Tarun Bastiampillai

Is depression contagious? The importance of social networks and the implications of contagion theory

Australian & New Zealand Journal of Psychiatry, 47(4) It is well recognised that mood and behaviour are significantly influenced by social and environmental circumstances. In particular, social contagion theory hypothesises that emotions can behave like infectious diseases spreading through groups of intimates in social networks (Hill et al., 2010), leading to population clusters with higher rates of mood symptoms. Hazell (1993) used the same infectious disease model to describe the potential clustering of adolescent suicide. Until recently, the social transmission of mood and behaviour has been hard to track. The complex and dynamic nature of human relationships makes it difficult to quantify the effect of mood contagion at a population level. Using sophisticated social network analysis of large datasets, such as the Framingham Heart Study (FHS), Christakis and Fowler (2012) have examined the structural and qualitative architecture of social networks and the dynamic changes that took place over a 32-year period in the FHS. Utilising complex mathematical modelling, they were able to assess how the social architecture of a community influenced the incidence and spread of a variety of health and behavioural outcomes in Framingham, Massachusetts. Emotional contagion is often considered to be transient but the FHS studies found the effects could be long term and profound. Obesity, smoking, alcohol use, depression, loneliness and happiness spread through the web of relationships within broader social networks, with effects occurring over decades (Cacioppo et al., 2009; Christakis and Fowler, 2007, 2008; Fowler and Christakis, 2008; Rosenquist et al., 2010, 2011). Using this unique longitudinal dataset of the FHS, the studies showed that there was a social contagion component for mood including depression, loneliness and happiness (Christakis and Fowler, 2008, 2012; Hill et al., 2010; Rosenquist et al., 2011). Their model (Christakis and Fowler, 2012) specifically demonstrated that these social health effects were not just a selection effect in that ‘birds of a feather flock together’ or that there was a shared environmental exposure. Depressed people not only sought out others with depressive symptoms, but also they changed each other’s mood over extended periods of contact. Interestingly, they found that ‘friends of a friend of a friend’ (up to three degrees of separation) were influenced by the contagious spread of mood (Hill et al., 2010; Rosenquist et al., 2011). Of particular importance was the finding that friends were significantly more influential than family members in the spread of mood, especially among women (Rosenquist et al., 2011). This latter finding of the more marked influence of peers compared to family members is somewhat surprising and certainly warrants further investigation. Positive and negative emotional states behaved much like infections, gradually spreading through social networks (Hill et al., 2010). The effects were cumulative, with increased risks associated with the number of contacts with low or positive mood. Contagion of mood states likely relates to a combination of the spread of ideas, behaviours and affect. The precise mechanism is not known but it likely has both unconscious and conscious elements. The unconscious element could relate to automatic mimicry (Hatfield et al., 1993) and the mirror neuron system (Ocampo and Kritikos, 2011). Through afferent feedback, the receiver feels the sender’s expressions, and this leads towards emotional convergence (Hatfield et al., 1993). The conscious component could be due to shared communication styles such as co-rumination, especially amongst young women (van Zalk et al., 2010). Peer influence mechanisms in the adolescent literature include engaging in high-status behaviours, matching the social norms of a valued or desired group, engaging in behaviours that are reinforced by peers and engaging in behaviours that contribute to a favourable self-identity (Brechwald and Prinstein, 2011). People may also adjust their communication styles based on social comparison in order to dynamically fit the social environment (Barsade 2002; van Zalk et al., Is depression contagious? The importance of social networks and the implications of contagion theory

Psychopathology in twins: ancient case study.

