Tackling Negative Symptoms of Schizophrenia with Memantine

We present a case of a 52-year-old male patient suffering from chronic schizophrenia stabilized on risperidone long-acting injection (37,5 mg/2 weeks) and biperiden 4 mg/day. Residual symptoms are affective flattening, alogia, avolition, and asociality. Memantine 10 mg/day was added. After 1.5 months, the patient spontaneously referred to “feel better being in company of my relatives.” The following scales have been completed: the Scale for the Assessment of Negative Symptoms (96), the Scale for the Assessment of Positive Symptoms (3), the Mini Mental Scale Examination (26), and the Calgary Depression for Schizophrenia Scale (2). Memantine was increased to 20 mg/day and biperiden was decreased to 2 mg/day. Two months later, apathy and asociality considerably improved and affective flattening, alogia, and attention slightly got better (SANS 76, SAPS 1, MMSE 26, and CDSS 1). After two more months, the improvement continued in the same domains (SANS: 70, SAPS: 1 MMSE: 27, and CDSS: 1). Positive symptoms remained in full remission. It has been hypothesized that one of the causes of schizophrenia is glutamate excitotoxicity. Memantine, a glutamate receptor antagonist, could possibly ameliorate schizophrenia symptoms, the negative ones among them, used as add-on therapy to atypical antipsychotics. Memantine could be of potential help in schizophrenia patients with severe residual negative symptoms.

The interaction of subjective experience and attitudes towards specific antipsychotic-related adverse effects in schizophrenia patients

Background:Discontinuation of antipsychotic drugs in schizophrenia patients is a major concern, since it results in relapse and re-hospitalizations. Non-adherence is strongly associated with negative-subjective response to antipsychotics, which is composed of the subjective experience of negative drug effects and attitude towards the treatment.Objective:To investigate the elements of subjective experience and subjective attitude towards specific drug-related adverse effects, leading to a generally negative-subjective attitude towards antipsychotics.Methods:Schizophrenia inpatients (n = 84) were administered a questionnaire measuring attitude and experience on eight subscales: weight gain, sedation, sexual anhedonia, extra-pyramidal syndrome, affective flattening, excessive sleep, diminished sociability and metabolic syndrome. DAI-30 was used to measure attitude towards drugs, and PANSS to assess psychopathology.Results:Weak correlation was found between subjective experience and attitude on most of the subscales. The only strong, albeit inverse, correlation between experience and attitude that was found was with regard to affective flattening, experienced by 37% of the sample, and it also predicted negative drug attitude as measured by the DAI-30, RR: 1.87 (95% CI: 1.06–3.3, df = 1, χ2 = 4.525, P < 0.05).Conclusion:Negative attitude towards most adverse drug effects did not correlate with personal experience. Drug-related affective flattening should be evaluated routinely, since experiencing it may predict negative attitude towards drugs, potentially leading to poor compliance and relapse.

Monoamine Oxidase A and B Gene Polymorphisms and Negative and Positive Symptoms in Schizophrenia

Given that schizophrenia is a heterogeneous disorder, the analysis of clinical characteristics could help to identify homogeneous phenotypes that may be of relevance in genetic studies. Linkage and association studies have suggested that a locus predisposing to schizophrenia may reside within Xp11. We analyzed uVNTR and rs1137070, polymorphisms from MAOA and rs1799836 of MAOB genes to perform single SNP case-control association study in a sample of 344 schizophrenia patients and 124 control subjects. Single polymorphism analysis of uVNTR, rs1137070 and rs1799836 SNPs did not show statistical differences between cases and controls. Multivariate ANOVA analysis of clinical characteristics showed statistical differences between MAOB/rs1799836 and affective flattening scores (F=4.852, P=0.009), and significant association between MAOA/uVNTR and affective flattening in female schizophrenia patients (F=4.236, P=0.016) after Bonferroni’s correction. Our preliminary findings could suggest that severity of affective flattening may be associated by modifier variants of MAOA and MAOB genes in female Mexican patients with schizophrenia. However, further large-scale studies using quantitative symptom-based phenotypes and several candidate variants should be analyzed to obtain a final conclusion.

Psychotic-like experiences and depressive symptoms in a community sample of adolescents

PurposeStudies of psychotic-like experiences (PLEs) within community samples of adolescents have explored predominantly positive experiences. There is a paucity of research examining the prevalence and correlates of negative PLEs, and whether particular subtypes of negative PLEs can be identified among the general population of adolescents. This study examined the association of both positive and negative PLEs with depressive symptoms, including detailed analysis of subtypes of positive and negative psychosis dimensions.MethodA community sample of 777 adolescents (50.9% girls: mean age 14.4 years) completed a questionnaire assessing positive and negative PLEs and depressive symptoms.ResultsPrincipal component factor analysis identified four factors of positive symptoms (persecutory ideation, grandiose thinking, first-rank/hallucinatory experiences and self-referential thinking), and three factors of negative symptoms (social withdrawal, affective flattening, and avolition). Depressive symptoms were associated positively with persecutory ideation, first-rank/hallucinatory experiences, social withdrawal, and avolition, whereas grandiose thinking related negatively with depressive symptoms. Neither self-referential thinking nor affective flattening related to self-reported depression.ConclusionsThese findings support the view that not all types of positive and negative PLEs in adolescence are associated with depression and, therefore, they may not confer the same vulnerability for psychotic disorders.

Production of atypical category exemplars in patients with schizophrenia

Previous studies have revealed semantic memory impairments in patients with schizophrenia, and suggested that certain of these impairments were related to thought disorganization. One explanation offered for this is a broadening of the boundaries of semantic categories in schizophrenia. We selected 16 semantic categories, and required a sample of 41 schizophrenia patients and 43 healthy control subjects to produce one exemplar from each category. The typicality of the subjects’ responses was rated. The exemplars produced by the patients were on average less typical than those produced by the healthy controls. No significant association between typicality of the response and thought disorganization was revealed in the patient sample. Affective flattening, alogia, and anhedonia were significantly and inversely associated with the typicality score, that is, higher ratings of these symptoms were associated with more typical responses. Our results suggest that a broadening of semantic category boundaries is observed in patients with schizophrenia, but is unrelated to thought disorganization. This semantic abnormality is not a feature of the patients with high ratings of certain negative symptoms. (JINS, 2010, 16, 822–828.)