Auditory Hallucinations

Etiology

Because auditory hallucinations manifest in a variety of disorders, the etiology is thought to be heterogeneous. Hallucinations most often precipitate in the setting of psychosis. Imaging studies--PET and fMRI--of patients with schizophrenia demonstrate increased activity in the striatal and thalamic subcortical nuclei, paralimbic regions, and hypothalamus. Further analysis reveals deficits in left temporal lobe functioning.[2][3] Further consideration has been placed on aberrant glutamatergic transmission, which coincides with the hypo-functioning glutamate receptor hypothesis of psychosis. 

Epidemiology

The prevalence of auditory hallucinations in the general population ranges from 5 to 28%.[4] Auditory hallucinations are most prevalent in patients who have psychosis.[5] They are observed in 75% of individuals with schizophrenia, 20-50% of individuals with manic depression, 10% of individuals with major depression, and 40% of individuals with PTSD.[6]

In children and adolescents, the prevalence is 9% and 5 to 16%, respectively.[7][8] It most often manifests in children in the setting of conduct disorder, migraine, and anxiety.[9][10][11] The remission rate of auditory hallucinations in adolescence ranges from 3 to 40% each year.[12]

Pathophysiology

The precise mechanism by which paracusias occur remains elusive. However, several postulations have been suggested.[13] 

fMRI findings have demonstrated spontaneous activation of the auditory network, consisting of the left superior temporal gyrus, transverse temporal gyri (Heschl's gyri), and the left temporal lobe.[14][15]

A neurocognitive model called the VOICE model has been offered, which attributes the paracusias to an unbalanced bottom-up limbic hyperexcitation mismatched against a hypoactive prefrontal inhibitory system.[16] This mismatch results in the spontaneous firing of sensory neurons in the absence of appropriate inhibitory mechanisms.

Some data suggest that the thalamus-amygdala pathways are activated, thereby processing an emotional response to the auditory hallucinations, further proved by another study detecting choline and N-acetyl aspirate ratio abnormalities in the thalamus.[13][17]

At a neurochemical level, of particular importance are dopamine (D2) and serotonin (5HT2a) receptors. Neuroimaging studies have demonstrated increased D2 receptor occupancy in the striatal system and 5HT2a receptor occupancy in the caudate nucleus.[18] 

History and Physical

Paracusias may be perceived as coming through the ears, on the surface of the body, in their mind, or anywhere in external space. They can occur as frequently as daily or as an isolated episode. The quality of the hallucination is also variable. They can be loud or soft. As mentioned previously, paracusias can be incoherent sounds or distinct voices. Depending on the level of insight maintained by the patient, the paracausias can be greatly impairing. Auditory hallucinations most often manifest in the setting of formal thought disorders; however, they can present in protean settings, as well.[19]

When associated with schizophrenia, paracusias vary according to the stage of the illness. In the late prodromal stages, inner speech becomes more objectified and externally perceived.[20]

Evaluation

The evaluation of paracusias consists of a general psychiatric interview that includes details regarding the evolution of the hallucinations, triggering factors, psychiatric review of systems, past psychiatric diagnosis, history of substance use, family history of psychiatric illness, and history of trauma. 

Additionally, a detailed medical history and medication regimen--including over-the-counter supplements--should be obtained.

The clinician's most valuable assessment tool is the mental status examination, addressing mood, affect, appearance, behavior, speech, thought content, thought process, insight, and judgment. Furthermore, determination of the presence of 'first-rank' or 'Schneiderian' hallucinations--voices speaking to each other or narrating one's thoughts aloud--should be completed. The clinician should determine if the hallucinations are temporally associated with affective disturbances and, if so, if they are congruent with mood. To further assess the patient's safety and the safety of others, the patient should be asked to elaborate on whether the hallucinations command him or her to perform certain acts.

Lastly, organic medical etiologies should be ruled out using analysis and neurologic imaging. Laboratory analysis includes: 

1. Urine toxicology
2. Complete blood count with differential
3. Vitamin B12 and D levels
4. Renal function test
5. Serum electrolytes
6. Hepatic function test
7. Blood alcohol
8. Computed tomography (CT) or magnetic resonance imaging (MRI) should be considered if organic brain abnormalities are considered in the differential diagnoses.
9. EEG for a seizure disorder 

Treatment / Management

First, any underlying organic disease should be addressed and treated accordingly. If the organicity acted in the capacity of the inciting precipitant then the paracusias should ostensibly resolve as the disease dissipates.

