Divergent Genomic Expression: Psychosis, and the Inversion of Capacity

Modern psychiatry is efficient at naming distress, but less so at explaining the architecture beneath it. A person hears voices, sees things others do not see, becomes overwhelmed by meaning, or begins to make connections in ways that are frightening, destabilising, or socially incomprehensible. The clinical system calls this psychosis. If the pattern persists or recurs within a particular diagnostic framework, it may be termed schizophrenia or Bipolar. This label does not explain the inherent biology, nor the neurological architecture; it describes the visible endpoint.

Autism, ADHD, bipolar, schizophrenia-spectrum traits and other forms of divergence may be better understood as overlapping but distinct expressions of inherited neurodevelopmental architecture. These architectures are not identical, but they are not detached categories either. They share genes, pathways, traits, vulnerabilities and family patterns. The boundaries we draw around them are often clinical, not biological. These architectures are influenced by different genomic expression and environmental exposures. The difference between them lies in which networks are involved, how those networks are regulated, and what happens when those systems are harmed, overloaded or destabilised.

A person is not diagnosed because they are subtly different, unusually perceptive, intensely associative, sensory-sensitive, highly energetic, verbally unique, creatively driven or cognitively non-standard. They are diagnosed when that difference causes distress, impairment, social conflict, educational failure, family crisis, occupational breakdown, psychosis, shutdown, self-injury, mood collapse or loss of function.

From that perspective, diagnostic categories typically describe the harmed-state of divergence rather than the original architecture itself.

Inherent neurodivergence is not caused by harm, and that is an important distinction to make. However, these complex divergent architectures can be harmed, profoundly so. They can be cumulatively burdened by immune activation, trauma, infection, sleep deprivation, toxins, nutritional disruption, chronic stress, social threat, inflammation, endocrine disturbance, metabolic overload or developmental exposures.

Once that happens, the underlying architecture may begin to express to what psychiatry defines as -'disorder.'

Difference is not the same as damage, but difference may carry specific vulnerability profiles. A highly sensitive system may detect more, process more, connect more, feel more, predict more or associate more. Under supportive conditions, this may appear as insight, creativity, deep perception, unique pattern recognition or intense cognitive capacity. Under hostile or biologically destabilising conditions, the same system may collapse into overwhelm, fragmentation, exhaustion, delusion, mania, shutdown or psychosis.

In 2016, major genetic work by Sekar et al. linked variation in complement component 4, particularly C4A expression, with schizophrenia. Higher C4A expression was associated with increased schizophrenia incidence, and C4 was shown to have a role in synapse elimination in developmental models. This provided a credible mechanism: immune-related genetic variation could influence how the brain’s connections are sculpted.

A study by Kalinowski et al. (2026) adds another layer of complexity. It reports that neutrophils - common white blood cells usually discussed in the context of infection and innate immunity - can produce C4A. C4A is part of the complement system, an immune pathway involved in tagging material for removal. In the brain, complement signalling has also been implicated in synaptic pruning: the process by which synapses are refined, reduced or remodelled during development. In schizophrenic populations, neutrophil C4 biology appears altered: C4 protein levels in neutrophils correlate with C4A gene copy number, and activation markers suggest that the system may be more active or more heavily consumed. This does not mean that neutrophil-derived C4A enters the brain and directly causes psychosis, but it does support a much broader point: schizophrenia biology is not confined to the brain. It involves body-wide immune architecture, genomic susceptibility, complement activation, inflammatory context and synaptic regulation.

This gives a concrete mechanism for a wider hypothesis: psychosis emerges as the result of genomic expression when a particular neurodevelopmental architecture is hit by environmental and biological stressors that destabilise immune-pruning, dopamine-salience, glutamate, sensory-integration and stress-response pathways.

The person’s system may be biologically overactivated, miscalibrated or pushed beyond its genomic capacity to regulate perception and meaning.

Psychosis is often misunderstood by society as pure irrationality, danger or madness. Psychosis is not meaningless; it involves identifiable brain functions: auditory processing, visual processing, sensory gating, salience assignment, memory, prediction, language, threat detection, symbolic association and belief formation.

