We previously reported that dual injections of lipopolysaccharide (LPS) in mice constitute a valuable tool for investigating the contribution of inflammation to psychotic disorders. The present study investigated how immune activation affects the kynurenine pathway and rat behaviour of relevance for psychotic disorders.

Male Sprague Dawley rats were treated with either dual injections of LPS (0.5 mg/kg + 0.5 mg/kg, i.p.) or dual injections of saline. Twenty-four hours after the second injection, behavioural tests were carried out, including locomotor activity test, fear conditioning test, spontaneous alternation Y-maze test, and novel object recognition test. In a separate batch of animals, in vivo striatal microdialysis was performed, and tryptophan, kynurenine, quinolinic acid, and kynurenic acid (KYNA) in the dialysate were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Dual-LPS treatment decreased spontaneous locomotion, exaggerated d-amphetamine-induced locomotor activity, and impaired recognition memory in male Sprague-Dawley rats. In vivo microdialysis showed that dual-LPS treatment elicited metabolic disturbances in the kynurenine pathway with increased extracellular levels of kynurenine and KYNA in the striatum.

The present study further supports the feasibility of using the dual-LPS model to investigate inflammation-related psychotic disorders and cognitive impairments.

Major depressive disorder is highly prevalent worldwide and has been affecting an increasing number of people each year. Current first line antidepressants show merely 37% remission, and physicians are forced to use a trial-and-error approach when choosing a single antidepressant out of dozens of available medications.

We sought to identify a method of testing that would provide patient-specific information on whether a patient will respond to a medication using in vitro modeling.

Patient-derived lymphoblastoid cell lines from the STAR*D study were used to rapidly generate cortical neurons and screen them for bupropion effects, for which the donor patients showed remission or non-remission.

We provide evidence for biomarkers specific for bupropion response, including synaptic connectivity and morphology changes as well as specific gene expression alterations.

These biomarkers support the concept of personalized antidepressant treatment based on in vitro platforms and could be utilized as predictors to patient response in the clinic.

This work was funded by Genetika+ Ltd, Jerusalem, Israel. YA, DK, EN, DL and TCS are employees of Genetika+ Ltd and received salary and/or stock options for the submitted work.

The aetiology of depression is not fully understood, which allows many different perspectives on aetiology to be adopted. Researchers and clinicians may be attracted to concepts of aetiology that parallel other diagnoses with which they are familiar. Such parallels may assume the role of informal models or metaphors for depressive disorders. They may even function as informal scientific theories of aetiology, energising research activities by guiding hypothesis generation and organising new knowledge. Parallels between different types of disease may ultimately prove valuable as frameworks supporting the emergence and maturation of new knowledge. However, such models may be counterproductive if their basis, which is likely to lay at least partially in analogy, is unacknowledged or overlooked. This could cause such models to appear more compelling than they really are. Listing examples of situations in which models of depression may arise from, or be strengthened by, parallels to other familiar conditions may increase the accessibility of such models either to criticism or support. However, such a list has not yet appeared in the literature. The present paper was written with the modest goal of stating several examples of models or metaphors for depression.

This paper adopted narrative review methods. The intention was not to produce a comprehensive list of such ideas, but rather to identify prominent examples of ways of thinking about depression that may have been invigorated as a result parallels with other types of disease.

Eight possible models are identified: depressive disorders as chemical imbalances (e.g., a presumed or theoretical imbalance of normally balanced neurotransmission in the brain), degenerative conditions (e.g., a brain disease characterised by atrophy of specified brain structures), toxicological syndromes (a result of exposure to a noxious psychological environment), injuries (e.g., externally induced brain damage related to stress), deficiency states (e.g., a serotonin deficiency), an obsolete category (e.g., similar to obsolete terms such as ‘consumption’ or ‘dropsy’), medical mysteries (e.g., a condition poised for a paradigm-shifting breakthrough) or evolutionary vestiges (residual components of once adaptive mechanisms have become maladaptive in modern environments).

Conceptualisation of depressive disorders may be partially shaped by familiar disease concepts. Analogies of this sort may ultimately be productive (e.g., through generating hypotheses by analogy) or destructive (e.g., by structuring knowledge in incorrect, but intellectually seductive, ways).