Schizo-obsessive disorder and neurosurgery for schizophrenia

Abstract

Schizophrenia likely represents a cluster of diseases presenting with delusions, hallucinations, disorganised behaviour and disorganised thought. Currently, medical therapy struggles to treat a substantial portion of patients, but with improved stratification of component diseases, it may be possible to better understand and treat schizophrenia. The overlap between schizophrenia, schizo-obsessive disorder and obsessive-compulsive disorder is discussed within the context of a clinical case and neuroimaging data. Furthermore, the use of obsessive-compulsive disorder deep brain stimulation protocols for schizo-obsessive disorder is discussed and may yield an advance in neurosurgical treatment of psychiatric conditions.

Background

Schizophrenia is a chronic and progressive disease. As the disease progresses, many patients become refractory to antipsychotic medication or are unable to tolerate and comply with the requisite doses of antipsychotics.¹ Neurosurgery holds the potential of last-line therapy for schizophrenia but is wrought with historical failures and moral shortcomings; Walter Freeman’s lobotomies stand as a stark example. However, in the era of deep-brain stimulation, it is becoming possible to overcome the failures of the past.

Difficulty still remains in surgical treatment of schizophrenia. Despite modern understanding of neural networks, localisation to specific therapeutic regions remains difficult. Research has identified the hippocampus, cingulate cortex, prefrontal cortex, striatum and globus pallidus in the pathogenesis of schizophrenia.² Mikell and colleagues have presented the associative striatum, ventral striatum and anterior hippocampus as possible therapeutic targets in schizophrenia.³ However, the possible neural targets remain quite broad and fairly non-specific. The issue of inability to identify a particular target or network may be due to schizophrenia representing a conglomeration of psychiatric conditions which have not been appropriately delineated.⁴ The formalisation of schizoaffective disorder in the diagnostic and statistical manual of mental disorders represents the first step in further delineating schizophrenia. Numerous structural and functional neuronal differences have already been identified between schizophrenia and schizoaffective disorder.^5–7 No neurosurgical target has yet been identified for schizoaffective disorder.

Recently work has suggested a subtype of schizophrenia called schizo-obsessive disorder may exist.^{8 9} This subtype of schizophrenia portends severe psychosis, severe depressive symptoms, more impaired social function and more suicidality. Typical symptoms present within the context of prodromal schizophrenia, clozapine use or true schizo-obsessive disorder.⁸ As has been reviewed by Scotti-Muzzi and Saide, schizo-obsessive disorder has unique structural and functional connectivity compared with schizophrenia, although there are various other regions of similarity.⁹ These differences are significant enough that functional neuroimaging of the two disorders may be distinguished 78%–91% of the time by robust functional MRI-based classification systems.^{10 11} Schizo-obsessive disorder has the potential to yield specific neural substrates for target by deep brain stimulation (DBS) based on clinical and neuroimaging differences.

Case presentation

A 25-year-old man with an 8-year history of schizophrenia presented to the emergency department with decompensation of auditory hallucinations and inability to cope with command hallucinations. Previously, he had been living in his parents’ home as further medical stay had nothing further to offer.

The patient’s delusions centred around the belief that the internal revenue service was threatening him and his family and had been for years. The patient often heard the voices of the internal revenue service speaking to him, belittling him daily. Typically, the voices would speak around topics of his delusions. However, the voices had never commanded him to perform actions.

Within the prior half-year, the nature of his hallucinations began changing. The voices began threatening to hurt his family unless he performed certain actions. The patient also described visions of actions he must perform to keep his family safe. The patient described these commands as highly anxiogenic, and in order to both protect his family and relieve stress from the commands, he must perform the action. These new behaviours varied from repeatedly asking interviewers ‘are you gay’, stating ‘I am gay’, spinning in circles when staff would look at him and winking during interviews. Most commonly, he would punch walls. However, if he did not perform actions correctly, he would have to repeat the action until done properly. This resulted in him causing significant damage and ulceration to his knuckles with repeat infections because his initial punches ‘did not hurt enough’ to satiate the voices. These behaviours were highly distressing to him, resulted in social seclusion, and were a source of medical concern.