Auditory hallucinations involve altered perception within auditory and language-related networks. Visual hallucinations involve visual processing, imagery and top-down prediction. Delusions involve salience: the brain’s system for decoding reality - what is connected, threatening, or meaningful and what demands attention.

This is why schizophrenic-spectrum divergence should not be understood only through deficit. A system capable of generating distinct perceptual experience may also be a system with heightened or adapted perceptual sensitivity. A system that finds abstract meaning in psychosis may, when regulated, be capable of powerful symbolic association, pattern recognition, intuition, metaphor, or creative synthesis.

The problem therein is not perception itself, but calibration.

A calibrated salience system can detect subtle patterns without clinical psychosis. An uncalibrated salience system may assign overwhelming meaning to coincidence, gesture, sound, image, number, memory or threat. A calibrated associative mind may produce art, philosophy, scientific insight or spiritual depth. An uncalibrated or harmed associative system may produce terror, paranoia or delusional certainty.

That is the inversion of exceptional capacity.

Bipolar 'disorder' already exposes the weakness in the idea that psychiatric labels represent simple deficit. Some research has found associations between bipolar liability and traits such as creativity, verbal ability and, in other studies, higher childhood IQ. The relationship is not simple, and illness can be devastating. However, the existence of this association matters because it shows that a psychiatric label can sit very close to cognitive ability, creative production and unique insight.

This is not romanticisation; mania can destroy lives, depression can be disabling, psychosis can be terrifying. It is important to acknowledge every potential aspect and it is wrong to erase the capacity that may exist beneath the environmentally/additionally overwhelmed state.

Bipolarity may be one of the easier examples for the public to grasp because its gifted side is already culturally visible: energy, verbal speed, creative intensity, ambition, associative thinking and emotional force. Schizophrenia-spectrum divergence is harder for the public to understand because psychosis is more frightening, more stigmatised and less socially legible. Yet the principle may be similar: the visible crisis may be the destabilised expression of an underlying architecture that, under different conditions, could support extrasensory perception, symbolic depth, pattern recognition or meaning-making.

There is now substantial evidence that psychiatric and neurodevelopmental diagnoses share genomic architecture. Genetic studies repeatedly show overlap across diagnostic boundaries, especially between schizophrenia and bipolar, and also across broader neurodevelopmental and psychiatric diagnoses such as autism and ADHD.

This supports what many families and lived-experience communities have recognised for decades: these labels often cluster, overlap and blur. A family may contain autism, ADHD, bipolar, schizophrenia, dyslexia, epilepsy, sensory sensitivity, connective-tissue differences, immune problems, anxiety, addiction, intelligence and creative intensity. The clinical system often separates these into different departments, but the biology is far more interconnected.

The question is why one person’s divergence expresses as autism, another’s as ADHD, another’s as bipolar, and another’s as schizophrenia-spectrum psychosis. The answer is likely to involve different genomic weightings across shared biological systems: synaptic pruning, dopamine, glutamate, GABA, calcium signalling, immune activation, mitochondrial function, circadian rhythm, sensory gating, connective tissue, neurobiology and developmental timing.

The gene-environment model of psychosis is not new. For decades, researchers have examined how genetic vulnerability interacts with environmental exposure: infection, stress, migration, social adversity, inflammation, obstetric complications, sleep disruption and many other factors. The mistake has been treating this as a narrow psychiatric risk model rather than a broader biological architecture model.

Aphantasia and hyperphantasia have opened an important scientific window into the diversity of human inner experience. Aphantasia refers to the absence or marked reduction of voluntary visual imagery: the inability to see an image in the mind’s eye despite understanding what the object, person, or scene is. Hyperphantasia describes the opposite end of the spectrum, where mental imagery is unusually vivid, detailed, and sometimes close to perceptual experience. Studies using neuropsychological testing, brain imaging, binocular rivalry, and pupillary light response have shown that imagery vividness has measurable behavioural and physiological correlates.

Hallucination also exists at the boundary between internally generated content and externally attributed perception. Visual imagery and visual perception appear to share overlapping neural mechanisms. When a person imagines a bright object, the pupil can respond as though brightness has been internally simulated, and people with aphantasia do not show the same imagery-linked pupillary response despite having intact perceptual pupil responses. This suggests that vivid imagination is a biologically active form of internal simulation.

