step-by-step treatment manual (2nd ed.). (pp. 396-441). New York, NY, US: Guilford Press.
Millon, T., Grossman, S., Millon, C., Meagher, S., & Ramnath, R. (2004). Personality disorders in modern life (2nd ed.). Hoboken, NJ, US: John Wiley & Sons Inc.
Mills, K. L., Teesson, M., Darke, S., Ross, J., & Lynskey, M. (2004). Young people with heroin dependence: Findings from the australian treatment outcome study (ATOS). Journal of Substance Abuse Treatment, 27(1), 67-73.
Mohanty, A., Egner, T., Monti, J. J., & Mesulam, M. M. (2009). Search for a threatening target triggers limbic guidance of spatial attention. The Journal of Neuroscience, 29(34), 10563-10572.
Newhill, C. E., Eack, S. M. , & Mulvey, E. P. (2009). Violent behavior in borderline personality. Journal of Personality Disorders, 23(6), 541-554.
Nunes, P. M., Wenzel, A., Borges, K. T., Porto, C. R., Caminha, R. M., & Reis de Oliveira, I. (2009). Volumes of the hippocampus and amygdala in patients with borderline personality disorder: A meta-analysis. Journal of Personality Disorders, 23(4), 333-345.
O'Leary, K. M., Brouwers, P., Gardner, D. L., & Cowdry, R. W. (1991). Neuropsychological testing of patients with borderline personality disorder. The American Journal of Psychiatry, 148(1), 106-111.
Pastors, M. C., Moltó, J., Vila, J., & Lang, P. J. (2003). Startle reflex modulation, affective ratings and autonomic reactivity in incarcerated spanish psychopaths. Psychophysiology, 40(6), 934-938.
Pole, N. (2007). The psychophysiology of posttraumatic stress disorder: A meta-analysis. Psychological Bulletin, 133(5), 725-746.
Ramachandran, V. S., & Blakeslee, S. (1998). Phantoms in the brain : Probing the mysteries of the human mind (1st ed.). New York: William Morrow.
Reiss, A. L., Eckert, M. A., Rose, F. E., Karchemskiy, A., Kesler, S., Chang, M., et al. (2004). An experiment of nature: Brain anatomy parallels cognition and behavior in williams syndrome. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 24(21), 5009-5015.
Reuber, M. (2008). Psychogenic nonepileptic seizures: answers and questions. Epilepsy & Behavior, 12, 622-635.
Rudrauf, D., David, O., Lachaux, J. P., Kovach, C. K., Martinerie, J., Renault, B., et al. (2008). Rapid interactions between the ventral visual stream and emotion-related structures rely on a two-pathway architecture. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 28(11), 2793-2803.
Sansone, R. A., Whitecar, P., & Wiederman, M. W. (2008). The prevalence of borderline personality among buprenorphine patients. International Journal of Psychiatry in Medicine, 38(2), 217-226.
Santos, A., Meyer-Lindenberg, A., & Deruelle, C. (2010). Absence of racial, but not gender, stereotyping in williams syndrome children. Current Biology : CB, 20(7), R307-8.
Scherer, S., Cheung, J., MacDonald, J., Osborne, L., Nakabayashi, K., Herbrick, J., Carson, A., Parker-Katiraee, L., Skaug, J., Khaja, R., Zhang, J., Hudek, A., Li, M., Haddad, M., Duggan, G., Fernandez, B., Kanematsu, E., Gentles, S., Christopoulos, C. (2003). Human Chromosome 7: DNA Sequence and Biology. Science, 300(5620), 767-772
Schmahl, C. G., Vermetten, E., Elzinga, B. M., & Bremner, J. D. (2003). Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Research: Neuroimaging, 122(3), 193-198.
Shin, L. M., Rauch, S. L., & Pitman, R. K. (2006). Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. In R. Yehuda (Ed.), The psychobiology of post-traumatic stress disorder, sep 2005, mount sinai school of medicine, new york, NY, US (pp. 67-79). Malden: Blackwell Publishing.
Stephan, H., Frahm, H. D. & Baron, G. (1987). Comparison of brain structure volumes in insectivore and primates VII. Amygdaloid components. Journal für Hirnforschung, 28, 571-584, as cited in Aggleton, J. P., & Young, A. W. (2000).
Tebartz van Elst, L., Woermann, F. G., Lemieux, L., Thompson, P. J., & Timble, M. R. (2000). Affective aggression in patients with temporal lobe epilepsy: a quantitative mri study of the amygdala. Brain, 123, 234-243.
Tuinier, S., Verhoeven, W.M.A, van der Berg, Y.W.M.M, Marijnissen, G., & van Ooy, E.J.M., Pepplinkhuizen, L. (1997). The Effect of resperidone on perceptual disturbances in borderline personality disorders. European Neuropsychopharmacology, 7(2), 283.
Vanman, E. J., Mejia, V. Y., Dawson, M. E., Schell, A. M., & Raine, A. (2003). Modification of the startle reflex in a community sample: Do one or two dimensions of psychopathy underlie emotional processing? Personality and Individual Differences, 35(8), 2007-2021.
Weniger, G., Lange, C., Sachsse, U., & Irle, E. (2008). Amygdala and hippocampal volumes and cognition in adult survivors of childhood abuse with dissociative disorders. Acta Psychiatrica Scandinavica, 118(4), 281-290.
Yang, Y., Raine, A., Narr, K. L., Colletti, P., & Toga, A. W. (2009). Localization of deformations within the amygdala in individuals with psychopathy. Archives of General Psychiatry, 66(9), 986-994.