It is entirely plausible that symptoms should have a direct causal relationship with one another and this relationship has a network structure. It is implausible that symptoms arise only from mutual causality. They cannot arise out of thin air. This commentary addresses the origins of anxiety and depression.
Modern Western medicine is based on an untested assumption of specificity: each disease has its own unique pathophysiology. The biological explanation of depression and anxiety is consistent with this assumption. A multi-billion dollar pharmaceutical industry stems from the hypothesis that depression results from low levels of serotonin, and anxiety from low levels of gamma-aminobutyric acid (GABA). According to this hypothesis, the “latent variables” referred to by Cramer et al. are not really latent (i.e., hidden) – they are known neurotransmitters. If only life were that simple. Not only is the serotonin hypothesis widely disputed (Lacasse & Leo Reference Lacasse and Leo2005), but drugs which enhance serotonin have a marginal effect on depression as the effectiveness of these drugs is largely placebo mediated (Kirsch Reference Kirsch2009). If the unique neurotransmitter explanations for depression and anxiety are an over-simplification, what is causing these symptoms?
According to infornet theory (Hyland, in press), the body is organised in two ways: (a) as a sequential processing system that leads to specific pathologies and the diseases associated with those specific pathologies, and (b) as a parallel processing system. The parallel processing system extends through the neural, immune, and endocrine systems; it is a psychoneuroimmunoendocrine information network system, or infornet for short. The infornet carries out a number of functions, including managing the reference criteria of homeodynamic control systems. Reference criteria of homeostatic control systems remain fixed; those of homeodynamic systems vary and are responsive to both internal and external events.
The infornet integrates information from external or psychological inputs with information from internal or biological inputs. Outputs from the infornet to the cortex generate mental states that modify behaviour and hence modify the external environment. For example, pain is a signal that leads to adaptive behaviour – such as, withdrawal of one's hand from a flame. According to infornet theory, anxiety and depression evolved as signals to modify behaviour. Anxiety is a signal of behavioural alarm and prepares the body for external danger. Depression is a signal of behavioural inhibition and is the consequence of behavioural patterns that fail to achieve a person's important goals (Hyland 1985). Depression helps disengage behaviour from unattainable or inappropriate goals (Carver & Scheier Reference Carver and Scheier1990). Anxiety and depression are therefore caused by outputs from a parallel processing system involving many different biochemicals, rather than being directly caused by a single biochemical.
Because it encodes meaning, the infornet can be described in terms of the meaning it contains – by analogy, a computer programme can be described in terms of what it does rather than a binary magnetic code. The meaning of the infornet is represented by infornet beliefs. Infornet beliefs create the instructions that alter the reference criteria of homeodynamic control loops and which provide the mental signals that alter behaviour.
The infornet beliefs that lead to anxiety can be characterised as “the external environment is dangerous.” The infornet beliefs that lead to depression can be characterised as “I am not achieving the goals I want to achieve” (Carver & Scheier Reference Carver and Scheier1990; Hyland Reference Hyland1987). Beliefs tend to be interconnected and mutually supporting. The infornet beliefs leading to depression and anxiety are interconnected via a network structure of linked beliefs. Both of these mood-altering infornet beliefs are part of a more general belief that “the external environment is unsatisfactory,” and this more general belief is part of a top-level belief that “the general situation is bad.” If the general situation is bad, then not only is there threat from the external environment but also threat to the internal environment (e.g., threat of infection or damage). Consequently, the top-level belief of “the general situation is bad” is also associated with beliefs that drive the inflammatory response system (Rosenkranz Reference Rosenkranz2007; Segerstrom & Miller Reference Segerstrom and Miller2004). Infornet dysregulation occurs when, through the application of network learning rules that normally create better self-regulation, the infornet develops maladaptive beliefs – for example, that the general situation is always very bad when it is not. Chronic depression and anxiety (i.e., mental states which cannot be attributed to the immediate situation) are signals of a dysregulated infornet; that is, an inappropriate response to the current situation. Correlations between depression and anxiety, on the one hand, and between depression, anxiety, and inflammatory mediators, on the other, arise because all these variables are outputs of an information system whose beliefs are interconnected and where maladaptive beliefs tend to spread.
Why do Cramer et al. observe a network structure in the relation to psychological symptomatology? My guess is that causality between symptoms plays a minor role. I suggest that the main the reason for the network structure of symptom comorbidity is because of an underlying biological network structure. That is, anxiety and depression are outputs from a dysregulated infornet that has multiple physiological and psychological outputs.
Infornet theory predicts that fuzzy boundaries between disease states will not be limited to psychological symptoms but will include somatic symptoms. Diseases without a specific pathology, such as chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS), have a variety of psychological and somatic symptoms: diagnosis is not based on a unique pattern of symptoms. Comorbid relationships between fatigue, the somatic symptoms associated with CFS and IBS, along with depression and anxiety, should all form part of a network structure. In particular, inflammatory somatic symptoms should be related to psychological symptomatology (Whalley Reference Whalley, Jacobs and Hyland2007). Dysregulated people have multiple and varied symptoms. Dysregulation varies continuously across the infornet's meaning space.
If diseases have a specific cause, then comorbidity is an inconvenience. Comorbidity is often a reason for exclusion in clinical trials. From the perspective of infornet theory, however, the study of comorbidity has the potential to provide unique insights into a hypothesised network system whose outputs are psychological symptoms along with physiological changes (typically, pro-inflammatory) that cause somatic symptoms.