However, if the hallucinations precipitated as a result of a primary psychiatric disorder then neuroleptics become the mainstay of treatment. Neuroleptics, colloquially referred to as antipsychotics, are a class of psychotropics that block dopamine receptors. The putative mechanism by which neuroleptics mitigate auditory hallucinations is by blocking dopamine D2 receptors in the mesolimbic tract. The initial subclass of neuroleptic's, the first generation antipsychotics (FGA), primary mechanism of action is the antagonism of the D2 receptor, whereas, the subsequent second-generation antipsychotics (SGA) act more indiscriminately on an expanded array of receptors.[21] Generally, debates between administering first or second-generation antipsychotics are resolved by considering the side effect profiles of the specific medications under consideration.[21]]

Independent of the subclass chosen, the perceptual anomalies should abate within a week of initiation of the psychotropic. Sometimes these auditory aberrations can persist and require the administration of an additional neuroleptic in conjunction with the first. In the event that the hallucinations still continue to demonstrate resistance--following the administration of 2 antipsychotics--the clinician is encouraged to switch to clozapine, an SGA. Clozapine has shown to be the most efficacious antipsychotic for the treatment of positive symptoms of schizophrenia--delusions, hallucinations, disorganized behavior, and speech--however, it is also associated with the greatest danger as it can induce blood dyscrasias, specifically agranulocytosis. This neuroleptic requires astute clinical monitoring, with weekly then biweekly blood draws.[21] 

If the hallucinations manifest in the setting of affective disorders, such as depression or mania, then corresponding psychotropics should be given, adjunctively (e.g., antidepressants and mood stabilizers, respectively).

Psychotherapy can also be applied in conjunction with pharmacotherapy. The most robustly researched psychotherapeutic modality has been cognitive behavioral therapy (CBT). CBT instructs the patient to modify how he or she experiences the paracusias, ultimately offering an improved sense of control over the hallucination. CBT uses Socratic interviewing rather than confrontation, implements reality testing, and can be provided in an individual or group format.[22](B3)

Other treatment approaches include ACT (acceptance and commitment therapy), HIT (hallucination-focused integrative treatment), ATT (metacognitive therapy attention training technique), relating therapy, distraction techniques, and HVN (hearing voices network) self-help group, all strategies to cope better with the voices.

Emerging Treatments

Several studies have shown efficacy in reducing auditory hallucinations using transcranial magnetic stimulation but the evidence is still lacking.[23](A1)

Differential Diagnosis

To differentiate the causes of auditory hallucinations, it is pertinent to focus on the following:

1. A detailed medical history along with laboratory analyses and neuroimaging to rule out organic etiologies.
2. Details regarding substance use (illicit and over the counter), medication profiles, and supplement use to rule out toxic-metabolic causes.[24][25]
3. Detailed psychiatric family history as many psychiatric illnesses show high heritability.

Manifestations of auditory hallucinations can occur in a multiplicity of psychiatric conditions, including schizophrenia, bipolar disorder, depression, trauma-related disorders, dissociative disorders, personality disorders, and parasomnias.[26] 

Furthermore, neurological conditions such as tinnitus, cerebral tumors, traumatic brain injury, epilepsy (particularly temporal lobe epilepsy), viral encephalitis, delirium, and cardiovascular events that involve the brainstem regions or areas of temporal, temporoparietal, or occipital pathways can present with auditory hallucinations.[27][28][27]

Other organic etiologies include neurodegenerative conditions, conditions that incur damage to the peripheral sensory pathways (e.g., acquired deafness, thyroid dysfunction, nutritional deficiencies), chromosomal abnormalities, autoimmune disorders, and acquired immunodeficiencies.[2][29][30][29][31][2][32] 

Research suggests that auditory hallucinations can also precipitate, transiently, in response to conditions of extreme physiological and psychological stress such as dissociative identity disorder, fatigue, and bereavement.[33] 

Prognosis

In the event that the etiology is that of an organic nature, the prognosis is contingent upon the underlying disease process. Therefore, the hallucinations should, in theory, resolve as the precipitant resolves. However, when the perceptual anomaly occurs in the setting of a primary psychiatric disorder, the remittance of the paracusias is more independent. Evidence demonstrates that the positive symptoms of schizophrenia respond well to the administration of neuroleptics; however, the actual psychotic disorder does not. Thus, the resolution of the hallucinations does not necessarily indicate the resolution of the underlying thought disorder.[34]

Generally, factors that increase the risk of poor treatment response include early age of onset, male gender, and multiple inpatient hospitalizations.

Complications

Complications occur when the hallucinations command the patient to hurt himself or others. The paracusias can also be so self-deprecating that they cause the patient to attempt suicide. More common complications result from the side effects of antipsychotics. These can include both short-term and long-term side effects, including extrapyramidal symptoms--dystonia, tardive dyskinesia, parkinsonism--and metabolic syndrome.

Individuals may lack insight and judgment, leading to self-neglect, and may have to be hospitalized involuntarily. Care needs to be taken to build trust and respect with the patients for maintaining regular follow-up even after discharge from hospitals, given a notable high chance of relapse due to non-compliance with medications and appointments.