Back to Journals » Neuropsychiatric Disease and Treatment » Volume 11

Psychiatric symptoms in glioma patients: from diagnosis to management

Authors Boele F, Rooney A, Grant R, Klein M

Received 19 March 2015

Accepted for publication 10 April 2015

Published 10 June 2015 Volume 2015:11 Pages 1413—1420

DOI https://doi.org/10.2147/NDT.S65874

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Roger Pinder



Florien W Boele,1 Alasdair G Rooney,2 Robin Grant,2 Martin Klein1

1Department of Medical Psychology, VU University Medical Center, Amsterdam, the Netherlands; 2Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK

Abstract: Patients with primary intrinsic brain tumors can experience neurological, cognitive, and psychiatric symptoms that greatly affect daily life. In this review, we focus on changes in personality and behavior, mood issues, hallucinations, and psychosis, because these are either difficult to recognize, to treat, or are understudied in scientific literature. Neurobehavioral symptoms are common, often multiple, and causation can be multifactorial. Although different symptoms sometimes require a different treatment approach, we advise a comprehensive treatment approach, including pharmacological treatment and/or psychotherapy where appropriate. Further research is needed to obtain a better estimate of the prevalence of psychiatric symptoms in glioma patients, and the extent to which these affect everyday functioning and family life.

Keywords: glioma, psychiatry, personality, mood, hallucinations, psychosis

Background

Gliomas (World Health Organization [WHO] grade II, III, or IV) are the most common primary malignant brain tumors, with an incidence of six per 100,000.1 Despite efforts in improving the treatment of gliomas, these tumors cannot be cured. Patients suffering from a low-grade glioma (WHO grade II) have a median survival of 5–15 years,2 while this is 2–3 years for patients with a WHO grade III tumor.3,4 For patients with WHO grade IV tumors, the median survival does not exceed 12–14 months.5 While survival is traditionally stratified by tumor grade, genetic markers including IDH mutation, 1p/19q codeletion, and MGMT methylation have more recently been established as important prognostic markers in glioma patients.6 The antitumor treatment usually consists of a combination of surgery, radiotherapy, and chemotherapy. In addition, drugs for symptom management, such as corticosteroids and anticonvulsants are often prescribed for a prolonged period of time.7,8

As the tumor progresses, various symptoms resulting from the disease often become more pronounced. As both the disease and its treatment have a direct effect on brain functioning, patients commonly experience neurological, cognitive, and psychiatric symptoms.9 Neurobehavioral symptoms may affect the patient’s ability to engage with clinical decision-making and ultimately may affect survival. Moreover, these symptoms can negatively affect patients’ direct social environment, such as spouses, family members, and close friends.10 With the patients’ increasing demand for mental and physical support, these significant others often become informal caregivers. Because of the substantial impact of the disease and its treatment on the everyday lives of patients and their loved ones, it is important to pay attention to symptom management and quality of life. Changes in personality and behavior, mood issues, hallucinations, and psychosis are either difficult to recognize, to treat, or are understudied in scientific literature. In this review, we will therefore focus on these neurobehavioral symptoms. Different treatment options are summarized and presented in Table 1.

Table 1 Treatment options for changes in personality and behavior, mood issues, and hallucinations and psychosis in patients with glioma

Changes in personality and behavior

Most studies focusing on changes in personality and behavior in brain tumor patients use a qualitative study approach, or are case reports. An estimation of the real frequency of behavioral problems experienced by glioma patients and their informal caregivers is uncertain, but these qualitative studies allow for a detailed description of commonly experienced issues.

Symptoms of anger, loss of emotional control, indifference, and change in behavior are commonly reported.1115 Changes in personality can lead to difficulties recognizing and interpreting social behavior. Such difficulties in social cognition can interfere severely with family life and social relationships. For other brain tumor patients, personality changes can manifest as exhaustion and anxiety, leading to withdrawal from social situations, and feelings of sadness and grief.14 These changes may, as in any cancer patient faced with a dismal prognosis or uncertainty concerning the future, in part be explained or compounded by processes of grief or an adjustment disorder. However, personality changes can also result directly from the presence of the tumor or its treatment. The precise extent to which tumor location impacts on psychopathology is not well understood.

Classically, three “frontal lobe syndromes” have been proposed to arise in patients with brain tumors located in specific prefrontal areas.16 In this model, damage to dorsolateral prefrontal areas is associated with impaired executive functioning, orbitofrontal damage may cause disinhibition and impulsiveness, and lesions in the medial frontal areas may result in apathy or abulia.17,18 It is worth acknowledging that this broad model is underpinned by relatively little recent, high-quality evidence that is specific to brain tumor patients. Brain tumor-specific studies may be important, given the considerable uncertainty over how tumor-related metabolic changes, diaschisis, and cerebral edema or mass effect may interact with location to mediate the behavioral phenotype.

