Brief psychotic episodes or full blown schizophrenia are often associated with memory issues, which are often attributed to the disruption in cognitive processes that accompany these mental health issues. Higgins and George (2013) began to explore the psychopathology of this, making the connection between working memory (which was initially made the center of attention with the case of Phineas Gage) and the coordinated firing of pyramidal neurons in the prefrontal cortex. GABA, the major inhibitory neuron, is required to synchronize the pyramidal neurons, and the disruption of this mechanism was related to a decrease in working memory.
To try and better understand the connection between psychosis/schizophrenia and memory issues, let’s first turn to a paper by Ragland et al. (2015) out of UC Davis. This study tried to decipher which specific areas of the brain were affected during relational encoding (trying to remember something based on its relationship to something, such as an ingredient to a recipe) and retrieval and item specific encoding (focusing on unique features of an object) for patients with schizophrenia. Classically, relational encoding is associated with regions of the prefrontal cortex and retrieval is associated with the medial temporal lobe. Schizophrenia, in particular, has been seen to negatively affect relational memory, and this study used fMRIs to identify biomarkers related to this deficit. They found that individuals with schizophrenia who performed poorly on relational item retrieval and relational encoding tasks had less activation in the hippocampus and dorsolateral prefrontal cortex, respectively. In other words, the combination of the hippocampus and dorsolateral prefrontal cortex accounts for poor relational memories in individuals with schizophrenia. This not only gives an explanatory model for improving relational memory, but also provides a more specific target on how to improve relational memory in patients with schizophrenia. Other studies have shown a relationship between the disconnection of the right middle frontal gyrus and right superior parietal lobule in at risk mental status and first episode psychosis patients with working memory deficits (Schmidt et al, 2013), while others have pointed to the medial frontal and medial posterior parietal cortex in patients in at-risk mental states and first episode psychosis with impaired spatial working memory (Broome et al., 2010). Twin studies have also shown poorer spatial working memory performance in both twins affected by and not affected by schizophrenia (twins discordant for schizophrenia) (Pirkola et al., 2005).
Other studies, such as the paper by Badcock et al. (2005), makes the connection between executive functioning and memory as it specifically relates to patients with schizophrenia. They found that manipulation of stored information was related to executive functioning, and that changes in the frontal-parietal circuitry in patients with schizophrenia were responsible for these memory related impairments.
This connection between working memory and schizophrenia has also been used from an assessment standpoint. Bendfeldt et al. (2015) looked to see if the working memory areas of their brain could be used to identify patients as being in a at-risk mental state or ARMS for schizophrenia. Analysis of working memory task induced fMRIs showed that they were able to differentiate ARMs from healthy controls with 76.2% accuracy, with the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus, with varying activation depending on the verbal working memory activity. It is notable that this study was not able to differentiate between fMRIs of individuals with first episode psychosis and at-risk mental state, which was attributed to the inability to differentiate between the two with the given methods of measurement.
From a genetic perspective, the catechol-O-methyltransferase (COMT) and dopamine transporter (DAT1) have been looked at in relation to memory and schizophrenia, where changes and vulnerabilities of these have been linked to poorer outcomes (Shifman et al., 2004). They both modulate dopamine inactivation in the prefrontal cortex, which is related to the effectiveness of the neuronal signal in working memory. Some studies have found COMT specifically affects more complex cognitive processes related to information maintenance and modulation in working memory (Brudger et al., 2005).
In speaking to treatment, antipsychotics have often been used to improve cognitive abilities in patients with schizophrenia and psychosis, such as with working memory (Schmidt et al., 2013). The use of other medications, such as anti-depressants, was explored by Steen et al. (2015), specifically looking at escitalopram, citalopram, and venlafaxine plus O-desmethylvenlaflaxine. It has been shown in other studies that antidepressants can increase neurogenesis in (Dranvnovsky and Hen, 2006) and be neuroprotective (Sheline et al., 2003) to the hippocampus, and Steen et al. (2015) point to Han et al. (2011) that suggests his combination may have improve cognition. They found that patients’ schizophrenia with serum levels of venlafaxine plus O-desmethylvenlaflaxine had better verbal memory and long term delayed recall, although this same effect was not found for citalopram or escitalopram. This was possibly attributed to the combined use of serotonin and norepinephrine in venlafaxine.
The psychopathological, genetic, assessment, and treatment related to memory and psychosis and schizophrenia still has more answers than questions, but promising research has provided us with solid starting points that have implications not only for further research, but possible intervention and treatment that can hopefully inform practical, clinical practice.
Badcock J.C., Michael, P.T., Rock, D. (2005). Spatial working memory and planning ability: Contrasts between schizophrenia and bipolar I disorder. Cortex, 41(6): 753–763.
Bendfeldt, K., Smieskova, R., Koutsouleris, N., et al. (2015). Classifying individuals at high-risk for psychosis based on functional brain activity during working memory processing. Neuroimag Clin., 9: 555-563. doi: 10.1016/j.nicl.2015.09.015
Broome M.R., Fusar-Poli P., Matthiasson P., et al. (2010). Neural correlates of visuospatial working memory in the ‘at-risk mental state’. Psychol. Med., 40(12): 1987–1999.
Brudger, G.E., Keilp, J.G., Xu, H., et al. (2005). Catechol-o-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations. Biol Psychiatry, 58(11): 901–907.
Dranovsky, A., and Hen, R.(2006). Hippocampal neurogenesis: regulation by stress and antidepressants. Biol. Psychiatry, 59: 1136-1143
Han X., Tong J., Zhang J., (2011). Imipramine treatment improves cognitive outcome associated with enhanced hippocampal neurogenesis after traumatic brain injury in mice. J. Neurotrauma, 28: 995-1007
Higgins, E. S., George, M. S. The Neuroscience of Clinical Psychiatry: The Pathophysiology of Behavior and Mental Illness, 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.
Pirkola, T., Tuulio-Henriksson, A., Glahn, D., et al. (2005). Spatial working memory function in twins with schizophrenia and bipolar disorder. Biol. Psychiatry, 58(12): 930–936.
Ragland, D.J., Ranganath, C., Harms, M.P., et al (2015). Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in Schizophrenia: A Functional Magnetic Resonance Imaging Study of the Relational and Item-Specific Encoding Task. JAMA Psychiatry, 72(9): 909-916. doi:10.1001/jamapsychiatry.2015.0276
Schmidt, A., Smieskova, R., Aston, J. (2013). Brain connectivity abnormalities predating the onset of psychosis: correlation with the effect of medication. J.A.M.A. Psychiatry, 70(9): 903–912.
Sheline Y.I., Gado M.H., and Kraemer H.C. (2003). Untreated depression and hippocampal volume loss. Am. J. Psychiatry, 160: 1516-1518
Shifman, S., Bronstein, M., Sternfeld, M., et al. (2004). COMT: A common susceptibility gene in bipolar disorder and schizophrenia. Am J Med Genet B Neuro Psychiatr Genet, 128B(1): 61–64.