Social approach and avoidance behaviour for negative emotions is modulated by endogenous oxytocin and paranoia in schizophrenia.

Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance.

Sex steroids and personality traits in the middle luteal phase of healthy normally menstruating young professional women.

OBJECTIVE: Sex steroids affect human behavior. The aim of the present study was to determine the associations, if any, between the circulating levels of gonadal and adrenal sex steroids in the mid luteal phase (21st day of a normal menstrual cycle, MC) of young professional women and psychometric parameters as assessed by the Minnesota Multiphasic Personality Inventory (MMPI). RESULTS: Our results are as follows: (a) The metabolic product of activated adrenal and gonadal androgens, 3alpha-diolG, was modestly but significantly associated with the social introversion scale (10-SI) (r=0.36, p<0.05), independently accounting for 13% of its variation across participants (R²=0.13, F(1,45)=6.58, p=0.014). (b) Total testosterone was significantly associated with the paranoia scale (6-Pa) (r=0.27, p<0.05). Multiple regression analyses indicated that 10% of the variability in paranoia scores could be independently explained by total testosterone levels (R²=0.10, F(1,57)=6.23, p=0.016). We were unable to find any association between the circulating androgens and scores on the masculinity-femininity scale (Mf). We were also unable to document any association between the weak adrenal androgens DHEA and DHEA-S and depression in contrast to several published reports. (c) Our data suggest a marginally significant association between progesterone and scores on the 7-Pt (obsessive/compulsive/psychasthenia) scale (r=0.27, p<0.05). However, only 7% of the 7-Pt variance was explained by progesterone (R²=0.071, F(1,50)=3.81, p=0.057). CONCLUSIONS: We have found that total testosterone was associated with the paranoia score, the metabolic product of activated androgens, 3alpha-diolG, to social introversion and, finally, progesterone to obsessive-compulsive behavior.

Polymorphisms in AKR1C4 and HSD3B2 and differences in serum DHEAS and progesterone are associated with paranoid ideation during mania or hypomania in bipolar disorder.

Paranoia is commonly a mood-incongruent psychotic symptom of mania which may be related to dopamine dysregulation. Progesterone and its metabolite allopregnanolone (ALLO) have been found in animals to antagonize the effects of dopamine. We therefore examined serum progesterone, its endogenous antagonist DHEAS and polymorphisms of the genes coding for certain steroidogenetic enzymes (AKR1C4, HSD3B2, and SRD5A1) in 64 males and 96 females with bipolar 1 or 2 disorder with or without paranoid ideation during mood elevation. Euthymic morning serum progesterone, DHEAS and cortisol concentrations were measured in males and in premenopausal women who were in follicular phase and not taking oral contraceptives. In women only, SNPs in AKR1C4 reduced the likelihood of having exhibited paranoid ideation by circa 60%. The haplotype of all 4 SNPs in the AKR1C4 gene reduced the risk of exhibiting paranoia by 80% (OR 0.19, 95% CI 0.06-0.61, p=0.05). A history of paranoid ideation was not, however, related to progesterone or DHEAS concentration. Serum DHEAS and progesterone concentrations were lower in men who had shown paranoid ideation during mania/hypomania compared with those who had not (F=7.30, p=0.006) however this was not coupled to polymorphisms in the selected genes. The ancestral G in rs4659174 in HSD3B2 was in men associated with a lower risk of paranoid ideation (likelihood ratio χ(2) 3.97, p=0.046, OR 0.31 (95% CI 0.10-0.96)) but did not correlate with hormone concentrations. Hence, gene variants in the steroidogenetic pathway and steroids concentration differences may be involved in the susceptibility to paranoia during mood elevation.

[Neuropsychiatric symptoms revealing pseudohypoparathyroidism with Fahr's syndrome]. / Manifestations neuropsychiatriques révélant une pseudohypoparathyroïdie avec un syndrome de Fahr.

