State of the art of the neurotrophin hypothesis in psychiatric disorders: implications and limitations

Topic: Brain proteins, microglia and lab models

The neurotrophin hypothesis proposes that repetitive neuronal activity enhances the expression, secretion and actions of neurotrophins to modify synaptic transmission and connectivity thereby providing a connection between neuronal activity and synaptic plasticity. Moreover, there is ample evidence that neurotrophins have numerous neuroprotective effects under pathological conditions, which might be important in particular for neurodegenerative diseases such as Alzheimer' disease. Current research postulates that effects during brain development lead to defective neural connectivity and altered biochemical functioning resulting in cognitive, emotional and intentional dysfunction later in life. This implicates a possible role in most psychiatric diseases including affective and schizophrenic disorders. This hypothesis is mainly based on new experimental evidence showing that psychiatric disorders are associated with neuronal atrophy and cell loss, impairments of structural plasticity and cellular resilience due to neurodevelopmental disturbances and morphological abnormalities of the brain. Thus, the potential role of neurotrophins in psychiatric disorders has been studied in different ways. Animal studies indicate the involvement of neurotrophins in psychopharmacological therapies and they show that gene expression of cerebral neurotrophins is changed in animal models of several psychiatric disorders. Whether such alterations are causatively associated with increased neural plasticity, improved cognitive function and decreased depressive mood states remains to be elucidated in further studies including man (e.g. in postmortem studies of patients). Association studies tried to link different variants in genes coding for neurotrophins, they have not been conclusive however. They partially allow to separate different subgroups of patients with differing therapy response profiles or indicate an increased vulnerability for a specific disorder. Finally, neurotrophin serum changes have been observed in most psychiatric disorders. The question remains though whether these alterations represent primary-causal or secondary-reactive changes.In conclusion, the issue of neuroprotection and neurotrophins is recognised as an important new lead in the quest for a deeper understanding of psychiatric disorders and the mechanisms of action of psychopharmacological interventions.

Key findings

• This hypothesis is mainly based on new experimental evidence showing that psychiatric disorders are associated with neuronal atrophy and cell loss, impairments of structural plasticity and cellular resilience due to neurodevelopmental disturbances and morphological abnormalities of the brain.
• Whether such alterations are causatively associated with increased neural plasticity, improved cognitive function and decreased depressive mood states remains to be elucidated in further studies including man (e.g. in postmortem studies of patients).
• The question remains though whether these alterations represent primary-causal or secondary-reactive changes.In conclusion, the issue of neuroprotection and neurotrophins is recognised as an important new lead in the quest for a deeper understanding of psychiatric disorders and the mechanisms of action of psychopharmacological interventions.

Why it matters

This review discusses the neurotrophin hypothesis, which proposes that neurotrophins link neuronal activity to synaptic plasticity and may have neuroprotective effects relevant to neurodegenerative diseases such as Alzheimer's disease. It is a discussion of a hypothesis and does not show that any treatment, cure or prevention works.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1007/s00702-003-0100-0
• PubMed: 14991461
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{lang2004-14991461,
  author  = {Lang, U. E. and Jockers-Scherübl, M. C. and Hellweg, R.},
  title   = {{State of the art of the neurotrophin hypothesis in psychiatric disorders: implications and limitations}},
  journal = {Journal of neural transmission (Vienna, Austria : 1996)},
  year    = {2004},
  doi     = {10.1007/s00702-003-0100-0},
  pmid    = {14991461},
  url     = {https://doi.org/10.1007/s00702-003-0100-0}
}

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