This post connects dopamine, serotonin, and oxytocin to schizophrenia and psychedelics, particularly in relation to social behavior. Being targeted by outgroup derogation may drive a switch from group orientation to self-orientation. Dopamine, serotonin, oxytocin, and social dynamics are explored. The section on oxytocin is the most interesting.

Disclaimer: The ideas in this article are based on some research that we should be cautious in accepting as true. There is a replication crisis targeting some of these fields, so keep this in mind while going through these ideas. Regardless, they may touch on some vague elements of truth and capture interest at the least.

Serotonin and Group Orientation

Serotonin has been explored by researchers in relevance to social behavior, revealing patterns across a wide range of animals. For example, even animals as far removed from humans as social insects show an induction of ‘swarm behavior’ via serotonin (Anstey et al 2009), which may be vaguely analogous to prosocial/cooperative behavior in mammals. In mammals, serotonin induces prosocial behavior (Siegel & Crockett 2013). Though, this is complicated as serotonin seems to play a role in social status in multiple species as well (Edwards & Kravitz 1997). Edwards and Kravitz noted that animals who were subordinate and facing social aggression would stop behaving inhibited and become agonistic when injected with serotonin. Both social status and aggression may be group-oriented behavioral patterns. Those with higher social status may have more influence over groups of individuals. Aggression can be used to control a group as an authoritarian style of group management (consider the police and bullies).

In humans, serotonergic drugs modify social behavior. Some researchers suggest that serotonin generally enhances sensitivity to social factors (Kiser et al 2012). Others have argued that serotonin induces a tendency to value the outcomes that other people face, leading to prosocial behavior (Siegel & Crockett 2013). More interestingly, psychedelics seem capable of inducing altruistic/prosocial behavior/empathy (Blatchford, Bright, & Engel, 2021; Hysek et al., 2014; Pokorny et al., 2017), which may be due to serotonin agonism. In a 2020 paper, it was found that awe-mediated increases of social connectedness were associated with decreased narcissistic traits, although this study was not longitudinal so it could just be that narcissistic individuals do not experience as much connectedness as others (van Mulukom, Patterson, & van Elk 2020). Another earlier paper from 2018 argued that connectedness plays a crucial role in the therapeutic benefits of psychedelics (Carhart-Harris et al., 2018). This reduction of narcissism and increase in connectedness falls in line with the notion that serotonin agonism induces group-orientation.

Serotonin mechanisms have been implicated in perspective-taking. Polymorphisms of the 5HT2a receptor gene have been associated with problems in perspective-taking and have also been linked to autistic tendencies (Gong et al 2015), though, keep in mind that such single-gene studies are not the best. The same polymorphism is also associated to schizophrenia in a meta-analysis, though many studies reported mixed results, particularly in Asian countries (Abdolmaleky et al 2004). A meta-analysis and systematic review from 2014 found reduced binding of the 5HT2a receptor in post-mortem studies on schizophrenic patients and in molecular imaging studies in unmedicated schizophrenics, although the studies analyzed in this paper often had mixed results (Selvaraj, Arnone, Cappai, & Howes, 2014). Individuals with schizophrenia often struggle with perspective-taking as well, though, in brain imaging, there seem to be patterns distinct from autism, despite an overlap in symptoms. This pattern emerged unassociated to antipsychotic medication (Eack et al 2017). A newer study reviewed fMRI literature, noting that there are mixed results in schizophrenic patients’ prefrontal cortex BOLD responses in perspective-taking tasks, some revealing increased activity and other studies showing the opposite (Kronbichler et al 2019). Failures of perspective-taking may be present in schizophrenia but manifest differently than those seen in autism, for unknown reasons.

