J. Indian Assoc. Child Adolesc. Ment. Health 2018; 14(3): Case report. Vitamin D deficiency in very early onset schizophrenia: A case series

Transcription

1 78 J. Indian Assoc. Child Adolesc. Ment. Health 2018; 14(3):78-84 Case report Vitamin D deficiency in very early onset schizophrenia: A case series Nidhi Chauhan, Susanta Kumar Padhy Address for correspondence: Dr Nidhi Chauhan, Assistant Professor, Department of Psychiatry, Government Medical College, Chandigarh. dr.nidhichauhan@gmail.com Abstract Vitamin D plays an important role in brain development and critical brain functions due to its myriad effects on the growth and functions of different brain cells. Association between vitamin D deficiency and depression, seasonal affective disorder and schizophrenia in adults is well known and few reports are available for association of vitamin D deficiency and neurodevelopmental disorders especially schizophrenia and autism in children. Very early onset schizophrenia (VEOS) i.e. onset before 13 years of age, has florid symptoms, chronic course and poorer outcome owing to the abnormalities occurring during brain development where vitamin D deficiency may play a role. Though literature reports the association between vitamin D deficiency and neurodevelopmental disorders, cause-effect relationship is not established. A few studies report better course and outcome following vitamin D supplementation in children with vitamin D deficiency and neurodevelopmental disorders, despite uncertainties in research evidence. This paper aim to present two cases of VEOS associated with vitamin D deficiency highlighting the need for identification of deficiency, and supplementation thereby, for a possible better outcome. Keywords: Schizophrenia, vitamin D, deficiency, children.

2 79 Introduction Vitamin D is increasingly being recognised as important for brain development and critical brain functions apart from its role in calcium homeostasis [1]. It affects early brain development by acting as a potent differentiating factor for brain cells by increasing neurite outgrowth, regulation of neurotrophic factors, etc. [1]. Low levels of vitamin D are associated with depression, seasonal affective disorder and schizophrenia in adults, but little is known about vitamin D deficiency and mental health in children and adolescents. Exact mechanism for association between childhood schizophrenia, autism and vitamin D deficiency is not clear [1]. Low vitamin D is more common during winter and spring, at higher latitudes and in dark skinned individuals [2] and literature suggests an increased risk of developing schizophrenia in children if born in winter & spring season [3], at higher latitudes [4] and in people with dark skin colour [2]. Given these findings, researchers have postulated that vitamin D deficiency during developmental period may contribute to risk of developing psychosis [5]. Studies have reported addition of vitamin D supplements during first year of life, decreases the risk of developing schizophrenia in males [5]. Vitamin D supplementation to ensure adequacy modifies the course of development [6] and improves core symptoms of autism [7]. No literature regarding vitamin D deficiency in children with schizophrenia is available from India. Very early onset schizophrenia (VEOS) is a severe form of schizophrenia with onset before 13 years of age, poorer course, outcome, and greater psychopathology and neurocognitive deficits with poorer response to treatment. The neurodevelopmental model of schizophrenia suggests that aberrant neurodevelopment in the form of excessive synaptic and/or dendritic elimination and pre-morbid social and cognitive impairments are important contributors for development of schizophrenia. Vitamin D deficiency during the growing phase of an individual may be one of the many factors responsible for aberrant brain development and

3 80 consequently have a potential role in the development of early psychosis. In this background, this paper aims to present two cases of VEOS associated with vitamin D deficiency. Case 1 Ms D is a 10 year old developmentally normal girl, 5 th standard student, from a village in north India. She was an obedient, intelligent girl, helped mother in household chores and was a loving sister to her younger brother. In 5 th standard, one of her close friend left school, following which she appeared sad, did not go to school, remained aloof, her interaction decreased, motor activities slowed down, appeared lost, irritable and angry for no apparent reason, was seen muttering and smiling to self, and had decreased self care. Over next 3-4 months, she reported auditory hallucination of commanding, commenting and discussing type, associated with shouting and screaming and asking parents for rescue. Treatment from faith healers and local psychiatrist was not helpful. Despite good compliance, over next 1 year symptoms worsened, became abusive, hit family members without reason, ran out of house aimlessly along with deterioration of self care, sleep and appetite. Examination revealed BMI kg/m 2, paucity of speech, blunted affect, auditory hallucination of discussing, commanding and commenting type and visual hallucinations. Electroencephalogram (EEG), Magnetic Resonance Imaging (MRI) brain, hemogram, renal, liver and thyroid function tests were normal. Serum Vitamin D level was 6.8 ng/ml (normal range ng/ml). Brief Psychiatric rating scale (BPRS) score was 42. Response to adequate trial of olanzapine (15 mg/d for a year, with side effect of excessive daytime sedation) and risperidone (4 mg/day for 3-4 months with marked extrapyramidal side effects) was insignificant. A diagnosis of schizophrenia was made according to ICD-10. Tablet clozapine was started at 12.5 mg/day, increased to 87.5 mg/day with close & regular monitoring. Oral vitamin D 60,000 IU/ day for 10 days followed by maintenance treatment with oral vitamin D 400 IU/day and elemental calcium 500 mg/day for 3 months was given

