27 Jul 2017 15 Sep 2017
There have been a number of studies conducted to find causes for, and reasons behind depression, and why it affects so many people around the world. One suggestible cause is season of birth. Some studies have shown that the environment can affect one's risk of developing depression, as humans grow a great deal during their first year of life, and the environment varies greatly depending on the season. This literature review will gather together these studies, discuss their findings and analyse their reliability in order to discern the possibility of a link.
Mental illness has increasingly become a more prominent aspect of health in the past decade, and with this, investigative research into its origins and causes has surged. A single consideration of this is season of birth, as it has been recorded a number of times that varying factors, both during pregnancy, and postnatally, have significant impacts upon the brain, in both structure and function.
Depression is known as the world's largest leading cause of disability, affecting 350 million people worldwide. This, in itself, is enough reason to consider research into the causes behind depression as vastly important to both medicine and society. Further investigation into mental health and its causation can provide better care to patients, as well as improving and increasing awareness of the devastating effects of depression worldwide.
Whilst there are number of theories surrounding the causes of depression, it has become evident that no single factor is necessarily causative; furthermore, a correlation does not necessarily determine causation.
This literature review will discuss season of birth and the hand it may play in mental illness, and more specifically, depression. Studies over the years have suggested a relationship between a birth in the autumn and winter months with an increased risk of developing mental illness, particularly in those with a genetic predisposition. These studies will also be appraised with regards to their approach to research, and the relative accuracy and reliability of their results; thus providing us with a more conclusive view on how season of birth could link to depression.
There are a number of suggestions of how season of birth could affect one's health, some of which are more established within the scientific community; as example of such is that of Seasonal Affective Disorder (SAD). SAD is defined as recurring episodes of major depression during certain times of the year, more specifically, in winter. The pathological mechanisms behind SAD are believed to be changes in exposure to light; this notion is fortified by the resounding success of light therapy, which has been the focus of seasonal affective disorder treatment since the 1980s.-
Research has found that patients with seasonal affective disorder were more frequently born in the autumn or winter, and less often in the spring or summer, compared with atypical depression. It was therefore concluded that when genetic factors were accounted for, season of birth could play a part in the development of SAD. However, moreÂ research was required to observe the underlying mechanisms for this correlation.
Further investigation into season of birth and its potential relationship with mental health has since been performed, and there are various suggestions as to how season of birth can affect exposure of light, infection and nutrients to a developing foetus, and a newborn child. These studies have found a correlation between changes in exposure to environmental factors to specific diseases such as schizophrenia and bipolar disorder. In fact, it was found that risk of developing schizophrenia or bipolar affective disorder later in life followed a seasonal distribution; hence directing towards an environmental factor as being potentially causative in disease.
As the seasons change, the climate in which a foetus or young child develops, also changes; there are alterations in diet, sunlight, and infection. Researchers also found evidence that suggests that vitamin D deficiency could be causative in the development of psychiatric conditions.
Vitamin D has previously shown itself as pivotal in healthy neurodevelopment of the foetus. The role of vitamin D was only found to have a significant impact on the risk of schizophrenia; whilst links were found to bipolar affective disorder, they were not as significant, and some factors, such as increasing latitude, are believed to have much a much greater impact upon the risk of developing psychiatric conditions.
Nevertheless, as vitamin D is crucial in healthy neurodevelopment, it is of note that patients with mental illnesses are shown to have differences in brain structure, more specifically, structural differences in the left superior temporal gyrus. The variations in brain development and structure were observed to have produced marked differences in personality traits and neurobehavioural disorders. An example of this was that males born in the autumn and winter exhibited a larger volume of the superior temporal gyrus; this area of the brain contains the auditory cortex, responsible for interpretation of human language and social interactions. It is fundamentally through the effects of both genetic expression environmental factors, such as perinatal photoperiod, that there are morphological variations in this region, resulting in differences in social interactions and behaviour.
It is through these findings that the following question arises; could treatment of vitamin D deficiency during gestation, and during the first few years of life have a significant enough effect upon neurodevelopment, so as to prevent the acquisition of psychiatric conditions?
