Despite significant research efforts aimed at understanding the neurobiological underpinnings of mood (depression, bipolar disorder) and psychotic disorders, the diagnosis and evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms as well as psychometric evaluations. Therefore, biological markers aimed at improving the current classification of psychotic and mood-related disorders, and that will enable patients to be stratified on a biological basis into more homogeneous clinically distinct subgroups, are urgently needed. The attainment of this goal can be facilitated by identifying biomarkers that accurately reflect pathophysiologic processes in these disorders. This review postulates that the field of psychotic and mood disorder research has advanced sufficiently to develop biochemical hypotheses of the etiopathology of the particular illness and to target the same for more effective disease modifying therapy. This implies that a “one-size fits all” paradigm in the treatment of psychotic and mood disorders is not a viable approach, but that a customized regime based on individual biological abnormalities would pave the way forward to more effective treatment. In reviewing the clinical and preclinical literature, this paper discusses the most highly regarded pathophysiologic processes in mood and psychotic disorders, thereby providing a scaffold for the selection of suitable biomarkers for future studies in this field, to develope biomarker panels, as well as to improve diagnosis and to customize treatment regimens for better therapeutic outcomes.

Objective: Co-morbid depression with post-traumatic stress disorder (PTSD) is often treatment resistant. In developing a preclinical model of treatment-resistant depression (TRD), we combined animal models of depression and PTSD to produce an animal with more severe as well as treatment-resistant depressive-like behaviours.Methods: Male Flinders sensitive line (FSL) rats, a genetic animal model of depression, were exposed to a stress re-stress model of PTSD [time-dependent sensitisation (TDS)] and compared with stress-naive controls. Seven days after TDS stress, depressive-like and coping behaviours as well as hippocampal and cortical noradrenaline (NA) and 5-hydroxyindoleacetic acid (5HIAA) levels were analysed. Response to sub-chronic imipramine treatment (IMI; 10 mg/kg s.c.×7 days) was subsequently studied.Results: FSL rats demonstrated bio-behavioural characteristics of depression. Exposure to TDS stress in FSL rats correlated negatively with weight gain, while demonstrating reduced swimming behaviour and increased immobility versus unstressed FSL rats. IMI significantly reversed depressive-like (immobility) behaviour and enhanced active coping behaviour (swimming and climbing) in FSL rats. The latter was significantly attenuated in FSL rats exposed to TDS versus unstressed FSL rats. IMI reversed reduced 5HIAA levels in unstressed FSL rats, whereas exposure to TDS negated this effect. Lowered NA levels in FSL rats were sustained after TDS with IMI significantly reversing this in the hippocampus.Conclusion: Combining a gene-X-environment model of depression with a PTSD paradigm produces exaggerated depressive-like symptoms that display an attenuated response to antidepressant treatment. This work confirms combining FSL rats with TDS exposure as a putative animal model of TRD.

Malaria is a deadly disease caused by protozoan pathogens of the Plasmodium parasite. Transmission to humans occurs through the bite of an infected female Anopheles mosquito. According to the World Health Organization (WHO), an estimated 247 million cases of malaria were recorded worldwide in 2021, with approximately 619 000 malaria deaths. The initial signs of malaria can be mild and challenging to diagnose due to the signs and symptoms being similar to those of other illnesses. The malaria burden remains largely concentrated in the WHO sub-Saharan African region and has been recognised as a significant contributor to morbidity and mortality. This review aims to contribute to the existing knowledge on malaria in South Africa, a region within sub-Saharan Africa, focusing on the epidemiology and life cycle of the malaria parasite as well as diagnostic approaches for detecting malaria. In addition, nonpharmacological and pharmacological interventions for treating and preventing malaria infections will also be discussed herein. While there has been a significant reduction in the global burden of this disease, malaria remains a public health issue in South Africa. As such, the implementation of effective preventative measures and strategies, early diagnosis, and appropriate treatment regimens are crucial to reducing the malaria burden in South Africa.

Objective: Post-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine.Methods: Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls. 7 days after the TDS procedures, immobility and coping (swimming and climbing), behaviours in the forced swim test (FST) as well as hippocampal and cortical 5-hydroxyindoleacetic acid (5HIAA) and noradrenaline (NA) levels were analysed. Response to imipramine, venlafaxine and ketamine treatment (all 10 mg/kg×7 days) alone and in combination were subsequently studied.Results: TDS exacerbated depressive-like behaviour of FSL rats in the FST. Imipramine, venlafaxine and ketamine were ineffective as monotherapy in TDS-exposed FSL rats. However, combining imipramine with either venlafaxine or ketamine resulted in significant anti-immobility effects and enhanced coping behaviours. Only ketamine+imipramine (frontal-cortical 5HIAA and NA), ketamine alone (frontal-cortical and hippocampal NA) and venlafaxine+imipramine (frontal-cortical NA) altered monoamine responses versus untreated TDS-exposed FSL rats.Conclusion: Exposure of FSL rats to TDS inhibits antidepressant response at behavioural and neurochemical levels. Congruent with TRD, imipramine plus venlafaxine or ketamine overcame treatment resistance in these animals. These data further support the hypothesis that exposure of FSL rats to a PTSD-like paradigm produces a valid animal model of TRD and warrants further investigation.