4 81 [8]. In the index case, vitamin D supplementation was started before clozapine was initiated and the patient had a significant response at just 87.5 mg/day within ~3 weeks of starting clozapine. At discharge she had ~60% improvement in symptomatology. Repeat Vitamin D level after 3 months was 57 ng/ml. She started going to school and overall functioning improved significantly. Case 2 Master DD, is a 11 year old developmentally normal boy; known to be a quiet child with difficulties in studies since childhood; however, had no disciplinary issues at home/school. Without any precipitating factor, he was observed to be more quiet than usual self, had lost interest in leisure activities, had decreased concentration in studies, had started muttering and smiling to self, gesticulating in air, voiced delusion of persecution against peers and auditory hallucinations of derogatory commenting type. His self care deteriorated and had sleep, appetite disturbances. Family history of schizophrenia in father was present. He hardly improved with olanzapine 20 mg/day, haloperidol 7.5 mg/day and aripiprazole 15 mg/ day, each medication was given for 4-6 months. Complete hemogram, renal function test, liver function test, computerised tomogram (CT) head were within normal limits. Though, he had ~50% improvement, with risperidone 9 mg/day, but after 4-5 months despite good compliance clinical evaluation revealed worsening of above mentioned symptoms. Diagnosis of treatment resistant schizophrenia was made and after family education, tablet clozapine was initiated and increased to 200 mg/day without any haematological adverse effects. Vitamin D level was 7.9 ng/ml following which vitamin D supplementation was given as in first case as per Indian Academy of Pediatrics guidelines [8]. He improved by 70% by 5-6 weeks. Repeat vitamin D level at 3 months was 35 ng/ml.

5 82 Discussion Vitamin D is involved in maintaining calcium balance and signalling, regulating neurotrophic factors, neuroprotection, neurotransmission, and synaptic plasticity and thus is an important factor in brain development [9]. The above two cases highlight the association between VEOS and vitamin D deficiency [1]. In both the cases, vitamin D deficiency and schizophrenia coexisted and vitamin D deficiency during the developmental years of a child may be acting as a risk factor for development of schizophrenia, a neurodevelopmental disorder, as has been reported in literature [1]. To best of our knowledge, this is the first paper to highlight association between VEOS in children and vitamin D deficiency. Clozapine is recommended for use in children and adolescents suffering from treatment refractory schizophrenia, in dose upto ~ 300 mg/day and response is expected to occur within 4-6 weeks of starting clozapine; studies showing that clinical response to clozapine may occur from 1 week to upto 1 year after treatment initiation [10]. Literature regarding the rate of response to clozapine treatment after vitamin D supplementation could not be found, but the first case support the notion that supplementing vitamin D in deficient patients with schizophrenia can lead to quicker response (within 3 weeks) and requirement of lower doses (87.5 mg/d) of clozapine. In the second case also, clozapine was required in lesser than the usual dose range (200 mg/d) for response. Apart from coexistent vitamin D deficiency, the second case also had additional developmental risk factor (in the form of genetic loading evident by schizophrenia in father) which may explain the requirement of higher dose of clozapine compared to first case. The cause and effect relationship between Vitamin D deficiency and schizophrenia is unclear, but as already mentioned; studies have reported that hypovitaminosis D during antenatal period, childhood and puberty may influence brain development and thus course and outcome

6 83 of schizophrenia [1]. VEOS being difficult to treat with poor course and outcome, any amount of additional response (beyond the response achievable by conventional treatment with antipsychotics) by supplementing vitamin D in deficient individuals after screening for vitamin D deficiency, may be worth considering for clinical implication. Conflict of interest: None declared. References 1. Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain functions and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinolo 2013, 34: Berg AO, Melle I, Torjesen PA, Lien L, Hauff E, Andreassen OA. A cross sectional study of vitamin D deficiency among immigrants and Norwegians with psychosis compared to general population. J Clin Psychiatry 2010, 71(12): Torrey EF, Miller J, Rawlings R, Yolken RH. Seasonality of births in schizophrenia and bipolar disorder: a review of literature. Schizophr Res 1997, 28: Saha S, Chant DC, Welham JL, McGrath JJ. The incidence and prevalence of schizophrenia varies with latitude. Acta Psychiatr Scand 2006, 114: McGrath JJ, Burne TH, Feron F, Mackay-Sim A, Eyles DW. Developmental Vitamin D Deficiency and Risk of Schizophrenia: A 10-Year Update. Schizophr Bull. 2010, 36(6): McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Jarvelin MR, et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res 2004, 67: Jia F, Wang B, Shan L, Xu Z, Staal WG, Du L. Core symptoms of autism improved after vitamin D supplementation. Pediatrics 2014, 135(1):e Khadilkar A, Khadilkar V, Chinappa J, Rathi N, Khadgawat R, Balasubramanian S, et al. Prevention and Treatment of Vitamin D and Calcium Deficiency in Children and Adolescents: Indian Academy of Pediatrics (IAP) Guidelines. Indian Pediatrics 2017, 54: Groves NJ, McGrath JJ, Burne THJ. Vitamin D as a neurosteroid affecting the developing and adult brain. Annu Rev Nutr 2014, 34:

7 Meltzer HY. Dimensions of outcome with clozapine. Br J Psychiatry 1992, 160: Dr Nidhi Chauhan, Assistant Professor, Department of Psychiatry, Government Medical College, Chandigarh; and Dr Susanta Kumar Padhy, Additional Professor, Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar.