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The Neuropsychiatry of Normal Pressure Hydrocephalus
Psychiatric and behavioral disturbance is a core, under-recognized dimension of idiopathic normal pressure hydrocephalus (iNPH), not an incidental comorbidity. A 2026 systematic review and meta-analysis of 22 studies found that 73.4% of iNPH patients have at least one neuropsychiatric symptom on the Neuropsychiatric Inventory, and roughly 46% carry at least one formal psychiatric diagnosis, yet the same task force concluded psychiatric morbidity in iNPH is likely underidentified and undertreated (Belessiotis-Richards et al., 2026).
This review covers the phenomenology and prevalence of psychiatric symptoms in NPH, the misdiagnosis problem in both directions, the diagnostic workup that separates NPH from primary psychiatric illness and dementia, and psychotropic management. The evidence base is dominated by observational studies and case reports; only one small pilot RCT has examined shunting's effect on psychiatric symptoms, so most conclusions are low-to-moderate certainty (Belessiotis-Richards et al., 2026).
Psychiatric and behavioral symptoms as manifestations of NPH
The psychiatric syndrome of iNPH is fundamentally a frontal-subcortical circuit disorder, driven by ventricular expansion compressing frontal cortical and subcortical structures, stretching white matter tracts (corona radiata, corpus callosum, anterior thalamic radiation), and reducing volume and perfusion of the caudate, putamen, and nucleus accumbens (Del Giovane et al., 2026; Pearce et al., 2024; Peterson et al., 2019). This explains why apathy and psychomotor slowing dominate the picture, and why some symptoms reverse quickly after CSF drainage: functional network abnormalities can partially normalize within 24 hours of a tap test (Griffa et al., 2020, 2021).
Pooled prevalence estimates from the 2026 meta-analysis, all with substantial heterogeneity, are summarized below.
| Symptom domain | Pooled prevalence (95% CI) | Notes |
|---|---|---|
| Apathy | 69.2% (63.1–74.6) | Most common feature; often mistaken for depression |
| Depression | 30.1% (20.1–42.3) | Severity markedly greater than controls (Hedge's g 1.31) |
| Agitation | 22.6% (11.8–39.1) | Few studies, wide confidence interval |
| Anxiety | 21.9% (13.2–34.2) | Frequently co-occurs with depression and apathy |
| Disinhibition | 21.0% (11.8–34.7) | NPI-based, small samples |
| Psychotic syndromes | 8.0% (3.3–18.3) | Hallucinations, delusions, schizophrenia; all low-quality studies |
| OCD symptoms | Not meta-analyzed | Prominent on SCL-90; case reports |
| Mania | Not meta-analyzed | Case reports of “secondary mania” only |
Source: Belessiotis-Richards et al., 2026; OCD and mania estimates from case reports (Kwentus & Hart, 1987; Leung et al., 2016; Markianos et al., 2009; Mishra et al., 2011; Reisch et al., 2005).
Apathy
Apathy is the signature psychiatric feature (~69%) and is clinically distinct from depression: it presents as reduced motivation, diminished goal-directed behavior, and emotional indifference without dysphoria, guilt, or rumination (Belessiotis-Richards et al., 2026; Steffens et al., 2022). It maps onto specific circuitry: right caudate hypoperfusion on SPECT, reduced postsynaptic D2-receptor binding in the nucleus accumbens on PET, and right precuneus compression on VBM. Improvement after shunting tracks with caudate reperfusion and Frontal Assessment Battery gains (Chadani et al., 2022; Kanemoto et al., 2019; Ouchi et al., 2007). Apathy also flags reversibility: apathetic patients show better gait improvement after tapping (Allali et al., 2018).
Depression
Depression (~30%, but up to 46\u201356% in some series) shows a frontal-subcortical phenotype: psychomotor retardation, lack of spontaneity, and cognitive slowing that overlaps heavily with iNPH's own cognitive profile and with late-life "vascular depression," since cardiovascular risk factors are overrepresented in iNPH (Andersson et al., 2024; Israelsson et al., 2016). In the INPH-CRasH study, suspected depression occurred in 46% of iNPH patients versus 13% of controls (adjusted OR 6.4, 95% CI 3.8\u201310.9) and was the strongest predictor of poor quality of life (Israelsson et al., 2016, 2020).
