Ethnic minority groups across the world face a complex set of adverse social and psychological challenges linked to their minority status, often involving racial discrimination. Racial discrimination is increasingly recognized as an important contributing factor to health disparities among non-dominant ethnic minorities. A growing body of literature has recognized these health disparities and has investigated the relationship between racial discrimination and poor health outcomes. Chronically elevated cortisol levels and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis appear to mediate effects of racial discrimination on allostatic load and disease. Racial discrimination seems to converge on the anterior cingulate cortex (ACC) and may impair the function of the prefrontal cortex (PFC), hence showing substantial similarities to chronic social stress. This review provides a summary of recent literature on hormonal and neural effects of racial discrimination and a synthesis of potential neurobiological pathways by which discrimination affects mental health.

Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described.

The hippocampus is a major limbic target of the brainstem serotonergic neurons that modulate fear, anxiety, and learning through postsynaptic serotonin _1A receptors (5-HT _1A receptors). Because chronic stress selectively down-regulates the 5-HT _1A receptors in the hippocampus, we hypothesized that mice lacking these receptors may exhibit abnormalities reminiscent of symptoms of stress-related psychiatric disorders. In particular, a hippocampal deficit in the 5-HT _1A receptor could contribute to the cognitive abnormalities often seen in these disorders. To test whether a deficit in 5-HT _1A receptors impairs hippocampus-related functions, we studied hippocampal-dependent learning and memory, synaptic plasticity in the hippocampus, and limbic neuronal excitability in 5-HT _1A -knockout (KO) mice. 5-HT _1A -KO animals showed a deficit in hippocampal-dependent learning and memory tests, such as the hidden platform (spatial) version of the Morris water maze and the delayed version of the Y maze. The performance of KO mice was not impaired in nonhippocampal memory tasks such as the visible platform (nonspatial) version of the Morris water maze, the immediate version of the Y maze, and the spontaneous-alternation test of working memory. Furthermore, paired-pulse facilitation in the dentate gyrus of the hippocampus was impaired in 5-HT _1A -KO mice. Finally, 5-HT _1A -KO mice, as compared with wild-type animals, displayed higher limbic excitability manifested as lower seizure threshold and higher lethality in response to kainic acid administration. These results demonstrate that 5-HT _1A receptors are required for maintaining normal hippocampal functions and implicate a role for the 5-HT _1A receptor in hippocampal-related symptoms, such as cognitive disturbances, in stress-related disorders.

Despite decades of research, no unifying pathophysiologic abnormalities have been identified for schizophrenia; consequently, in contrast to other fields of medicine, no physical or laboratory test is available to objectively affirm the diagnosis of schizophrenia. Current diagnostic classification systems (DSM-IV and International Statistical Classification of Diseases, 10th Revision) rely on psychopathology, social or occupational dysfunction, and time criteria to define a clinical diagnosis of schizophrenia if substance abuse, adverse effects of medication, or psychosis resulting from other medical conditions have been excluded by taking a thorough patient history, as well as performing a physical examination, routine blood tests, brain imaging, and screening for illegal drugs or alcohol addiction. Thus, as originally developed by Eugen Bleuler,¹ schizophrenia is still a diagnostic construct that describes a clinical syndrome rather than a clearly defined disorder. Notably, Bleuler used the term schizophrenias, which referred to the observed clinical heterogeneity that may be paralleled by different underlying pathophysiologic mechanisms.¹ Therefore, the identification of endophenotypes by clinical features or molecular markers may be a promising approach for future psychiatric research to detect clusters of patients with distinct pathophysiologic abnormalities and pave the way for the development of improved treatment strategies, which could progress from symptomatic to causal therapies.