Although previously anhedonic and flat in affect, the patient felt his depressed mood was progressing primarily due to the fact he felt his illness was worsening. The commanding nature of his hallucinations, social and physical repercussions of his commanded behaviours, inability to distinguish delusion or hallucination from reality and new anxiety during his commands were all sources of dismay. Multiple times he claimed ‘I cannot tell what is real or not anymore’.

He described decreased motivation, lack of interest in performing activities, guilt regarding threats to his family, persistent exhaustion and felt he could no longer think properly. From his perspective, the progression not only resulted in new features, but worsened all aspects of his disease. Quantitative evaluation revealed his Positive and Negative Syndrome Scale score was 128/200. Specifically, he scored 25/49 in positive symptoms, 32/49 in negative symptoms and 71/102 in general psychopathology. His Yale-Brown Obsessive Compulsive Scale overall score was 27/40, with 15/20 on the obsessions subscale and 13/20 in the compulsions subscale.

Differential diagnosis

The differential for a patient with psychotic and obsessive-compulsive symptoms includes several conditions. Specifically, schizo-obsessive disorder, schizotypal personality disorder with obsessive-compulsive disorder (OCD), comorbid schizophrenia with OCD, OCD with poor insight and schizophrenia with antipsychotic-induced compulsive symptoms. The symptoms were determined to be unrelated to antipsychotics given two facts. The patient’s dose of clozapine had not been changed in the months prior to admission and his symptoms paradoxically worsened off clozapine with relief on clozapine. The patient neither met full criteria for nor was fully explained by any diagnosis aside from schizo-obsessive disorder. This patient met four of five provisional diagnostic criteria suggested by Poyurovsky and colleagues.¹² The patient (1) demonstrated obsessions and compulsions, (2) the obsessions and compulsions were interrelated in nature to the delusions and hallucinations, (3) the obsessions and compulsions caused significant distress and (4) the symptoms were not secondary to organic cause or clozapine. The patient has not yet met the fifth criterion. He did not endorse these symptoms for the majority of his disease course as he developed them months prior to admission. It is possible that the natural history of his disorder had progressed to the point in which he manifested schizo-obsessive disorder.

Treatment

During his hospital stay, the patient had ongoing psychotic features, worsening obsessive-compulsive features and persistently depressed mood. On admission, clozapine was increased and the patient started 12 rounds of electroconvulsive therapy given concern of possible schizoaffective disorder. The patient had electroconvulsive therapy three times a week and clozapine was simultaneously increased 12.5 mg/day as tolerated. He completed electroconvulsive therapy after 1 month and continued to have his clozapine increased, reaching a maximum of 437.5 mg/day roughly a week after. However, there were minimal alterations in mood and psychotic features while obsessive-compulsive features worsened.

At 437.5 mg/day of clozapine, the patient’s compulsive behaviours worsened. Due to the relation between clozapine and obsessive-compulsive features, clozapine was weaned to discontinuation. At this point, the patient’s psychosis and obsessive-compulsive symptoms worsened significantly. This exacerbation suggested clozapine treated the patient’s symptoms rather than caused them, and so clozapine was re-initiated. Psychotic and obsessive-compulsive symptoms then returned to baseline with moderate dosage of clozapine, reaching 275 mg/day by time of discharge.

Considering the possibility of schizo-obsessive disorder, sertraline was started. However, the patient’s parents discontinued the sertraline against medical advice while on pass from the hospital. Given the risk of sertraline withdrawal during visits with his parents, sertraline was discontinued. Further selective serotonin reuptake inhibitors were not started as the patient refused this treatment based on discussion between him and his parents. He is not on regular adjunct antipsychotics given previous failure to treat symptoms and side effect profile. He uses 10 mg of haloperidol during acute exacerbations of his symptoms to calm him down and allow him to present to a hospital.

Outcome and follow-up

After 2 months of hospitalisation and maximal psychiatric intervention, the patient remains clinically unchanged. He has been discharged back to home and will continue to receive outpatient psychiatric follow-up monthly.

