A Case of Schizophrenia with Complete Agenesis of the Corpus Callosum

CASE REPORT

BR is a 24-year-old single Caucasian woman residing with her parents in a town in regional Victoria. She was referred by her private psychiatrist to the local area mental health service because of escalating periods of distress, resulting in threats of self-harm and self-injurious behaviours. BR presented with second-person auditory hallucinations of the voices of angels communicating with her and the devil disturbing her, erotic delusions directed at a male school teacher which led to withdrawal from school and bizarre delusions such as the belief that she was losing a baby every month when she was having menstrual periods. There was gross deterioration in her sleep and appetite. She felt depressed at times secondary to the auditory hallucinations and would inflict self-injuries in response to this distress. She had previously presented to psychiatric services at the age of 17 when she was diagnosed with schizotypal disorder and was treated with risperidone 3 mg per day.

The past medical history revealed that she had midline structural abnormalities such as a (corrected) cleft palate of the lower lip and left-sided hemiparesis. There was no history to suggest prenatal, natal or postnatal intrauterine insults such as infection or exposure to toxins. BR's mother was informed by the medical practitioner attending to her birth that BR had ‘cerebral palsy’ which had left BR with deficits in the left hand and left leg.

The developmental history indicated a mild delay in motor skills, but speech development was normal. School reports indicated that she managed her language tasks well but struggled with mathematics, and generally showed low self-confidence. She was reported to be a shy but generally social girl until high school. During her high school years, BR displayed interest in art, reading, table tennis and looking after animals. About halfway through high school, she became increasingly isolative, dishevelled and her academic performance began to decline. In her senior year, she developed a belief that she was malodorous and attracted flies, which led her to spend time alone in the toilets or library. It was at this time that she also developed the belief that she was visited by angels, and became infatuated with her teacher. Both of these beliefs have persisted and featured in her current presentation.

The diagnosis made on the current presentation was schizophrenia and BR was initially treated with risperidone, up to 6 mg daily, without a significant positive response. Risperidone was ceased and amisulpiride 1000 mg daily was commenced. She was also subsequently commenced on sodium valproate 1300 mg daily as an augmenting agent. The main issues in her management included her non-engagement with the treating team and noncompliance to medication, which posed significant challenges in her rehabilitation.

BR had been investigated at first presentation in 1997 with a cerebral CT scan. Following her second presentation in 2002, magnetic resonance imaging was undertaken as part of a more comprehensive neuropsychiatric assessment. Both cerebral CT and MRI revealed complete agenesis of the corpus callosum, with colpocephaly, a sunburst gyral pattern and a high-riding third ventricle.

BR had undertaken neuropsychological testing on two occasions, once on her initial presentation aged 17 and during the current presentation. The findings on both occasions were similar. BR's results in verbal tasks demonstrated high-average general knowledge, average abstract reasoning skills and social knowledge/reasoning ability. She demonstrated a weakness with mental arithmetic tasks. For non-verbal tasks, BR showed average performance on problem-solving and construction of abstract puzzles, but demonstrated poor self-monitoring and checking of her accuracy in performance, and a tendency not to persevere with tasks that she found challenging. She demonstrated low-average attention to visual tasks and details, and low-average performance in non-verbal reasoning tasks. She exhibited a significant weakness in psychomotor speed. BR's memory was described as average, with a weakness for immediate and delayed memory, but her performance improved with repetition of tasks, demonstrating a sound learning capacity. Executive functioning tasks revealed planning and organizational difficulties.

BR's overall cognitive function was deemed to be in the low-average range and her verbal skills were consistently reported to be better than non-verbal skills. The findings of reduced non-verbal skills and the history of a left hemiparesis at birth were consistent with a significant right hemisphere developmental insult while the observed psychomotor slowing and low-average intellect are consistent with the neuropsychological deficits seen in patients with ACC. Based on these findings, a formulation was made that the deficits in BR's non-verbal skills may have led to the misinterpretation of stimuli and misunderstanding in social situations. BR's coping response had been to withdraw and avoid social situations, which limited the potential for skill development and led to depressive features and poor self-esteem. In addition, the difficulties with non-verbal skills had hampered her ability to participate effectively in conventional rehabilitation processes.

