CHAPTER 1

1.1 Introduction

Mood disorders are a category of mental health conditions characterized by significant

disturbances in an individual's mood, leading to disruptions in their emotional state and overall

functioning. These disorders encompass a wide range of conditions, including major depressive

disorder (MDD), bipolar disorder, and persistent depressive disorder (PDD), among others.

Mood disorders can profoundly impact various aspects of a person's life, including their

relationships, work or school performance, and overall quality of life (APA 2013).

1.2 Definition and Classification of Biochemical Basis of Mood Disorders

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder, are complex

mental health conditions that involve dysregulation of various biochemical processes in the brain

(Krishnan & Nestler, 2008).

The biochemical basis of mood disorders involves complex interactions between

neurotransmitter systems, neuroendocrine pathways, inflammation, and oxidative stress. While

neurotransmitter imbalance, HPA axis dysregulation (Juruena, 2014), neuroinflammation (Miller,

2016), and oxidative stress are key mechanisms implicated in the pathophysiology of mood

disorders, the precise etiology remains incompletely understood (Maes, 2011).

1.3 Prevalence and Impact of the Biochemical Basis of Mood Disorders

Mood disorders, influenced by a complex interplay of genetic, environmental, and biochemical

factors, have a significant prevalence globally and exert profound impacts on individuals,

families, and societies (WHO, 2017).

1.3.1 Prevalence of Mood Disorders

1. Major Depressive Disorder (MDD): MDD is one of the most common mental health

disorders worldwide. According to the World Health Organization (WHO), depression

affects more than 264 million people globally, with prevalence rates varying across

countries and populations.

2. Bipolar Disorder: Bipolar disorder affects approximately 1-2% of the population

worldwide, with similar prevalence rates across different countries and cultures. The

disorder often manifests in late adolescence or early adulthood and can have a chronic

course if left untreated (Merikangas & Pato, 2009).

1.3.2 Impact of Biochemical Basis

1. Individual Impact: Mood disorders can significantly impair an individual's quality of

life, affecting various domains such as work, relationships, and physical health.

Symptoms such as persistent sadness, loss of interest or pleasure, fatigue, and cognitive

impairment can interfere with daily functioning and diminish one's sense of well-being.

2. Family Impact: Mood disorders can strain familial relationships and disrupt family

dynamics. Family members may struggle to understand and cope with the affected

individual's symptoms, leading to increased stress, conflict, and caregiver burden.

3. Societal Impact: Mood disorders impose substantial economic burdens on societies

through healthcare costs, lost productivity, and disability. Individuals with untreated

mood disorders are at higher risk of unemployment, substance abuse, homelessness, and

involvement in the criminal justice system (WHO 2017).

1.4 Biochemical Basis and Treatment Implications

1. Neurotransmitter Imbalance: Medications targeting neurotransmitter systems, such as

selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake

inhibitors (SNRIs), and mood stabilizers, are commonly used to manage symptoms of

mood disorders (Malhi & Mann, 2018).

2. HPA Axis Dysregulation: Therapeutic interventions that modulate the HPA axis, such as

antidepressant medications and psychotherapy, may help regulate cortisol levels and

reduce stress-related symptoms in individuals with mood disorders.

3. Neuroinflammation and Oxidative Stress: Emerging research suggests that anti-

inflammatory agents and antioxidants may have potential as adjunctive treatments for

mood disorders, particularly in individuals with evidence of neuroinflammation and

oxidative stress. Lifestyle interventions promoting healthy behaviors, such as regular

exercise, adequate sleep, and balanced nutrition, may also help mitigate inflammation and

oxidative damage (Köhler, 2016).

 CHAPTER 2

2.1 Neurotransmitters and Mood Regulation

2.1.1 Serotonin

1. Role in Mood Regulation: Serotonin, often referred to as the "feel-good"

neurotransmitter, plays a crucial role in mood regulation. It is involved in modulating

various physiological processes, including mood, sleep, appetite, and cognition. In the

brain, serotonin is primarily synthesized in serotonergic neurons located in the raphe

nuclei of the brainstem and is widely distributed throughout the central nervous system.