A few quantitative studies do indicate that behavioral problems are more evident in patients with frontal tumors than in controls without neurological compromise.19 Patients with frontal tumors report more executive dysfunction, apathy, and disinhibition than patients with nonfrontal tumors.20 However, clinically significant levels of apathy and executive dysfunction are reported by many patients with tumors located outside the frontal lobes too, and the relationship is not straightforward.20 Indeed, it is likely that highly complex interactions between cortical and subcortical damage adds to behavioral problems. For example, patients with heteromodal frontal or parietal tumors often experience negative mood states. When paralimbic structures are involved, mood problems become more aggravated. However, damage to motor and somatosensory cortex is associated with positive mood and seems to ameliorate negative mood states.21 It therefore seems unlikely that behavioral problems are a direct result of frontal or nonfrontal damage. One recent study using voxel-based lesion-symptom mapping (VLSM) provides some interesting evidence for more subtle neuropsychological effects of tumor location. The ability to discern the emotions and intentions of others was impaired in patients with tumors in the temporal lobe. More complex components of personality and behavior (such as the ability to conceptualize and describe internal emotions and the facets of one’s character) were adversely affected by tumors in prefrontal regions.22 The advent of more sensitive neuroimaging and analysis techniques such as VLSM brings the opportunity to explore the relationship between tumor location and psychopathology in greater detail than was previously possible.

Many patients have only limited awareness of their symptoms. Impaired emotion recognition and behavioral problems are associated with a lack of self-awareness, which can lead to perspective-taking difficulties. After surgery, brain tumor patients are more likely to underestimate their psychological problems and the negative impact of changes to their emotional functioning, interpersonal relationships, neurocognitive functioning, and coping skills.23 This can be distressing for partners and others who are closely involved.23 Moreover, lack of awareness of deficits can have a major impact on the outcome of rehabilitation after treatment.24 As social and behavioral problems are often very difficult to detect in clinical neuro-oncological practice, but can affect the lives of patients and their partners in a very profound way, these issues are of special concern.

Managing changes in personality and behavior

Recently, Chambers et al published a comprehensive overview of guidelines for psychosocial care in neuro-oncology.25 In terms of management of changes in personality and behavior, the authors advise patient education, early detection of symptoms, and referral to neuropsychology, neuropsychiatry, or neurorehabilitation services if needed.25

To encourage early detection of symptoms, health care professionals should enquire after behavioral problems in routine consultation. While patients may not be aware of problems in everyday life, the informal caregivers can usually indicate if behavioral changes cause issues. Although to our knowledge, there are no brain tumor-specific, validated paper-and-pencil screening instruments available to assess changes in behavior, a question such as the personality change item of the Functional Assessment of Cancer Therapy-Brain26 (“I am bothered by the change in my personality”, with answer options ranging from “not at all” to “very much”) may suffice in determining whether patients should be referred for extensive psychological assessment. Neuropsychological testing is then warranted to assess different aspects of the patients’ social cognition. However, development of screening instruments and validation of existing, more comprehensive questionnaires such as the Neuropsychology Behavior and Affect Profile27 and the Katz Adjustment Scale-Revised28 in the brain tumor patient population would be worthwhile.

To help patients and their informal caregivers cope with changes in personality and behavior, it is important to provide education. Improved education can reduce uncertainty and distress, and increase empowerment.29,30 In a recent systematic review, Langbecker and Janda investigated the available interventions to improve information provision for brain tumor patients and their informal caregivers.31 They conclude that although satisfaction rates of patients and their informal caregivers improve when an intervention is offered, more research is needed to determine the most effective intervention components and the most appropriate timing for the delivery of the intervention.

In usual practice, the focus is mostly on the physical recovery of the patient,32 but improvements in neurocognitive functioning are sometimes evaluated as well through brief screening measures such as the functional independence measure (FIM).3337 Some evaluation studies show modest improvement in brain tumor patients’ social cognition (assessed with the FIM as social interaction, problem-solving, and memory38), which does not appear to be related to the tumor type.35,36,39 However, it remains unclear whether the very brief FIM cognitive scores adequately reflect more subtle behavioral and personality changes and difficulties in social functioning in everyday life. Moreover, only inpatient groups were studied, which hinders the generalization of findings – especially with respect to patients with less malignant tumor such as low-grade gliomas. More prospective studies and randomized controlled trials (RCTs) to evaluate the role of neurorehabilitation in improving social functioning are therefore warranted.

Psychologists can support patients and informal caregivers to employ more effective coping strategies to deal with changes in personality and behavior.40 Alternatively, an adapted cognitive behavioral approach could be used. Defining the changed personality as the end behavior, an assessment can formulate an understanding of the patient’s thoughts and emotions, and where these might interact to cause the problematic behavior. With this approach, it may become possible to identify possible targets for therapeutic intervention. However, there are, to our knowledge, no intervention programs available aimed specifically at glioma patients’ difficulties with changes in behavior and personality. Although (neuro) psychologists aware of the disease-specific symptoms of brain tumors may effectively apply the principles of cognitive behavioral therapy (CBT), further studies are also warranted here.

