The Emotional Foundations of Personality

by Kenneth L Davis

  In a Norwegian study, Sigmund Karterud’s group (Karterud et al., 2016) reported ANPS data on over five hundred patients with specific personality disorder diagnoses, focusing on the two largest diagnostic categories, which together accounted for over 70 percent of the patients: borderline and avoidant personality disorders. Regression analyses on these two largest groups showed that the borderline group had high SEEKING scores, while the avoidant group had low SEEKING scores as well as low PLAY scores. Again, the positive emotions played an important role in distinguishing between the two groups. The regression analysis also showed that high FEAR was also a key factor in the avoidant group. Otherwise, the avoidant group showed lower RAGE/Anger, with the borderline group showing higher RAGE/Anger as well as higher PANIC/Sadness. Karterud’s work has reinforced the ideas not only that positive primary emotions also play a prominent role in personality disorders but also that personality disorders can be defined on the same continua as the ANPS-monitored primary emotional foundations of personality in general and that psychiatrically significant personality disorder diagnoses may not require special categories unique to “mental illness.”

  While there has not yet been any ANPS research on the serotonin transporter gene (5-HTT) discussed in Chapter 7, a research group at the University of Bonn has investigated the relationship of ANPS scales and other genes. For example, Reuter, Weber, Fiebach, Elger, and Montag (2009) investigated links between ANPS RAGE/Anger scores and the DARPP-32 (dopamine- and cAMP-regulated phosphoprotein 32 kDa) gene (a C→T single nucleotide polymorphism) based on previous demonstrations that RAGE/Anger was influenced by the dopamine system. DARPP-32 is a key regulatory molecule in the dopaminergic signaling pathway. The C-allele is more common in sub-Saharan Africa but rather infrequent in European populations. The genetic analysis of German subjects without psychopathology showed that carriers of the T-allele (either TT or TC) had significantly higher ANPS RAGE/Anger scores, and subjects with the CC genotype had significantly lower RAGE/Anger scores. MRI data on a subsample of subjects also revealed that higher RAGE/Anger scores were associated with lower gray matter volume in the left amygdala, a subcortical brain structure whose corticomedial regions are associated with RAGE/Anger circuitry (Panksepp, 1998a).

  Reuter, Panksepp, Schnabel, Kellerhoff, Kempel, & Hennig (2005) also demonstrated a link between the ANPS SEEKING scale and creativity. Using figural, verbal, and numeric creativity tests, subjects with higher SEEKING scores had higher numeric creativity scores and were significantly superior on figural and verbal creativity. SEEKING scores also explained more than 15 percent of the variance of total creativity. Using intelligence tests as a covariate indicated that the relationship of SEEKING to creativity was not related to measures of intelligence. Because of an interest in hormonal influences on creativity, subject’s testosterone was also measured. While testosterone did not predict creativity levels, subjects with higher testosterone had higher SEEKING scores, which may help explain the past finding of positive relations between testosterone levels and monotony avoidance (Mattsson, Schalling, Olweus, Löw, & Svensson, 1980). A path analysis using LISREL 8.51 software showed that 39 percent of the variance in SEEKING scores could be predicted by testosterone and creativity levels, with testosterone and creativity being nearly equal but uncorrelated predictors.

  Ideally, the ANPS will continue to be a useful tool for providing explicit assessment of primary brain emotion systems strengths and weaknesses for psychological and genetic research, as well as providing a useful tool for clinicians evaluating where their clients are situated temperamentally in emotional-affective space. Because these basic brain emotion systems influence the affective quality of mental life, clinicians can use the ANPS to evaluate individual profiles of key emotional dimensions for clues about emotional forces that may have become imbalanced (for a clinical case study that relied upon such ANPS results, see Turnbull, Evans, & Owen, 2005).

  OPIOID TREATMENT OF DEPRESSION

  A 1978 research report in the journal Biological Psychology (Panksepp et al., 1978) showed that very low doses of opioids such as morphine could easily quell plaintive separation distress cries in an animal model. The original demonstration was with young puppies in John Paul Scott’s canine research lab (see Chapter 8). This was soon followed by more extensive analyses with guinea pigs and chicks (for reviews, see Panksepp et al., 1980; Panksepp, 1998a). Of course, separation distress cries are well known to anyone who has been around human children and young mammals in general. These feelings of social pain and distress continue throughout life in the aftermath of a broken relationship or the death of a loved one. Humans have even developed a special evolved means for expressing the psychic pain of separation, namely, tears, as well as an odd affinity for songs and stories dealing with “broken hearts.”