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It is entirely plausible that symptoms should have a direct causal relationship with one another and this relationship has a network structure. It is implausible that symptoms arise only from mutual causality. They cannot arise out of thin air. This commentary addresses the origins of anxiety and depression.
Modern Western medicine is based on an untested assumption of specificity: each disease has its own unique pathophysiology. The biological explanation of depression and anxiety is consistent with this assumption. A multi-billion dollar pharmaceutical industry stems from the hypothesis that depression results from low levels of serotonin, and anxiety from low levels of gamma-aminobutyric acid (GABA). According to this hypothesis, the “latent variables” referred to by Cramer et al. are not really latent (i.e., hidden) – they are known neurotransmitters. If only life were that simple. Not only is the serotonin hypothesis widely disputed (Lacasse & Leo Reference Lacasse and Leo2005), but drugs which enhance serotonin have a marginal effect on depression as the effectiveness of these drugs is largely placebo mediated (Kirsch Reference Kirsch2009). If the unique neurotransmitter explanations for depression and anxiety are an over-simplification, what is causing these symptoms?
According to infornet theory (Hyland, in press), the body is organised in two ways: (a) as a sequential processing system that leads to specific pathologies and the diseases associated with those specific pathologies, and (b) as a parallel processing system. The parallel processing system extends through the neural, immune, and endocrine systems; it is a psychoneuroimmunoendocrine information network system, or infornet for short. The infornet carries out a number of functions, including managing the reference criteria of homeodynamic control systems. Reference criteria of homeostatic control systems remain fixed; those of homeodynamic systems vary and are responsive to both internal and external events.
The infornet integrates information from external or psychological inputs with information from internal or biological inputs. Outputs from the infornet to the cortex generate mental states that modify behaviour and hence modify the external environment. For example, pain is a signal that leads to adaptive behaviour – such as, withdrawal of one's hand from a flame. According to infornet theory, anxiety and depression evolved as signals to modify behaviour. Anxiety is a signal of behavioural alarm and prepares the body for external danger. Depression is a signal of behavioural inhibition and is the consequence of behavioural patterns that fail to achieve a person's important goals (Hyland 1985). Depression helps disengage behaviour from unattainable or inappropriate goals (Carver & Scheier Reference Carver and Scheier1990). Anxiety and depression are therefore caused by outputs from a parallel processing system involving many different biochemicals, rather than being directly caused by a single biochemical.
Because it encodes meaning, the infornet can be described in terms of the meaning it contains – by analogy, a computer programme can be described in terms of what it does rather than a binary magnetic code. The meaning of the infornet is represented by infornet beliefs. Infornet beliefs create the instructions that alter the reference criteria of homeodynamic control loops and which provide the mental signals that alter behaviour.
The infornet beliefs that lead to anxiety can be characterised as “the external environment is dangerous.” The infornet beliefs that lead to depression can be characterised as “I am not achieving the goals I want to achieve” (Carver & Scheier Reference Carver and Scheier1990; Hyland Reference Hyland1987). Beliefs tend to be interconnected and mutually supporting. The infornet beliefs leading to depression and anxiety are interconnected via a network structure of linked beliefs. Both of these mood-altering infornet beliefs are part of a more general belief that “the external environment is unsatisfactory,” and this more general belief is part of a top-level belief that “the general situation is bad.” If the general situation is bad, then not only is there threat from the external environment but also threat to the internal environment (e.g., threat of infection or damage). Consequently, the top-level belief of “the general situation is bad” is also associated with beliefs that drive the inflammatory response system (Rosenkranz Reference Rosenkranz2007; Segerstrom & Miller Reference Segerstrom and Miller2004). Infornet dysregulation occurs when, through the application of network learning rules that normally create better self-regulation, the infornet develops maladaptive beliefs – for example, that the general situation is always very bad when it is not. Chronic depression and anxiety (i.e., mental states which cannot be attributed to the immediate situation) are signals of a dysregulated infornet; that is, an inappropriate response to the current situation. Correlations between depression and anxiety, on the one hand, and between depression, anxiety, and inflammatory mediators, on the other, arise because all these variables are outputs of an information system whose beliefs are interconnected and where maladaptive beliefs tend to spread.
Why do Cramer et al. observe a network structure in the relation to psychological symptomatology? My guess is that causality between symptoms plays a minor role. I suggest that the main the reason for the network structure of symptom comorbidity is because of an underlying biological network structure. That is, anxiety and depression are outputs from a dysregulated infornet that has multiple physiological and psychological outputs.
Infornet theory predicts that fuzzy boundaries between disease states will not be limited to psychological symptoms but will include somatic symptoms. Diseases without a specific pathology, such as chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS), have a variety of psychological and somatic symptoms: diagnosis is not based on a unique pattern of symptoms. Comorbid relationships between fatigue, the somatic symptoms associated with CFS and IBS, along with depression and anxiety, should all form part of a network structure. In particular, inflammatory somatic symptoms should be related to psychological symptomatology (Whalley Reference Whalley, Jacobs and Hyland2007). Dysregulated people have multiple and varied symptoms. Dysregulation varies continuously across the infornet's meaning space.
If diseases have a specific cause, then comorbidity is an inconvenience. Comorbidity is often a reason for exclusion in clinical trials. From the perspective of infornet theory, however, the study of comorbidity has the potential to provide unique insights into a hypothesised network system whose outputs are psychological symptoms along with physiological changes (typically, pro-inflammatory) that cause somatic symptoms.