Mood issues

Following the diagnosis of glioma, many patients experience psychological distress and mood issues. Mania, feelings of anxiety, depression, and even suicidal ideation can occur. Furthermore, shock and disbelief, anger and despair, dysphoria and anxiety, or intrusive thoughts about the disease may be prominent.41 Often, these emotional reactions are transient in nature, but sometimes their severity and/or persistence suggests an adjustment disorder or a major depressive disorder.42 Moreover, mania and other mood disorders may in rare cases occur secondary to the brain lesion itself,43 although the underlying mechanisms are not well understood.44,45 Therefore, a biopsychosocial framework, taking into account the dynamic interactions between neurocognitive factors, psychological processes, and the social environment has been suggested as useful to conceptualizing these disorders.46 For example, patients with a personal or family history in psychiatric disease are more susceptible to psychological maladjustment after brain tumor.47,48 Moreover, mood issues can be attributed variously to side effects of treatment (eg, antiepileptics49), biochemical changes in the brain,45 changes in cytokine levels,50 elevated intracranial pressure, or the location of the tumor.51 Frontal cortex lesions and lesions in the parietal association cortex and paralimbic structures have been associated with mood changes, specifically.21 Demographic variables such as sex, age, marital status, ethnicity, and education level are not consistently associated with anxiety and depression in glioma patients, but increased physical disability and cognitive impairment often co-occur with mood issues.52

Systematic reviews and longitudinal studies suggest that approximately 15%–20% of glioma patients will develop clinical major depressive symptoms during the first 8 months after diagnosis.52,53 In this, no clear distinction between low- and high-grade gliomas can be made based on the available literature.52 The increased risk for depression may be maintained up to a year after surgical intervention.54 This makes depression considerably more likely than in the general population (where the point prevalence is approximately 5%).55 However, there is no consistent evidence that brain tumor patients are at a higher risk of depression than patients with cancer not involving the central nervous system.48,56

To date, very little research has been performed to examine the prevalence of suicidal ideation among brain tumor patients. In a large retrospective study among adult survivors of a childhood brain tumor, approximately 12% of patients experienced suicidal ideation.57 In this study, depression, psychoactive medication use, history of seizures, and observation or surgical treatment were associated with suicidal ideation. With regard to successful suicide, there are indications that brain tumor patients are at an increased risk for death by suicide.58,59 However, others have reported that patients with brain tumors are less likely to commit suicide than other patients with cancer,60 and are more likely to die an accidental death instead.61 Nevertheless, the use of glucocorticoids such as dexamethasone, which is often prescribed in glioma patients, increases the risk for suicide or suicide attempt, depression, and panic disorder considerably.62 From the epilepsy literature, we know that suicidal thoughts can co-occur after temporal lobe surgery.63

It is a commonly acknowledged problem that mood issues, when understandable given the disease stage or process, can be difficult to discuss for health care professionals.64 In neuro-oncology, this likely not only pertains to understandable psychological reactions, but also to what can be expected based on the tumor type, location, and treatment side effects.65 Mood issues that are potentially treatable may then be overlooked and undertreated.66 This can have serious negative consequences for glioma patients’ quality of life,67 and even their morbidity and survival.47,68

Managing mood issues

As mentioned above, recognizing mood issues may be difficult in the glioma patient population. When it is suspected, either from the patient’s perspective or the informal caregiver’s point of view, that mood issues interfere with everyday functioning, clinical assessment is needed to diagnose or exclude mood disorders. While it remains necessary to conduct a thorough psychiatric assessment to assess the degree of mood issues, there are screening measures that could be useful in the clinic. Recently, efforts have been made to validate three of these instruments in the glioma patient population.69 The Hospital Anxiety and Depression Scale70 and the Patient Health Questionnaire-971 can be useful to screen for mood issues. The Beck Depression Inventory-II72 is also often used in clinical practice but has not yet been validated in glioma patients. However, the utility of any screening scale for mood issues in glioma patients with significant cognitive impairment, or in patients in the palliative phase, is currently unknown.

National and international guidelines suggest that depression in patients with a chronic physical condition should, where possible, be treated with a combination of medication (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors, anxiolytics), and a high-intensity psychological treatment such as CBT or interpersonal therapy.73,74 Generally, pharmacological treatment and psychotherapeutic treatment are thought to contribute equally to beneficial effects.75

A lack of RCTs in glioma patients makes it difficult to gauge whether the same treatment strategies should be pursued in patients with brain tumor.76 Glioma patients are at a high risk of cognitive deficit and fatigue and may struggle to fully benefit from CBT. Antidepressant treatment brings the possibility of adverse drug interactions, for example, an increased risk of antiepileptic drug (AED) toxicity secondary to inhibition of metabolizing liver enzymes. Although antidepressants generally do not trigger epilepsy in healthy individuals, their risk of precipitating seizures in patients with a tumor growing in their brain is unknown. Regardless, both physicians and patients may at times be reluctant to initiate new pharmaceutical treatment.77 RCTs are therefore warranted to investigate the effectiveness of the standard treatment for mood disorders. Some retrospective evidence suggests that SSRIs may be well tolerated by patients with glioblastoma but more research is clearly required.78