There are many ways in which cranial structure varies as a result of season of birth. A number of studies have displayed changes in brain structure linked to season of birth, with visible differences seen on MRI.9 There are also a number of changes to the brain on a physiological level.
Patients with depression have been found to have reduced volumes of the hippocampus and amygdala, as well as changes in brain physiology; more extreme responses to the stress hormone, cortisol, and upregulation of the HPA axis.
It is widely established that patients with psychiatric conditions have variations in brain structure relative to the normal population, most characterised by the HPA axis, a feedback interaction between the hypothalamus, pituitary gland, and theÂ adrenal cortex.
This interaction is initiated through the release of corticotropic-releasing-hormone (CRH), into the blood of portal circulation by the parvocellular neurosecretory neurones in the paraventricular nucleus of the hypothalamus. In response to this, adrenocorticotropic hormone (ACTH) is released by the anterior pituitary gland. This results in an excessive release of glucocorticoids (cortisol) into the blood. The increased concentrations of cortisol results a release of proinflammatory cytokines in the brain, and dysregulation of the amygdala.
The dysregulation of the HPA axis frequently is a result of stress, which can be defined as any environmental factor that induces stress on the body. Such stresses can include imbalances in nutrition or exposure to infection, both of which could affect the developing foetus or neonate in a profound way. As patients born in the autumn and winter are found to have an increase in exposure to infection, reduced exposure to sunlight (in the northern hemisphere) and a poorer diet relative to those born in the warmer months, a link between season of birth and the increased activity of the HPA axis, and by proxy, depression, becomes evident.
The hippocampus and amygdala, two crucial parts of the brain, are components of the limbic system, responsible for emotions and social interactions. It is through their reduced volumes that feelings such as despair and distress remain unregulated, fundamentally resulting in depression. Is it believed that the reduced volume of these parts of the brain are a consequence of a lack of neuroplasticity in patients with depression, as it is disrupted. It is through this that the hippocampus and amygdala are markedly smaller in patients with depression than the normal population.
Neuroplasticity allows 'pruning' of synaptic connections that are used less often, and the strengthening of connections used most often. It is believed that under stress, a patient with depression fails to make these adaptations to stressful stimuli, and instead, cell atrophy occurs - the reduction or shrinkage in cell size; resulting in a reduced volume of the hippocampus and amygdala. It is through this that the hippocampus and amygdala are markedly smaller in patients with depression than the normal population, thus preventing any recovery, as negative feelings begin to dominate the psyche.
The changes in brain structure have multiple causes; it has been found that patients with a reduced volume of the hippocampus and amygdala have so due to modified behavioural expression of dopaminergic interactions. Due to the presence of proinflammatory cytokines, there is an increase in the activity of the monoamine oxidase enzyme (MAO), resulting in reduced levels of serotonin, noradrenaline, and dopamine. The cytokines also reduce levels of brain-derived neurotrophic factor (BDNF), responsible for neuronal growth; this leads to a reduction in neurogenesis, and hence a reduction in hippocampal volume.
The dyregulated hippocampus and amygdala maintain abnormal levels of glucocorticoids, neurotrophic factors, and cytokines, thus creating a vicious cycle in which patients develop a depressive state from which it is difficult to recover.
As brain structure has such a profound effect upon a patient's likelihood to develop depression, and the structure of the brain is intricately linked with season of birth, it could be argued that season of birth would indirectly alter the risk of developing depression, with a birth in the winter months causing an increase.