  John Bowlby’s classic volumes on attachment and loss (Bowlby, 1960, 1980) had made the links between excessive early social separation, problematical parental bonding, and depression occurring later in life. So, it would seem a short step to treating an overactive PANIC/Sadness system cascading into depression with opioid drugs. It turns out that opiates were actually used to treat depression until the mid-1950s (Bodkin, Zornberg, Lukas, & Cole, 1995; Tenore, 2008). It was around then that new antidepressant drugs, knows as monoamine oxidase inhibitors and tricyclic antidepressants, emerged, which gave psychiatrists an alternative to the addiction problems with opiates. The tricyclic drug Tofranil (imipramine) was first tried as a treatment for psychotic disorders, where it failed, but was later tried more successfully with depressed patients. Imipramine, like most tricyclics, increases the availability of the neuromodulators norepinephrine and serotonin. Soon, Eli Lilly introduced Prozac (fluoxetine), which was a more selective serotonin reuptake inhibitor (SSRI) with fewer side effects, and the SSRIs became the new drug of choice for depression. However, even the SSRIs have never had a sterling track record for treating depression (as highlighted by the STAR-D report: Sinyor, Schaffer, & Levitt, 2010), with some SSRIs even thought to increase the probability of suicide. Prozac was first reported to lead to suicide in 1990 (Healy & Aldred, 2005).

  But what about those individuals where loss of love, and resulting “broken hearts,” promotes suicide? What if there were an opioid that could help with depression-related suicide but that was less addictive, or perhaps not addictive at all (Panksepp & Yovell, 2014)? A study out of Harvard (Bodkin et al., 1995) reported that buprenorphine, a “safer” opioid with much reduced dependence and abuse liabilities, produced significant improvements in patients with major depression that had never previously responded to conventional antidepressant treatments. The term “conventional” should be emphasized here since buprenorphine has never been approved by the FDA for treating depression.

  Although it has been demonized as a gateway drug to opiate addiction, buprenorphine is in fact one of the safest opioids: it produces much less respiratory depression, which can be lethal, while retaining opioid analgesic qualities that could directly reduce psychological pain at very low doses (Dahan et al., 2006). Hypothesizing that it is the “psychological pain” that leads to increased suicidal thoughts, Jaak Panksepp and Yoram Yovell (2014) designed a double-blind pilot study to see if very low doses of buprenorphine could help depressed patients who were already receiving treatment but still had frequent thoughts of committing suicide. The project was finally completed in Israel because it could not be approved in the United States.9 After two weeks, results showed that those patients receiving the buprenorphine reported fewer depressive symptoms and fewer suicidal thoughts. Based on the encouraging pilot results, a much larger and equally successful phase 3 clinical trial was completed (Yovell et al., 2016). Thus, focusing on primary emotional affects can make a substantial difference in treatment of psychiatric disorders characterized by psychological pain. Buprenorphine specifically targets the opioid receptors that can reduce the psychological pain of the PANIC/Sadness system, in contrast to the more broadly acting SSRI drugs, whi
ch increase serotonin levels but are not particularly effective in reducing depression (remember the STAR-D report by Sinyor et al., 2010), and which mildly subdue many other primary affects, both positive and negative.

  TREATING DEPRESSION WITH DEEP BRAIN STIMULATION

  Major depression is not just extremely psychologically debilitating; it is commonly very difficult to treat. Various treatments for depression have shown some early promise that subsequently proved overly optimistic (Sinyor et al., 2010). Cognitive therapy (CT) is the most popular form of psychotherapy for depressed patients and theoretically works by teaching patients new sets of cognitive skills, which they can use to control their depression. However, success with CT has been difficult to demonstrate versus control groups, including those on antidepressant medications. In a critical review of research into evidence-based explanations for psychotherapeutic interventions, Yale University’s Alan Kazdin concluded, “whatever may be the basis of changes with CT [cognitive therapy], it does not seem to be the cognitions as originally proposed” (2007, p. 8), implying that effective therapeutic interventions may typically impact affective dimensions of the BrainMind more than just the cognitive, information-processing ones (a theme we revisit in Chapter 19). As a last line of intervention for patients with major depressive disorders, electroconvulsive therapy, often referred to as shock treatment, is still effectively used in cases of treatment-resistant depression, although about half the responders relapse within a year (Jelovac, Kolshus, & McLoughlin, 2013).

