In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on a model of hippocampal dysfunction in schizophrenic psychosis, we postulated increased NMDA receptor signaling in CA3. Here we demonstrate that the GluN2B-containing NMDA receptors (GluN2B/GluN1) and its associated postsynaptic membrane protein PSD95 are both increased in human hippocampal CA3 from schizophrenia cases, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons show an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. AMPA receptor subunit proteins are not altered in CA3 or CA1 subfields, nor are several additional related signaling proteins. These hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state which may contribute to development of long term potentiation with subsequent stimulation and ‘un-silencing’. These changes are plausibly associated with increased associational activity in CA3, degraded declarative memory function and with psychotic manifestations in schizophrenia. The influence of these hyperactive hippocampal projections onto targets in limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.
Background
The use of cannabis has garnered more attention recently with ongoing efforts at marijuana legalization. The consequences of cannabis use are not clearly understood and remain a concern.
Objectives
to review the acute and persistent effects of cannabis use and associations with psychiatric disorders
Methods
Using Pubmed and PsychInfo, we conducted a narrative review of the literature on cannabis and psychiatric comorbidity using the keywords cannab*, marijuana, schizo*, psychosis, mood, depression, mania, bipolar and anxiety.
Results
There is substantial evidence of cannabis use leading to other illicit drug use and of an association between cannabis use and psychosis. A few reports suggest an association with bipolar disorder while the association with depression and anxiety disorders is mixed.
Conclusions
Whenever an association is observed between cannabis use and psychiatric disorders, the relationship is generally an adverse one. Age at the time of cannabis use appears to be an important factor with stronger associations observed between adolescent onset cannabis use and later onset of psychiatric disorders. Additional studies taking into account potential con-founds (such as withdrawal symptoms, periods of abstinence and other substance use) and moderators (such as age of initiation of cannabis use, amount and frequency of drug use, prior history of childhood maltreatment and gender) are needed to better under-stand the psychiatric consequences of cannabis use.
Human infants may be exposed to opiates through placental transfer from an opiate-using mother or through the direct administration of such drugs to relieve pain (e.g., due to illness or neonatal surgery). Infants of many species show physical dependence and tolerance to opiates. The magnitude of tolerance and the nature of withdrawal differ from those of the adult. Moreover, the mechanisms that contribute to the chronic effects of opiates are not well understood in the infant but include biological processes that are both common to and distinct from those of the adult. We review the animal research literature on the effects of chronic and acute opiate exposure in infants and identify mechanisms of withdrawal and tolerance that are similar to and different from those understood in adults. These mechanisms include opioid pharmacology, underlying neural substrates, and the involvement of other neurotransmitter systems. It appears that brain circuitry and opioid receptor types are similar but that NMDA receptor function is immature in the infant. Intracellular signaling cascades may differ but data are complicated by differences between the effects of chronic versus acute morphine treatment. Given the limited treatment options for the dependent infant patient, further study of the biological functions that are altered by chronic opiate treatment is necessary to guide evidenced-based treatment modalities.
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