Other initiatives should not be overlooked. Presently, we are conducting an RCT to evaluate the effects of an internet-based guided self-help course on depressive symptoms in glioma patients.79 Other interventions that are already evidence-based in other patient populations include problem-solving therapy80 and mindfulness.81,82 Moreover, interventions based on exercise programs appear to have a positive impact on both mood and the quality of life,83 and nurse-delivered interventions based on information provision and supportive attention show beneficial effects on mood in newly diagnosed cancer patients.84 Adapting existing and effective interventions to the glioma patient situation, by taking their disease-specific symptoms into account, could lead to improved evidence-based care for mood issues in glioma patients.

Hallucinations and psychosis

Although rare, some brain tumors present themselves through neurobehavioral or psychiatric symptoms only.85 Hallucinations16 and even psychosis86 have been reported in brain tumor patients. These symptoms can be very unsettling to patients and their informal caregivers. Currently, there is no evidence of a causative relationship between classical paranoid schizophrenia and brain tumors. Although large studies are lacking, there are indications that idiosyncratic psychoses can occur after resection of the (mesial) temporal lobes. Case studies describe acute psychosis, agitation, and suicidal/homicidal ideations with paranoia following surgery.86

Indeed, most studies of hallucinations and psychosis in glioma patients are case reports. As case reports often feature highly complex cases, with glioma patients who are suffering not only from the tumor, but also from epilepsy that is difficult to treat, psychosis, behavioral problems, and/or suicidal ideation,63,87,88 it is very difficult to make general statements about the prevalence of these symptoms in glioma patients per se. A review of case studies found that 22% of 148 cases experienced psychotic symptoms (here defined as delusions or hallucinations).89

Psychiatric symptoms seldom occur in isolation from other (psychiatric) symptoms in patients with brain tumors, eg, as shown in a study by Sokolski and Denson.90 Hallucinations in any sensory modality may occur as an epileptic phenomenon. In such cases, the hallucinations may subside after effective AED treatment, or surgical removal of the tumor.91 In addition, associations have been found between epilepsy and mood disorders. For example, manic or hypomanic states have been reported in patients undergoing temporal lobectomy for epilepsy, and postoperative mood disorders seem to be associated with preoperative postictal psychosis.92 Although psychosis appears to be more common in patients with temporal lobe epilepsy (~5%–15% of patients)93 than in brain tumor patients, it can occur and can have a major impact on people’s lives.

Managing hallucinations and psychosis

It is important to obtain a clear view of the patients’ hallucinations, and/or psychotic symptoms. In general, patients are able to describe their hallucinations if prompted. Hallucinations suggestive of an organic cause, such as brain tumor, are often visual, and auditory hallucinations tend to be nonpersecutory in nature.

Treatment of hallucinations usually consists of pharmacological treatment (eg, antipsychotics).94 Olanzapine or risperidone for example have been shown to counteract hallucinations.95 However, it is unclear how well these drugs work to reduce unimodal hallucinations not accompanied by other psychiatric symptoms, but mainly resulting directly from the lesion. On the other hand, hallucinations and psychosis often co-occur with other psychiatric symptoms.90 This is important to note, as the treatment used for the management of other symptoms can have an adverse effect on hallucinations and psychosis, and vice versa. For example, the use of steroids or AEDs can induce psychosis in brain tumor patients.96 Steroid psychosis generally arises at or shortly after the onset of corticosteroid treatment, and a higher dose increases the risk. The psychosis is characteristically, but not inevitably, affective and may fluctuate. Furthermore, although rare, antidepressants (SSRIs) may evoke hallucinations, which generally subside after cessation of medication.97 In close collaboration with the treating neuro-oncology team, reduction or cessation of medications that may cause the hallucinations and/or psychosis can be indicated. Alternatively, a regular low-dose antipsychotic such as haloperidol can be useful.

As hallucinations and psychotic symptoms can be very unsettling for both patients and their significant others, a nonpharmacological approach can prove beneficial as well. To reduce anxiety and disorientation, nursing provided by a familiar face, regular reassurance, de-escalation, and reorientation can provide relief. Other options include CBT for psychosis,98 or a combination with coping enhancement such as hallucination-focused integrative therapy, which has been shown to improve the quality of life.99 Mindfulness-based interventions100 and acceptance and commitment therapy101 for treating the emotional problems that may follow a psychotic episode have also been investigated, and show promising results. For auditory hallucinations specifically, Thomas et al recently provided a rather complete overview of the recent developments in treatment, including RCTs focusing on different types of CBT, and avatar therapy.102 Here, computer-generated avatars allow the patient to role-play with different responses to their auditory hallucination.

