Spurious autobiographical memories of psychosis: a dopamine-gated neuroplasticity account for relapse and treatment-resistant psychosis

Abstract

Psychotic disorders are known to be associated with elevated dopamine synthesis; yet, nondopamine factors may underlie the manifestation of some psychotic symptoms that are nonresponsive to dopamine-blocking agents. One under-explored nondopamine mechanism is neuroplasticity. We propose an account of the course of psychotic symptoms based on the extensive evidence for dopamine facilitation of Hebbian synaptic plasticity in cortical and subcortical memory systems. The encoding of psychotic experiences in autobiographical memory (AM) is expected to be facilitated in the hyperdopaminergic state associated with acute psychosis. However, once such 'spurious AM of psychosis' (SAMP) is encoded, its persistence may become dependent more on synaptic factors than dopamine factors. Under this framework, the involuntary retrieval of residual SAMP is postulated to play a key role in mediating the reactivation of symptoms with similar contents, as often observed in patients during relapse. In contrast, with active new learning of normalizing experiences across diverse real-life contexts, supported by intact dopamine-mediated salience, well-integrated SAMP may undergo 'extinction', leading to remission. The key steps to the integration of SAMP across psychotic and nonpsychotic memories may correspond to one's 'recovery style', involving processes similar to the formation of 'non-believed memory' in nonclinical populations. The oversuppression of dopamine can compromise such processes. We synthesize this line of evidence into an updated dopamine-gated memory framework where neuroplasticity processes offer a parsimonious account for the recurrence, persistence, and progression of psychotic symptoms. This framework generates testable hypotheses relevant to clinical interventions.

Keywords: autobiographical memory; dopamine; relapse; treatment-resistant psychosis.

Figure 1.

Illustration of Spurious Autobiographical Memory of Psychosis (SAMP). Dark backgrounds denote SAMP memories formed during psychosis. Each unit represents autobiographical memory (AM) encoded over a period of time. Arrows on the right of each row indicate current life experience. A light gray background indicates partially normalized AM. Arrows represent integrative processes between new and old memories. From the top, (a) SAMP associated with short duration of active psychosis (DAP); (b) SAMP associated with a longer DAP; (c) AM integration in remission: (ci) SAMP in remission; well-integrated SAMP enables extinction and reduction in SAMP (cii); (d) poorly integrated SAMP does not benefit effectively from normalization, instead, (di) relapses can add to SAMP; and (dii) increasing treatment resistance; (e) premorbid threat-prone schema generally facilitates SAMP reactivation and persistence.

Figure 2.

Flow diagram showing the relationship between clinical processes and the postulated SAMP status. Circumscribed psychotic symptoms not involving elevated dopamine activities do not lead to SAMP formation. Clinical high-risk states and schizotypal conditions may involve mild dopamine elevation leading to low-grade SAMP which may lead to persistent mild psychotic symptoms or decompensate into a frank psychotic episode. The first psychotic episode (FEP) results in SAMP formation. SAMP potency may depend on the content and duration of the FEP. Antipsychotic treatment results in remission except when SAMP potency is high, resulting in early treatment resistance. In remission, SAMP potency may reduce if integration with nonpsychotic autobiographical memory (AM) is good, and subsequent extinction is facilitated via exposure to normalized experiences. If SAMP-AM integration is poor, extinction is limited. If a relapse occurs, the new psychotic experience will strengthen the SAMP potency. Positive symptoms re-emergence depends on SAMP potency and dopamine state. A high-potency SAMP increases the risk of relapse and treatment resistance.