Serotonin exerts its effects by binding to specific receptors, particularly 5-HT1A and 5-

HT2A receptors, located on postsynaptic neurons and modulating neuronal activity.

Dysregulation of serotonin neurotransmission has been implicated in the pathophysiology

of mood disorders, particularly depression. Decreased levels of serotonin or alterations in

serotonin receptor sensitivity have been associated with symptoms of low mood,

anhedonia, and sleep disturbances observed in depression (Belmaker & Agam, 2008).

2. Mechanisms of Synthesis, Release, and Reuptake: The synthesis of serotonin begins

with the conversion of the amino acid tryptophan into 5-hydroxytryptophan (5-HTP) by

the enzyme tryptophan hydroxylase. Subsequently, 5-HTP is converted into serotonin (5-

hydroxytryptamine) by the enzyme aromatic L-amino acid decarboxylase. Once

synthesized, serotonin is stored in synaptic vesicles within presynaptic neurons and

released into the synaptic cleft in response to neuronal stimulation (Cipriani, 2018). Upon

release, serotonin binds to postsynaptic receptors, exerting its effects, and is then rapidly

cleared from the synaptic cleft by reuptake transporters, primarily the serotonin
 transporter (SERT). SERT facilitates the reuptake of serotonin back into presynaptic

neurons, where it can be either repackaged into synaptic vesicles for future release or

metabolized by the enzyme monoamine oxidase (MAO) to inactive metabolites (Nutt,

2008).

3. Implications for Mood Disorders: Dysfunction in serotonin neurotransmission has

significant implications for the development and treatment of mood disorders. Low levels

of serotonin or alterations in serotonin receptor functioning have been implicated in the

pathophysiology of depression and related mood disorders. Medications that target the

serotonin system, such as selective serotonin reuptake inhibitors (SSRIs), act by blocking

the reuptake of serotonin, thereby increasing serotonin levels in the synaptic cleft and

enhancing neurotransmission. SSRIs are commonly used as first-line pharmacological

treatments for depression due to their efficacy in alleviating depressive symptoms.

Alterations in genes encoding for serotonin-related proteins, such as the serotonin

transporter gene (SLC6A4) and serotonin receptors, have been linked to susceptibility to

mood disorders, highlighting the genetic basis of serotonin dysfunction in these

conditions (Lin & Wittenauer, 2018).

2.1.2 Dopamine

1. Role in Reward and Pleasure: Dopamine is a neurotransmitter that plays a central role

in the brain's reward system, which is involved in motivation, pleasure, and

reinforcement learning. Dopamine is synthesized primarily in dopaminergic neurons

located in various regions of the brain, including the substantia nigra and the ventral

tegmental area (VTA). These neurons project to different areas of the brain, such as the

nucleus accumbens, prefrontal cortex, and limbic system, forming dopaminergic

 pathways involved in reward processing. Dopamine release in response to rewarding

stimuli, such as food, sex, or drugs, reinforces behaviors associated with obtaining

pleasure and contributes to feelings of enjoyment and satisfaction. Dysregulation of the

dopamine system has been implicated in various psychiatric disorders, including mood

disorders, addiction, and schizophrenia (Grace, 2016).

2. Dysregulation in Mood Disorders: In mood disorders, such as depression and bipolar

disorder, abnormalities in dopamine neurotransmission have been observed, contributing

to mood dysregulation and symptom manifestation. While the role of dopamine in mood

disorders is complex and not fully understood, alterations in dopaminergic activity have

been associated with specific symptoms characteristic of these disorders. For example, in

depression, decreased dopaminergic activity in the mesolimbic pathway, which projects

from the VTA to the nucleus accumbens, may contribute to symptoms of anhedonia,

reduced motivation, and decreased pleasure in previously enjoyable activities (Belujon &

Grace, 2017). In bipolar disorder, dysregulation of dopamine neurotransmission during

manic or hypomanic episodes may lead to increased energy, impulsivity, and heightened

reward-seeking behaviors.