LSD has also produced effects on social cognition opposite to those observed in schizophrenic individuals. LSD was found to enhance emotional empathy and reduce fear recognition (Dolder et al 2016). I suspect this could vary by context (social threat) or set and setting. In another study, people who were considered to be high-risk for experiencing psychosis had decreased emotional, but not cognitive, empathy. This reduction in emotional empathy correlated to higher prodromal scores (Gallinat 2020). Fear recognition seems to be hyperactive in schizophrenia, with neutral faces appearing to express fear (Hall et al., 2008). Combined, these studies suggest there could be differences between the schizophrenic state and the psychedelic state, which may be self-focus versus group-oriented respectively. Self-focus may serve a function during social threat experiences to help in protecting the self and also for building distrust in others who are perceived to be dangerous.

Dopamine and Self-Focus

On the other hand, dopaminergic substances have been shown to induce a decrease in hyper-altruistic behavior in humans (Crockett et al 2015). Some researchers have suggested that selfish behavior is particularly elicited in humans by dopaminergics in the absence of a punishment threat (Pedroni et al 2014). A study on human women found that the D2/D3 agonists produced a decrease in generous behavior (Oroz Artigas et al., 2019), which is particularly interesting as D2 agonists can also produce psychotic effects (Koprich et al., 2013). Furthermore, a central element of the dopaminergic hypothesis of schizophrenia is that individuals with schizophrenia have elevated D2 receptors in the striatum (Howes & Kapur, 2009). An experimental study using dopaminergic drugs in humans found that dopamine appears to be involved in paranoia and attributions of social harm (Barnby, Bell, Deeley, & Mehta, 2020). Cocaine (a dopaminergic drug) users often have decreased prosocial behavior, which was found to improve upon cessation, and decreased perspective-taking abilities (Vonmoos et al., 2019; Quednow, 2016). Cocaine use can also lead to schizophrenic-like symptoms such as delusions and hallucinations as well (Cubells et al., 2005). This suggests that dopamine may alter pro- and anti-social behavior, with a tendency towards self-focus and that the schizophrenic spectrum may involve antisocial mechanisms.

Social rejection may lead to self-focus through dopaminergic mechanisms, although most motivated behavior would likely also involve dopaminergic mechanisms. Paranoia may arise due to the way outsiders of a group are typically treated worse, ie tribalism, bigotry, ingroup-outgroup biases, and so on. Being self-focused may protect oneself if one suspects others are against them. There is a hypothesis known as the social defeat hypothesis of schizophrenia that arose due to the pattern for minorities, immigrants, and socially disadvantaged people to have greater risks for developing schizophrenia (Selten et al., 2013), further supporting this notion. Selten points out that animals studies found evidence that social defeat causes dopamine hyperactivity, which may be related to schizophrenia symptoms. For a great elaboration on this hypothesis and its’ connections to the endogenous hallucinogen (maybe) dynorphin, check out Making Sense of Madness.

Social group conflict and ‘otherness’ may lead people into paranoia. One study found that differences in belief and social threat stimulate paranoia, even in healthy subjects (Saalfeld, Ramadan, Bell, & Raihani, 2018). Being outside of a group or ‘othered’ may naturally give rise to defensiveness and a sense of threat, due to humans’ tendency towards ingroup favoritism and outgroup derogation (Johnson, Rowatt, & LaBouff 2012). There have even been evolutionary arguments that paranoia serves benefits in these sorts of in-group versus out-group scenarios (Raihani & Bell, 2019). One might also wonder if paranoia generates as part an effect of decreased perspective-taking. Though, it seems that our paranoia is not just a product of failing to perspective-take but there seems to be a bias towards expecting negative or hostile social interactions.

For perspective-taking to shut down during scenarios in which one is persecuted may be adaptive. This can allow one to dehumanize the other, avoiding possible empathizing and maladaptive altruism for the individual targeting oneself. Once the psychotic has formed a sense of being persecuted, perspective-taking may go offline. We see this in the way many people respond to antisocial situations. People often dehumanize perceived criminals or “bad” people. Empathy may help an individual justify the abuser’s performed harm to a victim, thus making the abuser’s harmful behavior permissible, making empathy maladaptive when used towards harmful people. In line with the hypotheses, individuals with social phobia shift their attention inward, towards self-focus in circumstances that they fear, namely social circumstances (Wells & Papageorgiou 1998). This trend fits within the social defeat theory and also fits the research on schizophrenia. Schizophrenia has also been associated with social phobia (Mazeh et al., 2009).

