DYNAMICAL UNIQUE TRAIT OF PERSONALITY AND CONDITIONING: BLOOD GLUTAMATE IN RESPONSE TO METYLPHENIDATE
Salvador Amigó. Departament de Personalitat, Avaluació i Tractaments Psicològics. Universitat de València
Antonio Caselles. Departament de Matemàtica Aplicada. Universitat de València (Antonio.Caselles@uv.es)
Joan C. Micó. Institut Universitari de Matemàtica Pura i Aplicada. Universitat Politècnica de Valéncia
Abstract
The Unique Personality Trait Theory (UPTT) postulates that glutamate is the most significant biological substrate of personality. In this study, the analysis of personality dynamics by glutamate’s reactivity to one dose of stimulant drug, the methylphenidate, is performed. Moreover, the conditioning dynamic of drug effects by using the self-regulation therapy is also studied. An ABC single case experimental design with replication with two subjects has been performed. In the three phases each subject fills the Sensation Seeking Scale (SSS) of the MAACL each 15 minutes (17 registers for each phase). The sensation seeking is considered an acceptable approximation to the measure of the unique trait. Blood samples was obtained each one hour (5 samples for each phase). The first phase was the base-line, while for the second phase both subjects consumed 20 mg of methylphenidate. For the third phase, subject 1 consumed 40 mg of methylphenidate and subject 2 applied the self-regulation therapy to reproduce the drug effect. The results confirm a dynamical pattern (curve of inverted U) of the glutamate blood concentration as a response to one dose of methylphenidate. In addition, individual differences between the two subjects have been observed; concretely, a tolerance effect for subject 1 and a sensitizing effect to the subject 2 in the phase C have been observed. The conditioning effect of the plasma glutamate increase was observed in subject 2 by application of the self-regulation therapy. This outcome can be interpreted as an effect of “personality conditioning”. It opens considerable implications in the future understanding personality and its therapeutic modification.
Resumen
La Teoría del Rasgo Único de Personalidad (UPTT) postula que el glutamato es el substrato biológico más significativo de personalidad. En este estudio se analiza la respuesta dinámica de la reactividad del glutamato a una dosis de droga estimulante, el metilfenidato. Además, también se estudia la dinámica condicionante de los efectos de una droga como consecuencia de la terapia auto-regulativa. El diseño experimental es del tipo ABC de caso único con replicación de dos sujetos. En las tres fases cada sujeto rellena la Escala de Búsqueda de Sensaciones (SSS) de la MAACL, cada 15 minutos (17 registros para cada fase). La búsqueda de sensaciones se considera una aproximación aceptable a la medida del rasgo único. Muestras de sangre se obtuvieron cada hora (5 muestras para cada fase). La primera fase es la línea base, mientras que durante la segunda fase ambos sujetos consumieron 20 mg de metilfenidato. Durante la tercera fase el sujeto 1 consumió 40 mg de metilfenidato y al sujeto 2 se le aplicó la terapia auto-regulativa para reproducir el efecto de la droga. Los resultados confirman un patrón dinámico (curva de U invertida) de la concentración de glutamato en sangre como respuesta al consumo de una dosis de metilfenidato. También se han observado diferencias individuales entre los dos sujetos, en concreto se observó un efecto de tolerancia en el sujeto 1 y un efecto de sensibilización en el sujeto 2 en la fase C. Se hace hincapié en el efecto de condicionamiento del incremento de glutamato en plasma como consecuencia de la realización de la terapia auto-regulativa. Este resultado puede ser interpretado como un efecto de “personalidad condicionada”, y abre considerables implicaciones en la futuro comprensión de la personalidad y su modificación terapéutica.
Key words: Glutamate, Personality, Unique Trait, Dynamics, Self-Regulation Therapy.
1. Introduction
Glutamate neurotransmitter has been postulated as the most significant biological substrate of personality in the Unique Personality Trait Theory (UPTT) (Amigó, 2005). This theory proposes a hierarchical model where the highest level corresponds to the unique trait, extended from an impulsivity and aggressively pole (approach tendency) to an anxiety and introversion pole (avoidance tendency).
Glutamate is not only a neurotransmitter, but a widely distributed substance round organism with multiple functions, such as: substrate for protein synthesis, active sites of enzymes, citric acid cycle intermediate and energy source for some tissues. However, glutamate has regulatory functions in immune-component cells and in nervous system; it serves as well as a signalling agent between the immune and nervous receptors (Boldyrev, Carpenter and Johnson, 2005). Thus, glutamate is an indicator of the organism’s general state of activation.
A dynamic mathematical model has been proposed to explain personality change due to acute administration of psycho-stimulant such as cocaine (Amigó et al., 2008a). It has been performed using a personality adjectives scale. Besides, a dynamic model of personality and gene expression change produced by caffeine has been proposed (Amigó, et al., 2008b).
This study uses an experimental design of unique case with replication. The goals are: 1. the measure of the activation subjective effects from adjective scales; 2. the measure of glutamate reactivity by blood concentration, as a response to a dose of a stimulant drug, methylphenidate. The level of L-glutamate was measured in blood because of two causes: its central position in mammalian metabolism and its almost exclusive presence in nature respect to D-glutamate (Young and Ajami, 1998).