3. Neurotransmitter Pathways and Receptors: Dopamine exerts its effects by binding to

specific receptors located on postsynaptic neurons, of which there are five main subtypes:

D1, D2, D3, D4, and D5. These receptors are distributed throughout the brain and

mediate the diverse physiological actions of dopamine (Nestler & Carlezon Jr, 2006). For

example, activation of D1-like receptors (D1 and D5) is generally associated with

excitatory effects, whereas activation of D2-like receptors (D2, D3, and D4) is associated

with inhibitory effects. The mesolimbic and mesocortical pathways, originating from the
 VTA and projecting to the nucleus accumbens and prefrontal cortex, respectively, are

particularly implicated in reward processing, motivation, and emotion regulation.

Dysregulation of these dopaminergic pathways and alterations in receptor sensitivity have

been implicated in mood disorders and other neuropsychiatric conditions (Schultz, 2022).

2.1.3 Norepinephrine

1. Stress Response and Arousal: Norepinephrine, also known as noradrenaline, is a

neurotransmitter and hormone that plays a key role in the body's stress response and

arousal. It is synthesized from dopamine in noradrenergic neurons located in the locus

coeruleus, a nucleus in the brainstem. Norepinephrine is involved in the regulation of

various physiological functions, including attention, alertness, and the fight-or-flight

response. During times of stress or threat, the locus coeruleus activates, leading to

increased release of norepinephrine throughout the brain and body. This heightened

norepinephrine activity helps mobilize energy resources, enhances vigilance, and

prepares the body to respond to the perceived danger. Dysregulation of the

norepinephrine system has been implicated in the pathophysiology of anxiety disorders,

post-traumatic stress disorder (PTSD), and depression (Sara & Bouret, 2012).

2. Implications for Anxiety and Depression: Dysfunction in norepinephrine

neurotransmission has significant implications for the development and maintenance of

anxiety and mood disorders. In anxiety disorders, excessive norepinephrine activity may

contribute to symptoms such as hypervigilance, increased heart rate, and heightened

arousal. Chronic stress or trauma can lead to dysregulation of the norepinephrine system,

resulting in persistent anxiety symptoms and an increased risk of developing anxiety

disorders such as generalized anxiety disorder (GAD) or panic disorder. In depression,

 alterations in norepinephrine neurotransmission have also been observed (Ressler &

Nemeroff, 2010). While serotonin has historically been the primary focus in depression

research, the role of norepinephrine is increasingly recognized. Dysregulation of

norepinephrine signaling in key brain regions, such as the prefrontal cortex and

amygdala, may contribute to symptoms of sadness, fatigue, and cognitive impairment

observed in depression. Medications that target the norepinephrine system, such as

selective norepinephrine reuptake inhibitors (SNRIs), are commonly used in the

treatment of both anxiety and depression, highlighting the importance of norepinephrine

dysregulation in these disorders.

3. Neurotransmitter Functions and Regulation: Norepinephrine exerts its effects by

binding to adrenergic receptors, of which there are two main subtypes: alpha-adrenergic

receptors and beta-adrenergic receptors. These receptors are distributed throughout the

central and peripheral nervous systems and mediate the diverse physiological actions of

norepinephrine. Activation of alpha-adrenergic receptors generally leads to excitatory

effects, such as vasoconstriction and increased blood pressure, whereas activation of beta-

adrenergic receptors can have both excitatory and inhibitory effects, depending on the

specific subtype and cellular context. Norepinephrine activity is tightly regulated by a

balance between synthesis, release, and reuptake mechanisms. After release from

presynaptic neurons, norepinephrine is quickly cleared from the synaptic cleft by

reuptake transporters, primarily the norepinephrine transporter (NET), and metabolized

by enzymes such as monoamine oxidase (MAO) and catechol-O-methyltransferase

(COMT) (Charney, 2004).

2.2 Neuroendocrine System and Mood Disorders

2.2.1 Hypothalamic-Pituitary-Adrenal (HPA) Axis

1. Stress Response and Cortisol Regulation: The hypothalamic-pituitary-adrenal (HPA)

axis is a crucial neuroendocrine system involved in the body's response to stress. The

HPA axis consists of three main components: the hypothalamus, the pituitary gland, and

the adrenal glands. In response to stress, the hypothalamus releases corticotropin-

releasing hormone (CRH), which stimulates the pituitary gland to release

adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal glands, located

atop the kidneys, to produce and release cortisol, the primary stress hormone. Cortisol

plays a key role in regulating various physiological processes, including metabolism,

immune function, and stress response. It mobilizes energy reserves, suppresses

inflammation, and enhances cardiovascular function to help the body cope with stressors.