Psychosis, mania, and OCD
Psychosis (~8%) is real but atypical; the NEJM review notes that hallucinations and marked personality change are not typical of iNPH and should prompt consideration of comorbidity (Johnson & Williams, 2025). Notably, there is an epidemiologic and genetic link with schizophrenia: schizophrenia prevalence is elevated in iNPH (~3.1% vs 0.9%), and Mendelian randomization suggests shared genetic predisposition (OR 1.03, 95% CI 1.01\u20131.05) (Belessiotis-Richards et al., 2026; Vanhala et al., 2019). Mania and OCD in NPH rest on case reports only; a distinctive neurochemical finding is that CSF serotonin metabolite (5-HIAA) is normal while dopamine metabolite (HVA) is elevated, which the authors used to explain the observed lack of SSRI benefit for OCD symptoms in NPH (Markianos et al., 2009).
NPH misdiagnosed as psychiatric illness, and vice versa
The dominant misdiagnosis pathway is apathy and psychomotor slowing read as major depression, delaying recognition of a structural, potentially reversible condition (Marouf et al., 2021). People with iNPH have 2.48-fold higher odds of a recorded psychiatric diagnosis, and the adjusted odds of depression are strikingly elevated (mild OR 8.5; moderate OR 12.3; severe OR 27.8) (Belessiotis-Richards et al., 2026). The classic case literature illustrates both the trap and the payoff of correct diagnosis:
- Presenting as depression
- Rosen & Swigar and Price & Tucker described NPH presenting as agitated or retarded depression, with apathy, inattention, and poverty of thought mimicking depressive illness (Price & Tucker, 1977; Rosen & Swigar, 1976).
- Psychosis before neurology
- Pinner et al. reported a 68-year-old with paranoid psychosis and mild cognitive impairment before any neurological signs; gait disturbance and incontinence developed later, and psychosis fully remitted after lumboperitoneal shunt (Pinner et al., 1997).
- Decades of misdiagnosis
- Lying-Tunell described two patients with roughly 20-year psychiatric histories (one having received over 120 ECT treatments) whose psychotic symptoms ceased entirely after shunting (Lying-Tunell, 1979).
- The reverse error
- The 2021 NEJM case (a 70-year-old with pre-existing bipolar disorder) shows the opposite trap: attributing new gait, cognitive, and urinary decline to the known psychiatric illness. Most of his chronic mood symptoms were bipolar, while the new triad was NPH (Marouf et al., 2021).
Red flags for NPH masquerading as psychiatric disease
- New-onset apathy, affective, or psychotic symptoms in an older adult without a prior psychiatric history
- Gait disturbance, the usual earliest and most prevalent sign (>90%)
- Urinary urgency
- Insidious progression over months
- Cognition that does not respond to psychotropic adjustment
- MRI showing ventriculomegaly out of proportion to atrophy
(Marouf et al., 2021; Maroufi et al., 2026; Price & Tucker, 1977; Rosen & Swigar, 1976)
Differentiating NPH from primary psychiatric illness and dementia
Distinguishing apathy from depression is the central bedside task: apathy features emotional indifference, passivity, and absence of rumination, whereas depression features dysphoria, hopelessness, guilt, and often anxiety, though the two co-occur in 14\u201338% of neurocognitive disorders (Lanct\u00F4t et al., 2023; Steffens et al., 2022). Against neurodegenerative dementia, iNPH is a subcortical dementia (slowed processing, executive dysfunction, memory that benefits from cueing, preserved naming and remote memory), contrasting with Alzheimer's cortical pattern of prominent amnesia, aphasia, and agnosia (Johnson & Williams, 2025; Skalick\u00FD et al., 2020). The complication is that iNPH and Alzheimer's disease co-exist in 20\u201357% of cases, and comorbid AD reduces shunt response and blunts neuropsychiatric improvement (Belessiotis-Richards et al., 2026; Soderlund et al., 2025).