In addition, we also pretend to assess the drug conditioning effects. Since Pavolv’s conditioning drug effects experiment (1927), the drug-associated conditioning responses have been well established (Lynch et al., 1976; O’Brien et al., 1992; Stewart et al., 1984). Significant increases in glutamate levels in the nucleus accumbens has been obtained in cocaine-conditioned responses (Hotsenpiller, Giorgeti and Wolf, 2001). To increase the therapeutic efficacy of the contioning mechanism, the self-regulation therapy (Amigó, 1992) was created. This therapy uses conditioning techniques to reproduce all kinds of sensorial sensations. It has been effective to reproduce (conditioning) stimulant drug effects as ephedrine (Amigó, 1994) or methylphenidate (Amigó, 1997).
A first objective is to know the dynamic response to a stimulant drug. A second objective is to make out if glutamate concentration is a good biological observable variable of personality changes, measured by adjective scales. The third objective is to know if the conditioning of glutamate increase in blood is possible. Finally, in a four objective, we attempt to base qualitatively the problem of the dynamic equivalence between subjective and biological descriptions. This last objective is an attempt to face the classical problem of the “mind-body problem” for human behavior, in order to be dealt mathematically in future investigations.
2. Methodology and subjects
a) Subjects:
Two voluntary male subjects of 45 and 46 years old participated in the experiment.
b) Instruments:
1. Sensation Seeking Scale (SSS) of the MAACL (Zuckerman & Lubin, 1965). The 12 adjectives are: active, adventurous, aggressive, daring, energetic, enthusiastic, merry, mild, quiet, tame, wild and bored.
2. Biological analysis: In a first step, the blood samples were obtained. In a second step, a mass spectrometer was used to obtain the L-glutamate level in blood.
c) Experimental design and procedure
An ABC single case experimental design with replication was performed. In all phases the subject filled the SSS scale each 15 minutes (17 registers for each phase). The blood samples were obtained each 1 hour (5 samples for each phase).
The phase A is the base-line, without treatment. In the phase B the subjects consumed 20 mg of methylphenidate, immediately after filling the first SSS scale. In this moment, the first blood sample was obtained. After that, the subjects filled 16 SSS scales each 15 minutes. A blood sample was obtained each one hour along the following 4 hours.
In the phase C, the experimental condition is different for both subjects. Subject 1 consumes 40 mg of methylphenidate after filling the first SSS scale. In this moment, the first blood sample was obtained. As in phase A, the subjects filled 16 SSS scales each 15 minutes and a blood sample was obtained each one hour along the following 4 hours. Subject 2 filled the SSS sale half an hour later without treatment and the blood sample was obtained. Second hour later, the subject applied the self-regulation therapy to reproduce the drug effects obtained in phase B. The SSS scale was filled and the blood samples were obtained as in phase B.
The sequence of the experiment was:
First day: the subject goes to the medical laboratory. Phase A: baseline.
Second day, phase B: the subjects consumed 20 mg of methylphenidate.
Third day: subject 1 consumed 40 mg of methylphenidate, and subject 2 reproduces the stimulant effects with the self-regulation therapy.
3. Results
In Figure 1, for the phases, the glutamate registers in blood are presented. On a hand, a clear effect of the methylphenidate is observed in glutamate dynamics in phases B and C (inverted U shape). On the other hand, in phase A (base-line) a U shape is observed. The response of the methylphenidate in phase C (40 mg) is lesser than in phase B (20 mg); this can be due to a drug tolerance effect.
In Figure 2, the registers of the glutamate in blood for subject 2 are presented for the three phases. A very clear difference for glutamate dynamics in phase B (20 mg) and in phase C (self-regulation therapy) respect to phase A (base-line) is observed. In phase A, a U-shape dynamics is observed. In phases B and C an inverted U-shape is observed. Take into account that, in phase C, the self-regulation therapy starts close before the third register. Thus, in the third register, the glutamate level continues decreasing. But the glutamate level is the highest when the subject applies the therapy for half and one hour. This level decreases radically in the last register.
In Figure 3, the SSS scale registers and the glutamate in blood for subject 1 are presented for the three phases. In phase B (20 mg) the increase of glutamate concentration coincides with a high subjective activation. However, the glutamate increase happens before than the subjective increase. In addition, the first one stays in higher levels when the second one decreases. In phase C (40 mg), the glutamate increase delays respect to the subjective increase. Moreover, a general increase of the glutamate level in phase B (20 mg) is observed respect to phase A (base-line). Nevertheless, a decrease in phase C (40 mg) is observed respect to phase A, which can be interpreted as drug tolerance.
In Figure 4, the SSS scale registers and the glutamate in blood for subject 2 are presented for the three phases. In phase B (20 mg) the increase of glutamate concentration coincides with a high subjective activation. The difference respect to subject 1 is the delay of the glutamate increase respect to the subjective increase. In phase C (self-regulation), a glutamate decrease at the beginning of the subjective effects is observed. However, the glutamate increases strongly after more than an hour of self-regulation applying. This high glutamate concentration is even higher than the concentration obtained in the subjective activation of phase B. It can be interpreted as a sensitizing effect.