Cortisol levels typically follow a diurnal rhythm, peaking in the early morning and

declining throughout the day (Sapolsky, 2015).

2. Dysregulation in Depression and Anxiety: Dysregulation of the HPA axis has been

implicated in the pathophysiology of mood disorders, particularly depression and anxiety.

In individuals with depression, abnormalities in HPA axis function, such as hyperactivity

and impaired negative feedback inhibition, have been observed. Chronic stress and

elevated cortisol levels associated with HPA axis dysregulation can lead to neuronal

damage, impaired neurogenesis, and alterations in brain structure and function,

particularly in regions implicated in mood regulation such as the hippocampus and

prefrontal cortex (Belmaker & Agam, 2008). Similarly, dysregulation of the HPA axis has
 been implicated in anxiety disorders, with evidence of increased cortisol reactivity to

stressors in individuals with anxiety disorders such as generalized anxiety disorder

(GAD) and post-traumatic stress disorder (PTSD). Dysfunctional HPA axis activity may

contribute to persistent anxiety symptoms and exacerbate the risk of developing anxiety

disorders following exposure to stress or trauma (Yehuda & Seckl, 2011).

3. Impact on Neurotransmitter Systems: Dysregulation of the HPA axis can have

significant downstream effects on neurotransmitter systems implicated in mood

regulation, such as serotonin, dopamine, and norepinephrine. Chronic stress and elevated

cortisol levels associated with HPA axis hyperactivity can disrupt neurotransmitter

balance and function, leading to alterations in mood, cognition, and behavior (Belmaker

& Agam, 2008). For example, prolonged exposure to stress may reduce serotonin

neurotransmission, contributing to symptoms of depression and anxiety. Similarly,

dysregulation of dopamine and norepinephrine systems has been observed in individuals

with mood disorders, with evidence of altered receptor sensitivity and neurotransmitter

release. These neurochemical changes may underlie the development and persistence of

mood disorders and represent potential targets for pharmacological interventions aimed at

restoring neurotransmitter balance and HPA axis function.

2.2.2 Thyroid Hormones

1. Role in Metabolism and Mood Regulation: Thyroid hormones, primarily thyroxine

(T4) and triiodothyronine (T3), are critical regulators of metabolism and play a

significant role in mood regulation. Produced by the thyroid gland, these hormones

influence the body's metabolic rate, energy production, and thermoregulation. Thyroid

hormones exert their effects by binding to thyroid hormone receptors located in various
 tissues throughout the body, including the brain. In the central nervous system, thyroid

hormones modulate neurotransmitter synthesis, receptor sensitivity, and synaptic

plasticity, thereby influencing mood, cognition, and behavior. Dysregulation of thyroid

hormone levels, either due to hypo- or hyperthyroidism, can have profound effects on

mood and mental health (Bauer, 2008).

2. Thyroid Dysfunction and Mood Disorders: Thyroid dysfunction, characterized by

either insufficient (hypothyroidism) or excessive (hyperthyroidism) thyroid hormone

production, has been associated with mood disorders such as depression and anxiety. In

hypothyroidism, decreased thyroid hormone levels can lead to symptoms of fatigue,

lethargy, and depressed mood, resembling those observed in depression. Hypothyroidism

has been linked to alterations in neurotransmitter systems, including reduced serotonin

and dopamine activity, which may contribute to mood disturbances (Hage & Azar, 2012).

Hyperthyroidism, characterized by elevated thyroid hormone levels, can result in

symptoms such as irritability, anxiety, and agitation. The neurobiological mechanisms

underlying the association between thyroid dysfunction and mood disorders are complex

and involve interactions between thyroid hormones, neurotransmitters, and

neuroendocrine pathways (Bauer, 2008).