Conclusion

Neurobehavioral symptoms are common in brain tumor patients, often occur concurrently, and are difficult to tell apart. For example, affective disorders can co-occur with or mirror alexithymia,103 fatigue, and apathy, whereas a different approach in treatment may be necessary. Symptoms should preferably not be treated separately, but comprehensively. Depending on the severity of symptoms, pharmacological treatment and/or psychotherapy may be advisable. Therapists supporting brain tumor patients should always have thorough knowledge of the disease-specific symptoms of brain tumors to adequately address patients’ and informal caregivers’ needs. More research is needed to obtain a better estimate of the prevalence of the different psychiatric symptoms in glioma patients, and the extent to which these affect everyday functioning and family life.

Disclosure

The authors report no conflicts of interest in this work.


References

1.

Ho VK, Reijneveld JC, Enting RH, et al; Dutch Society for Neuro-Oncology (LWNO). Changing incidence and improved survival of gliomas. Eur J Cancer. 2014;50(13):2309–2318.

2.

van den Bent MJ, Afra D, de Witte O, et al; EORTC Radiotherapy and Brain Tumor Groups and the UK Medical Research Council. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet. 2005;366(9490):985–990.

3.

Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005;64(6):479–489.

4.

van den Bent MJ, Brandes AA, Taphoorn MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31(3):344–350.

5.

Stupp R, Mason WP, van den Bent MJ, et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996.

6.

Cohen AL, Colman H. Glioma Biology and Molecular Markers. Current Understanding and Treatment of Gliomas. Springer; 2015:15–30.

7.

Kostaras X, Cusano F, Kline GA, Roa W, Easaw J. Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline. Curr Oncol. 2014;21(3):e493.

8.

Weller M, van den Bent M, Hopkins K, et al; European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15(9):e395–e403.

9.

Mukand JA, Blackinton DD, Crincoli MG, Lee JJ, Santos BB. Incidence of neurologic deficits and rehabilitation of patients with brain tumors. Am J Phys Med Rehabil. 2001;80(5):346.

10.

Sherwood PR, Given BA, Donovan H, et al. Guiding research in family care: a new approach to oncology caregiving. Psychooncology. 2008;17(10):986–996.

11.

Andrewes DG, Kaye A, Murphy M, et al. Emotional and social dysfunction in patients following surgical treatment for brain tumour. J Clin Neurosci. 2003;10(4):428–433.

12.

Cavers D, Hacking B, Erridge SE, Kendall M, Morris PG, Murray SA. Social, psychological and existential well-being in patients with glioma and their caregivers: a qualitative study. Can Med Assoc J. 2012;184(7):373–382.

13.

Janda M, Steginga S, Dunn J, Langbecker D, Walker D, Eakin E. Unmet supportive care needs and interest in services among patients with a brain tumour and their carers. Patient Educ Couns. 2008;71(2):251–258.

14.

Lucas MR. Psychosocial implications for the patient with a high-grade glioma. J Neurosci Nurs. 2010;42(2):104–108.

15.

Sterckx W, Coolbrandt A, Dierckx de Casterlé B, et al. The impact of a high-grade glioma on everyday life: a systematic review from the patients and caregivers perspective. Eur J Oncol Nurs. 2013;17(1):107–117.

16.

Filley CM, Kleinschmidt-DeMasters BK. Neurobehavioral presentations of brain neoplasms. West J Med. 1995;163(1):19.

17.

Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol. 1993;50(8):873–880.

18.

Fuster JM. The prefrontal cortex – an update: time is of the essence. Neuron. 2001;30(2):319–333.

19.

Mattavelli G, Casarotti A, Forgiarini M, Riva M, Bello L, Papagno C. Decision-making abilities in patients with frontal low-grade glioma. J Neurooncol. 2012;110(1):59–67.

20.

Gregg N, Arber A, Ashkan K, et al. Neurobehavioural changes in patients following brain tumour: patients and relatives perspective. Support Care Cancer. 2014;22(11):2965–2972.

21.

Irle E, Peper M, Wowra B, Kunze S. Mood changes after surgery for tumors of the cerebral cortex. Arch Neurol. 1994;51(2):164–174.

22.

Campanella F, Shallice T, Ius T, Fabbro F, Skrap M. Impact of brain tumour location on emotion and personality: a voxel-based lesion-symptom mapping study on mentalization processes. Brain. 2014;137(9):2532–2545.

23.

Andrewes HE, Drummond KJ, Rosenthal M, Bucknill A, Andrewes DG. Awareness of psychological and relationship problems amongst brain tumour patients and its association with carer distress. Psychooncology. 2013.

24.

Dams-O’Connor K, Gordon WA. Role and impact of cognitive rehabilitation. Psychiatr Clin North Am. 2010;33(4):893–904.