In a letter to this journal Pridmore provided an account of the Aboriginal myth ‘The Jealous Twins’ Perindi and Harrimiah, which Pridmore suggests is likely to be 5000 years old, followed by his psychiatric diagnostic speculations about the figures of the myth [1]. Pridmore treats the myth as an historical account, and the characters involved as if they were real people, to whom psychiatric diagnoses may be applied, as for example, ‘the information that is provided on symptoms is presented in ordinary, clear language rather than technical terms’, and ‘Perindi may have suffered a paranoid psychosis and Harrimiah a major depressive disorder’. When we consider the myth of Icarus and Daedalus we are unlikely to conclude that this father and son really fashioned wings with wax and feathers and really flew with them, or that the sun really did melt the wax of Icarus’ wings so that he fell to his death. We understand that the myth is a story of the imagination, a communication that represents something emotionally and culturally real, but not an account of real events or real people. Possibly it was not Pridmore’s explicit intention to convey the impression that Perindi and Harrimiah were real people, but if not then we are left with the conclusion that he has failed to grasp that psychiatric diagnosis is not applicable to the figures of myth. If one adopts the epistemological framework of psychiatric diagnosis, its potential validity must remain limited to real human beings; it cannot be logically or validly applied outside of this frame. It makes sense to suggest that the myth of Icarus and Daedalus deals with hubris, pride, and grandiosity, but it makes no sense to attribute a diagnosis of, say, narcissistic personality disorder to Icarus. Similarly it makes sense to consider, as Pridmore does, that the figures of Perindi and Harrimiah reflect elements of a split situation, and as reflecting psychotic and depressive aspects of the mind respectively, but this cannot be taken to support his conclusion ‘Perindi may have suffered from a paranoid psychosis and Harrimiah a major depressive disorder’. It would have made sense to consider the myth as an exploration of the nature of jealousy, as its name ‘The Jealous Twins’ suggests, but Pridmore makes no reference at all to this central theme. The second disturbing aspect of Pridmore’s analysis is the kind of psychiatric cultural imperialism that it conveys. I think it is unwise to simply superimpose a psychiatric perspective, which inevitably has significant cultural dimensions of its own, onto the imaginative creation of another culture. This is after all an Aboriginal myth, and in seeking to understand the meaning of this myth one might expect to begin by enquiring about the place of its origin, that is, in the Aboriginal culture and psyche. It is, of course, quite possible to argue that the scientific perspective has potential application that transcends cultural perspectives. Even if this possibility is allowed, however, Pridmore’s analysis remains invalid for the reasons outlined. It lies in the realm of pseudoscience rather than science. Pridmore suggests that his diagnostic conclusions may be ‘parsimonious and reasonable’; I would suggest they are parsimonious in every sense of the word, and quite unreasonable. Myths, like fairy tales and poetry, exist in what Winnicott has called the ‘transitional area’ of relating [2]. They are no one’s property and they defy reductionism.

Clozapine use in Australia

Clozapine is a well-recognized treatment for treatment-resistant schizophrenia. The Royal Australian New Zealand College of Psychiatrists (RAN ZCP) guidelines 1 and National Institute for Health and Clinical Excellence (NICE) guidelines 2 state that a trial of clozapine should be initiated in patients who do not respond adequately to trials of at least two different antipsychotics including one non-clozapine second generation antipsychotic. The guidelines have been supported by a number of studies, including the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) 3 and Cost Utility of The Latest Antipsychotic drugs in Schizophrenia Study (CUtLASS). 4

Exacerbation of tics secondary to clozapine therapy.

Pathological jealousy has been associated with conditions such as schizophrenia, delusional disorder, paranoid personality, bipolar disorder, alcohol use and head injury [1]. Irresistible and repetitive jealous thoughts, found in patients with obsessive compulsive disorder (OCD), has often been termed ‘obsessional jealousy’ [2 5], but the term is yet to find official recognition in literature. Available data on this subject have shown that obsessional jealousy is limited to marital or committed relationships [2 5]. We report obsessional jealousy arising in a young man, focused on his elder brother’s wife, which has not been reported until now. The patient was a 19-year-old, unmarried, Muslim man who was brought to the clinic at G. B. Pant Hospital by his family members because he would not let his sister-in-law go out of the house and had threatened to kill her if she did not comply with his demands. The patient lived in a joint family household, as is customary in Indian society. Soon after the marriage of his elder brother, 5 years prior to consultation, the patient started touching his sisterin-law casually, to which she had no objection initially. Two years prior to consultation he saw her dancing with another man and reprimanded her. Since that time he did not allow her to talk to any man and followed her around when she went out. He would frequently make comments to her for wearing provocative clothes. This persisted despite objection from the woman herself as well as from other family members. The patient confessed that he was ashamed of his behaviour at home but was unable to control himself. He said that he experienced unwanted and irresistible sexual thoughts towards women and feared that other men might be viewing his sister-in-law in the same way. He experienced excessive concerns regarding contamination, symmetry, bodily symptoms and harm coming to him. The patient was aware of the absurdity of these thoughts, despite which they persisted. There was no previous history of substance use or head injury. Earlier he had received imipramine for 6 weeks and escitalopram for 7 weeks, without any response. A diagnosis of OCD was made on the basis of clinical presentation. His baseline Yale Brown Obsessive Compulsive Scale score was 30, which decreased to 3 after 6 weeks on clomipramine 75 mg day . This case is atypical in the sense that the patient’s jealousy was focused on his sister-in-law, who was not his romantic or married partner. He did not oppose his brother’s relationship with her, while at the same time restricting her from interacting with other men. It can be argued that the patient had been brought up in an orthodox household but the patient’s views were not endorsed by the rest of the family. That the patient’s jealousy responded to clomipramine supports the view that it was obsessional in nature. This report highlights the point that obsessional jealousy can emerge in people not connected by a romantic or married relationship. It also emphasizes the importance of the person’s sociocultural and ethnic background in the development of psychopathology.