3. Interactions with Neurotransmitter Pathways: Thyroid hormones interact with

neurotransmitter systems implicated in mood regulation, including serotonin, dopamine,

and norepinephrine. Thyroid hormones influence the synthesis, release, and metabolism

of neurotransmitters, modulating their availability and activity in the brain. For example,

thyroid hormones enhance the synthesis and turnover of serotonin and dopamine, which

are critical for mood regulation and emotional well-being. Additionally, thyroid hormones
 can affect the sensitivity of neurotransmitter receptors, such as serotonin receptors,

thereby influencing neurotransmitter signaling and mood-related behaviors.

Dysregulation of thyroid function can disrupt these neurochemical interactions,

contributing to mood disturbances observed in thyroid disorders. Moreover, thyroid

hormones can also affect the hypothalamic-pituitary-adrenal (HPA) axis, which plays a

central role in stress response and mood regulation, further implicating thyroid

dysfunction in the pathophysiology of mood disorders (Bunevicius & Prange Jr, 2010).

2.3 Neuroplasticity and Mood Disorders

2.3.1 Brain-Derived Neurotrophic Factor (BDNF)

1. Role in Neurogenesis and Synaptic Plasticity: Brain-Derived Neurotrophic Factor

(BDNF) is a crucial neurotrophin involved in various aspects of brain function, including

neurogenesis and synaptic plasticity. BDNF plays a pivotal role in promoting the

survival, growth, and differentiation of neurons, particularly in regions of the brain

associated with learning, memory, and emotion regulation, such as the hippocampus and

prefrontal cortex. BDNF also modulates synaptic transmission and plasticity, influencing

the strength and connectivity of neural circuits. Through its interactions with synaptic

proteins and signaling pathways, BDNF facilitates the formation and remodeling of

synapses, thereby shaping neural networks and facilitating adaptive responses to

environmental stimuli. Dysregulation of BDNF signaling has been implicated in the

pathophysiology of mood disorders, particularly depression, where alterations in

 neuroplasticity contribute to symptoms of cognitive dysfunction and emotional

dysregulation (Autry & Monteggia, 2012).

2. Implications for Depression and Anxiety: BDNF has garnered significant attention in

the field of mood disorders due to its role in regulating mood-related behaviors and

vulnerability to psychiatric illness. In depression, reduced BDNF levels and impaired

BDNF signaling have been observed, particularly in brain regions critical for mood

regulation and stress response. Animal studies have demonstrated that chronic stress, a

major risk factor for depression, can downregulate BDNF expression and disrupt

neuroplasticity, contributing to the development of depressive-like behaviors.

Antidepressant treatments, such as selective serotonin reuptake inhibitors (SSRIs), have

been shown to increase BDNF levels and promote neurogenesis and synaptic plasticity,

suggesting that enhancing BDNF signaling may be a key mechanism underlying the

therapeutic effects of antidepressants. Similar alterations in BDNF signaling have been

implicated in anxiety disorders, where deficits in neuroplasticity and stress resilience may

predispose individuals to heightened anxiety and fear responses (Castren & Rantamaki,

2010).

3. Molecular Mechanisms and Regulation: BDNF exerts its effects by binding to

tropomyosin receptor kinase B (TrkB) receptors located on the surface of neurons,

triggering intracellular signaling cascades that promote cell survival, growth, and

synaptic plasticity. Activation of TrkB receptors initiates various downstream signaling

pathways, including the mitogen-activated protein kinase (MAPK) pathway and the

phosphoinositide 3-kinase (PI3K) pathway, which regulate gene expression, protein

synthesis, and cytoskeletal dynamics. BDNF expression is regulated by a variety of

 factors, including neuronal activity, neurotransmitters, hormones, and environmental

stimuli. For example, experiences such as exercise, social interaction, and cognitive

stimulation can increase BDNF expression and enhance neuroplasticity. Conversely,

chronic stress, inflammation, and aging have been associated with decreased BDNF

levels and impaired neuroplasticity, highlighting the importance of environmental factors

in modulating BDNF signaling and mood-related behaviors (Martinowich & Lu, 2008).