| Feature | NPH | Primary depression | Alzheimer's disease |
|---|---|---|---|
| Gait | Wide-based, shuffling, “magnetic”; >90% | Usually normal (retardation possible) | Late finding |
| Cognitive pattern | Frontal-subcortical; memory aided by cues | Effort-dependent, inconsistent | Cortical amnesia, aphasia, agnosia |
| Predominant affect | Apathy, emotional indifference | Dysphoria, guilt, anxiety | Apathy, anxiety |
| Urinary symptoms | Urgency / detrusor overactivity (75–90%) | Not typical | Late |
| Imaging | Ventriculomegaly (Evans ≥0.3), DESH, acute callosal angle | Normal / age-appropriate | Cortical + hippocampal atrophy |
| Response to CSF drainage | Gait improves within hours | None | None |
| Hallucinations / delusions | Not typical (~8%) | Possible if severe | More common |
(Johnson & Williams, 2025; Marouf et al., 2021; Maroufi et al., 2026; Skalick\u00FD et al., 2020; Soderlund et al., 2025)
Diagnostic workup
Imaging (MRI first-line per ACR 2024): the Evans index (\u22650.3) is a required marker of ventriculomegaly but is nonspecific (AUC 0.87), whereas an acute callosal angle (\u226490\u00B0) is far more discriminating (AUC up to 0.97); the NEJM case had a callosal angle of 66\u00B0 (Marouf et al., 2021; Soderlund et al., 2025; Zi\u00F3\u0142kowski et al., 2023). DESH (disproportionately enlarged subarachnoid space hydrocephalus) has a positive predictive value ~77% for shunt response but poor negative predictive value (~25%), and is present in ~60% of patients (Al-Tarawni et al., 2024; Johnson & Williams, 2025). A newer CT-based splenial angle showed near-perfect separation of NPH from Alzheimer's and Parkinson's diseases and controls (AUC 0.999) in a single study and awaits replication (Kaya et al., 2026).
CSF drainage tests: the high-volume tap test (30\u201350 mL) has high positive predictive value (~90%) but poor sensitivity (~58%) and negative predictive value (~20%); a negative tap does not exclude iNPH (Johnson & Williams, 2025; Mihalj et al., 2016; Zi\u00F3\u0142kowski et al., 2023). Extended lumbar drainage (24\u201372 h) reaches ~90% sensitivity and specificity and is the next step when suspicion is high but the tap is negative; the main risk is meningitis (1\u20132%) (Johnson & Williams, 2025; Maroufi et al., 2026). The NEJM diagnostic-and-treatment algorithm captures this stepwise logic, with feedback loops to reconsider alternative (including psychiatric) diagnoses when expected improvement fails to appear.
Effect of CSF shunting on psychiatric symptoms
Shunting is the definitive treatment and improves gait in 75\u201380% of patients (gait velocity up ~30%, for example 0.67 to 0.96 m/sec), with less consistent cognitive benefit (2024 Cochrane review: "unclear," SMD 0.35, 95% CI \u22120.04 to 0.74) (Maroufi et al., 2026; Pearce et al., 2024; Williams et al., 2022). Psychiatric outcomes are favorable but less robustly proven:
- Depression
- The pooled effect of shunting on depression scores was small and non-significant (−0.30, 95% CI −0.62 to 0.01), though individual studies show large drops (for example, prevalence 36% to 5% at 3 months). Importantly, depression remained overrepresented (46% vs 13%) at 1–3 years post-shunt in INPH-CRasH, so it does not uniformly resolve (Andersson et al., 2024; Belessiotis-Richards et al., 2026; Israelsson et al., 2016).
- Apathy
- Improves after shunting (for example, 86% to 73%; significant Apathy Evaluation Scale gains at 1 month in a 2026 multicenter series), correlating with cognitive improvement (Belessiotis-Richards et al., 2026; Peterson et al., 2016; Scalia et al., 2026).
- Psychosis
- Case reports document full remission after shunting, including decades-long psychotic illness (Lying-Tunell, 1979; Pinner et al., 1997).
The corollary is clinical: psychiatric symptoms secondary to NPH may respond to CSF diversion rather than psychotropics, so recognizing and treating the hydrocephalus comes first.
Psychotropic management in NPH
No controlled trials of any psychotropic exist specifically in iNPH, and antidepressant efficacy in this population has explicitly not been established, so management is extrapolated from geriatric and dementia evidence with NPH-specific cautions (Andersson et al., 2024; Virhammar et al., 2026).
- Antipsychotics
- Use with particular caution. Drug-induced parkinsonism worsens the already-impaired gait and raises fall and institutionalization risk; first-generation agents and risperidone carry the highest extrapyramidal risk, while quetiapine, aripiprazole, and olanzapine are lower-risk options. Antipsychotic sensitivity (intolerance to low doses) has been reported in NPH. Anticholinergic agents for extrapyramidal symptoms (for example, benztropine) should be avoided given cognitive risk. Comorbid schizophrenia does not preclude shunting: 75% of such patients still had a verified shunt response (Divac et al., 2014; Factor et al., 2019; Mishra et al., 2011; Rogowska et al., 2023; Vanhala et al., 2019).