UNLABELLED: Fahr's syndrome is characterized by the presence of intracerebral, bilateral and symmetrical non-arteriosclerotic calcifications, located in the central grey nuclei. One of its main etiologies is pseudohypoparathyroidism (PHP), due to a resistance to the action of parathormone (PTH) with essentially hypocalcaemia and a normal or a high rate of PTH. CASE REPORT: Mr B.A. is a 36-year-old man, admitted to hospital because of refractory psychotic symptoms associated with alcohol abuse and fits of convulsion, for diagnostic and therapeutic update. Mr B.A. had presented convulsions since the age of 10, without regular medical treatment. He showed a decrease in his school performances and started using alcohol. Since the age of 17, he began expressing delusions of persecution and of enchantment fed by the persistence of the convulsions. He was administered phenobarbital, and classic antipsychotics (haloperidol and levomepromazine) and developed serious extrapyramidal side effects, treated with an anticholinergic (trihexyphenidyl). Evolution was rather disadvantageous: more epileptic fits, exaggeration of tremors; abuse of alcohol and persistence of psychotic symptoms. On admission, psychiatric examination objectified paranoid delusions of being possessed and persecuted by others. Neurological examination revealed the presence of limb tremors, with a positive Froment's sign on the right, and dysarthria. Other than this, the patient was shorter in comparison with his siblings and exhibited bad dentition. A CT brain scan found bilateral, symmetric basal ganglia calcifications, confirmed by MRI, in favour of Fahr's syndrome. Phosphocalcic investigations revealed a low concentration of serum calcium (65 mg/l) and a hyperphosphataemia (60.1mg/l). The blood level of parathyroid hormone was in the upper limit of normal (66 ng/l), and levels of thyroid hormones and thyroid-stimulating hormone were normal. The diagnosis of Fahr's syndrome, revealing a pseudohypoparathyroidism was posed, and the patient was orientated to endocrinology after readjustment in his therapy (sodium valproate and olanzapine). DISCUSSION: About 40% of the patients with Fahr's syndrome are seen with primarily cognitive and other psychiatric findings. For this patient, hypocalcaemia was at the origin of his convulsions, and the use of phenobarbital, known for its hypocalcemiant action, provoked the inverse result. Alcohol drinking also aggravated hypocalcaemia, and maintained the fits. The use of classic antipsychotics and anticholinergic agents, amplified the extrapyramidal signs caused by Fahr's syndrome. Recognizing the origin of the symptoms allowed rethinking the therapeutic strategy according to all these elements. CONCLUSION: Psychiatrists should consider Fahr's syndrome as a differential diagnosis in the evaluation of psychosis associated with convulsions. This case, along with others in the literature, further emphasizes the importance of the role of neuro-imaging and the search for disrupted phosphocalcic metabolism in patients with atypical or refractory psychotic symptoms.

Factors affecting the development of spontaneous recurrence of methamphetamine psychosis.

The process triggering spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks) was studied in 41 flashbackers, along with 84 non-flashbackers with a history of MAP psychosis. Plasma monoamine metabolite levels were assayed in 25 of the 41 flashbackers, 16 of the 84 non-flashbackers, 9 subjects with persistent MAP psychosis and 28 control subjects. All flashbackers had experienced threatening events or frightening paranoid-hallucinatory states during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. Plasma norepinephrine levels were elevated during flashbacks. The results suggest that a mild fear of other people may have elicited memories of MAP psychosis associated with threatening experiences through increased sensitivity to psychosocial stressors. As a result the flashbacks occurred, including an increase in peripheral noradrenergic activity.

[Carbamazepine-fluvoxamine interaction. Consequences for the carbamazepine plasma level]. / Interaction carbamazépine-fluvoxamine. Conséquences sur le taux plasmatique de carbamazépine.

The current practices concerning psychotropic drugs use plasma levels for the therapeutic adaptation and for the prevention of overdose and side effects. We observed, among two patients treated with constant dosages of carbamazepine (CBZ), that the addition of fluvoxamine (FLV) has increased significantly plasma levels of CBZ. The first patient, suffering of an affective bipolar trouble (ICD-10), was hospitalized for major depression. His admission treatment was CBZ (800 mg/day) and cyamemazine (75 mg/day). The introduction of the FLV (200 mg/day) was justified by the symptomatology. Then, plasma levels of CBZ increased progressively. No clinic or biological side effect was observed. Rapidly, CBZ oral dosages were decreased, but the plasma levels of CBZ reached the therapeutic window only when the FLV prescription was definitively stopped. The other patient was hospitalized for an acute exacerbation of a paranoiac disorder. He was treated with haloperidol for this episode. For five years, he received CBZ for neuralgia of the Trigeminus. The emergence of a depressive disorder justified a FLV treatment. From the introduction of FLV, plasma levels of CBZ were significantly increased. The reduction, then the stop of the FLV treatment, has allowed the standardization of plasma concentrations of CBZ. Three similar studies were found in the literature. The danger of this interaction was notified in two studies (one case each). Furthermore, in the third study (three cases) was put forward the hypothesis of a new therapeutic pathway. this hypothesis was suggested by the fact that these two medications were proposed independently to treat impulsive behaviors.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lithium and hyperthyroidism]. / Lithium und Hyperthyreose.

The development of hypothyroidism and the forming of a goiter are well-known complications associated with lithium medications. But there are also occasional references to cases of hyperthyroidism in the wake of both continual and of discontinued lithium medication. In the case being reported on here of a lady patient aged 64 and suffering from a toxic adenoma not recognized at the time, thyrotoxicosis accompanied by above-normal FT-3 results and the characteristic clinical symptoms developed when lithium medication was discontinued. Medical literature consulted in the context discussed pharmacological mechanisms which may be responsible for the said complications.