Mental health services reach the tipping point in Australian acute hospitals

As an independent commission, the NMHC has encourageddebate about their report. In a recent article in the Journal, Professor Ian Hickie, an NMHC Commissioner, supported “shifting the emphasis” from acute hospitals to community-based services, and he urged the federal government to act. The NMHC chair, Professor Allan Fels, echoed these views in his National Press Club Address in August 2015.He criticised federal government expenditure on acute-care hospitals as “payment for failure” and argued that mental health problems should be treated earlier to “catch people before they fall”.

Clozapine prescription patterns in Australia over the last 10 years

Clozapine is a clinically effective and well accepted therapy for patients with treatment-resistant schizophrenia. Both NICE guidelines and RANZCP guidelines recommend a trial of clozapine therapy if more conventional anti psychotic therapy is ineffective in the management of symptoms [1,2]. Our previous study was based on analysing the current use of clozapine in Australia (2009) and any interstate variations that were present [3]. The aim of this correspondence is to examine how the rates of clozapine use in Australia have changed over the last 10 years (2000 – 2009) and consider the possible reasons behind any variations. Through personal communication and access to the Hospira database we were able to ascertain the amount of clozapine that had been imported into Australia from 2000 – 2009 [Hospira, personal communication]. This allowed us to calculate the amount of clozapine being imported into Australia, per 1000 people over the age of 16 (Australian Bureau of Statistics) [4], per year (Table 1). As can be seen below, clozapine importation has signifi cantly increased over the last 10 years from 134 mg/1000 population in 2000 to 238 mg/1000 population in 2009. Since this data is comparing the amount of clozapine imported to the number of people in Australia (over age 16), an increase

Recurrent clozapine and lorazepam withdrawal psychosis with catatonia.

There is emerging evidence to suggest that downregulation in gamma-aminobutyric acid (GABA) neurotransmission may be involved in the expression of schizophrenia (Guidotti et al., 2005). Given this, pharmacological agents that enhance GABAergic signal transduction may have potential therapeutic benefits in the treatment of schizophrenia. We describe a case where GABAergic mechanisms are likely implicated in the clinical presentation and outcome of a patient with schizophrenia. Ms S is a thirty-nine year old woman who had been diagnosed with schizophrenia ten years ago. At the time of presentation she had been on clozapine for eight years. On therapeutic doses of clozapine 200mg daily her condition had been in remission. However, she had been episodically non-compliant with clozapine and on four previous occasions in the immediate period following clozapine cessation, the patient developed florid psychotic symptoms in the form of persecutory, grandiose delusions, disorganised behaviour and auditory hallucinations. She also displayed catatonic features (Bush Francis Catatonia rating scale of 20 indicating severe catatonia) with excitement, mutism, posturing, staring, negativism and echolalia. Each of these episodes required closed ward management and on every occasion, the patient’s symptoms resolved following reinstitution of clozapine. Of note, there was no history of catatonia prior to clozapine commencement. Given the history of clozapine non-compliance and the episodes of clozapine withdrawal psychosis with catatonia, the patient was commenced on a combination of risperidone depot and lorazepam, which resulted in a partial remission of her psychosis and no catatonic symptoms. During her admission lorazepam 2mg was ceased and within 48 hours she developed acute psychosis with catatonic features, identical to that, which occurred following clozapine withdrawal. The deterioration in mental state required closed ward management. Lorazepam was recommenced with significant reduction of psychotic symptoms and complete resolution of catatonia. Over the next seven months, and on a further four separate occasions, lorazepam 2mg was ceased. On each occasion, within 48 hours the patient became floridly psychotic with marked catatonia Given the above presentations following lorazepam withdrawal, the patient was maintained on risperidone depot and regular lorazepam. She was successfully discharged home on this combination with partial resolution of psychosis, no catatonic symptoms and adequate functioning. This case initially described a patient who presented with clozapine withdrawal psychosis. This has been previously well described (Moncrieff, 2006). However, the patient also had accompanying clozapine withdrawal catatonia which is less well-recognised and poorly understood (Bastiampillai et al., 2009), especially when in association with clozapine withdrawal psychosis. One possible explanation is that clozapine, along with its other mechanisms of action, potentiates GABA (Bragina et al., 2007; Marx et al., 2011). The association between clozapine and GABA is suggested in our case by the fact that catatonia is well known to be linked with GABA dysregulation (Northoff, 2002) and that the patient developed a similar psychosis with catatonia following withdrawal of lorazepam, a benzodiazepine that potentiates GABA. While lorazepam withdrawal catatonia has previously been described (Manjunatha et al., 2007), this patient also experienced lorazepam withdrawal psychosis – a clinical presentation that has not been reported. In this case, given the similar clinical presentations for clozapine and lorazepam withdrawal, we hypothesise that GABA dysregulation may be involved in the development of psychosis with catatonia in susceptible patients with schizophrenia. This case suggests that clozapine may potentiate GABA; and clozapine withdrawal psychosis and clozapine withdrawal catatonia may be associated with downregulation of GABA receptors. This potential link between GABA dysregulation and clozapine withdrawal psychosis has not been previously postulated and possibly has important clinical implications. In addition, GABAergic agents such as lorazepam may have specific antipsychotic effects in a subset of patients in addition to relieving catatonia. Given this, clinicians should be aware that some patients could experience a relapse of psychosis with catatonia when clozapine or lorazepam are withdrawn.

