Vitamin B12 is one of the essential vitamins affecting various systems of the body. In case of deficiency; hematologic (megaloblastic, macrocytic anemia), neurologic (demyelinization, paresthesia), gastrointestinal (anorexia, glossitis) as well as psychiatric symptoms arise. The psychiatric symptoms may not be concurrent with symptoms arising from other systems and even may precede them [1–3]. The symptoms may include agitation, irritability, negativism, confusion, disorientation, amnesia, impaired concentration and attention and insomnia; while psychiatric disorders that may be diagnosed in patients having vitamin B12 deficiency include depression, bipolar disorder, panic disorder, psychosis, phobias and dementia [1–6]. In adult patients, the clinical picture may especially involve affective or psychotic symptoms. These observations may be explained by the importance of vitamin B 12, folate and homocysteine in carbon transfer metabolism (methylation) required for the production of serotonin, other monoamine neurotransmitters and catecholamines [1–6]. Up to now, reports of psychiatric disorders due to vitamin B12 deficiency mostly focused on middle aged and elderly patients and pediatric cases are reported to be rare [7–9]. This study aimed to report a case of vitamin B 12 deficiency in an adolescent who presented with mixed mood disorder symptoms with psychotic features.
A sixteen-year old male adolescent was brought to our department with complaints of “irritability, regressive behavior, apathy, crying and truancy”. Upon questioning of his parents it was learned that the complaints have been present for the past year. The patient had started to display anxiety during separation from his mother, wept frequently and complained of vague pains, lethargy, forgetfulness and reduced concentration alternating with racing thoughts, irritability, anhedonia, distractibility, reduced sleep and appetite. Speech was reduced and he became progressively isolated from his peers. He refused to go to school and when sent became truant frequently. His parents reported that he was frequently agitated, spent his free time in front of his computer and that he ran excessive debts on their credit cards buying items on-line. There was no previous history of compulsive shopping or buying sprees. Premorbid personality of the adolescent was described as extrovert, euthymic and active. He was well liked by his friends although the academic staff reported problems in attention starting from the second grade. His teachers also reported fidgetiness and impulsivity which was especially prominent in mathematics lessons.
In the mental status examination, impaired attention, concentration, as well as insomnia, reduced working and short-term memory, elementary auditory (i.e. knocking and ringing), olfactory (i.e. burnt rubber, perfumes and tobacco), and visual hallucinations (i.e. a white, man-like shape, especially present in the evenings), as well as passive suicidal ideation were noted. Judgment, abstract thought and reality testing were impaired. Speech was hypo-phonic, thought process was sluggish. Thought content was found to be impoverished and dominated by somatic complaints, delusions of reference, guilt and thought broadcasting. Mood was blunted and the affect was restricted in range. Psychomotor activity and appetite were reduced.
The patient reported that those complaints arose in the past year and that hallucinations were added in the past three months. Within the last month, delusions of reference (i.e. thinking that others were looking at and talking about him), delusions of guilt (i.e. that he had sinned and would be punished) arose and the patient reported that his thoughts were broadcast so that others can read and understand his thoughts. No history of psychoactive substance use, encephalitis, use of antipsychotics/antiemetics, exposure to carbon-monoxide or organophosphate compounds or stressors was present. The patient was not vegetarian. Past medical history and family history was unremarkable for both psychopathology and chronic medical disorders. Physical and neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present although no signs or symptoms of peripheral neuropathy could be observed. Evaluation with The Extrapyramidal Symptom Rating Scale (ESRS) yielded a score of 19, with items of bradykinesia and parkinsonism being positive .
Electroencephalography, electromyography, somatosensorial evoked potentials, cerebrospinal fluid analysis, cranial MRI, thyroid and liver function tests, pancreatic enzymes, electrolytes, parathormone, ceruloplasmin and whole blood count were within normal limits. HIV (ELISA) was negative. Twenty-four hour urine copper level was within normal ranges. An ophthalmologic examination ruled out the presence of a Kayser Fleischer ring. A peripheral blood smear with Wright’s stain was found to be normal. Endoscopy revealed atrophy of the gastric mucosa while a biopsy sample taken during endoscopy revealed colonization with Helicobacter Pylori. A Schilling test was administered to determine the etiology of Vitamin B12 deficiency and it was observed that radiolabeled Vitamin B12 levels were low both for Stage I and II of the test which was thought to reflect malabsorbtion .
Psychometric testing with the Beck Depression (BDI) and Anxiety Inventories (BAI) revealed scores of 35 (Cut-off score = 17, Severe Depressive Symptoms) and 36 (Without a clinically defined cut-off score albeit denoting severe anxiety), respectively [12,13]. An evaluation with the Turkish version of the Young Mania Rating Scale (YMRS), which does not have clinically designated cut-off score, yielded a score of 13 . Psychotic symptoms were evaluated with Positive and Negative Syndrome Scale and the patient scored 20, 23 and 56 for the Positive, Negative and General Psychopathology subscales (Total 99) . Vitamin B 12 levels were found to be 166 ng/mL in two subsequent tests after 6–8 hours of fasting with immunoassay method via Advia Centaur XTTM (Normal 197–400 ng/mL) while folate and transcobalamine levels were normal. Hemoglobin was found to be 10 g/dL (Normal 14–18 g/dL) and MCV was 98 fL (Normal 80- 100 fL) . Bone marrow examination did not reveal megaloblastic changes.
As a result of the history and evaluations and noting that the psychotic symptoms were superimposed on affective-anxious symptoms, the patient was diagnosed as having Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency according to DSM-IV-TR criteria and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started for treatment . Risperidone was chosen because of it being one of the most commonly used atypical antipsychotics for management of psychosis, pervasive developmental disorders, mental retardation, mood disorders and disruptive behavior disorders in children and adolescents and having no known interaction with vitamin B12. The usual dose range of risperidone for acute psychosis and mood disorder is reported to be 2–8 mg/day while we have started risperidon at 0.5 mg/day to help stabilize the patient while the medical work-up and treatments were being completed . Vitamin B12 was the only vitamin supplement started.
At the same time the patient was referred for treatment of Helicobacter pylori and was prescribed clarithromycin 1000 mg/day, lansoprazole 60 mg/day and amoxicillin 2000 mg/day. A follow-up visit on the second week revealed that no psychotic features were present, Romberg’s sign was negative and that cerebellar tests were within normal limits. Extrapyramidal symptoms were reduced. Both the patient and his mother reported that apathy, crying, regressive behavior and truancy were reduced. An evaluation with BDI and BAI revealed scores of 9 and 15, respectively while Evaluation with ESRS and YMRS yielded a score of 3 for both. PANSS scores for positive, negative and general psychopathology subscales were 13, 15 and 36 respectively (Total 64). Vitamin B12 levels were measured at this visit as 595 ng/mL. At the scond week, risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. The time course of changes in BDI, BAI, PANSS and its subscales, YMRS and ESRS according to Vitamin B12 levels is illustrated in Figure .