2.3.2 Glutamate and GABA

1. Excitatory and Inhibitory Neurotransmission: Glutamate and gamma-aminobutyric

acid (GABA) are the two primary neurotransmitters responsible for excitatory and

inhibitory neurotransmission, respectively, in the central nervous system. Glutamate is

the most abundant excitatory neurotransmitter in the brain and plays a crucial role in

synaptic transmission, learning, and memory. Glutamate binds to ionotropic receptors,

such as N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-

4-isoxazolepropionic acid (AMPA) receptors, as well as metabotropic receptors,

modulating neuronal excitability and synaptic plasticity. In contrast, GABA is the

primary inhibitory neurotransmitter in the brain and acts to reduce neuronal excitability

and dampen synaptic transmission. GABA binds to GABA-A and GABA-B receptors,

leading to hyperpolarization of the postsynaptic membrane and inhibition of

neurotransmitter release. The balance between glutamatergic excitation and GABAergic

inhibition is critical for maintaining optimal neuronal function and network activity

(Sanacora & Banasr, 2013).

2. Dysregulation in Mood Disorders: Dysregulation of glutamate and GABA

neurotransmission has been implicated in the pathophysiology of mood disorders,

 including depression and anxiety. Alterations in glutamatergic signaling, such as

dysfunction of NMDA receptors or disturbances in glutamate release and uptake, have

been observed in individuals with mood disorders. Excessive glutamate activity can lead

to excitotoxicity, neuronal damage, and impaired synaptic plasticity, contributing to

neurobiological changes associated with depression and anxiety. Conversely, deficits in

GABAergic inhibition have also been implicated in mood disorders, with evidence of

decreased GABA levels or altered GABA receptor function in affected individuals.

Dysfunctional glutamate-GABA balance may disrupt neural circuitry and contribute to

the development and persistence of mood symptoms observed in these disorders

(Luscher, et al., 2011).

3. Impact on Neuroplasticity and Circuitry: Glutamate and GABA play key roles in

regulating neuroplasticity, the brain’s ability to adapt and reorganize in response to

experience and environmental stimuli. Glutamate-mediated synaptic plasticity, such as

long-term potentiation (LTP) and long-term depression (LTD), underlies learning and

memory processes and is critical for adaptive behavioral responses. GABAergic

inhibition regulates the timing and strength of excitatory synaptic transmission, shaping

neural circuitry and network dynamics. Dysregulation of glutamate and GABA

neurotransmission can disrupt neuroplasticity mechanisms, impair synaptic remodeling,

and compromise circuit function. Altered glutamate-GABA balance may lead to aberrant

neuronal connectivity, maladaptive changes in synaptic strength, and disrupted circuitry

implicated in mood regulation (Duman & Aghajanian, 2012).

 CHAPTER 3

3.1 Pharmacological Interventions: Antidepressants

1. Selective Serotonin Reuptake Inhibitors (SSRIs): Selective serotonin reuptake

inhibitors (SSRIs) are a class of antidepressant medications that primarily target the

serotonin neurotransmitter system. SSRIs work by inhibiting the reuptake of serotonin,

thereby increasing the availability of serotonin in the synaptic cleft and enhancing

serotonin neurotransmission. Commonly prescribed SSRIs include fluoxetine (Prozac),

sertraline (Zoloft), and escitalopram (Lexapro). SSRIs are considered first-line treatments

for depression due to their favorable side effect profile and efficacy in reducing

depressive symptoms (Mrazek & Hornberger, 2010).

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Serotonin-norepinephrine

reuptake inhibitors (SNRIs) are another class of antidepressant medications that target

both the serotonin and norepinephrine neurotransmitter systems. SNRIs work by

inhibiting the reuptake of both serotonin and norepinephrine, thereby increasing the

availability of these neurotransmitters in the synaptic cleft. Enhancing both serotonin and

norepinephrine signaling, SNRIs are believed to provide additional therapeutic benefits

compared to SSRIs, particularly in individuals with symptoms of both depression and

anxiety. Commonly prescribed SNRIs include venlafaxine (Effexor), duloxetine

(Cymbalta), and desvenlafaxine (Pristiq) (Mrazek & Hornberger, 2010).

 3. Mechanisms of Action and Efficacy: The mechanisms of action of SSRIs and SNRIs

involve the enhancement of serotonin and/or norepinephrine neurotransmission, leading

to downstream effects on neural circuits implicated in mood regulation. These

neurobiological effects are thought to underlie the therapeutic efficacy of SSRIs and

SNRIs in reducing symptoms of depression, anxiety, and other mood disorders. However,

the precise mechanisms by which SSRIs and SNRIs exert their antidepressant effects are

still not fully understood and likely involve complex interactions with multiple

neurotransmitter systems and neuroplasticity mechanisms (Cipriani, 2018).