  Because as many as 33 percent of patients with major depression do not respond to depression treatments (Rush et al., 2006), treatment-resistant depression remains a major psychiatric challenge. Affective neuroscience research suggests that more effective treatments are likely to emerge by addressing primary-process emotional affects. Specifically, an affective neuroscience approach to depression, has proposed “that sustained over activity of the PANIC and under activity of the SEEKING and PLAY networks substantially contribute to depression” (Panksepp et al., 2014, p. 477; see also Panksepp & Yovell, 2014). When these emotional systems are out of balance, depression is likely to occur.

  One hypothesis is that increasing activity of the SEEKING brain system could be a viable treatment option for treatment-resistant patients. This is exactly what a German research group has done, by using tiny electrical currents to the brain to increase activity of the SEEKING system. In an initial study with three treatment-resistant patients, they first selected the nucleus accumbens as a therapeutic target for deep brain stimulation (DBS) of treatment-resistant patients (Schlaepfer et al., 2008), thus arousing a subcortical way station that is heavily controlled by the mesolimbic dopaminergic pathway, a key node of the brain SEEKING network. Their results were remarkable in that two patients after only sixty seconds of stimulation spontaneously mentioned plans to engage in interesting activities (one wished to take up bowling again). In a follow-up study involving ten treatment resistant patients, 50 percent of the patients exhibited sustained antidepressant effects after twelve months of DBS, including elevated enthusiasm and positive active planning for the future (Bewernick et al., 2010). However, a further study achieved even greater results by shifting the placement of the electrodes slightly to the “heart” of the medial forebrain bundle, a central part of the mesolimbic pathway and the most rewarding DBS site in the SEEKING system (for the human anatomy of this system, see Coenen et al., 2012) This adjustment led to the highest recovery rate in treatment-resistant depression ever reported. Six of the seven patients in the study improved over 50 percent on a standard measure of depression within three weeks and were still above that mark at the end of the thirty-three-week study (Schlaepfer, Bewernick, Kayser, Madler, & Coenen, 2013). A single patient may not have responded because of surgical problems (minor vascular damage at one of the DBS sites).

  It is important to note that after DBS of their SEEKING systems, which probably included activation of dopamine systems, these patients did not act like cocaine or amphetamine users. They were not wildly euphoric, and they did not report any explicit “rewarding” or “pleasurable” feelings during their brain stimulation. Their experiences were not of consummatory pleasures, as one might experience eating exquisite Belgian chocolate, for example; theirs was an anticipatory enthusiasm, as when a chocolate lover approaches the Belgian chocolate shop and looks in its appetizing, well-stocked window. Their SEEKING system affect was one of energetically looking forward to life’s rewards, which may have also explicitly counterbalanced the psychological pain engendered by overactive PANIC/Sadness separation distress networks. The mesolimbic pathway also projects to the frontal cortical areas (see Coenen et al., 2012), where DBS may have positively colored their perceptions and thoughts, with life beginning to look more inviting again. It is also notable that no negative psychological side effects were observed in any of the patients that have received this treatment so far.

  TREATING DEPRESSION WITH PLAYFUL JOY

  Most of you probably cannot image playing with a rat. Most people do not like rats. People have even been diagnosed with “musophobia,” or the fear of mice and rats, and even elephants have a reputation for being afraid of mice.

  So, who wants to play with a rat? Actually, the second author has acquired a reputation for playing with rats, so much so he has been nicknamed the “rat tickler.” Rats, like all mammals, love (and perhaps even need) to play. However, play is the domain of the young, and rats, along with humans, decline in their tendency to play and respond to tickling as they age. But while they are young, little play-prone rats love to be tickled by a human hand and, like human children, are always ready for more.