It has been found that treatments for depression and other psychiatric conditions also contribute towards cranial structure. Antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs), have been shown to improve the neuroplasticity of the brain in patients with depression, thus preventing the dysregulation of the limbic system, relieving symptoms such as anhedonia and avolition. SSRIs inhibit the 5HT reuptake transporter (5HTT, SERT), which would normally allow for the breakdown of serotonin, in the synaptic terminals of neurones in the brain. Through this,Â there is a sustained increase in extracellular serotonin, and increased action of serotonin within the synaptic cleft. Long-term use of antidepressants has been shown to causes changes in the volumes of the hippocampus and amygdala, as BDNF levels rise to allow for neurogenesis. This allows for the restoration of normal action of serotonin.These changes in brain structure further fortify the belief that cranial structure has a powerful impact upon the likelihood of depression; as season of birth itself can affect the development of the brain in utero, it can be argued that a patient's season of birth could potentially increase or reduce their likelihood of developing depression.
The Circadian System
The regulation of circadian rhythms can be altered in those with mental illnesses; studies have shown that patients with major depressive disorder and SAD have altered function of the circadian clock. There are a number of genes responsible for biological rhythms and light sensitivity, and those for melanopsin have been found to have variations in their expression.
The circadian clock is the means of which allow humans to follow a routine; located in the hypothalamus, it is a key component of homeostasis, allowing organisms to maintain their sleep cycle, body temperature, blood pressure, and other important functions. Circadian periodicity is dictated by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The suprachiasmatic nucleus evokes responses in neurons synapsing in the paraventricular nucleus (PVN), also in the hypothalamus.Â These neurones modulate other neurones in the superior cervical ganglia (SCG), those axons project to the pineal gland. This mechanism ultimately results in the secretion of melatonin into the bloodstream. Melatonin levels increases as the light in the environment decreases, peaking in the early hours of the night.
Melanopsin is a photopigment found in intrinsically photosensitive ganglion cells (ipRGCs) in the retina, and is involved in responses to light in the environment, more specifically, circadian photoentrainment and the pupillary reflex.Â (Hattar et al., 2003; Lucas et al., 2003; Panda et al., 2002, 2003). It has been found that variations in melanopsin function could be connected to differences in light sensitivity between individuals. Variations in circadian photoentrainment can occur as a result of sequence variations in genes mediating expression of melanopsin.Â (Hatori & Panda, 2010)
Studies have found that in humans, short wavelength light (blue light) during the dark phase acutely causes alertness, even in humans who are blind.Â Zaidi et al. (2007) The effect was significantly more profound in light of shorter wavelengths relative to longer wavelengths.This potentially suggests that ganglion cells in the eye that express melanopsin mediate alertness through projections to the suprachiasmatic nucleus, and other centres in the brain responsible for sleep and alertness, such as the ventral lateral preoptic nuclei (VLPO). Both the SCN and VLPO receive direct input from the ganglion cells expressing melanopsin, and the VLPO is more specifically involved in the regulation of non-rapid eye movement (NREM) sleep.Â (Lu et al., 2000)
It can hence be stated that the connection from melanopsin-expressing cells to regulatory nuclei in the brain is the cause for the significant impact of light upon the circadian regulation of sleep. Variations in melanopsin function could lead to decreased alertness during periods of less environmental light - such as during the winter. Furthermore, differences in melanopsin function could lead to seasonal variations in circadian timings and sleep. These factors compound and may, in turn, contribute to SAD. ( Melanopsin Gene Variations Interact With Season to Predict Sleep Onset and Chronotype) It was found that SAD patients had reduced behavioural engagement during times when days were shorter. It was interpreted that the change could be attributed to a delay in phase or slowing of homeostatic drive ( Melanopsin Gene Variations Interact With Season to Predict Sleep Onset and Chronotype) However, it was also argued that a change in chronotype across seasons could be a consequence, rather than a cause, of reduced mood. ( Murray and colleagues (2003))
Thus, it is certainly probable that environmental light levels combined with genetic variation in the expression of photopigments such as melanopsin could affect both sleep cycles and mood, and therefore one's season of birth could impact the risk of developing depression. However, this brings into question whether this would apply to major depressive disorder itself, or more specific to seasonal disorders. Further research into the r
ole of melanopsin and the effects of environmental light levels could shed some light on potential links to depression and mental health.