It is important to consider that selfish or selfless behavior can be quite complex. One could be interested in the well-being of others because of how it grants them social capital.

Low Oxytocin and Persecution

Oxytocin is a hormone often described as a trust or bonding hormone, although this is oversimplified. This hormone seems to play a role in social behaviors and potentially schizophrenia. Recent research on oxytocin has shown that this hormone promotes ingroup favoritism and outgroup derogation (De Dreu et al 2011). Schizophrenics have been observed to have decreased serum oxytocin (Liu et al., 2019). Oxytocin is being explored as a treatment for schizophrenia and even decreased the hyperactivation of the amygdala in response to neutral and fearful faces (Shin et al., 2015).

Reduced oxytocin function may tend to lead one to social rejection. In a small study (n=28) (too small really), injections of oxytocin appear to make individuals more suggestible and susceptible to social persuasion (Bryant & Hung 2013), which might function well for facilitating the sharing of beliefs and attitudes within groups. The schizophrenic may lack this tendency to adopt shared beliefs and attitudes, leading to quicker social rejection for the reason of nonconformity. Once they are not part of the belief-sharing social groups, they may develop beliefs that strongly contradict with those social groups’ beliefs, for example, conspiracy theories or other odd beliefs that are taboo to the social group in question. This may make them especially prone to outgroup derogation, which is essentially persecution. This persecution may facilitate the development of delusional ideas, namely persecutory delusions. There are likely many mechanisms other than oxytocin that factor into such dynamics.

Relevance For Psychedelics

Interestingly, the serotonin psychedelics MDMA and psilocybin have been shown to alleviate social rejection mediated psychological problems (Preller et al., 2016; Preller et al., 2019), suggesting that these drugs could be useful for social defeat and that psychedelics may function with effects contrary to the social defeat hypothesis of schizophrenia. MDMA in particular increases oxytocin which the researchers hypothesize may factor into the drug’s prosocial effects (Kirkpatrick et al., 2014). This may warrant exploration of MDMA in individuals with schizophrenia.

Psychedelics have been barely tested on schizophrenics, though some ancient research revealed a reduced sensitivity to the drugs in the case of LSD and DMT (Cholden, Kurland, & Savage, 1955; Böszörményi & Szara 1958). At first, one may wonder if they were on antipsychotics, something these studies didn’t mention, possibly because antipsychotics barely came into medicine at this point. If these results were unexpected, we should expect that antipsychotics would be mentioned by the authors as a seemingly obvious confound. Antipsychotics have been administered in a case of psilocybin induced “psychotic” symptoms, with dopamine-specific antipsychotics producing a worsening of the patient’s condition, while the 5HT2a receptor antagonist antipsychotic reduced symptoms expectedly (Vollenweider et al., 1998). Even in the case of HPPD, antipsychotics have been observed to worsen symptoms, although the issue seems quite complex, involving mixed results from the use of antipsychotics (Hermle, Simon, Ruchsow & Geppert, 2012). This may suggest that antipsychotics were not necessarily reducing the effects of DMT and LSD in schizophrenics. This is speculative since there is almost no data on this subject and there is also an anecdotal culture that suggests using antipsychotics to “end trips”.

A strange logical trap exists where people may rationalize different things depending on whether schizophrenics are sensitive to psychedelics or not. I’ve seen an argument suggesting an innate tolerance to psychedelics may exist in those with schizophrenia because they are constantly exposed to endogenous DMT. Though, it seems easily imaginable that researchers might similarly find that schizophrenic individuals are more sensitive to psychedelics and argue that this reveals an increased propensity for psychotic symptoms via exposure to psychedelics in those with schizophrenia. This is problematic because both contradicting results would seem to somehow support the notion that schizophrenia is some sort of endogenous psychedelic kind of problem. Keep this in mind when looking into such research.

. . .

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