Impact of a psychiatric unit’s daily discharge rates on emergency department flow:

Objective: To investigate relationships between time spent in the emergency department (ED) in patients requiring admission to the psychiatric ward, the day of the week of presentation and the daily number of discharges from the psychiatric ward. Method: Retrospective analysis of patient flow as a function of day of week, time of day (a.m., p.m.), number of patients requiring admission and number of ward discharges over a one-year period, for all mental health related presentations to the ED of the Queen Elizabeth Hospital in Adelaide, South Australia, before their admission to the psychiatric inpatient facility. Results: The time spent by patients in the ED waiting for admission to the psychiatric ward was significantly greater on weekends. There were significantly fewer discharges from the psychiatric ward during weekends compared with weekdays. The average time spent by patients in the ED requiring admission to the psychiatric ward for those days when there were vacant beds was 17.9 hours (SD=14.5). More people presented to the ED with a psychiatric diagnosis in the afternoons. There was a significant inverse correlation between the time spent by patients in the ED requiring admission to the psychiatric ward per day and the number of discharges from the psychiatric ward per day. Conclusion: These findings demonstrate that patient flow is significantly slower on weekends because of fewer discharges from the ward, leading to longer times spent in the ED before ward transfer. Waiting times in the ED were very substantially greater than the proposed 4-hour target even when vacant beds were available, raising considerable doubt about that target being realistic for psychiatric patients.

Could modafinil be a drug of dependence

Modafinil is a novel, nonamphetaminebased wake promoting medication approved for narcolepsy and obstructive sleep apnoea. Owing to its activating and cognitive enhancing effects, there is an expanding list of off-label use, including the treatment of methamphetamine and cocaine withdrawal. Although modafinil was previously thought to be nonaddictive (Jasinski, 2000),we present a possible case of modafinil dependence. Mr A is a 23-year old man prescribed modafinil 200 mg for 6 weeks as an adjunctive treatment for daytime hypersomnolence and fatigue following methamphetamine withdrawal. The patient was admitted 6 months later with a methamphetamineinduced psychosis. It was discovered Mr A had also been abusing modafinil at a self-increased dose of 400 mg daily. His psychosis resolved and modafinil was to be ceased owing to lack of evidence in the long-term treatment of methamphetamine withdrawal. Mr A became extremely agitated regarding the planned cessation. He stated that since commencing modafinil, his chronic methamphetamine use had decreased significantly from daily to episodic use. He spoke positively about modafinil helping him concentrate, feeling energised and becoming more productive. Mr A’s accounts were contrary to the history provided by his parents, who attributed his daily modafinil use as the cause for his recent difficulties in social and occupational functioning. Following protracted discussions, Mr A reluctantly agreed to cease modafinil and did not experience any withdrawal symptoms. In our opinion, Mr A satisfied the DSM 5 criteria for substance abuse disorder as highlighted by his psychological craving, unwillingness to cease use, social and occupational impairment, risky use, self-initiated increase in dose and continued attempts to source modafinil. Our literature search identified only one report of modafinil dependence in a patient with schizophrenia taking supratherapeutic doses of 2000 mg daily for 12 months (Kate et al., 2012). At a neurobiological level Volkow et al. (2009) demonstrated that modafinil exhibited a dose-dependent inhibition of dopamine transporters. This action reduces reuptake of dopamine and increases synaptic dopamine concentrations, particularly within the nucleus accumbens, an essential component in the biological pathway of addiction. This case highlights the potential of modafinil to be a drug of dependence. On this basis, clinicians should adopt a cautious approach when prescribing modafinil, especially in patients with a known history of substance abuse problems. Further clinical and basic science research is warranted focusing on its potential for abuse and dependence.