Questions for Further Studies and Conclusions
Much research has been done to investigate the possible effects of season of birth on the risk of developing depression. From these studies one could conclude that a birth during autumn or winter increases the risk of developing depression as a consequence of alteration in both brain structure, and circadian physiology. This is due to the lower light levels a neonate is exposed to, resulting in alterations in melanopsin expression and reduced levels of vitamin D. However, as these factors primarily come into play after birth, the question of environmental effects upon the mother during gestation come into play; travel, for example, from one hemisphere to the other, could result in a 'summer' rather than a 'winter' birth. This seems advantageous at first, seemingly providing a lower risk of developing depression, however, the stress of travel during gestation could potentially have impacts upon the developing foetus. Further to this, one could question the effects of travel shortly after birth, as the environmental factors that a child is exposed to, such as diet, infection, and light levels, drastically change; this is in combination with the stressor that is traveling itself.
There are also some current limitations when conducting studies; as patients birth dates are protected by the Health Insurance Portability and Accountability Act (HIPAA), the accuracy of results and conclusions made is reduced. It would hence be advantageous if birth date could be used in this research as results would be significantly more accurate. Thus, it must be noted that the current investigations into season of birth and its links to depression are subject to unreliability.
Taking the above factors into consideration, it can be concluded that there is potentially a link between of season of birth and depression, as some links to other psychiatric conditions have already been somewhat established. We have found that season of birth has marked effects upon the cranial structure of neonates, which then result in alterations in risk of illness.
We see that the changes in structure are inherently linked to variations in the environment, which renders a link between season of birth and depression highly probable.
The changes in brain structure and their physiological effects should be researched further, particularly due to the role that the circadian clock plays in depression, as an alteration in the structure of its components would further explain its effects upon risk. Circadian rhythms have been established to be intricately related to one's mental health; however, it remains unconfirmed whether changes in sleep homeostasis are causative or a consequence of psychiatric conditions.
Therefore, more research should be conducted in order to understand the exact effects of environmental factors on depression and how they can alter risk; fundamentally, no steadfast conclusion can be given as of yet, but the door for further research remains open.
 World Health Organisation, Depression Fact sheet, Available from: http://www.who.int/mediacentre/factsheets/fs369/en/ [Accessed 1st March 2017]
 Lurie SJ1, Gawinski B, Pierce D, Rousseau SJ, Seasonal Affective Disorder. 2006 Nov 1;74(9):1521-4
 National Institute of Mental Health, Seasonal Affective Disorder. Available from: https://www.nimh.nih.gov/health/topics/seasonal-affective-disorder/index.shtml [Accessed 1st March 2017]
 McGrath JJ, Burne TH, Feron F, Mackay-Sim A, Eyles DW (2010) Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull 36(6): 1073-1078.
Â Davies G, Welham J, Chant D, Torrey EF, McGrath J (2003) A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia.Schizophrenia Bulletin,29(3), 587-593..
 Disanto, G., Morahan, J., Lacey, M., DeLuca, G., Giovannoni, G., Ebers, George C ; Ramagopalan, Sreeram V Gravenor, Mike B. (2012). Seasonal Distribution of Psychiatric Births in England (Season of Birth and Psychiatric Disease). PLoS ONE, 7(4), E34866.
 Pantazatos, S. (2014). Prediction of individual season of birth using MRI. NeuroImage, 88, 61-68.
 Bigler, E., Mortensen, S., Neeley, E., Ozonoff, S., Krasny, L., Johnson, M Lu, J., Provencal, S.L., McMahon, W. Lainhart, J. (2007). Superior Temporal Gyrus, Language Function, and Autism. Developmental Neuropsychology, 31(2), 217-238.
 Christopher M Ciarleglio, John C Axley, Benjamin R Strauss, Karen L Gamble, & Douglas G Mcmahon. (2010). Perinatal photoperiod imprints the circadian clock. Nature Neuroscience,14(1), 25.
Get in touch with our dedicated team to discuss about your requirements in detail. We are here to help you our best in any way. If you are unsure about what you exactly need, please complete the short enquiry form below and we will get back to you with quote as soon as possible.