Are Animal Models Relevant in Modern Psychiatry?

Diagnosing “depression” in a monkey is at odds with the successful ongoing process of clarifying psychiatric diagnoses by using DSM criteria. It is not possible to ascertain feelings of worthlessness and excessive guilt, indecisiveness, and thoughts of death from observations of monkeys.³⁵ Harlow’s student Stephen Suomi became more circumspect in 1995, when he carefully referred to the condition in monkeys as “something equivalent to depression” rather than “depression.”

The non-human primate is considered by some researchers to be the most appropriate model for the study of brain function. Among non-human primates, the rhesus macaque is the animal of choice for cognitive studies. While there may be similarities between the brains of humans and non-human primates, the monkey brain is not a scaled down version of the human brain.³⁶ Rather, each primate brain is the unique result of evolutionary biology, molded over millions of years in response to environmental, social, and genetic influences (Figure). With the human brain, the effects of cultural evolution are also considered.

There are numerous differences in the anatomy and physiology of the CNS in monkeys and humans, including differences in locations of specialized areas in the brain. The visual 1 area accounts for 10% of the total cortex in the monkey but only 3% in humans, and anatomically corresponding visual areas in monkeys and humans can perform very different functions.³⁷ The human brain’s architecture and physiology is far more complex than that of the monkey brain. One indication of this is the length of time it takes for the brain to develop in its major phase: 136 days for monkeys and 470 days for humans.³⁸ Other significant differences include the number of synapses a human neuron makes (between 7000 and 10,000) compared with the number a rhesus monkey neuron makes (between 2000 and 6000) and the expression of at least 91 genes involved in a variety of neural mechanisms that differ between monkeys and humans.^37,39 According to Kreiman and associates³⁷:

Even though the hippocampus appears to be one of the most conserved areas of the brain (most similar among mammals), there are still considerable differences. Neurotransmitter receptor distribution varies widely between species. For example, there is an additional small layer of high-density kainate receptors in the deepest part of the hippocampal molecular layer in the monkey, but not in humans. The inhibitory GABA_A receptors are located with high density in the human CA 1 hippocampal region, but not in the same region in monkeys. These results demonstrate considerable changes of the regional and laminar distribution of important signaling molecules in an otherwise evolutionary conservative brain region.