Psychosocial treatment issues included a dependency on her family and support agencies for self-care, and an inability to be distracted once distressed. Initially, the psychosocial treatment was aimed at improving distress tolerance and implementing adaptive stresscoping responses. BR's reluctance to engage and poor expectations of treatment led to a shift in treatment towards a behavioural management model which was also informed by the neuropsychological formulation. The target maladaptive behaviours were identified along with personal strengths, and the family and agencies were educated on a consistent response programme. The goals of the treating team were to increase her capacity for independent living and to improve her ability to form and enjoy meaningful relationships with others.

As a result of the management plan, significant gains were made in BR's ability to communicate appropriately and self-manage her distress. This allowed a cognitive behavioural treatment programme to be implemented, targeting her ongoing delusional beliefs and resultant distress. BR increased her capacity to learn and adapt, and her motivation improved as her autonomy increased. These changes have allowed her to persist with her treatment and to develop insight that her delusional beliefs about having lost children and committed crimes were not true. BR's skills for self-monitoring and self-management of distress improved greatly and episodes of distress have significantly decreased in frequency and intensity. BR's prognosis was considered to be very favourable given the gains made in the treatment. Following the treatment, she was placed in a residential psychosocial rehabilitation programme with the expectation that she would move into independent accommodation with minimal supports over the ensuing 12–18 months.

DISCUSSION

The corpus callosum is formed early in embryogenesis, and insults during early embryogenesis may lead to complete callosal agenesis. ^{14 – 16} Insults at this early stage also lead to other midline defects in association with agenesis of corpus callosum such as cleft palate, hypertelelorism, lowset ears and costovertebral abnormalities. ^{17 – 19} The clinical presentations of corpus callosal deficits vary and the commonest presentation is that of severe mental retardation and early focal seizures. ²⁰

The most consistent neuropsychological impairments in acallosal subjects are low IQ, clumsiness, slow performance on tasks involving bimanual motor coordination and significantly slowed interhemispheric transmission times with manual responses to lateralized light stimuli. ²¹ Other impairments, such as inaccuracy in cross-localizing touched fingers, contralateral mirror movements and reduced intermanual transfer of complex tasks learning have been reported in some acallosal subjects but not in others. ²²

As the corpus callosum forms the roof of the lateral ventricles, agenesis is associated with cystic dilation of the third ventricle and a septum pellucidum. ²³ Although cases of corpus callosum deficits in schizophrenia have been reported, complete agenesis has been described in only a few previous reports. With the advent of neuroimaging techniques and refinement of quantifying brain measurements, several studies have described a significant reduction in the size of the corpus callosum in patients with schizophrenia together with poor development of the callosal structures. ^{24 – 28} In addition, there have been reports of an increased prevalence of cavum septum pellucidum in MRI scans and post-mortem specimens of patients with schizophrenia. ^{29 – 32} These findings have stimulated the notion that abnormalities of the corpus callosum may have a role in the pathogenesis of schizophrenia. ³³ , ³⁴

BR exhibited many of the neurological, somatic and cognitive features described in patients with ACC together with deficits attributable to right hemispheric dysfunction secondary to an early insult. BR subsequently developed symptoms typical of schizophrenia in her late adolescence. While it is not possible to state that the relationship between these neurodevelopmental disorders and schizophrenia is a causal one, it is likely that their effect modified and influenced BR's presentation and treatment. BR presented with pronounced social withdrawal and behavioural disturbance secondary to her psychotic symptoms. These symptoms were understood in the context of her poor non-verbal skills and her misinterpretation of social situations. On the basis of the neuropsychological formulation, it was possible to develop a treatment plan which took into account BR's cognitive and psychosocial difficulties and moved the focus towards a behavioural management plan.