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Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms

      Abstract

      Background

      Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder.

      Methods

      Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (Nt) of IR neurons were measured. Time of death was used to test associations with circadian rhythms.

      Results

      SST-IR neurons were decreased in the lateral amygdala nucleus in BD (Nt, p = .003) and SZ (Nt, p = .02). In normal control subjects, Nt of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected.

      Conclusions

      Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala.

      Keywords

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      Linked Article

      • Reduced Somatostatin Expression or Somatostatin-Positive Gamma-Aminobutyric Acid Neurons: A Shared Pathology Across Brain Disorders
        Biological PsychiatryVol. 81Issue 6
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          The clinical and biological heterogeneity that pervades the field of neuropsychiatry has hindered progress in uncovering the pathophysiological mechanisms of psychiatric illnesses. Indeed, it is rare to come across well-replicated pathological findings within or across disorders, and when such findings do arise they merit our attention and focus. In this issue, Pantazopoulos et al. (1) bring forward a pathological feature that is common to postmortem brains of patients with schizophrenia and bipolar disorder and that is shared by other psychiatric or neurodegenerative brain disorders (2).
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