3.2 Pharmacological Interventions: Mood Stabilizers

1. Lithium and its Mechanisms: Lithium is a well-established mood stabilizer used in the

treatment of bipolar disorder, a condition characterized by mood swings between

episodes of mania and depression. While the exact mechanisms of lithium's therapeutic

effects are not fully understood, several hypotheses have been proposed. One prominent

theory suggests that lithium modulates neurotransmitter systems, including serotonin,

norepinephrine, and dopamine, which are implicated in mood regulation (Yatham, 2018).

Lithium may also influence intracellular signaling pathways, such as the cyclic adenosine

monophosphate (cAMP) and glycogen synthase kinase-3 (GSK-3) pathways, which

regulate neuronal function and synaptic plasticity. Additionally, lithium may exert

neuroprotective effects by promoting the growth and survival of neurons and inhibiting

apoptosis (Malhi, et al., 2017).

2. Anticonvulsants and their Neurobiological Effects: In addition to lithium, anticonvulsant

medications are also used as mood stabilizers in the treatment of bipolar disorder.

Anticonvulsants such as valproate (valproic acid), carbamazepine, and lamotrigine have

 demonstrated efficacy in reducing mood symptoms and preventing mood episodes in

individuals with bipolar disorder. The neurobiological effects of anticonvulsants are diverse

and may involve modulation of neurotransmitter systems, including gamma-aminobutyric

acid (GABA), glutamate, and voltage-gated ion channels (Baldessarini, et al., 2019). For

example, valproate enhances GABAergic neurotransmission and inhibits glutamatergic

excitotoxicity, whereas carbamazepine and lamotrigine inhibit voltage-gated sodium

channels, thereby stabilizing neuronal excitability and reducing hyperactivity in mood

circuits. Anticonvulsants may also exert neuroprotective effects and promote neurogenesis,

contributing to their therapeutic efficacy in bipolar disorder.

3,3 Implications for Diagnosis and Treatment

Understanding the biochemical basis of mood disorders has important implications for their

diagnosis and treatment. Advances in neuroimaging, genetics, and molecular biology have led to

the development of biomarkers and diagnostic tools that aid in the identification of individuals at

risk for mood disorders and guide personalized treatment approaches (Cipriani, 2018).

Pharmacological interventions targeting specific neurotransmitter systems, such as selective

serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and

mood stabilizers like lithium, remain cornerstone treatments for mood disorders (Kessler, 2012).

However, the heterogeneity of mood disorders necessitates a multimodal approach to treatment,

including psychotherapy, lifestyle modifications, and adjunctive interventions targeting

neuroplasticity and neuroprotection. Emerging therapeutic strategies, such as ketamine and other

glutamatergic agents, hold promise for refractory cases and represent a shift towards novel

mechanisms of action in mood disorder therapeutics. Additionally, early intervention and

prevention strategies aimed at modulating stress responsivity, promoting resilience, and

enhancing neuroplasticity may help mitigate the burden of mood disorders and improve long-

term outcomes for affected individuals (Kessler, 2012).

Conclusion

Mood disorders, including depression and bipolar disorder, are complex psychiatric conditions

characterized by disturbances in mood, cognition, and behavior. While the precise etiology of

mood disorders remains incompletely understood, accumulating evidence suggests that

dysregulation of neurotransmitter systems, neuroendocrine pathways, and neuroplasticity

mechanisms plays a central role in their pathophysiology. Serotonin, dopamine, norepinephrine,

glutamate, and GABA are key neurotransmitters implicated in mood regulation, with alterations

in their levels, receptor sensitivity, and signaling pathways observed in individuals with mood

disorders. Dysfunctional hypothalamic-pituitary-adrenal (HPA) axis activity, disrupted

neuroplasticity, and aberrant circuitry contribute to the development and maintenance of mood

symptoms. Additionally, genetic factors, environmental stressors, and epigenetic mechanisms

interact with neurobiological vulnerabilities to increase susceptibility to mood disorders.

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