The auditory equivalent is equally important. The term anauralia has been proposed for absent or markedly reduced auditory imagery: the lack of a “mind’s ear”. At the other end of the auditory spectrum is hyperauralia, unusually vivid auditory imagery. This may include vivid inner music, remembered voices, tonal patterns, soundscapes, verbal rhythm, or internally generated auditory scenes. Hinwar and Lambert found strong associations between visual and auditory imagery vividness: many people with aphantasia also reported weak auditory imagery, while hyperphantasia often co-occurred with hyperauralia. However, dissociations were also observed, meaning that some individuals may have reduced imagery in one modality while retaining stronger imagery in another.

This is where the framework becomes more interesting; people have different internal sensory divergent genomics, therefore the form of hallucination(s) may not be random. A visually dominant internal-representation system may, under certain biological conditions, be more likely to produce visual hallucination-like experiences. An auditory-verbal dominant system may be more likely to express crisis through voices, inner speech, verbal intrusion, or sound-based phenomena. A person with reduced visual imagery but preserved auditory-verbal imagery may not experience psychosis visually at all; their crisis may route through language, meaning, voice, narrative, or salience. Conversely, a person with vivid multisensory imagery may experience more immersive, embodied, or complex perceptual phenomena.

This does not mean that hyperphantasia is pathological, nor does it mean that aphantasia protects against psychosis. The point is subtler: the form of psychosis may partly reflect the person’s underlying internal-representation architecture. The same biological stressor produces different clinical presentations depending on the person’s sensory imagery profile, language network dominance, source-monitoring capacity, immune state, neurotransmitter balance, developmental wiring, and genomic background.

Psychosis has long been associated with altered salience. Kapur’s (2003) aberrant salience model proposed that dysregulated dopamine signalling can cause ordinary internal or external stimuli to become excessively meaningful, urgent, threatening, symbolic, or personally significant. Predictive-processing models add another layer: perception is not passive reception, but active inference. The brain constantly predicts what is happening and compares those predictions with sensory input. When predictive weighting becomes unstable, internally generated material may be given too much authority, while external sensory correction may be weakened.

This maps directly onto hallucination. A hallucination may occur when internally generated sensory or verbal material is not correctly marked as self-generated. In auditory verbal hallucinations, one major model proposes that inner speech or verbal thought may be misattributed as an external voice due to disruptions in self-monitoring, corollary discharge, or source attribution. In visual hallucinations, similar mechanisms may involve confusion between visual imagery and external visual perception. The relevant failure is not imagination itself, but boundary regulation: the capacity to distinguish internal simulation from external signal.

This provides a more precise way to link hyperphantasia and psychosis. Hyperphantasia may provide vivid internal visual material, and hyperauralia may provide vivid internal auditory material. Biological burden may alter salience, and source-monitoring disruption may impair the ability to identify the material as internally generated. Predictive-processing instability may assign excessive reality value to the internally generated content. The result may be hallucination, delusion, or altered perceptual meaning. In this model, psychosis is a state in which internally generated content becomes amplified, poorly gated, and misassigned.

Schizophrenia and bipolar are highly polygenic, involving many divergent genomics across synaptic, immune, calcium-channel, neurodevelopmental, and neurotransmitter-related pathways. The complement component 4 gene, particularly C4A expression, has been linked to schizophrenia risk through mechanisms involving synaptic pruning and immune-mediated synapse elimination. Voltage gated calcium-channel (VGCC) genes such as CACNA1C have also been implicated across psychiatric phenotypes including bipolar disorder, schizophrenia, depression, and autism-related traits, suggesting shared mechanisms involving neuronal excitability and synaptic signalling.

The imagery literature is less genomically developed, but it is beginning to point in relevant directions. A genome-wide association study of visual imagery vividness did not identify a genome-wide significant variant, but reported subthreshold findings near SYT1, a gene involved in calcium-dependent synaptic vesicle release. This should not be overstated. There is no confirmed aphantasia gene or hyperphantasia gene. However, the candidate biology is conceptually interesting because imagery strength, hallucination vulnerability, and psychosis risk all converge on systems involving synaptic transmission, cortical excitability, network connectivity, calcium signalling, and sensory gating.