25.

Chambers SK, Grassi L, Hyde MK, Holland J, Dunn J. Integrating psychosocial care into neuro-oncology: challenges and strategies. Front Oncol. 2015;5:41.

26.

Weitzner MA, Meyers CA, Gelke CK, Byrne KS, Levin VA, Cella DF. The functional assessment of cancer therapy (FACT) scale. Development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer. 1995;75(5):1151–1161.

27.

Nelson LD, Drebing C, Satz P, Uchiyama C. Personality change in head trauma: a validity study of the Neuropsychology Behavior and Affect Profile. Arch Clin Neuropsychol. 1998;13(6):549–560.

28.

Goran DA, Fabiano RJ. The scaling of the Katz Adjustment Scale in a traumatic brain injury rehabilitation sample. Brain Inj. 1993;7(3):219–229.

29.

Fallowfield L, Ford S, Lewis S. No news is not good news: information preferences of patients with cancer. Psychooncology. 1995;4(3):197–202.

30.

Ream E, Richardson A. The role of information in patients’ adaptation to chemotherapy and radiotherapy: a review of the literature. Eur J Cancer Care. 1996;5(3):132–138.

31.

Langbecker D, Janda M. Systematic review of interventions to improve the provision of information for adults with primary brain tumors and their caregivers. Front Oncol. 2015;5:1. [in press].

32.

Formica V, Del Monte G, Giacchetti I, et al. Rehabilitation in neuro-oncology: a meta-analysis of published data and a mono-institutional experience. Integr Cancer Ther. 2011;10(2):119–126.

33.

Fu JB, Parsons HA, Shin KY, et al. Comparison of functional outcomes in low-and high-grade astrocytoma rehabilitation inpatients. Am J Phys Med Rehabil. 2010;89(3):205–212.

34.

Huang ME, Cifu DX, Keyser-Marcus L. Functional outcomes in patients with brain tumor after inpatient rehabilitation: comparison with traumatic brain injury. Am J Phys Med Rehabil. 2000;79(4):327–335.

35.

Marciniak CM, Sliwa JA, Heinemann AW, Semik PE. Functional outcomes of persons with brain tumors after inpatient rehabilitation. Arch Phys Med Rehabil. 2001;82(4):457–463.

36.

Roberts PS, Nuño M, Sherman D, et al. The impact of inpatient rehabilitation on function and survival of newly diagnosed patients with glioblastoma. PM R. 2014;6:514–521.

37.

Tang V, Rathbone M, Dorsay JP, Jiang S, Harvey D. Rehabilitation in primary and metastatic brain tumours. J Neurol. 2008;255(6):820–827.

38.

Keith RA. The functional independence measure: a new tool for rehabilitation. Adv Clin Rehabil. 1987;2:6–18.

39.

Bartolo M, Zucchella C, Pace A, et al. Early rehabilitation after surgery improves functional outcome in inpatients with brain tumours. J Neurooncol. 2012;107(3):537–544.

40.

Anson K, Ponsford J. Evaluation of a coping skills group following traumatic brain injury. Brain Inj. 2006;20(2):167–178.

41.

Valentine AD, Passik S, Massie MJ. Psychiatric and Psychosocial Issues. Cancer in the Nervous System. 2nd ed. Oxford: University Press; 2002:572–589.

42.

Anderson SI, Taylor R, Whittle IR. Mood disorders in patients after treatment for primary intracranial tumours*. Br J Neurosurg. 1999;13(5):480–485.

43.

Starkstein SE, Mayberg HS, Berthier ML, et al. Mania after brain injury: neuroradiological and metabolic findings. Ann Neurol. 1990;27(6):652–659.

44.

Cummings JL. Neuropsychiatric manifestations of right hemisphere lesions. Brain Lang. 1997;57(1):22–37.

45.

Starkstein SE, Fedoroff P, Berthier ML, Robinson RG. Manic-depressive and pure manic states after brain lesions. Biol Psychiatry. 1991;29(2):149–158.

46.

Starkweather A, Sherwood P, Lyon DE, McCain NL, Bovbjerg DH, Broaddus WC. A biobehavioral perspective on depressive symptoms in patients with a cerebral astrocytoma. J Neurosci Nurs. 2011;43(1):17.

47.

Mainio A, Hakko H, Timonen M, Niemelä A, Koivukangas J, Räsänen P. Depression in relation to survival among neurosurgical patients with a primary brain tumor: a 5-year follow-up study. Neurosurgery. 2005;56(6):1234–1242.

48.

Wellisch DK, Kaleita TA, Freeman D, Cloughesy T, Goldman J. Predicting major depression in brain tumor patients. Psychooncology. 2002;11(3):230–238.

49.

Turjanski N, Lloyd GG. Psychiatric side-effects of medications: recent developments. Adv Psychiatr Treat. 2005;11(1):58–70.

50.

