Mental Illness upon reaching the Maximal skeletal growth of the skull [the cranio-skeleton] .

Humans increase in size and complexity from conception to physical maturity, which occurs about 16 to 18 years of age. It is often after this period that problems with mental illness begin, in particular in attacks of bipolar illness.

If we look specifically at the growth of the head over this time, you will see different growth patterns of the cranial vault, the facial skeleton and the cranial base. Everything must come together just right as these different bones finally settle to their permanent [more or less] positions. If you read about the complexities of growth of the head and neck you will see it is nothing short of miraculous. Especially as certain parts of the skull achieve their maximal growth around age 10 to 12 [following the neural growth pattern] where as other parts of the head follow the somatic growth pattern. [achieving their permanent positions around the age of 20. The cranial base follows the neural growth pattern at first and then adopts its own patterns after age 12. And all this mishmash growth must FIT and WORK together once a person reaches their 20’s and thirties. By this stage, the skeleton must establish molecular integration of growth between the cranial base and other cranial regions .

It is not accidental that the period between age 20 and 30 is a peak time for bipolar attacks to occur. Something has gone wrong. Something is perturbing brain function, just when skeletal growth of the head and the rest of the body is at its most complex and has no more wiggle room because at this stage of young adulthood, most of the bones are done growing .

The cranial base is a central and integral component of the cranioskeleton, yet we are just beginning to learn about its growth.  Front Cell Dev Biol 2020 Aug 11;8:706. doi: 10.3389/fcell.2020.00706.eCollection 2020. New Insights Into Cranial Synchondrosis Development: A Mini Review Noriko Funato

The cranial base is a complex area that varies in depth and has numerous openings for the passage of cranial nerves, the blood vessels and the spinal cord.The cranial base cradles part of the frontal lobe, the temporal lobe, and the cerebellum.


Long bones and the cranial base are both formed through endochondral ossification. Elongation of long bones is primarily through the growth plate, which is a cartilaginous structure at the end of long bones made up of chondrocytes. Growth plate chondrocytes are organized in columns along the longitudinal axis of bone growth. The cranial base is the growth center of the neurocranium. Synchondroses, consisting of mirror-image growth plates, are critical for cranial base elongation and development. Over the last decade, considerable progress has been made in determining the roles of the parathyroid hormone–related protein, Indian hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling pathways in various aspects of skeletal development. Furthermore, recent evidence indicates the important role of the primary cilia signaling pathway in bone elongation. Here, we review the development of the growth plate and cranial synchondrosis and the regulation by the above-mentioned signaling pathways, highlighting the similarities and differences between these 2 structures.Keywords: chondrocyte, PTHrP, Ihh, FGF, Wnt, primary cilia

J Dent Res. 2016 Oct; 95(11): 1221–1229. Published online 2016 Jun 1. doi: 10.1177/0022034516651823 Developmental Regulation of the Growth Plate and Cranial Synchondrosis X. Wei,1,2M. Hu,2Y. Mishina,1 and  F. Liu1

Complexities regarding the growth of the skeleton during the period of growth and development seem to be key in understanding what begins to go wrong after that period of growth is mostly finished and the brain and the skeleton has to make due with the final structure, for better or for worse.

 Growth of the cartilage models for the vertebrae, ribs, and sternum allow for enlargement of the thoracic cage during childhood and adolescence. The cartilage models gradually undergo ossification and are converted into bone [the xiphoid process of the sternum typically turns to bone around the age of 40.]

Apparently serotonin, [important in psychiatric medication called S.S.R.I.s ] control bone metabolism and this can have implications for the skull.

Adv Exp Med Biol 2017;1033:35-46. doi: 10.1007/978-3-319-66653-2_3.

Regulation of Bone Metabolism by Serotonin

Brigitte Lavoie 1 2Jane B Lian 3Gary M Mawe 4Affiliations expand


The processes of bone growth and turnover are tightly regulated by the actions of various signaling molecules, including hormones, growth factors, and cytokines. Imbalances in these processes can lead to skeletal disorders such as osteoporosis or high bone mass disease. It is becoming increasingly clear that serotonin can act through a number of mechanisms, and at different locations in the body, to influence the balance between bone formation and resorption. Its actions on bone metabolism can vary, based on its site of synthesis (central or peripheral) as well as the cells and subtypes of receptors that are activated. Within the central nervous system, serotonergic neurons act via the hypothalamus to suppress sympathetic input to the bone. Since sympathetic input inhibits bone formation, brain serotonin has a net positive effect on bone growth. Gut-derived serotonin is thought to inhibit bone growth by attenuating osteoblast proliferation via activation of receptors on pre-osteoblasts. There is also evidence that serotonin can be synthesized within the bone and act to modulate bone metabolism. Osteoblasts, osteoclasts, and osteocytes all have the machinery to synthesize serotonin, and they also express the serotonin-reuptake transporter (SERT). Understanding the roles of serotonin in the tightly balanced system of bone modeling and remodeling is a clinically relevant goal. This knowledge can clarify bone-related side effects of drugs that affect serotonin signaling, including serotonin-specific reuptake inhibitors (SSRIs) and receptor agonists and antagonists, and it can potentially lead to therapeutic approaches for alleviating bone pathologies.

Keywords: Enterochromaffin cell; LRP5; Osteoblast; Osteoclast; Osteocyte; Osteoporosis; Raphe nucleus; Serotonin receptor; Serotonin transporter; Tryptophan hydroxylase.

Somehow, all of this is connected and it will be important to understand how.

It is not impossible that a mismatch occurs during development, especially if the child is born initially to conditions not suitable to skeletal growth, but the moves to a better place with better conditions and catchup skeletal growth which ends up sometimes causing problems once skeletal growth is all done.

This may have happened to Paula, who was born into poverty and bad breathing conditions. At the age of 2 and 1/2 years of age she moved across the world into a cleaner, safer, richer environment. Her mouth was small and she did not have enough room for all her teeth, which grew in one on top of one another. Is it possible that she had just enough space for her brain, and less wiggle room than is needed during periods of, let’s say, hypercapnia and the chronic cerebral vasodilation it brings and the hyper perfusion of the brain that accompanies it?

Just a thought, maybe even a hypothesis…..


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