4. The dynamic equivalence approach
Here, we discuss the way to face the problem of the relationship between subjective data and biological data. In other words, in the context of this study, how we can represent the equivalence between SSS scale dynamics and glutamate dynamics.
Figures 3 and 4 show a same dynamic pattern for SSS and glutamate dynamics. They are consequence either of the methylphenidate consumption or of the self-regulation therapy. Thus, our hypotheses to find the future equivalences are:
1. Both, SSS dynamics and glutamate dynamics can be described mathematically by the delay differential equation provided in (Amigó et al., 2008a).
2. Both methylphenidate and self-regulation therapy can be described mathematically by the two coupled differential equations that define the stimulus dynamics in (Amigó et al., 2008a).
These two hypotheses are the base to find the mathematical dynamic equivalence between both descriptions: the biological one, given in our context by the glutamate evolution, and the subjective one, given by the SSS evolution. In addition, the equivalence must involve the stimulus, both of the methylphenidate and of the self-regulation therapy. This last assertion implies to define an equivalent drug dose and two equivalent absorption and consumption rates for the therapy, as if it were a drug, but coming from the inside brain.
Mathematically, if z is the glutamate level variable, y is the SSS level variable and t is the time variable, our goal is to find the function F such as: z=F(t,y). In general, this equation represents a dynamic equivalence principle among a subjective variable of personality and a biological variable that describes it. This principle means a co-evolution of both variables as a consequence of an only dose consumption of a stimulant drug or of a self-regulation therapy. That is, given a value of a subjective variable, and a value of a stimulus, in a determined time instant t, the value of a glutamate level can be deduced via this equation.
This equation would represent the openness of personality theory to a new approach to the secular problem of the “mind-body problem”. We would have a dynamic theory of personality defined by the equivalence between the two visions, mind and biology, from a unified perspective. Its validation would confirm the common dynamics and their correlated evolution as a consequence of an outer or inner stimulus.
5. Conclusions
The Unique Personality Trait Theory (UPTT) postulates that glutamate is the most significant biological substrate of personality (Amigó, 2005). In this study, an single case experimental design with replication has been developed. It has demonstrated that glutamate concentration in blood is a good indicator of the general activation level. Thus, it is as well an indicator of the unique trait of personality.
The Sensation Seeking Scale (SSS) of the MAACL (Zuckerman & Lubin, 1965) has been used. With this scale, phase B (20 mg) reproduces a clearer effect than phase A (base-line) as a consequence of the methylphenidate consumption. A personality dynamics represented by an inverted U-shape is observed. It is measured by both a an adjective scale and glutamate concentration, using the model provided in (Amigó et al., 2008a). The patterns of the joined dynamics depend on the experimental subject. For subject 1 the increase of the glutamate accompanies the increase of the subjective activation. For subject 2, the relationship has an inverse character. This comparison arises the individual pattern of co-variation of the subjective and biological measures.
In addition, the outcomes of phase C are also interesting. They show different individual patterns, although the experimental conditions are different as well. For subject 1, a possible tolerance effect arises in phase C, with a double dose (40 mg), respect to phase B. In this subject, the dynamics of both subjective and biological effects in phase B show a similar pattern. In phase C, the co-variation takes an inverted shape, and a delay of the glutamate is detected respect to the subjective activation.
Subject 2 applied the self-regulation therapy form the third hour in phase C. A very similar pattern (inverted U-shape) is observed between subjective activation and the drug effect, although shorter in time. Moreover, a much greater increase of the glutamate level in the fourth blood extraction is observed, when the subject felt a clear decrease of the subjective effect of activation. Nevertheless, the subject had felt the drug effects from more than one hour before. It could be interpreted as a possible sensitizing effect produced by the self-regulation therapy on the biological variable. The same delay pattern of the glutamate increase respect to the subjective effect of activation is observed, such as in phase B is observed.
The personality conditioning effect arises for subject 2 in phase C as a consequence of the self-regulation therapy. This conditioning affects to personality as a complex system, not only to a describing factor of personality. This outcome can be interpreted as an effect of “personality conditioning”. This is a new trend to change overall personality from the use of drugs and the therapy of self-regulation.
In general, the results obtained are coherent with the postulate that considers glutamate as a good observable of organism’s general activation, and therefore of the personality unique trait.
This conclusion must be considered jointly to a possible equivalence principle enounced in section 4. The unification in a unique description of the subjective and biological dynamic patterns of personality could solve in a future the secular problem of the “mind-body problem” for human behavior.
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Figure 1. For the three phases: glutamate concentration in blood (lines) for subject 1.
Figure 2. For the three phases: glutamate concentration in blood (lines) for subject 2.
Figure 3. . For the three phases: SSS registers (points) and glutamate concentration in blood (lines) for subject 1.
Figure 4. . For the three phases: SSS registers (points) and glutamate concentration in blood (lines) for subject 2.