This is where divergent genomics becomes a useful explanatory lens. A psychiatric diagnosis describes an outcome; it does not describe the pathway that produced it. Two people may both receive a diagnosis of schizophrenia while having very different genomic architecture, immune status, sensory representation profiles, trauma histories, inflammatory burden, metabolic vulnerabilities, and neurodevelopmental trajectories. One person may be visually hyperphantasic, another anauralic, another hyperauralic, another multisensory, another primarily conceptual or somatic. The diagnostic label may be the same, but the biological route into crisis may be entirely different.

Environmental and biological triggers may then act as threshold shifters. Infection, autoimmune activity, chronic inflammation, sleep deprivation, trauma, endocrine disruption, metabolic stress, substance exposure, nutritional depletion, mitochondrial strain, or prolonged psychosocial threat may all alter the stability of perception and salience systems. In first-episode psychosis, inflammatory biomarkers and cytokine alterations have been repeatedly investigated, with evidence of elevated inflammatory signals in antipsychotic-naive populations. The kynurenine pathway, which links immune activation, tryptophan metabolism, glutamate signalling, and NMDA receptor function, is also increasingly relevant to psychosis biology, though findings remain complex and not fully settled.

Autoimmune psychosis further demonstrates that some psychotic presentations may arise from immune-mediated brain dysfunction rather than primary psychiatric disease. International consensus guidance now recognises possible, probable, and definite autoimmune psychosis, including cases where neuronal autoantibodies, inflammatory markers, neurological signs, or treatment response suggest immune involvement. This does not mean that all psychosis is autoimmune; it means that psychosis can be a final common pathway for multiple biological disturbances.

These fields suggest a new model: psychosis may represent an inversion of capacity when a high-complexity internal representation system is pushed beyond regulatory threshold. Hyperphantasia and hyperauralia may represent forms of vivid internal simulation. Aphantasia and anauralia show that cognition can also function through non-visual or non-auditory routes. Schizophrenia and bipolar psychosis may emerge when salience, source monitoring, predictive processing, immune signalling, neurotransmission, and genomic vulnerability interact in a destabilising way.

The implication is that hallucinations should not be treated as a single phenomenon. A visual hallucination, an auditory voice, a somatic presence, a symbolic delusion, and a meaning-saturated coincidence may involve overlapping mechanisms but different representational routes. The person’s internal blueprint may determine the doorway through which crisis appears. A hyperphantasic person may experience destabilisation through imagery. A hyperauralic person may experience it through sound or voice. A person with reduced sensory imagery may experience psychosis more conceptually, somatically, linguistically, or through altered salience rather than vivid sensory scenes.

A more accurate model would be:

VGCC variants / VGCC sensitivity

→ altered calcium influx

→ altered neurotransmitter release and cortical excitability

→ altered glutamate/GABA/dopamine balance

→ altered salience assignment and sensory gating

→ imagery, inner speech, hyperphantasia/hyperauralia, hallucination modality

→ psychosis under biological burden

or

Inherited divergent architecture + pathway-specific susceptibility + environmental or biological stressor = diagnostic presentation.

This allows us to understand why not everyone exposed to the same stressor develops psychosis, and why not everyone with schizophrenia-associated genomics develops schizophrenia-psychosis. It also helps explain why many people can carry intense, unusual or divergent traits for years without crisis, until a particular combination of stressors pushes the system beyond regulation.

The future of mental health must progress beyond diagnostic labels and towards personalised mechanisms. Diagnoses do not currently tell us what kind of architecture that person carries, what capacities may exist beneath the distress, or what kind of environment would allow that architecture to remain regulated. Schizophrenia may be one of the most misunderstood forms of divergent neurobiology: a perceptual and meaning-making architecture that becomes incoherent when stripped of calibration, safety and biological stability.

The key is to understand that capacity in these populations is not deficient - evidently, it is exceptional - but that same exceptionality carries a vulnerability that may invert into crisis when biological burden exceeds threshold, and genomic expression shifts.

Artist: Pietro Berrettini da Cortana, Tabulae anatomicae, 1741

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