Ljubomir Hotujac

The influence of 5-HT2C and MDR1 genetic polymorphisms on antipsychotic-induced weight gain in female schizophrenic patients

We investigated the relationships between functional genetic variants of the 5-HT(2C) receptor and multidrug-resistant protein (MDR1), coding for P-glycoprotein, and second generation antipsychotic (SDA)-induced weight gain among 108 female schizophrenic patients treated with olanzapine or risperidone for up to 4 months. No significant differences in -759C/T allelic and genotype variants of 5-HT(2C) were found between patients who gained more than 7% of their initial weight compared with those who gained less. Haplotype-based analysis of two MDR1 loci, exon 21 G2677T and exon 26 C3435T, revealed a slightly lower representation of the G2677/C3435 haplotype in the >or=7% group. In the subgroup of patients treated with risperidone, we found borderline overrepresentation of 2677T, significant overrepresentation of 3435T variant and borderline overrepresentation of 2677T/3435T haplotype the >or=7% group, whereas G2677/C3435 haplotype was found to be less represented in the >or=7% group. Our data indicate a nonsignificant role of 759C/T 5-HT(2C) in SDA-induced weight gain, and a stronger influence of the MDR1 G2677T and C3435T polymorphisms on risperidone-induced weight gain in female schizophrenic patients. 3435T and 2677T MDR1 variants, both associated with lower P-gp function, might predispose to higher risperidone accessibility to the brain that would lead to stronger effects, including weight gain.

Psychiatric symptoms in idiopathic intracranial hypertension

IDIOPATHIC INTRACRANIAL HYPERTENSION (IIH) is a medical condition defined by intracranial hypertension without hydrocephalus or brain lesion, usually presented with neurological symptoms. We describe a case of a woman, age 26 years, mother of a 1-year-old child, living with the child’s father, employed and recently promoted, who was diagnosed as IIH after experiencing unspecific neurological and prominent psychiatric symptoms ranging from affective to dissociative spectrum disorders. The patient gave informed consent to the publication of this letter. The first symptoms occurred 1 year before hospital admission, soon after childbirth. She displayed anxiety, depressed mood, loss of energy, decreased pleasure in activities, mood swings with aggressive behavior towards her mother and intensive fear that something bad would happen to the child. She also complained about mild headaches, occasional vomiting and transient visual obscurations. On the day of hospital admission she suddenly began to show inadequate behavior, a trance-like state, with agitation, narrowed awareness, derealization, depersonalization, perseverations, occasional mutism and disorganization behavior characterized by repetitive movements of standing up and sitting, unresponsive to verbal commands. The next day she displayed adequate behavior and was partially amnestic for yesterday’s events describing them as blurred. She complained about vomiting and intensive headaches, resistant to analgesics. Psychiatric evaluation revealed features of borderline and histrionic personality disorder: tendency to overdramatization, theatricality and exaggerated expressions of emotions, affect of predominantly angry nature and impulsivity. Standard laboratory tests, including drug screenings and electroencephalogram were normal. An ophthalmologist diagnosed bilateral chronic papilledema. Multislice computed tomography showed widened cerebrospinal fluid space around the ophthalmic nerves and partial empty sella. After reviewing these findings, the neurologist diagnosed IIH. After acetazolamide was introduced she displayed no more neurological or psychiatric symptoms from that time or during the 1-year follow up period. There are few reports of IIH presenting with psychiatric symptoms: affective, psychotic and dissociative. The underlying mechanisms are unclear. Poor psychosocial functioning in patients with headache, whether of general origin or related to IIH, might suggest that IIH rather facilitate the expression of predisposed psychiatric states than cause them directly. Apart from biological factors, based on this case, we could hypothesize that psychological factors might be important in evaluating IIH. Borderline/histrionic personality traits of our patient and stressful events (e.g. job promotion) are associated with increased susceptibility to affective and dissociative disorders. We believe that underlying IIH might have helped the expression of those symptoms.