Platelet serotonin in subtypes of schizophrenia and unipolar depression.

In subtypes of schizophrenia and unipolar depression, both increased and decreased levels of platelet serotonin were found. Hyperserotonemia was usually observed in patients with psychotic features (i.e., in paranoid schizophrenia and psychotic depression). Hyposerotonemia, although less common than hyperserotonemia, was present in nonparanoid schizophrenia and nonpsychotic depression (i.e., in patients without psychotic symptoms). A sex difference in platelet monoamine oxidase activity was observed among healthy subjects, but not among schizophrenic patients. The activity of platelet monoamine oxidase in paranoid and nonparanoid schizophrenic patients did not differ from that in healthy subjects. The findings in this study suggest that biological differences between subtypes of unipolar depression or schizophrenia might depend upon the presence of psychotic symptoms.

[Therapy control of perphenazine. 2. Clinical aspects]. / Terapistyring af perfenazinbehandling ved paranoide tilstande. 2. Kliniske aspekter.

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects]. / Terapistyring af perfenazinbehandling ved paranoide tilstande. 1. Organisatoriske aspekter.

A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.

Cocaine psychosis.

A 28-year-old divorced black male intranasal cocaine abuser presented three times in seven days to the psychiatric emergency service of a general hospital with complaints of psychotic symptoms in the context of a cocaine binge. His repeated visits provided the opportunity to correlate his clinical picture with serum cocaine levels. This article describes that correlation and reviews the current literature on cocaine abuse and the cocaine abstinence syndrome.

Selenium concentrations in blood and serum from patients with mental diseases.

Blood and serum concentrations of selenium have been determined in a group of psychiatric patients and in 35 healthy controls. The psychiatric group consisted of 14 schizophrenics, seven paranoid disorders, six affective psychosis (manic-depressive), four reactive psychosis, 11 dementia senilis, 17 with a diagnosis of neurosis and two with delirium tremens. Normal values were found in all groups except for delirium tremens where decreased blood and serum values were found.

Reduced platelet serotonin in depression.

Platelet serotonin levels were measured in several psychiatric disorders to determine whether they distinguish among major depressive disorder (one or more depressive episodes and no manic episodes), dysthymic disorder (depressive neurosis), and schizophrenic and paranoid disorders. Serotonin levels in 141 subjects were determined using high performance liquid chromatography with electrochemical detection. Serotonin (5HT) levels in control subjects were significantly lower in males than in females. A marked reduction in 5HT levels, as compared to controls, was found in male and female patients with major depressive disorder, but not in dysthymic disorder. A slight but significant reduction in serotonin levels was found in female schizophrenic patients. The reduction in serotonin levels found in major depressive disorder could not be attributed to chronic antidepressant treatment. Liquid chromatography with electrochemical detection used in the present study permits a large-scale investigation.

[Reduction of platelet serotonin in major depression (endogenous depression)]. / Diminution de la sérotonine plaquettaire dans la dépression majeure (dépression endogène).

Serum serotonin (5-HT) levels were measured in several patients with psychiatric disorders using high pressure liquid chromatography with electrochemical detection. A marked reduction in 5-HT levels was found in male and female patients with major depressive disorder, as compared to controls, but not in dysthymic disorder. These modifications may constitute biochemical changes suggestive of major depressive disorders; they could not be attributed to chronic antidepressant treatment.

Electrocardiographic changes and serum concentrations in thioridazine-treated patients.

Electrocardiograms and serum concentrations of thioridazine and its metabolites were studied in 43 patients with paranoid psychosis. Two types of T-wave changes were distinguished: Type I with rounded, leveled, or notched T-waves, and Types II with diphasic waves. Significant positive correlations were found between serum drug concentrations and the Type I changes, while the Type II changes showed no concentration dependence. The two types of T-wave changes also differed in respect of prevalence, time of onset, duration, and variation with sex. The ECG response to thioridazine provides useful information about the serum drug concentrations.

The dexamethasone suppression test as a diagnostic aid in late onset paranoia.

A case of acute paranoia in a 64-year-old woman with a previous history of one depressive episode is described. Accurate diagnosis was hampered by her illogical and tangential answers to questions and the development of an organic brain syndrome while on neuroleptics and anticholinergics. She did not tolerate tricyclic antidepressants and was unresponsive to three electroconvulsive therapy (ECT) treatments. Because of the previous history of depression and the presence of some depressive symptoms, the possibility of a depression underlying her paranoid psychosis was considered. A dexamethasone suppression test (DST) was performed to confirm this and was found to be abnormal. ECT was then continued with the eventual result of complete remission in symptoms. The authors discuss the potential usefulness of the DST in confirming a diagnosis of depression in selected cases of late onset psychosis.