Starkweather AR, Sherwood P, Lyon DE, et al. Depressive symptoms and cytokine levels in serum and tumor tissue in patients with an astrocytoma: a pilot study. BMC Res Notes. 2014;7(1):423.

51.

Armstrong TS, Cohen MZ, Eriksen LR, Hickey JV. Symptom clusters in oncology patients and implications for symptom research in people with primary brain tumors. J Nurs Scholarsh. 2004;36(3):197–206.

52.

Rooney AG, Carson A, Grant R. Depression in cerebral glioma patients: a systematic review of observational studies. J Natl Cancer Inst. 2011;103(1):61–76.

53.

Rooney AG, McNamara S, Mackinnon M, et al. Frequency, clinical associations, and longitudinal course of major depressive disorder in adults with cerebral glioma. J Clin Oncol. 2011;29(32):4307–4312.

54.

D’Angelo C, Mirijello A, Leggio L, et al. State and trait anxiety and depression in patients with primary brain tumors before and after surgery: 1-year longitudinal study. J Neurosurg. 2008;108(2):281–286.

55.

Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617.

56.

Krebber AM, Buffart LM, Kleijn G, et al. Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments. Psychooncology. 2014;23(2):121–130.

57.

Brinkman TM, Liptak CC, Delaney BL, Chordas CA, Muriel AC, Manley PE. Suicide ideation in pediatric and adult survivors of childhood brain tumors. J Neurooncol. 2013;113(3):425–432.

58.

Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med. 2012;366(14):1310–1318.

59.

Storm HH, Christensen N, Jensen OM. Suicides among Danish patients with cancer: 1971 to 1986. Cancer. 1992;69(6):1509–1512.

60.

Kendal WS. Suicide and cancer: a gender-comparative study. Ann Oncol. 2007;18(2):381–387.

61.

Kendal WS, Kendal WM. Comparative risk factors for accidental and suicidal death in cancer patients. Crisis. 2012;33(6):325.

62.

Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry. 2012;169(5):491–497.

63.

Shaw P, Mellers J, Henderson M, Polkey C, David AS, Toone BK. Schizophrenia-like psychosis arising de novo following a temporal lobectomy: timing and risk factors. J Neurol Neurosurg Psychiatry. 2004;75(7):1003–1008.

64.

Singer S, Brown A, Einenkel J, et al. Identifying tumor patients’ depression. Support Care Cancer. 2011;19(11):1697–1703.

65.

Rooney AG, Brown PD, Reijneveld JC, Grant R. Depression in glioma: a primer for clinicians and researchers. J Neurol Neurosurg Psychiatry. 2014;85(2):230–235.

66.

Fallowfield L, Ratcliffe D, Jenkins V, Saul J. Psychiatric morbidity and its recognition by doctors in patients with cancer. Br J Cancer. 2001;84(8):1011.

67.

Pelletier G, Verhoef MJ, Khatri N, Hagen N. Quality of life in brain tumor patients: the relative contributions of depression, fatigue, emotional distress, and existential issues. J Neurooncol. 2002;57(1):41–49.

68.

Mainio A, Tuunanen S, Hakko H, Niemelä A, Koivukangas J, Räsänen P. Decreased quality of life and depression as predictors for shorter survival among patients with low-grade gliomas: a follow-up from 1990 to 2003. Eur Arch Psychiatry Clin Neurosci. 2006;256(8):516–521.

69.

Rooney AG, McNamara S, Mackinnon M, et al. Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments. Neuro Oncol. 2013;15(1):122–129.

70.

Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale: an updated literature review. J Psychosom Res. 2002;52(2):69–77.

71.

Kroenke K, Spitzer RL, Williams JB. The Phq-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–613.

72.

Beck AT, Steer RA, Brown GK. Beck Depression Inventory-II. San Antonio: 1996.

73.

Pilling S, Anderson I, Goldberg D, Meader N, Taylor C. Guidelines: depression in adults, including those with a chronic physical health problem: summary of NICE guidance. BMJ. 2009;339:b4108.

74.

Hart SL, Hoyt MA, Diefenbach M, et al. Meta-analysis of efficacy of interventions for elevated depressive symptoms in adults diagnosed with cancer. J Natl Cancer Inst. 2012;104(13):990–1004.

75.

Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry. 2013;12(2):137–148.

76.

Rooney A, Grant R. Pharmacological treatment of depression in patients with a primary brain tumour. Cochrane Database Syst Rev. 2010;3:CD006932.

77.

Boele FW, Klein M, Reijneveld JC, Verdonck-de Leeuw IM, Heimans JJ. Symptom management and quality of life in glioma patients. CNS Oncol. 2014;3(1):37–47.

78.

Caudill JS, Brown PD, Cerhan JH, Rummans TA. Selective serotonin reuptake inhibitors, glioblastoma multiforme, and impact on toxicities and overall survival: the mayo clinic experience. Am J Clin Oncol. 2011;34(4):385–387.

79.