  Is it possible that Ponce de Leon was looking in the wrong place as he searched for the fountain of youth? Is it possible that the fountain of youth is not a geographical place but might actually be found in the BrainMinds of playful little rat pups and happy human beings? That was one of novel therapeutic ideas developed by the extended affective neuroscience group at the Falk Center for Molecular Therapeutics at Northwestern University. They were building on research from Bowling Green State University where extensive research on “rough-and-tumble” play in rat pups began in the late 1970s (Panksepp, 1981c; Beatty & Costello, 1982; Panksepp et al., 1984) but especially on later work discovering that rats frequently emitted 50-kHz ultrasonic vocalizations during rat play sessions that could be used as a psychological assay for positive affect in rats (see Chapter 9). It turns out these 50-kHz vocalizations are also promoted by many positive events, such as the anticipation of sexual activity, daily feeding, being tickled, rewarding brain stimulation, and addictive psychostimulants. Notably, rats will work to receive DBS at all brain sites that evoke 50-kHz calls (Burgdorf et al., 2007). Also, rats will approach places where they have emitted these 50-kHz “chirps” as if anticipating finding some positive event (Wohr & Schwarting, 2007).

  During social play, juvenile rat pups abundantly emit these ultrasonic 50-kHz rat chirps that are akin to the laughter of joyful children playing. While rat pups, like dog puppies, normally give each other little nips during their play bouts, if one rat pup bites too hard, the play and the joyous chirping (rat laughter?) are at least temporarily interrupted. Indeed, these enthusiastic ultrasonic chirps also halt at the hint of cat smell (as well as to practically all aversive experiences), during which animals often begin to emit 22-kHz “complaints,” which can be used as a validated psychological-affective assay for unpleasant feelings in rats, as indicated by the fact that, if given the chance, rats readily avoid or turn off playback of such sounds.

  Overall, the study of rat play and laughter led to a profound proposition: that we could neuroscientifically begin to understand the feelings of social joy in an animal model, and that such a state of mind in rats is dramatically diminished in clinical depression. Further, these assays of playful social joy in rats could lead to the study of the gene expression patterns of the brain that might reveal new pathways for antidepressant develop
ment (for overviews, see Panksepp, 2015, 2016). In short, the Falk affective neuroscience group wondered whether play could increase the production of brain chemicals that would give clues to the development of new antidepressants. The key question was what genes were being overexpressed in the brains of rats that had just played for half an hour, and whether some of the identified neurochemistries could be targets for novel antidepressants (Burgdorf et al., 2011).

  This search led to a variety of possible novel medications, some of which did not have the safety profiles needed to go into human testing. However, one of the most intensely expressed genes was selected as a very safe pathway, and potential medicinal agents were constructed (Burgdorf et al., 2011). The key molecule, a neuropeptide named GLYX-13, was “a partial agonist for glycine sites on N-methyl-D-aspartate receptors, promoting glutamate transmission in low doses and blocking it in high doses” (Moskal et al., 2011). As hypothesized, GLYX-13 promoted the positive-affective 50-kHz ultrasonic vocalizations in rats during social play (Burgdorf et al., 2011). More importantly, GLYX-13 passed all toxicology trials, and in human phase 2b clinical trials has so far demonstrated robust and sustained antidepressant effects, with a rapid onset of antidepressant activity in as little as two hours (Preskorn et al., 2015)—this may be the first novel psychiatric medicine that has come from human knowledge of animal emotional processes. Many more are bound to emerge as more investigators understand the power of “affective modeling” of psychiatric disorders rather than the traditional “never-mind” behavior-only modeling that remains so abundant in the field.

  SUMMARY

  We believe all three of these new antidepressant treatments, which were all developed from focusing on the affective nature of the mammalian BrainMind, highlight the value of an affective neuroscience approach to psychopathology (Panksepp, 2015, 2016). Affective imbalances can best be approached from an understanding of the homologous mammalian subcortical anatomies that control primal animal emotionality and thereby our own deeply affective nature. As we gain a fuller understanding of the affective brain systems that we have inherited as ancestral birthrights, hopefully additional evidence-based treatments, based on taking the affective processes of other animals as models for our own, will be discovered. But at this point, affective neuroscience orientations to research in this field are still disproportionately small, because of a century of belief that the feelings of other animals could not be empirical penetrated.