- Antidepressants
- Avoid anticholinergic agents (tricyclics); anticholinergic antidepressants are associated with increased dementia risk (adjusted odds ratio up to 1.29) and with falls and cognitive decline in older adults. In dementia broadly, antidepressant efficacy for depression is weak, and they are ineffective (possibly harmful) for apathy. The normal CSF serotonin turnover in NPH offers a mechanistic rationale for observed SSRI ineffectiveness against OCD symptoms (Belessiotis-Richards et al., 2025; Büyükgök et al., 2026; Coupland et al., 2019; Markianos et al., 2009; Reuben et al., 2024).
- Apathy
- Methylphenidate has the best (albeit indirect) evidence: a double-blind single-patient study in a shunted NPH patient showed dose-dependent improvement, and multiple Alzheimer's disease RCTs support modest benefit (start 5 mg AM/noon, titrate to 10 mg BID, monitor BP/HR) (Azhar et al., 2022; Cummings et al., 2024; Keenan et al., 2005).
- ECT
- Appears safe and effective in NPH, including with VP shunts: a systematic review found no shunt malfunctions across 12 studies, and case reports describe marked, sustained response in both shunted and non-shunted NPH. Two caveats: ECT can transiently raise intracranial pressure (evidence is mixed), and programmable shunt valves can change setting after ECT (or MRI) and should be verified and reprogrammed; decisions should be multidisciplinary (psychiatry, anesthesia, neurosurgery) (Aksoy et al., 2025; Benn et al., 2026; Hanretta & Malek-Ahmadi, 2001; Johnson & Williams, 2025; Parker et al., 2026).
- Anticholinergic burden generally
- NPH patients are especially vulnerable given baseline cognitive and gait impairment. Bladder antimuscarinics (for example, oxybutynin) commonly prescribed for the urinary symptoms in 75–90% of patients add anticholinergic dementia risk (adjusted odds ratio ~1.65 at high exposure), so prefer lower-risk agents or non-pharmacologic strategies (Coupland et al., 2019; Hook et al., 2022; Maroufi et al., 2026).
Evidence gaps and emerging data
The field's central weakness is the absence of controlled psychotropic trials in NPH and reliance on low-quality, heterogeneous observational data for shunting's psychiatric benefit (Belessiotis-Richards et al., 2026). Psychosis remission after shunting and methylphenidate for apathy rest on case-level evidence needing replication (Keenan et al., 2005; Pinner et al., 1997). Screening for depression should be built into the iNPH workup, and the effect of antidepressant treatment in this population is a stated research priority (Israelsson et al., 2016, 2020). Emerging genetic (shared schizophrenia/iNPH liability), CSF proteomic, and dopaminergic-imaging work may eventually clarify whether psychiatric symptoms are caused by, comorbid with, or mechanistically shared with the hydrocephalus (Belessiotis-Richards et al., 2026; de Geus et al., 2025; Lee et al., 2020).
Summary
Psychiatric symptoms, led by apathy (~69%) and depression (~30%), with less common psychosis (~8%) and rare mania/OCD, are intrinsic to iNPH and reflect frontal-subcortical circuit disruption (Belessiotis-Richards et al., 2026; Peterson et al., 2019). Because NPH readily mimics depression and dementia and can be misread as primary psychiatric illness (and vice versa), an older adult with new apathy, affective, or psychotic symptoms plus gait disturbance, urinary urgency, and disproportionate ventriculomegaly warrants an NPH workup (MRI with callosal angle and DESH assessment, then tap test or extended lumbar drainage) (Johnson & Williams, 2025; Maroufi et al., 2026; Zi\u00F3\u0142kowski et al., 2023). Shunting is first-line and can improve, and sometimes remit, psychiatric symptoms, though depression may persist (Belessiotis-Richards et al., 2026; Israelsson et al., 2016). Psychotropics have no NPH-specific trial base; when used, minimize anticholinergic and extrapyramidal risk, consider methylphenidate for apathy, and regard ECT as safe with attention to programmable-valve settings (Keenan et al., 2005; Mishra et al., 2011; Parker et al., 2026).
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