Boele FW, Verdonck-de Leeuw IM, Cuijpers P, Reijneveld JC, Heimans JJ, Klein M. Internet-based guided self-help for glioma patients with depressive symptoms: design of a randomized controlled trial. BMC Neurol. 2014;14(1):81.

80.

Bell AC, D’Zurilla TJ. Problem-solving therapy for depression: a meta-analysis. Clin Psychol Rev. 2009;29(4):348–353.

81.

Bohlmeijer E, Prenger R, Taal E, Cuijpers P. The effects of mindfulness-based stress reduction therapy on mental health of adults with a chronic medical disease: a meta-analysis. J Psychosom Res. 2010;68(6):539–544.

82.

Hofmann SG, Sawyer AT, Witt AA, Oh D. The effect of mindfulness-based therapy on anxiety and depression: a meta-analytic review. J Consult Clin Psychol. 2010;78(2):169.

83.

Mishra SI, Scherer RW, Snyder C, Geigle PM, Berlanstein DR, Topaloglu O. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev. 2012;8:CD008465.

84.

Galway K, Black A, Cantwell M, Cardwell CR, Mills M, Donnelly M. Psychosocial interventions to improve quality of life and emotional wellbeing for recently diagnosed cancer patients. Cochrane Database Syst Rev. 2012;11:CD007064.

85.

Madhusoodanan S, Danan D, Brenner R, Bogunovic O. Brain tumor and psychiatric manifestations: a case report and brief review. Ann Clin Psychiatry. 2004;16(2):111–113.

86.

Shah AH, Gordon CE, Bregy A, Shah N, Komotar RJ. Considering iatrogenic psychosis after malignant glioma resection. BMJ Case Rep. 2014;2014:bcr2013201318.

87.

Karyem BH, Dunn NR, Swift RG. Psychosis after right temporal lobe tumor resection and recurrence. J Neuropsychiatry Clin Neurosci. 2015;26(1):E47.

88.

Mace CJ, Trimble MR. Psychosis following temporal lobe surgery: a report of six cases. J Neurol Neurosurg Psychiatry. 1991;54(7):639–644.

89.

Madhusoodanan S, Opler MG, Moise D, et al. Brain tumor location and psychiatric symptoms: is there any association? A meta-analysis of published case studies. Expert Rev Neurother. 2010;10(10):1529–1536.

90.

Sokolski KN, Denson TF. Exacerbation of mania secondary to right temporal lobe astrocytoma in a bipolar patient previously stabilized on valproate. Cogn Behav Neurol. 2003;16(4):234–238.

91.

Young WB, Heros DO, Ehrenberg BL, Hedges TR. Metamorphopsia and palinopsia: association with periodic lateralized epileptiform discharges in a patient with malignant astrocytoma. Arch Neurol. 1989;46(7):820–822.

92.

Kanemoto K, Kawasaki J, Mori E. Postictal psychosis as a risk factor for mood disorders after temporal lobe surgery. J Neurol Neurosurg Psychiatry. 1998;65(4):587–589.

93.

Trimble MR. The Psychoses of Epilepsy. Raven Press; 1991.

94.

Braun CM, Dumont M, Duval J, Hamel-Hébert I, Godbout L. Brain modules of hallucination: an analysis of multiple patients with brain lesions. J Psychiatry Neurosci. 2003;28(6):432.

95.

Edell WS, Tunis SL. Antipsychotic treatment of behavioral and psychological symptoms of dementia in geropsychiatric inpatients. Am J Geriatr Psychiatry. 2001;9(3):289–297.

96.

Ross DA, Cetas JS. Steroid psychosis: a review for neurosurgeons. J Neurooncol. 2012;109(3):439–447.

97.

Kolthof HJ. Moderne antidepressiva en hallucinaties. Tijdschr Psychiatr. 2014;56(6):407–412.

98.

Sivec HJ, Montesano VL. Cognitive behavioral therapy for psychosis in clinical practice. Psychotherapy. 2012;49(2):258.

99.

Wiersma D, Jenner JA, Nienhuis FJ, Willige G. Hallucination focused integrative treatment improves quality of life in schizophrenia patients. Acta Psychiatr Scand. 2004;109(3):194–201.

100.

Chadwick P. Mindfulness for psychosis. Br J Psychiatry. 2014;204(5):333–334.

101.

White R, Gumley A, McTaggart J, et al. A feasibility study of acceptance and commitment therapy for emotional dysfunction following psychosis. Behav Res Ther. 2011;49(12):901–907.

102.

Thomas N, Hayward M, Peters E, et al. Psychological therapies for auditory hallucinations (voices): current status and key directions for future research. Schizophr Bull. 2014;40(suppl 4):S202–S212.

103.

Ricciardi L, Demartini B, Fotopoulou A, Edwards MJ. Alexithymia in neurological disease: a review. J Neuropsychiatry Clin Neurosci. 2015.

Creative Commons License © 2015 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.