Varenicline induced psychosis in schizophrenia

Patients with schizophrenia have significantly reduced life expectancy compared to the general population. Much of this increased mortality could possibly be attributed to smoking related illness as rates of smoking are high (up to 75%) in this population (Hennekens et al., 2005). Varenicline is a pharmacologic agent used to help with smoking cessation. It has partial agonist and antagonist effects at α4β2 nicotinic acetylcholine receptors (Stahl, 2008). As an agonist with high affinity it counters the smoking cessation-induced reduction in mesolimbic dopamine levels, potentially relieving withdrawal symptoms. As an antagonist it prevents nicotine-induced dopaminergic activation on reward circuits. However there has been a reported association between varenicline use and neuropsychiatric events in patients with a history of mental illness (Lorenz et al., 2010). Due to the strength of this relationship varenicline has been given an FDA ‘boxed warning’ label advising caution in prescribing it for patients with a known history of mental illness (US Food and Drug Administration, 2009). We present a report of a 42-yearold woman, Ms Z, with a history of Schizophrenia commencing at the age of 35 years. Ms Z’s maintenance medication to prevent relapse was risperidone depot preparation 25mg given fortnightly. On risperidone depot she had no hospital admissions in the preceding 12 months. Ms Z was a chronic heavy smoker and consulted her GP about quitting. She was prescribed varenicline on a normal dose regime (0.5 mg for 3 days and 1mg/d for next 4 days followed by 2 mg/day). Within 5-6 days of varenicline initiation she started becoming unwell, characterised by sleep disturbance, irritability, disorganisation and increasing paranoia. A week after commencing varenicline therapy, Ms Z was detained by the Community Mental Health Team. On admission, Ms Z presented with florid psychosis warranting closed ward management. On day two of admission, varenicline was ceased, prn benzodiazepines were administered and risperidone depot was continued. With these interventions Ms Z’s mental state quickly improved over the next four days and she was discharged after one week in hospital. On discharge her mental state was back to a baseline state. She remained in remission the following 12 months. This symptom presentation was given a Naranjo score of 6 (Naranjo et al., 1981), suggesting a probable adverse drug reaction. We would speculate that Ms Z’s psychotic episode described herein was precipitated by her varenicline use given the temporal association, the resolution of symptoms with withdrawal of the drug, the neurobiological plausibility (Stahl, 2008) and previous similar case reports (Lorenz et al., 2010). Our patient developed breakthrough psychosis even though she was on risperidone depot 25 mg fortnightly. It is of note that a recent study (Hong et al., 2011) mentions lack of neuropsychiatric side effects when varenicline was administered to patients with schizophrenia (n=69) on slow dose titration and moderate final daily dosing regime (1 mg/day). Doses at this level can still maintain a reasonable anti-smoking efficacy (Oncken et al., 2006). Varenicline may induce psychosis by producing prolonged bursts of action potentials on mesolimbic dopamine neurons, leading to supraphysiological dopamine release (Stahl, 2008). Clinicians should be aware of the potential for varenicline to induce psychosis in predisposed individuals. However, the efficacy of varenicline and overall health benefits of smoking cessation in psychiatric population is well documented. We hypothesize that slower dose titration and a moderate final dose regime (1mg/day) could potentially allow the receptors to adapt to the surge of dopamine, thereby minimising emergence of psychosis in the longer term whilst maintaining reasonable antismoking efficacy.