A. R. Van Gool

Family system characteristics and psychological adjustment to cancer susceptibility genetic testing: a prospective study.

This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis colorectal cancer‐related mutation. Family functioning, differentiation to parents, hereditary cancer‐related family communication and perceived support from relatives were assessed in 271 participants for genetic testing before test result disclosure. Hereditary cancer distress (assessed by the Impact of Event Scale) and cancer worry (assessed by the Cancer Worry Scale) were assessed before, 1 week after, and 6 months after test result disclosure. Participants reporting more cancer‐related distress over the study period more frequently perceived the communication about hereditary cancer with relatives as inhibited, the nuclear family functioning as disengaged‐rigid or enmeshed‐chaotic, the support from partner as less than adequate and the relationship to mother as less differentiated. Especially, open communication regarding hereditary cancer and partner support may be important buffers against hereditary cancer distress. Identifying individuals with insufficient sources of support and addressing the family communication concerning hereditary cancer in genetic counseling may help the counselee to adjust better to genetic testing.

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C

Aliment Pharmacol Ther 2011; 34: 1306–1317

Influence of pegylated interferon-α therapy on plasma levels of citrulline and arginine in melanoma patients

Summary.The aim of this study was to evaluate the effect of pegylated interferon-alpha (PEG-IFN-α) on the plasma citrulline/arginine ratio, regarded as an index of nitric oxide (NO) synthesis, in patients with high-risk melanoma. Forty patients were randomly assigned to either PEG-IFN-α treatment (n = 22) or to observation only (control group, n = 18). The treatment group received 6 µg PEG-IFN-α/kg once a week during 8 weeks, followed by a maintenance dose of 3 µg/kg/wk. Blood was collected at different time points, plasma concentrations of citrulline and arginine were measured and the ratio of citrulline/arginine was calculated. Patients treated with PEG-IFN-α showed a significant decrease in the concentrations of citrulline and in the citrulline/arginine ratio during the whole study period, both compared to baseline values and to the control group. The data suggest that therapy with PEG-IFN-α results in a marked decrease in the synthesis of NO in melanoma patients.

Interferon, tryptophan and depression.

Depression is a frequent comorbid disorder of many inflammatory diseases and it is suggested that brain inflammatory processes have a pathogenic role in mood dysregulation. Several immunocompromised patients have been treated with cytokines and long-term treatments have resulted in a variety of neuropsychiatric side-effects. The objective of the study was to present evidence for an association between the induction of neuropsychiatric side-effects during treatment with interferon-α (IFN-α) and changes in serotonergic and immunological parameters. Moreover, the use of IFN-α-induced depression as a paradigm for research into the pathophysiology of depressive disorders in general will be discussed. This literature review focused on the relationships between tryptophan, serotonin, cytokines and depression associated with interferon treatment. Immunotherapy with IFN-α influences several immunological and serotonergic parameters, and induces in most patients neurovegetative, somatic and depressive symptoms. Literature findings indicate that the development of depressive symptoms in patients undergoing cytokine therapy are secondary to cytokine induction and could be mediated by a reduced availability of tryptophan to the brain, resulting ultimately in decreased serotonergic activity. Changes in the metabolism of tryptophan and consequently of serotonin may play a role in the pathophysiology of interferon-induced depression. Studies on interferon-induced neuropsychiatric side-effects may be a promising research paradigm and shed light on the role of immunological and serotonergic factors in the pathogenesis of depressive disorders in general. However, first the appropriate symptomatology of the interferon-induced depressive states has to be documented.

Psychiatric Side Effects and Fluctuations in Serotonergic Parameters in the Treatment of Chronic Hepatitis C Infection

Introduction: Treatment of hepatitis C with peginterferon induces psychiatric side effects. These might include changes in serotonergic function. Methods: Twenty-two hepatitis C patients were treated with peginterferon. At different time points, psychometric assessment was performed using the Profile of Mood States. Plasma samples were taken to study serotonergic parameters. Results: Anger and depression increased compared to baseline, starting with anger (from week 3 onwards), followed by depression (from week 7 onwards). Other scores did not show consistent changes. No consistent changes were observed in tryptophan, tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic acid. The tyrosine/large neutral amino acids ratio, neopterin, phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to baseline. Prolactin levels were associated with the occurrence of depression and anger. Discussion: Particularly anger and depression increased during treatment. Neither a decrease in tryptophan and tryptophan availability was seen, nor a relationship between these parameters and the development of psychopathology. Therefore, other mechanisms in the induction of psychopathology should be considered. The observed increases in neopterin and phenylalanine/tyrosine ratio are indicative of changes in tetrahydrobiopterin, which is involved in the metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the increase in prolactin. The increase in prolactin levels and its relationship with depression and anger needs further exploration.