Discussion

The condition of schizo-obsessive disorder itself is controversial. This controversy dates back to the conception of the dual-diagnosis of schizophrenia and OCD in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Some neuropsychological experiments fail to demonstrate a unique clinical entity while other neuropsychological testing and imaging studies provide evidence for existence of schizo-obsessive disorder.^{11 13 14} Further neuropsychological profiling demonstrates distinct symptomatology in schizo-obsessive disorder and a predilection for uniquely poorer prognosis.⁸ Proving the existence of the condition has been difficult for various reasons. The Diagnostic and Statistical Manual of Mental Disorders changes regularly, research in psychiatry is developing at a rapid pace, and the nature of schizo-obsessive disorder makes it difficult to distinguish from similar conditions on the differential diagnosis. Ultimately, there is evidence for the existence of schizo-obsessive disorder as an entity separate from the diagnoses of comorbid schizophrenia with OCD, schizotypal personality disorder with OCD, OCD with poor insight and schizophrenia with antipsychotic-induced compulsive symptoms.^{8 9} Moreover, the consideration of schizo-obsessive disorder presents a unique opportunity to consider how schizophrenia spectrum disorders may develop unique neuroanatomical pathology.

Considering the clinical overlap in presentation of OCD with schizophrenia in schizo-obsessive disorder, it is reasonable to hypothesise similar brain structures are affected. Recent work by Wang and colleagues demonstrates dysregulation in multiple networks, specifically including the subcortical network in schizo-obsessive disorder.¹¹ Importantly, they also demonstrate similar white matter changes in the sagittal stratum between schizo-obsessive disorder and OCD, a region involved in cortical-thalamic processing related to obsessive symptoms. Functional neuroimaging by Bleich-Cohen and colleagues demonstrated obsessive hallucinations in schizo-obsessive disorder actually involved the dorsolateral prefrontal cortex, orbitofrontal cortex, inferior frontal gyrus, middle frontal gyrus and middle temporal gyrus, regions shared between hallucinations and obsessions.¹³ Critical structures involved in OCD are the anterior limb of the internal capsule, ventral capsule, ventral striatum, nucleus accumbens and ventral caudate, anterior cingulate, and are targeted in neurosurgeries.¹⁵ Critical surgical structures in schizophrenia are anterior corpus callosum, frontal white matter, subcaudate region, hippocampus and anterior cingulate.^{3 16} There are a variety neurosurgical treatment options for targeting these regions; capsulotomies, cingulotomies, leukotomies and tractotomies are all possible but results in permanent destruction of brain matter. DBS exists as the current gold standard of psychiatric neurosurgical intervention, affording reversible treatment.¹⁷ Schizophrenia neurosurgery has been underwhelming compared with OCD neurosurgery, but the neuroanatomy and symptomatology in schizo-obsessive disorder may allow effective neurosurgical treatment.^{16 18} However, no studies have investigated similarities between the nodes typically targeted in OCD nor schizophrenia neurosurgery and their nature in schizo-obsessive disorder.⁹

Notably, DBS for treatment of OCD is highly successful.¹⁵ OCD patients treated by DBS typically report that not only compulsions but the obsessions underlying them resolve.¹⁹ Given the intertwined nature of OCD symptoms with psychosis in schizo-obsessive disorder, treating OCD symptoms may address psychosis. This interrelated treatment of symptomatology relies on the neuroanatomy of schizo-obsessive disorder combining neuroanatomy of OCD and schizophrenia. This is supported by functional neuroimaging demonstrating hallucinations and delusions share a network with obsessions in schizo-obsessive disorder.¹³ To determine if OCD DBS may be adapted to schizo-obsessive disorder, further research is necessary. The similarity between OCD and schizophrenia DBS targets in schizo-obsessive disorder must be assessed. As well, the neuroanatomical relationship for interrelated schizophrenia/OCD symptoms needs to be understood. Utilisation of OCD targets in schizo-obsessive disorder holds possibility for successful treatment of schizophrenia subtype by DBS.

Learning points.

• Schizo-obsessive disorder is a new subtype of schizophrenia.

• Schizo-obsessive disorder mixes features and neuronal network of schizophrenia and obsessive-compulsive disorder (OCD).

• Schizo-obsessive disorder does not yet have appropriate treatment.

• Neurosurgery may be a possible treatment for schizo-obsessive disorder by targeting OCD anatomical targets.