Alterations of glutamate, energy and glutathione metabolism contribute to the pathogenesis of psychotic disorders

Revealing clinical-biological correlations in patients with late onset schizophrenia and delusional disorder by determining clinical parameters and activity of platelet enzymes of energy, glutamate, and glutathione metabolism.

27 women of 45-80 years old were studied, with late onset schizophrenia or delusional disorder. Activity of platelet cytochrome c-oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione-S-transferase (GST), and scores by PANSS, HAMD, MMSE, and CGI-S were evaluated twice: before and after the 28-th day of treatment. Activity of COX, GDH, GR, and GST was measured once in 23 women of 44-81 years old comprising the control group.

As compared with controls, only GDH activity was found significantly decreased (before and after treatment, p<0.001). Clusterisation of patients by enzymatic activities resulted in 3 clusters significantly different by COX, GDH and GST. Significant correlations were found between enzymatic activities and scores by psychometric scales: in the cluster 1 (n=9) baseline COX activity correlated with scores by PANSS positive subscale (R=0.9, p=0.001) and with scores by MMSE (R=-0.9, p=0.002); in the cluster 2 (n=12) GR activity after treatment negatively correlated with scores by PANSS (R=-0.9, p=0.001), PANSS negative subscale (R=-0.8, p=0.004), and CGI-S (R=-0.9, p=0.001).

The revealed correlations between enzymatic activities and clinical parameters give hope on detection of useful biochemical markers which, after enlargement of patients’ group with late onset psychotic disorders, would be validated for prediction of the pharmacotherapy efficiency and outcome of treatment.

No significant relationships.

Anxiety disorders are frequent comorbidity in patients with schizophrenia. Their frequency in late-onset psychosis is unknown.

We aimed to study life-time anxiety disorders as well as other psychiatric pathology in patients with late-onset schizophrenia (LoS) and late-onset delusional disorder (LoDD).

42 patients with LoS (age 64,1±9,2, 12% males) and 15 patients with LoDD (n=15; age 69,9±10,9, 14% males ) underwent clinical assessment (PANSS, HDRS-17), cognitive examination (MMSE, MoCA), structured interviewing on life-time pathology. Control group included 24 subjects with no signs of depression or psychosis (age 58,1±10,8, 50% males). Kruscal-Wallis and χ2statistic was used.

Patients with LoS and LoDD had higher frequency of social phobia (50% and 30% compared to 16,7 in control group, χ2 (2)= 6,834, p= 0,033) and more animal phobias (KW χ2 (2)=15,536, p<0,001). The number of habitual anxiety reaction was increased in LoS but not LoDD patients compared to controls (KW χ2 (2)=7,275, p= 0,026) with more severe motor (KW χ2 (2)=8,516, p= 0,014), vegetative (KW χ2 (2)=8,633, p= 0,013 and ideatory symptoms (KW χ2 (2)=6,969, p= 0,031) of anxiety. There was no group difference in life-time frequency of depression. Patients and controls had similar rate of complicated grief, but controls had often no reaction in response to loss and LoS patients responded to loss with manifestation of psychosis (χ2 (6)= 14,473, p= 0,025).

Social phobia and other anxiety disorders are frequent in late-onset psychosis. Symptoms of generalized anxiety are more specific to LoS than to LoDD.

No significant relationships.

Prodromal stage of psychosis may be an aim of prevention first episode psychosis. In late-onset psychosis it’s low described.

The aim of this investigation is to describe prodromal phase of late-onset psychosis and their connection with psychopathology.

74 women with late-onset psychosis (age 64,3±6,7) - late-onset schizophrenia (LOS) (n=49, age 63±8,4), schizoaffective disorder (n=17, age 62,4±6,5), late onset delusion disorder (LoDD) (n=8, age 76,6±4,3) underwent clinical assessment (SOPS, PANSS, HAMD-17), cognitive examination (MMSE, MoCA), structured interviewing on life-time pathology. Spearman’s rho statistics was used.

LOP patients have low prodromal symptoms according to the SOPS score. In LOS patients middle score of SOPS is 18±8,5, in schizoaffective patients middle score of SOPS is 12,3±6,8, and for LoDD SOPS is 13,4 ±4,6. Prodromal disturbances are represented mainly by fragmentary paranoid ideas, thoughts of unusual content, acoasms and affective fluctuations. In LOS patients SOPS negative subscale correlate with HAMD (r=0,384, p<0,05), desorganisation subscale correlate with PANSS common psychopathology subscale (r=0,32, p<0,05) and total PANSS (r=0,28, p<0,05), generous subscale and common SOPS correlate with HAMD (r=0,29, r=0,3, p<0,05). For patients with schizoaffective disorder there is no correlations, and in patients with LoDD SOPS desorganisation subscale negative correlate with PANSS negative subscale (r=-0,71, p<0,05).

In patients with late psychoses, the severity of disorders in the prodromal period is minimal. However, prodromal features are associated with the psychopathology.

No significant relationships.

Social phobia is frequent comorbidity in schizophrenia. It`s clinical correlates and consequencies for clinical practice in late-onset schizophrenia (LoS) are unclear.

The study aimed to compare clinical correlates and therapeutic options in LoS patient with and without social phobia.

16 LoS patients with social phobia (ICD-11 diagnosis, age 59,6±6,2, 25% males) were compared with 16 LoS patients without social phobia (69,9±10,9, 0% males). Results of clinical assessment (PANSS, HDRS-17), cognitive examination (MMSE, MoCA), CT data were analysed. Type of antipsychotics (conventional\conconventional) was registed, dose of antipsychotics and antidepressants was randed from 1 (low) to 3 (high). Mann-Whitney test and χ2statistic was used.

There was no group differences in age, age manifestation, illness duration, number of psychotic episodes, PANSS and HADRS scores, rates results of cognitive tests, atrophy scores, length of hospital state, types of received antipsychotics. LoS patients with social phobia received more frequently medium and high doses of antipsychotics than LoS patient without social phobia (χ2 (2)=6,432, p=0,040).

Increased doses of antypsychotics in patients with social phobia don`t correlate with severity of psychotic symptoms and nay reflect some treatment resistance as well as misinterpretation of symptoms of social phobia as insufficient retreat of the psychosis. Active detection of social phobia is significant for treatment optimization.

No significant relationships.